Osteoporosis and its main health outcome, fragility fractures, are large and escalating health problems. Skeletal damage may be the critical result of low-level prolonged exposure to several xenobiotics in the general population, but the mechanisms of their adverse effects are not clearly understood. The current study was aimed to investigate the possible ability of simultaneous subchronic peroral administration of selenium (Se) and diazinon (DZN) to induce changes in bone of adult male rats.2SeO3/L and 40 mg of DZN/L in drinking water, for 90 days. Ten 1-month-old males without Se and DZN intoxication served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy.In our study, twenty 1-month-old male Wistar rats were randomly divided into two experimental groups. In the first group, young males were exposed to 5 mg NaP < 0.05). These rats also displayed different microstructure in the middle part of the compact bone where vascular canals expanded into central area of substantia compacta. The canals occurred only near endosteal surfaces in rats from the control group. Additionally, a smaller number of primary and secondary osteons, as well as a few resorption lacunae were observed near endosteal surfaces in rats simultaneously administered to Se and DZN. The resorption lacunae as typical structures of bone resorption manifestation are connected with an early stage of osteoporosis. Histomorphometric analysis revealed that area, perimeter, maximum and minimum diameters of primary osteons’ vascular canals were significantly increased (P < 0.05) in the Se-DZN-exposed rats. On the other hand, all measured variables of Haversian canals and secondary osteons were considerable reduced (P < 0.05) in these rats.The body weight, femoral length and cortical bone thickness were significantly decreased in rats simultaneously exposed to Se and DZN (Simultaneous subchronic peroral exposure to Se and DZN induces changes in macroscopic and microscopic structures of the femurs in adult male rats, and also it can be considered as possible risk factor for osteoporosis. The current study contributes to the knowledge on damaging impact of several xenobiotics on the bone. Bone is a dynamic mineralized connective tissue constantly being remodelled. Bone growth, mineralization and remodeling are regulated by a complex array of feedback mechanisms depending on age, genetic, nutritional and environmental factors -3. ToxicSelenium (Se) is an essential trace element which occurs in various concentrations in the soil, water leading to variable Se contents in food . Industret al. [et al. [Organophosphorus (OP) compounds are one of the most common types of organic pollutants found in the environment . Residuaet al. . Finally [et al.  revealedHuman and animal exposures to several xenobiotics in the environment do not occur in isolation, and also pharmacological agents, other toxins, and diet can induce or supress their toxicity.Protective effects of Se  against DZN-induced histopathological changes in various organs have been noted in many studies -28, usinBased on known effects of DZN and Se on the bone and other organs already mentioned above we focused on detailed structural analysis of exposed bones in animal model. Therefore, the aim of our study was to determine in detail the effect of simultaneous subchronic peroral administration of Se and DZN on macroscopic and microscopic structure of femoral bone in adult male rats.Twenty 1-month-old male Wistar rats were obtained from the accredited experimental laboratory (number SK PC 50004) of the Slovak University of Agriculture in Nitra (Slovakia). These clinically healthy rats were randomly divided into two experimental groups of 10 individuals. Male rats were used, as they are less susceptible than females to xenobiotics’ toxicity -31.ad libitum. The first group (n = 10 rats) was daily exposed to 5 mg Na2SeO3/L  and 40 mg of DZN/L  in their drinking water for a total of 90 days. The doses of Se and DZN were chosen on the basis of studied literature [The rats were housed individually in plastic cages in an environment maintained at 20–24°C, 55 ± 10% humidity. They had access to water and food  terature -34 and oterature ,36 with terature . The secet al. [et al. [At the end of 90 days, all the rats were euthanized, weighed and their femurs were used for macroscopic and microscopic analyses. The right femurs were weighed on analytical scales with an accuracy of 0.01 g and the femoral length was measured with a sliding instrument. For histomorphometric analysis, the right femurs were sectioned at the midshaft of the diaphysis and the segments were fixed in HistoChoice fixative . The segments were then dehydrated in increasing grades 40 to 100%) of ethanol and embedded in Biodur epoxy resin  according to the method described by Martiniaková et al. . Transveet al. . The qua to 100%  [et al. , who claP < 0.05) between both experimental groups.Statistical analysis was performed using SPSS 8.0 software. All data were expressed as mean ± standard deviation (SD). The unpaired Student’s t-test was used for establishing statistical significance (P < 0.05) in comparison with the control group. Also, cortical bone thickness was significantly lower (P < 0.05) in these rats. On the contrary, femoral weight did not differ between the two groups  were also identified in anterior, posterior and lateral views. We found some primary and secondary osteons  near the endosteal surfaces. In the middle part of the compact bone, primary and secondary osteons were observed. The periosteal border was again composed of non-vascular bone tissue, mainly in the anterior and posterior views Figure .The rats simultaneously exposed to Se and DZN displayed a similar microarchitecture to that of the control rats, except for the middle part of the compact bone in the medial and lateral views. In these views, vascular canals were shown to have expanded into the central area of the bone. The expansion in some cases was so enormous that the canals also occurred near periosteal surfaces. Therefore, a smaller number of primary and secondary osteons was identified in these rats. Moreover, a few resorption lacunae were found near endosteal surfaces in rats co-administered by Se and DZN which indicate the early stage of osteoporosis Figure .P < 0.05). However, these rats displayed significantly decreased levels of all variables of Haversian canals and secondary osteons (P < 0.05).For the quantitative histological analysis, 424 vascular canals of primary osteons, 410 Haversian canals and 410 secondary osteons were measured in total. The results are summarized in Table 2SeO3/L and 40 mg of DZN/L in drinking water for 90 days resulted in a significant decrease in body weight and femoral length in adult male rats. Thorlacius-Ussing et al. [2SeO3 in their drinking water which is associated with reduced production of growth hormone (GH) and insulin-like growth factor I (IGF-I). The results by Gronbaek et al. [2SeO3/L in drinking water for 35 days related to Se-induced significant reduction in circulating IGF-I. In our previous study [2SeO3/L in their drinking water for 90 days was also observed. DZN is known to show its toxic effects by inhibiting cholinesterase activity. According to Kalender et al. [et al. [et al. [via gavage was identified. DZN-induced inhibition in growth of some skeletal elements, such as femur, tibia, metatarsi and digits of the leg in chick embryos was also demonstrated [Simultaneous subchronic peroral exposure to 5 mg Nag et al.  observedk et al.  also docus study , the decr et al.  and Raza [et al.  the redu [et al. , decreasnstrated .et al. [et al. [2SeO3/L in their drinking water for 90 days [et al. [The thickness of cortical bone is generally accepted as an important parameter in the evaluation of cortical bone quality and strength. The values of cortical bone thickness in rats from the control group differed from those reported by Comelekoglu et al.  and Chov [et al. , who ana 90 days . Moreove [et al. , demonst [et al. .et al. [According to Szarek et al. , Se is aet al. -53. Thuset al. . Accordiet al. -58, Se cet al. . Similaret al. .The results of the qualitative histological analysis of the control rats corresponded to those of previous works -63. We iet al. [2SeO3/kg of diet for a period of 12 weeks). Also, it is known that Se at high doses induces apoptosis in mature osteoclasts [et al. [et al. [Simultaneous subchronic exposure to Se and DZN induced changes in the middle part of compact bone where primary vascular radial bone tissue was observed. We proposed that the formation of this type of bone tissue could be explained as an adaptive response to Se and DZN toxicity to protect bone tissue against cell death and subsequent necrosis. The study by Turan et al.  demonstreoclasts , osteobleoclasts , and osteoclasts . In resp [et al.  reported [et al.  observed [et al. . In our et al. [testes in rats co-administered by Se and DZN (at the same levels as were used in our study) were damaged and significantly dilated. Additionally, Ruseva et al. [Data obtained from the histomorphometric analysis showed a significant increase in area, perimeter, maximum and minimum diameters of the primary osteons’ vascular canals and on the other hand, a significant decrease of the Haversian canals’ variables in the Se-DZN-exposed rats. In general, the vascular system is a critical target for toxic substances and their effects on the vascular system may play an important role in mediating the pathophysiological effects of these substances in specific target organs . Blood vet al.  demonstra et al.  showed ta et al.  that theet al. [et al. [2SeO3/kg for 4 weeks. The incorporation of carbonate ions into the crystal structure of hydroxyapatite (HA) results in changes in the physical and chemical properties of HA [We found significantly lower values of all variables of secondary osteons in rats simultaneously exposed to Se and DZN. According to Jowsey , the valet al.  who foun [et al. , decreas [et al.  showed tes of HA . HA cryses of HA  creatinges of HA  through Our study demonstrates that simultaneous subchronic exposure to Se and DZN had a significant impact on bone structure and causes early stage of osteoporosis in rats. The obtained results can support the better understanding of osteoporosis mechanisms induced by environmental pollutants. However, possible extrapolation of the results to humans may be an interesting topic for discussion. The laboratory rat is preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome through detailed knowledge of its specific traits or with certain techniques. The similarities in pathophysiologic responses between the human and rat skeleton, combined with the husbandry and financial advantages, have made the rat a valuable model in osteoporosis research.2SeO3/L and 40 mg DZN/L in drinking water for 90 days affects the body weight, femoral length, cortical bone thickness, and both the qualitative and quantitative histological characteristics of femoral bone tissue in adult male rats. In addition, it induces early stage of osteoporosis. The results can be applied in experimental studies focusing on the effects of various xenobiotics on bone structure, especially when they are considered as possible risk factor for osteoporosis.This study demonstrates that simultaneous subchronic peroral administration of 5 mg NaThe authors declare that they have no competing interests.MM was responsible for qualitative histological analysis of bones and writing an article. IB was responsible for quantitative histological analysis of bones. RO was responsible for the statistical analysis. BG was responsible for preparation of histological sections. HC was responsible for macroscopic analysis of bones. JS was responsible for photodocumentation of histological sections. RT was responsible for animal care and sampling of femora. All authors read and approved the final manuscript.


BMC Genomics explore the genetic variation of chemosensory receptor gene repertoires in humans and mice and provide unparalleled insight into the causes and consequences of this variability.Chemosensory receptor genes encode G protein-coupled receptors with which animals sense their chemical environment. The large number of chemosensory receptor genes in the genome and their extreme genetic variability pose unusual challenges for understanding their evolution and function. Two articles in http://www.biomedcentral.com/1471-2164/13/414 and http://www.biomedcentral.com/1471-2164/13/415See research articles  BMC Genomics present comprehensive characterizations of the entire human OR and mouse VR repertoire.Humans sense odors with olfactory sensory neurons in the olfactory epithelium. Each olfactory sensory neuron expresses one G protein-coupled receptor from the large odorant receptor (OR) gene family. Different ORs have different ligand specificity and each odor therefore activates a different combination of sensory neurons. Many other mammals, including mice, have an additional olfactory organ, the vomeronasal organ. Instead of ORs, the sensory neurons in the vomeronasal organ express one gene from a repertoire of vomeronasal receptor (VR) genes. The VR gene repertoire consists of three families of G protein-coupled receptors: V1Rs, V2Rs, and formyl-peptide receptors (FPRs). The vomeronasal organ and the VRs play an important role in the detection of pheromones. Two articles in et al. [Mus musculus domesticus. The other four were wild-derived strains of Mus musculus subspecies and a different mouse species, Mus spretus. The authors' analysis led to the identification of over 6,000 non-synonymous single nucleotide polymorphisms (SNPs) in 366 VR genes. Mouse VR genes are 2.3 times as variable as other mouse genes. Olender et al. [Wynn et al.  interrogThere are likely to be several evolutionary processes driving the high variability of chemosensory receptor genes, including a substantial contribution from neutral genomic drift, the process of random gene duplication, deletion, or inactivation . Receptoet al. [et al. [et al. [It has been a challenge to identify directed evolutionary processes that shaped the chemosensory receptor gene repertoires in the background of the variability resulting from undirected effects of genomic drift . The datasets analyzed by Olender et al.  and Wynn [et al.  are larg [et al.  demonstret al. [et al. [Similar results were obtained by Wynn et al.  for the  [et al.  provide et al. [Genomic drift with purifying selection that acts only on a subset of the genes and a combination of balancing and perhaps also positive selection result in genetically highly diverse chemosensory receptors. What are the consequences of this genetic variability? In humans, genetic diversity will result in perceptual diversity. Each individual perceives olfactory stimuli with their personal set of ORs. Olender et al.  identifiet al. .et al. [et al. [Similar to the findings in human ORs, Wynn et al.  found thet al. , this va [et al.  and it iet al. [Although for most VRs the ligands are unknown, groups of V2Rs that respond preferentially to conspecific odor cues, odors from other rodent species and subspecies, or predator odors have recently been identified . Intereset al.  found moet al. . Rather et al. [et al. [We are only just beginning to understand the causes and consequences of the unusual genetic and functional variability of large chemosensory receptor gene repertoires in different species. The comprehensive data on genetic variability in the human OR and mouse VR repertoire presented in the articles by Olender et al.  and Wynn [et al.  will be


Linked Comment: Jackson. Int J Clin Pract 2013; 67: 385.Linked Comment: Walach et al. Int J Clin Pract 2013; 67: 385–6.Linked Comment: Posadzki and Ernst. Int J Clin Pract 2013; 67: 386–7.Linked Comment: Grimes. Int J Clin Pract 2013; 67: 387.Linked Comment: Tournier et al. Int J Clin Pract 2013; 67: 388–9. We would like to respond to the comments by Tournier et al.  as folloThe issues regarding the case report of Geukens, were addressed in our previous response .Regarding the articles by Barquero-Romero (2004), Lim (2011), Luder (2000) and Prasad (2006) we see no good reason for the notion that the four deaths following ingestion of homeopathic remedies could have been prevented if a ‘competent qualified homeopath’ had acted more ‘responsibly’. In fact, we very broadly covered the issues of some homeopaths' professional irresponsibility and its consequences in the discussion section.Tournier et al., seem to confuse the report by Zuzak et al. (2010) with the one by Von Mach et al. (2006). The former included nine cases of intoxications following the ingestion of homeopathic remedies, whereas the latter reported the figure of 1070 cases. In the case series by Zuzak, the 2143 cases were omitted because they referred not to therapeutic but to accidental intake of homeopathic remedies. Perhaps we should have included those cases too. Then the total number of patients who experienced AEs of homeopathy would have amounted to 3293!We provided clear definitions of homeopathy in the introduction to our review.Rhus tox (2CH). Tincture of aconite presented in the case by Guha et al. (1999) is technically speaking, a homeopathic remedy. Tournier et al. know of course that the method of preparation of Aconitum napellus varies in different pharmacopoeias and therefore safety issues arise when these differences are neglected (Sasseville (1995) provided full details of the composition of the ointments along with the level of dilution, e.g. Rhus tox CH. Tincteglected .In our view, the data extraction of the CR by Bernez et al. (2008) and its interpretations were correct. We regret, however, that the translation of the Danish text has led to confusion.In view of these arguments, we reject the accusation of Tournier et al. that our results  are unre


Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. Bone Bone tissue engineering (BTE) has been emerging as a valid approach to the current therapies for bone regeneration . In contet al. at the University of Florida. It can promote gene expression and production of osteocalcin [Among various kinds of biomaterials, bioactive ceramics are considered as the most promising material for BTE. Some bioactive ceramics such as hydroxyapatite (HAP), tricalcium phosphate (TCP), bioactive glass (BG) and calcium silicate (CS) have been profusely investigated as biomaterials owing to their capability to form direct bonds with living bone after implantation in bone defects . HAP is eocalcin . CS has eocalcin . TherefoThis article summarizes the research progress and status of bioactive ceramics scaffolds for BTE at home and abroad. The materials, structure and fabrication technology of ceramic scaffold used in recent years are discussed in detail. The interaction mechanisms between bioactive ceramics and cells are presented. The developments of bioactive nanoceramics and ceramic-based composite materials are also reviewed. Moreover, the problems existed and developing trends of ceramic scaffold for BTE are described.2.A scaffold must have appropriate mechanical properties to match and form firm connections with the newly formed tissue due to the complicated stress environment of human skeleton system . High elBioactive ceramics are known to enhance osteoblast differentiation as well as osteoblast growth. However, their clinical applications have been limited because of their brittleness, difficulty of shaping, and an extremely slow degradation rate in the case of HAP. Also, they have poor fidelity and reliability and new bone formed in a porous ceramic scaffold cannot sustain the mechanical loading needed for weight-bearing bone –23.et al. [1/2 have been fabricated via conventional sintering. Fielding et al. [1/2; compressive strength: 130–180 MPa) in the human body [Wang et al.  reportedg et al.  fabricatman body ,27. Ther3.The brittleness of ceramic is attributed to the crack prior to fracture. The control of crack growth prior to fracture can improve the toughness and reduce the stress concentration caused by the acute angle effect of the crack . Therefo3.1.et al. [co-glycolide (PLGA) fiber as second-phase addition. The results showed that fiber-reinforced calcium phosphate bone cement exhibited more superior structural integrity and material strength than nonreinforced calcium phosphate bone cement. Zhang et al. [et al. [Losquadro et al.  used polg et al.  combined [et al.  investig3.2.et al. [et al. [et al. [Whisker is a filament of material that is structured as a single and defect-free crystal. Typical whisker materials are known for having very high tensile strength (on the order of 10–20 GPa) due to the ordered atomic arrangement and periodic structure of lattice . Müller et al.  reported [et al.  used HAP [et al.  investig3.3.et al. [2) nanocrystals within HAP matrix. The results revealed that nanocomposites possessed significantly higher mechanical strength compared with pure HAP and conventional HAP-based composites. Wei et al. [l-lactic acid) (nano-HAP/PLLA) composite using thermally induced phase separation techniques. The compressive modulus reached 8.3 MPa when the weight ratio of nano-HAP to PLLA was 50:50. Gentile et al. [w/w/w)) for bone repair. The tensile modulus increased from 4.72 ± 0.23 MPa for G1 to 6.46 ± 0.05 MPa for G4. Recently, they fabricated porous scaffolds made of chitosan/gelatin (POL) blends containing different amounts of CEL2 by freeze-drying [w/w). Zhu et al. [in situ synthesized ZrO2 nanoparticles on the surface of carbon nanotubes as second-phase addition. The results showed that the mechanical properties of alumina ceramics mixed with these composites were much better than that of ceramics alone.Ahn et al.  reportedi et al.  preparede et al.  preparede-drying . The comu et al.  used in The above methods could improve the strength and toughness of ceramics to some extent. However, some negative effects, including toxicity of whisker and depressed biological properties, are generated by the second-phase additions into matrix ,42. In p4.4.1.Nanotechnology is predominately directing the research of biomedical materials for attaining both sufficient mechanical properties and excellent biological performances . It is wBesides, the scaffold fabricated with nanoceramics also has superior properties in other respects. For example, scaffold degradation could match the growth rate of new bone by controlling the size of crystalline grain, which is important to improve bone graft healing rate and reduce complications. Researchers also found that nano-HAP can significantly suppress the growth of cancer cell line while have no effect on normal cells . There a4.2.It is known that nano-materials have tremendously specific surface area, high surface energy and that their atoms lack coordination . It is dIn order to restrain grain growth during fabrication of scaffold, many methods have been adopted to accelerate the sintering process. Lots of researchers tried to fabricate nanoceramics by hot pressing sintering or vacuum sintering –55. Howeet al. [et al. [Selective laser sintering (SLS) method is one of widely used rapid prototype technology . It is aet al.  fabricat [et al.  fabricat5.Besides the proper mechanical properties, it is a key point to obtain porous structure to create a microenvironment for cell adhesion and proliferation. Nature bone has multi-level three-dimensional pore structure which ranges from several nanometers to several hundreds of micrometers . It can 5.1.etc. [et al. [et al. [et al. [Conventional methods for the fabrication of porous structure mainly include pore-forming method, sintered microsphere method and chemical foaming method, etc. . The por [et al.  fabricat [et al.  fabricat [et al.  fabricat5.2.et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [Several methods have been applied successfully for the fabrication of scaffold with controlled pore structure and shape, such as fused deposition modeling (FDM), stereo lithography appearance (SLA), SLS and 3D printing technology. Espalin et al.  investig [et al.  fabricat [et al.  fabricat [et al.  investig [et al.  prepared [et al.  designed [et al.  designed [et al.  successf6.et al. [et al. [In vitro cell tests using the MC3T3 cell line demonstrated excellent biocompatibility and high level of bioactivity. In vivo animal experiments using Sprague-Dawley albino rats revealed good bone regeneration capability of PCL/BGNF composite when implanted in a calvarial bone defect. Xu et al. [in vivo bone-regenerative capacity and resorption of porous β-calcium silicate (β-CS) bioactive ceramics. The ceramics were implanted in rabbit calvarial defects and harvested after 4, 8 and 16 weeks. Results suggested a cell-mediated process involved in the degradation of β-CS in vivo. Silva et al. [et al. [et al. [Bone repair and regeneration are a complex interaction processes among scaffolds, cells and microenvironment . The suret al.  investig [et al.  fabricatu et al.  investiga et al.  evaluate [et al.  seeded h [et al.  cultured [et al. .7.Natural bone is a connective tissue largely composed of organic protein, collagen, inorganic mineral and cells . Obvious7.1.et al. [in situ co-precipitation and investigated the porosity, morphology, microstructure and mechanical properties of the scaffolds. The results showed that the introduction of HAP improved the compressive strength of scaffold and the pore size gradually decreased with the increase of HAP content. Cheng-zhen et al. [In vivo implantation in rats showed no inflammatory response after several weeks, and nano-HAP/collagen composite scaffold was found to promote new blood vessels formation and bone regeneration. Jingushi et al. [Natural biomaterials such as collagen, chitin, coral and chitosan demonstrate good biocompatibility and cellular affinity . Not onlet al.  preparedn et al.  producedi et al.  inoculat7.2.et al. [et al. [in vitro proliferation of the osteoblast-like cells was significantly enhanced on the nano-hydroxyapatite coated titanium-niobium alloy compared to the titanium-niobium alloy without coating.Metallic materials , Co-Cr-Mo alloy and titanium-nickel alloy) have become the material of choice for load-bearing implant applications due to high strength, good fatigue resistance and well machining properties. Among these materials, Ti is bioinert, resistant to corrosion and biocompatible with bone tissue. However, some metallic materials may produce adverse effects such as the release of significant amounts of metal ions into the tissues, which may result in complications such as inflammatory and immune reactions . Thus, tet al.  prepared [et al.  found th7.3.et al. [et al. [Biodegradable polymers are widely used as biomaterials for the fabrication of cartilage tissue engineering scaffolds. Besides, polymers have great design flexibility because their composition and structure can be tailored to specific needs . Biodegret al.  fabricat [et al.  fabricat7.4.et al. [w/w) composite as a bone graft extenders. The results showed the composite increased new bone formation in the calvarial defect model both quantitatively and qualitatively. Lin et al. [et al. [Bioactive ceramics differ from each other in mechanical properties and biological properties. A combination of two or more bioactive ceramics will provide a wide space for ceramic material design. Moreover, multiphase ceramic is expected to remedy the drawback of some materials and reach a better comprehensive performance . A singlet al.  fabricatn et al.  fabricat [et al.  develope8.An ideal scaffold should be biocompatible, bioactive and biodegradable for osteogenesis, osteoinduction and osteoconduction. In addition, the scaffold should possess sufficient porosity to accommodate cell proliferation and differentiation. It is also desirable for scaffolds to have adequate mechanical property and appearance in accordance with the defect parts. Our research team developed a homemade selective laser sintering system in order to prepare nano-ceramic artificial bone with outstanding mechanical properties. The minimum spot diameter of laser can reach 50 μm with the focusing system. The SLS system could realize arbitrary complex movements based on the non-uniform rational B-Spline (NURBS) theory ,107. We in vitro experiment in SBF indicates the gradual degradation of scaffold with the increase of immersing time (An ing time . A layering time . Human bing time . The hig9.in vivo experiments are necessary to master the evolution mechanism of mechanical properties and degradation of bioactive nanoceramics. We believe bioactive nanoceramics will become an ideal bone substitute material that is widely used in bone repair and regeneration in the future.The development of BTE provides an effective approach for bone repair and regeneration. The selection of scaffold material and structure optimization is quite important in order to fully mimic the 3D network structure of bone ECM. Among various kinds of biomaterials, bioactive ceramics are drawing more and more attention due to excellent biocompatibility, degradability and osteogenesis. Furthermore, bioactive ceramics possess the ability to induce differentiation of various stem cells. This paper summarizes the latest research progress of bioactive ceramics as bone scaffold materials, including main types of bioactive ceramics, mechanical properties, strengthening and toughening methods, bone-like apatite mineralization ability and cellular biocompatibility. The wide range of chemical composition of bioactive ceramics provides superior material foundation for control and optimization of the physicochemical and biological properties. Nanotechnology and composite materials provide new ways to improve the strength and toughness of bioactive ceramics, which further sophisticates the physicochemical and mechanical properties for BTE applications. Moreover, bioactive nanoceramics are exhibiting great potential for bone repair than conventional ceramics due to better mechanical and biological properties. Future studies should be focused on the responding mechanism between bioactive nanoceramics and cells on molecular and genetic level. On the other hand,


Ingvar , p. 21 tKlein et al. , p. 240 Notably, Klein et al.  includedNonetheless, some studies have failed to demonstrate a mnemonic advantage for encoding conditions that foster planning as compared to survival processing . Yet in the everyday situations discussed by Ingvar , it may So far, studies concerning “memory of the future” have focused mainly on cognitive processes. Although little is known about the neural processes that support encoding of simulated future events, a recent study by Martin et al.  indicateOver the last four decades, the concept of episodic memory has evolved into a multifaceted construct that is of great interest to researchers in various areas of psychology and neuroscience (for recent overviews, see Szpunar and McDermott,


The Comprehensive Geriatric Assessment (CGA) is an analytical tool increasingly implemented in clinical practice. Breast cancer is primarily a disease of older people; however, most evidence-based research is aimed at younger patients.A systematic review of literature was carried out to assess the use of CGA in older breast cancer patients for clinical decision making. The PubMed, Embase and Cochrane databases were searched.A total of nine useful full text article results were found. Only five of these were exclusively concerned with early breast cancer; thus, studies involving a variety of cancer types, stages and treatments were accepted, as long as they included early breast cancer.The results comprised a series of low sources of evidence. However, all results shared a common theme: the CGA has a use in determining patient suitability for different types of cancer treatment and subsequently maximizing the patient’s quality of life.There is not yet sufficient high level evidence to instate CGA guidelines as a mandatory practice in the management of breast cancer, due to the heterogeneity of available studies. More studies need to be conducted to cement current work on the benefits of the CGA. An area of particular interest is with regard to treatment options, especially surgery and chemotherapy, and identifying patients who may be suitable for these treatments. The Comprehensive Geriatric Assessment (CGA) is a multidisciplinary management tool aimed at determining an older person’s medical, psychological and functional capability .Current evidence regarding breast cancer is mainly appropriate to younger patients (≤65 years) as older patients are often excluded from clinical trials ,3. ThereDisadvantages of CGA include additional time of implementation and limited consensus regarding methodology, evaluation and utilization . ComprehCurrently, CGA is not used routinely in breast cancer patients worldwide; however, three main areas where CGA could potentially be implemented include the following.Since age alone may not be an accurate predictor of treatment outcome , CGA couGreater comorbidity increases risk of death from causes other than breast cancer ,6. ConseThere is the need for identification of patients with confounding health problems, social needs or other issues that may have otherwise remained undetected , which cAssessment in these areas allows establishment of targeted treatment plan specific to the individual patient, leading to potential benefits, such as optimization of medical treatment; improved diagnostic accuracy and prognosis; maintained function; and improved quality of life (QOL) -11.The aim of this systematic literature review was to analyze current evidence regarding CGA in early breast cancer and highlight possible areas for further research.Three online databases were searched for relevant literature, including full-text articles and abstracts. These were PubMed, Embase and the Cochrane Library, which cover most clinical studies with high level evidence. The following key words were used: comprehensive geriatric assessment, breast cancer, primary, operable. Studies published in English in the past 10 years  were included. Studies were excluded if: a form of geriatric assessment was not used in the methodology; there was no relation to cancer; or no early breast cancer patients were included ; number of participants (N); lower age cut-off of participants; type of cancer the participants had; stage of cancer; uniqueness of study; overall findings.Level of evidence was assessed using the system proposed by Harbour and Miller , where eNine full-text articles met our search criteria and all graded Level 3 for quality of evidence.Despite the aim of this review to evaluate CGA in early operable breast cancer, we found a minimal number of studies being this specific, so all studies which contained any number of early breast cancer patients are discussed.et al.[1. A pilot study by Extermann et al., recruitAfter CGA, cancer treatment was adjusted in four participants (36%); adjuvant endocrine therapy was selected in two patients and adjuvant chemotherapy in one patient. No information is available on the fourth patient.In addition, CGA addressed problems indirectly impacting on treatment, in a further six patients (55%), for example, patient cognition, social support and contra-indicating medications. These problems were effectively resolved.et al.[This study is unique in using the Functional Assessment of Cancer Treatment-Breast (FACT-B) instrument to measure QOL, validated by Extermann et al.. MeasureDue to the small number of patients (N = 15), findings from this study may not be comparable to all older primary breast cancer patients. Thus, more patients need to be recruited from several centers, to verify findings.et al.[2. A pilot study by Hurria et al., consistAverage completion time was 27 minutes (range 8 to 45 minutes) and 78% of the patients were able to complete with no assistance. Approximately 90% of participants were happy with the questionnaire length and 83% agreed it was easy to understand.This study used a cancer-specific geriatric assessment and has proven this is feasible. Of the 40 participants, 25% had breast cancer. The percentage of patients with primary operable cancer is unknown; findings specific to these patients cannot be determined.The potential of applying this cancer-specific geriatric assessment tool could be evaluated in a multicenter study.et al.[3. A prospective study by Pope et al. recruiteet al.[Pope et al. used an As age of the patient increased, functional status decreased. There was less comorbidity among breast patients, when compared to those with gastro-intestinal tumors (GIT) and genito-urinary tumors (GUT). This could be due to the large number of patients with early breast cancer included in this study, compared with GIT and GUT, which consisted of patients with more evenly distributed cancer stages; patients in later stages may experience more severe symptoms. Alternatively, this could be explained by gender; greater comorbidity may exist in the male rather than female population; breast cancer patients are mainly female and GIT and GUT patients largely male.This is an excellent international study using a large number of patients. All patients were receiving surgery, however only 47% for breast cancer, 87.3% being primary cases. Results appropriate to GIT and GIT cannot be differentiated from breast tumors in this study.4. Albrand and Terret  conducteet al.[This study suggests CGA components related to function, mentality, nutrition and comorbidity assist in determining fitness for oncological treatments. Comorbidity was measured using the Cumulative Index Rating Scale-Geriatric (CIRS-G), which is only used by this study and the study by Extermann et al. and, theet al..Similar studies need to be conducted on a larger scale in multiple centers. Comparison of participants to matched patients not receiving CGA would be useful to determine if patient factors are acknowledged due to CGA or by increasing awareness of the patient’s own disease status.et al.[5. A prospective, transversal study by Gironés et al. was condet al.[The study showed these older breast cancer survivors were able to maintain function, but had high comorbidity; consequently, long-term follow-ups are recommended for cancer survivors. Gironés et al. suggest Similarly, it would be useful if patients in this study were matched to patients not receiving CGA.6. A cross-sectional observational study by Molina-Garrido and Guillen-Ponce  was concThis CGA showed correlation to the briefer measures of BQ and VES-13; patients who had a score indicative of frailty on CGA were more likely to score a high level of frailty on BQ and VES-13. Therefore, there is potential to develop a screening tool for administration of CGA. This study suggests CGA should be implemented when VES-13 score is <3 .Of 41 patients, 56.1% had no daily medications and no one had more than three daily medications, indicating a possible level of good health in this cohort; it is expected that older people will have greater comorbidity and thus more daily medications. Furthermore, 78% of participants were married, which is a larger proportion relative to others studies  and, henet al.[7. A retrospective study in a single center conducted by Barthélémy et al. attemptePrognostic factors, for example, estrogen and progesterone receptor status, and tumor stage were recorded. The CGA included elements focusing on the domains of comorbidity, mood, medication, social support, environmental assessment, nutritional status and motor function.In this sample, 118 out of the 192 patients had at least one or more risk factors which would ordinarily justify the use of adjuvant chemotherapy. However, only 70 of these patients (59%) were actually recommended adjuvant chemotherapy after discussion with the multidisciplinary team. The patients who did not receive chemotherapy despite showing good indications, received adjuvant endocrine therapy as an alternative.et al.[Barthélémy et al. concludeIt is, however, worth noting that this study is largely regarding administration of chemotherapy, which is often not necessary for primary operable breast cancer cases, rather than assessing these patients at diagnosis aiming to formulate a management plan for primary therapy.et al.[8. Lazarovici et al. carried The CGA was conducted by a single geriatrician with oncological training. Where CGA was carried out before a treatment decision was made, this was done on the patient’s first visit to the geriatrician. The CGA assessed functional status, cognition, mood, nutritional status and comorbidity.P = 0.031). These patients were subsequently later taking fewer medications (P = 0.036) and more likely to received adjusted cancer treatment (P = 0.051).Recent weight loss of >10% was more frequent among the group of patients who had geriatric assessment before cancer treatment decision had been made  had metastatic disease. Therefore, there might be some selection bias in this study, as patients with primary operable breast cancer alone would have been less likely to be referred to the geriatrician under the criteria used in this study, and thus would not have undergone CGA.et al.[9. A further multicenter study by Hurria et al. aimed toet al.[Geriatric assessment was carried out before chemotherapy began. This study uses the same form of cancer-specific CGA as previously mentioned in the earlier study by Hurria et al..Regarding geriatric assessment, functional status, level of social activity, poor hearing and assistance required to take own medications, were important factors when considering chemotherapy toxicity.This study was conducted on a large scale with the aim to identify any general factors relevant to all cancer types and stages with regards to toxicity from chemotherapy. The study did not look at whether there were any additional or different factors based on particular cancer types or stages.Due to the heterogeneity of our sample papers, it is difficult to draw comparisons relating to our original aim of evaluating CGA use in early breast cancer.et al.[et al.[et al.[et al.[et al.[The studies by Extermann et al., Albrandet al., Gironésl.[et al. Molina- l.[et al. and Bartl.[et al. were soll.[et al. (N = 460l.[et al. conducteet al.[et al.[et al.[et al. [et al.[et al.[et al.[All studies used CGA to recognize comorbidities and significant factors present in their patients, which could potentially impact on treatment recommendation. The studies by Extermann et al., Hurria l.[et al. and Girol.[et al. looked a.[et al.  and Moli.[et al.  was to a. [et al., Hurria l.[et al. and Hurrl.[et al. were priAll studies were Level 3 grade of evidence; conclusions made may not be strong enough to require immediate change to clinical practice ,22.et al.[Most of the studies used a similarly designed CGA, excluding the studies using cancer-specific CGA, by Hurria et al.,20. The A number of studies ,13,15 imIt appears that of CGA may be difficult to complete due to impediments present in the older population in general ,27. ThisDue to the focused nature of this review, it appears that a number of important articles may have been excluded by our criteria, which are now discussed here.et al.[Girre et al. recruiteet al.[et al.[et al.[et al.[Also, an update of the study by Pope et al. was writl.[et al.. In addil.[et al. and Audil.[et al. underlinFrom the literature, there is not yet enough evidence to recommend CGA in early breast cancer patients. Currently, literature suggests that CGA may be useful in regard to treatment decision making in older cancer patients. This is consistent with the clinical and pilot research experience of the authors .This literature review is hampered by lack of evidence currently available concerning use of CGA in early breast cancer patients. Analysis of some studies was inhibited by the extent of information available, resulting in difficultly in drawing comparisons between studies. Evidence so far suggests that CGA is an important factor in determining treatment and management of early breast cancer by identifying confounding health and personal issues of the patient and their suitability for different treatments, where this is possible. Case–control and cohort studies need to be completed to compare outcomes of patients who receive CGA to those who do not.BQ = Barber Questionnaire; CGA = Comprehensive Geriatric Assessment; CIRS-G = Cumulative Index Rating Scale-Geriatric; FACT-B = Functional Assessment of Cancer Treatment-Breast; GIT = Gastro-intestinal tumours; GUT = Genito-urinary tumours; MGA = Multidimensional geriatric assessment; PACE = Pre-operative Assessment of Cancer in the Elderly; QOL = Quality of life; VES-13 = Vulnerable Elderly Survey.The authors declare that they have no competing interests.RMP carried out the literature research, data acquisition, data analysis and prepared the manuscript. KLC is the guarantor of the integrity of the study and defined the intellectual content. KLC, DALM and KC created the study concept and design. All authors edited the manuscript and read and approved the final manuscript.


There was an error in the Funding statement.http://www.arc-cancer.net), The Ligue Nationale Contre le Cancer (http://www.ligue-cancer.net). Muriel Busson was supported by FRM  (http://www.frm.org). DV was a recipient of the Ligue Nationale contre le Cancer. CB was supported by a HFSP fellowship (http://www.hfsp.org/). The K. B. lab is supported by the Agence Nationale de la Recherche  , the Université Paris-Sud, the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Ligue Nationale Contre le Cancer , and is a member of the Laboratory of Excellence LERMIT (Laboratory of Excellence in Research on Medication and Innovative Therapeutics) supported by a grant from ANR (Investissements d´Avenir). Dr Madly Brigitte was supported by the Fondation ARC and Dr Carine Jacquard by INCA . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The correct statement is: This work was supported by grants from ARC  (


Forty mice were randomly divided into four groups on the basis of the diet to be fed as follows: 5% (low) fat diet (T1: LF); 20% (high) fat diet (T2: HF); 20% fat containing 1% conjugated linoleic acid (CLA) (T3: HFC); and 20% fat containing 1% CLA with 0.5% biopolymers (T4: HFCB). The high-fat with CLA diet groups (HFC and HFCB) and the low-fat diet group (LF) tended to have lower body weights and total adipose tissue weights than those of the high-fat diet group (HF). Serum leptin and triglyceride were significantly lower in the high fat with CLA-fed groups (HFC and HFCB) and the low-fat diet group (LF) than those in the high-fat diet group (HF). It is noteworthy that the high-fat with CLA and biopolymers group (HFCB) showed the lowest serum triglyceride and cholesterol concentrations. In the high-fat-fed group (HF), voluntary travel distance as a measure of physical activity decreased after three weeks of feeding. However, the CLA-fed groups showed increased physical activity. The groups fed high-fat diets supplemented with CLA alone and with CLA and biopolymers had higher viscosity of small intestinal contents than that in the low- and high-fat dietary groups. It has long been proposed that increased energy expenditure due to physical activity may be the most important factor in body weight control. Pescatello and VanHeest  reportedet al. reportedl.[et al. also repl.[et al.. Thus, il.[et al. first rel.[et al.. Despitel.[et al.–10, how l.[et al. reportedl.[et al.. HoweverThere were no significant differences in food intake among the dietary groups  and 2. ATotal adipose tissue weight was calculated as the sum of perimetrial, mesenteric and retroperitoneal adipose tissue weights . The groet al.[et al.[et al.[et al.[Increased food intake and decreased energy expenditure may increase body weight. Westerterp-Plantenga  reportedet al. reportedet al. reportedl.[et al. reportedl.[et al. reportedl.[et al. reportedl.[et al.. Anotheret al.[et al.[Leptin is a protein hormone with important effects on the regulation of body weight and lipid metabolism. It is secreted by adipocytes in proportion to the amount of lipid stored and may function as a signal of body energy stores to the brain . Severalet al. suggesteet al.. Sneddonl.[et al. reportedl.[et al.. In our l.[et al., we founl.[et al.. Thus, oet al.[trans-10, cis-12 isomer of CLA decreases triacylglyceride concentrations. Baumgard et al.[de novo fatty acid synthesis, desaturation of fatty acids and triglyceride synthesis. Our findings in the present study agree with these results. In this study, serum glucose concentrations were not significantly different among the groups fed a high-fat diet . Conversely, Roche et al.[trans-10, cis-12 supplementation in mice was associated with increased serum glucose and insulin concentrations, whereas the cis-9, trans-11 supplementation group showed no weight loss, but had lower concentrations of triglyceride and free fatty acids. Lee et al.[Brown et al. reportedrd et al. reportedhe et al. reportedee et al. reportedet al.[tran-10, cis-12 isomer was administered, but not when a mixture of the trans-10, cis-12 and the cis-9, trans-11 isomer was administered; in contrast, Terpstra [et al. [et al.[In this study, serum triglyceride and cholesterol concentrations decreased in mice fed a high-fat diet supplemented by CLA and biopolymers. In previous studies, Riserus et al. found thTerpstra  reported. [et al. reportedet al.[et al. [et al.[Earlier studies have suggested that energy sources have a large influence on physical activity and weight gain. Wells et al. reported.[et al.  reported.[et al. . Mizunoy. [et al. also sugIn the present study, the viscosity of small intestinal contents may be associated with lipid digestion and absorption in the small intestine; in addition, differences in the viscosity of small intestinal contents would cause impairment in the hydrolysis and solubilization of lipids . Meyer atrans-10, cis-12 CLA, 26% cis-9, trans-11 CLA and 7% other. CLA isomers (>96% pure) were purchased from Matreya . Chitosan, pectin, Tween 20, acetic acid, sodium acetate, sodium chloride, monobasic sodium phosphate, dibasic sodium phosphate and Nile red were purchased from Sigma-Aldrich Chemical Company . Serum triglyceride, cholesterol and glucose assay kits were purchased from Thermo Electron, Inc. .CLA mixture used in this study contained 63% ad libitum throughout the experiment. Fresh food was given on days 0, 2 and 5. After 2 weeks of adaptation to the environment and voluntary travel distance testing, 40 animals were randomly divided into 4 groups and fed the following diets: 5% fat (T1: LF); 20% fat (T2: HF); 20% fat containing 1% CLA (T3: HFC); and 20% fat containing 1% CLA with 0.5% biopolymer per kg (T4: HFCB). All groups were fed their respective diets for 6 weeks. The formulation of the experimental diets and treatment groups are listed in Forty female ICR mice  and a semi-purified powdered diet were purchased from Harlan Teklad . Isocaloric diet formulations were designed by Harlan Teklad . Animals were housed in individual, wire-bottomed cages in a windowless room with a 12-h light/dark cycle, under a protocol approved by the Animal Care Committee of Konkuk University. Food and water were provided Ten mass percentage of chitosan was dissolved in acetate buffer solutions . Ten mass percentage of pectin was dissolved in phosphate buffer solutions . These solutions were stirred for 12 h and then mixed for 3 h using a magnetic stirrer. During mixing, 1 mL of Tween 20  was added dropwise to reduce surface tension and enhance formation of encapsulation. Biopolymer encapsulation was prepared by mixing a final volume of 10 wt% biopolymer solution and CLA together for 1 h using a bio-homogenizer. The mixture was continuously stirred for 15 min using power ultrasound at a frequency of 10 MHz, and this was then mixed with the experimental diets . This process was aimed at developing a coating layer around the lipophilic CLA. Encapsulation of biopolymers and CLA solution was confirmed using confocal microscopy .2 asphyxiation sacrifice.Food intake and body weight gain were measured weekly, and adipose tissues were weighed after COg for 15 min at 4 °C. Serum leptin and adiponectin concentrations were measured using ELISA kit  techniques, as specified by the manufacturers. Serum triglyceride, cholesterol and glucose concentrations were measured using the enzymatic assay kits , as per the manufacturers’ instructions.Blood was collected by cardiac vessel bleeding from anesthetized mice. Serum was obtained by centrifugation at 3,000 × Voluntary travel distance as a measure of physical activity was determined using wheel running systems. Mice were placed in an individual case (35 × 20 × 15 cm) containing a running wheel with a diameter of 10 cm under a 12-h light/dark cycle. After a period of familiarization (1 week), mice were allowed to run freely on the wheels. Data were collected daily for a period of 6 weeks. Voluntary travel distances were calculated through the use of the National Instruments Compact-DAQ, an NI 9411 module and a custom-designed LabVIEW program, which converted wheel revolution data to daily voluntary travel distance.et al.[Small intestinal contents were collected by gentle finger stripping. The small intestinal contents were pooled per tube. The viscosity of small intestinal contents was determined by the modified method of Turabi et al.. The visSmall intestinal contents were collected by gently finger stripping. The small intestinal contents and biopolymer encapsulation were analyzed through confocal microscopy. A confocal scanning fluorescence microscope  with a 20× objective lens was used to capture confocal images. Nile red (a lipid fluorescent dye) was excited with a 488-nm argon laser line. The fluorescence emitted from the sample was monitored using a fluorescence detector (543 nm) with a pinhole size of 150 μm. The resulting images consisted of 512 × 512 pixels, with a pixel size of 414 nm and a pixel dwell time of 5 s.The influences of dietary CLA and biopolymer encapsulation on lipid metabolism in mice fed high- and low-fat-fed diets were analyzed using SAS software  by the generalized linear model procedure. The Student-Newman-Keuls multiple range test was used to compare differences between means.From the results of this study, we conclude that the increase in the voluntary travel distance as a measure of physical activity resulting from dietary supplementation with CLA may be one of the main reasons for lipid depletion. Groups of mice fed a high-fat diet supplemented with CLA and biopolymers showed higher viscosity of small intestinal contents than the controls. This increase in viscosity may be one of the main reasons for triglyceride and cholesterol depletion. Thus, we assume that the lipid depletion effect of CLA may be accelerated by the addition of biopolymers. However, the nature of the relationship between increased physical activity and dietary CLA remains to be elucidated. The effect of CLA on lipid metabolism could be influenced to a large degree by the mixture of CLA isomers, CLA contents (or purity), dietary period or subjects. Therefore, future studies are needed to investigate how dietary CLA influences physical activity in animal models and how dietary supplementation with biopolymers is related to changes in lipid metabolism. The nature of the interaction between CLA and biopolymers  also requires further investigation.


Single-port, single-incision laparoscopy is part of the natural development of minimally invasive surgery. Refinement and modification of laparoscopic instrumentation has resulted in a substantial increase in the use of laparoendoscopic single-site surgery (LESS) in urology over the past 2 years. Since the initial report of single-port nephrectomy in 2007, the majority of laparoscopic procedures in urology have been described with a single-site approach. This includes surgery on the adrenal, ureter, bladder, prostate, and testis, for both benign and malignant conditions. In this review, we describe the current clinical applications and results of LESS in Urological Surgery. To date this evidence comes from small case series in centres of excellence, with good results. Further well-designed prospective trials are awaited to validate these findings. Natural orifice translumenal endoscopic surgery (NOTES) and laparoendoscopic single-site surgery (LESS) represent the latest evolution of minimally invasive surgery. They have been developed with the aim of preventing port-site complications, decreasing discomfort, and improving cosmetic outcomes associated with standard laparoscopic/robotic surgery.et al.[NOTES involves diagnostic or therapeutic interventions performed via existing orifices of the human body . In 2002,et al. reportedet al.The first urological use of LESS was reported in 2007 with theet al in 2005.[et al reported mean operative times of 2 h, with estimated blood loss of 10–150 mL, and mean length of hospital stay 2.2 days.[®, Covidien) used to enter the retroperitoneum. A 30° endoscope was subsequently used to bluntly develop the space with high CO2 pressures (20–30 mmHg). The 10 mm port was then replaced with two 5-mm ports through which a 5-mm endoscope and a 5-mm bipolar scissor were placed to complete the surgery. SARA was possible in 41 cases with similar complication rates between the two groups. While the mean operative times were significantly higher for SARA (56 vs 40 min), postoperative analgesic requirements and hospital length of stay were significantly less.Attempts to perform urological surgery through a single-incision began with a report by Hirano  in 2005. The inve in 2005.8 Desai e2.2 days. A singleSince the first laparoscopic nephrectomy was performed in 1991, laparoscet al.[The first single-port, nontransumbilical, simple nephrectomy was presented at the World Congress of Endourology in 2007. An R-poret al. Three huet al. A simpleet al[®. This was located in a 7 cm paramedian incision and operating time was 96 min. There were no complications and the specimen was retrieved intact.LESS radical nephrectomy has been described in several studies. Ponsky et al describeet al[® device was used through a single transumbilical incision. All nephrectomies were performed successfully without the need for conversion to conventional laparoscopic surgery, and without intra- or postoperative complications. Their median operative times were 141 min, and mean blood loss was 103 mL. They subsequently published their technique in detail, documenting that while this technique is indeed possible, it is challenging requiring high levels of laparoscopic skill.[Stolzenburg et al have pubet al[®. An additional 5-mm grasper was used in one case and the mean tumour size was 3 cm. Operating times were long (median 270 min), and average warm ischemia time was 20 min (11–29 min). All the margins were negative and there were no intraoperative complications. One patient had postoperative bleeding and pulmonary embolism. Kaouk et al[® provided intraabdominal access. One patient required conversion to conventional laparoscopy due to intraoperative bleeding. There was one positive margin but no postoperative complications.Nephron sparing surgery (NSS) has been shown consistently to have similar oncological outcomes for small renal tumours (<7 cm) as radical nephrectomy.16 NSS maet al publisheouk et al recentlyet al[et al[The two largest urological LESS series to date reported on 200 procedures.20 Included al[et al performeet al[Cryoablation of renal masses offers an alternative to open or laparoscopic nephron sparing surgery. Standard laparoscopic technique utilizes three ports either trans- or retroperitoneally. Goel et al successfet al[et al[® device. This allowed open access to the distal ureter but bariatric instruments were required for length.Nine cases of LESS nephroureterectomy were included in the two large LESS series.21 Cystoset al used a h al[et al performeet al,[® for access. The procedure was successful in all four patients with a median operating time of 3.3 h and minimal blood loss. The median warm ischaemia times were only 6.2 min, and the length of the harvested renal artery, vein, and ureter was excellent. There were no complications and all the allografts functioned immediately on transplantation. A subsequent matched-pair analysis comparing LESS donor nephrectomy (LESS-DN) with standard laparoscopic donor nephrectomy (LLDN) showed equivalence in operating time, blood loss, and hospital stay.[P < 0.0001), however, allograft function was comparable between groups. The patient convalescence after discharge  was significantly faster in the LESS-DN group. The two largest series to report on urological LESS surgery include 17[LESS transumbilical live donor nephrectomy was first reported by Gill et al, using a tal stay. The meannclude 17 and 19[2nclude 17 LESS donet al[et al[LESS pyeloplasty for pelvi-ureteric junction obstruction has been reported on with seemingly good results. Desai et al performe al[et al performeOther LESS renal procedures reported are renal cyst excision, renal biet al[Despite its high median stone-free rate, open ureterolithotomy is no longer recommended as a first-line treatment for ureteric stones, because of longer hospitalization and greater postoperative morbidity. Ureterolithotomy does remain a primary or salvage option in difficult situations with large, impacted or multiple ureteric stones. Laparoscopic ureterolithotomy is preferable because of its decreased invasiveness, and resultant reduced morbidity, and has been well described in this setting. One caseet al performeet al[et al[Desai et al performe al[et al performeet al[Autorino et al reportedet al[Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for patients with muscle invasive urothelial carcinoma of the bladder. It is also an option for patients in whom conservative treatment has failed in high-risk nonmuscle invasive bladder cancer. There is, however, significant morbidity associated with it, and this has led to the development of laparoscopic and robotic approaches. Although long-term data are lacking, in the short term at least laparoscopic (including robotic-assisted) radical cystectomy appears to offer equivalent oncological control, with reduced blood loss and analgesic requirements as well quicker return to bowel function. Kaouk etet al have recet al.[2 were operated on through the umbilicus using a single three-channel port. The urethrovesical anastomosis was performed with interrupted sutures and extracorporeal knot tying. The mean operative time was 285 min and the mean blood loss 288 mL. The average length of stay was 2.5 days and there were no intraoperative complications. One patient, however, developed a recto-urethral fistula. Short-term oncological and functional results were equivalent to other laparoscopic series. The same series was extended to six patients subsequently, with three having positive margins but remaining biochemically free of disease.[Minimally invasive radical prostatectomy is fast becoming the standard of care for prostate cancer. Robotic-assisted laparoscopic prostatectomy using the Da Vinci surgical system  is widespread, and although randomized prospective studies do not exist, clinical outcomes seem to be excellent in high volume centres. LESS radical prostatectomy was first described in 2008 by Kaouk et al. Four pat disease.et al. reported, in 2009, the first successful series of single-port robotic procedures in humans, including radical prostatectomy.[Kaouk atectomy. A robotiThe authors noted an improved facility for intracorporeal dissecting and suturing due to robotic instrument articulation and stability.et al. also reported their experience with a hybrid LESS robotic-assisted radical prostatectomy in a single patient.[Together with their preliminary experience in a cadaver model, Barret  patient. They pla patient. They utiet al published the initial series of single-port transvesical simple prostatectomy (STEP).[® or Quadport®) was inserted percutaneously into the bladder through a 2–3 cm incision in the suprapubic skin crease. The prostate adenoma was enucleated transvesically using standard laparoscopic instruments, and extracted in pieces through the port. Digital assistance was required in 55% of cases. One patient died in this series of uncontrolled haemorrhage, a Jehovah’s Witness who refused blood products. In addition, there was one bowel injury and two open conversions were necessary. Digital enucleation required extension of the incision by 1–2 cm. Average length of stay was 3 days, and at follow-up there was significant improvement of obstructive parameters with no patient catheter dependent or incontinent. One case in this series utilized the Da Vinci surgical platform. The authors commented that the Endowrist™ technology allowed better maneuverability in the transvesical environment. Specifically, the robotic grasper provided excellent retraction of the adenoma as it was progressively enucleated.Desai y (STEP). This sery (STEP). Mean proSingle-site laparoscopic surgery has been reported in small numbers for a variety of other urological conditions. Paediatric varicocoeles have been successfully operated open through a single transumbilical port. A mesh sLESS in urology is in its relative infancy but to date has proven to be safe and feasible in the hands of experienced laparoscopic surgeons, using specially designed ports and instruments in selected patients. Further refinements in instrumentation and operative techniques will be required before this method of surgical access can be widely accepted. LESS in urology requires prospective randomized studies to define the benefits of this technique for patients, as well as to elucidate the cost-effectiveness of the approach.The introduction of robotics into LESS may make these techniques finally realize their potential. Improvements in existing robotic platforms may pave41


In vitro, MSCs have the capacity to differentiate into multiple mesodermal and non-mesodermal cell lineages. Besides, MSCs possess immunosuppressive effects by modulating the immune function of the major cell populations involved in alloantigen recognition and elimination. The intriguing biology of MSCs makes them strong candidates for cell-based therapy against various human diseases. Type 1 diabetes is caused by a cell-mediated autoimmune destruction of pancreatic β-cells. While insulin replacement remains the cornerstone treatment for type 1 diabetes, the transplantation of pancreatic islets of Langerhans provides a cure for this disorder. And yet, islet transplantation is limited by the lack of donor pancreas. Generation of insulin-producing cells (IPCs) from MSCs represents an attractive alternative. On the one hand, MSCs from pancreas, bone marrow, adipose tissue, umbilical cord blood and cord tissue have the potential to differentiate into IPCs by genetic modification and/or defined culture conditions In vitro. On the other hand, MSCs are able to serve as a cellular vehicle for the expression of human insulin gene. Moreover, protein transduction technology could offer a novel approach for generating IPCs from stem cells including MSCs. In this review, we first summarize the current knowledge on the biological characterization of MSCs. Next, we consider MSCs as surrogate β-cell source for islet transplantation, and present some basic requirements for these replacement cells. Finally, MSCs-mediated therapeutic neovascularization in type 1 diabetes is discussed.Mesenchymal stem cells (MSCs) can be derived from adult bone marrow, fat and several foetal tissues.  IntroductionBiological characterization of mesenchymal stem cells- Isolation and culture of human MSCs- Phenotypic properties of MSCs- Multi-potent differentiation of MSCs- Immunomodulatory effects of MSCsAetiology and current treatment of type 1 diabetesMesenchymal stem cells in type 1 diabetes therapy- MSCs with potential to differentiate into insulin-producing cells- MSCs as cellular vehicle for insulin gene therapy- Induction of IPCs from stem cells by protein transduction technology- Minimum requirements for replacement β-cells- MSCs for therapeutic neovascularization in type 1 diabetesConcluding remarksMesenchymal stem cells (MSCs) were first identified by Friedenstein and his colleagues , who desIn vitro. Thus, MSCs provide an alternative β-cell source for islet transplantation.Diabetes mellitus is a devastating metabolic disease, which falls into two categories. Type 1 diabetes results from autoimmune-mediated destruction of β cells in the islets of Langerhans of the pancreas, while type 2 diabetes is due to systemic insulin resistance and reduced insulin secretion by islet β cells. In comparison with conventional or intensive insulin treatment, islet transplantation is the only therapy for type 1 diabetes that achieves an insulin-independent, constant normoglycemic state and avoids hypoglycemic episodes. However, the application of this treatment is restricted by the limited availability of primary human islets from heart-beating donors. Some recent studies indicate that MSCs can differentiate into insulin-producing cells by genetic and/or microenvironmental manipulation In this review, we will summarize the major biological features of MSCs, and their possible applications in the treatment of type 1 diabetes.in vitro culture conditions MSCs obtained from young donors can grow to 24–40 population doublings and the proliferative potential of the cells obtained from older donors is more compromised [in vitro[in vitro led to genetic instability and resulted in MSCs transformation [Standard conditions for generation of bone marrow derived mesenchymal stromal cultures have been reported , 9. Howepromised . Afterwapromised . Replica[in vitro, 16 due [in vitro, 18. Som[in vitro, 19, 20.ormation . It seemConsiderable progress has been made towards characterizing the cell surface antigenic profile of human bone marrow-derived MSC populations using fluorescence activated cell sorting (FACS) and magnetic bead-sorting techniques. Nevertheless, to date there is no specific marker or combination of markers that specifically identifies MSCs. Therefore, MSCs have been defined by using a combination of phenotypic markers and functional properties. It is generally agreed that adult human MSCs express Stro-1 , 22–23, In vitro and in vivo, including bone [e. g. neurons) [A large number of studies demonstrate that bone marrow-derived MSCs from human, canine, rabbit, rat and mouse have the capacity to differentiate into mesenchymal tissues both ing bone , 32, caring bone , fat [34ing bone , tendon ing bone , 37, musing bone , 39 and ing bone . In addineurons)  and endoneurons) .et al.[In vitro differentiation strategy, Song et al.[Individual colonies derived from single MSC precursors have been reported to be heterogeneous in terms of their multi-lineage differentiation potential , 42. Theet al. propose et al., 45, whiet al.–48. Usinng et al. showed tIn vitro and in vivo in a non-MHC restricted manner [In vitro, MSCs are able to suppress T lymphocyte proliferation induced by alloantigens [+ regulatory T cells that were responsible for inhibition of allogeneic lymphocyte proliferation [+ CD25+ regulatory T cells has been demonstrated in mitogen-stimulated peripheral blood mononuclear cell (PBMCs) cultures in the presence of MSCs [+ CD25+ regulatory T cells had no effect on the suppression of T cell proliferation by MSCs [MSCs have been shown to suppress immune reactions both d manner . These sd manner , 51, 52.antigens , 54, mitantigens , 55–58, antigens , 60. Supantigens , 61. Ano by MSCs . Apart f by MSCs , MSCs ca by MSCs , natural by MSCs , 64 and  by MSCs , 66. Alt by MSCs , 67, hep by MSCs , 63, pro by MSCs –70. Addi by MSCs , 69.in vivo. First, intravenous administration of MSCs derived from BM of baboons prolonged the survival of allogeneic skin grafts [et al.[et al.[The immunomodulatory capacity of MSCs has also been evaluated n grafts . Subsequn grafts . In phass [et al., 73 estis [et al.. In conts [et al.. Grinneml.[et al. observedIn the year 2000, 150 million people worldwide were found to be affected by diabetes mellitus, and this number is considered to double in 2025 . Type 1 Since 1920s, insulin therapy has changed diabetes from a rapidly fatal disease to a chronic disease associated with significant secondary complications, such as renal failure, cardiovascular disease, retinopathy and neuropathy. It is now well-established that the risk of diabetic complications is dependent on the degree of glycaemic control in diabetic patients. Long-term studies strongly suggest that tight control of blood glucose achieved by conventional or intensive insulin treatment, self blood glucose monitoring, and patient education can significantly prevent the development and retard the progression of chronic complications of this disease –82. Whilex vivo that include their ability to adopt a pancreatic endocrine phenotype. It has been demonstrated that MSCs residing in various tissues and organs are able to differentiate into functional insulin-producing cells, such as MSCs from pancreas, bone marrow, adipose tissue, cord blood and cord tissue. This will help to meet the demand of β cells for islet transplantation, and the goal of a permanent cure for type 1 diabetes will be realized.Among adult stem cells, MSCs appear to have a particular developmental plasticity ex vivo[et al.[In vitro[et al.[et al.[In vitro. Huang et al. [The mature pancreas has two functional compartments: the exocrine portion 99%), including acinar and duct cells, and the endocrine portion (1%), including the islets of Langerhans. Islets are composed of four cell types that synthesize and secrete distinct peptidic hormones: β-cells (insulin), α-cells (glucagon), δ-cells (somatostatin) and PP-cells (pancreatic polypeptide). It has been described that adult rat and human islets of Langerhans contain nestin-positive progenitor cells, which can be differentiated into insulin-expressing cells ex vivo. In anotvo[et al. displaye[In vitro. Then, Bro[et al. considerro[et al.. Recentll.[et al. showed tg et al.  further g et al. . In agreg et al.  successfg et al.  reportedg et al. , 96, 97,g et al. . However%, includg et al. . In concet al.[et al.[via enhanced endothelial proliferation by donor cells. In a similar study, Lee et al.[et al.[et al.[et al.[In vitro, bone marrow derived-cells obtained from mice [et al.[et al.[In vitro. In another study, Moriscot et al. [et al.[In vitro. Their results provide the direct evidence for the feasibility of using patient's own BM-MSCs as a source of IPCs for beta-cell replacement therapy.Bone marrow is an important source of easily accessible adult stem cells, and bone marrow transplantation (BMT) is considered to be effective for the treatment of autoimmune type 1 diabetes. However, there is a great debate on the issue of the fate of transplanted bone marrow stem cells. Ianus et al. showed tl.[et al. reportedee et al. demonstrl.[et al., Lechnerl.[et al. and Tanel.[et al. showed ll.[et al.. On the rom mice  and ratsrom mice  could bee [et al. proposede [et al. and Wu el.[et al. isolatedl.[et al. proved tt et al.  indicatet et al. , 116 hav. [et al. demonstret al.[MSCs from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes , 118–119et al. isolatedin vivo studies give support to this point. In one study [in vivo capacity of HUCB-derived cells to generate insulin-producing cells. Following transplantation of HUCB cells into NOD/SCID/β2mnull mice, IPCs of human origin were found in recipient pancreatic islets. Double FISH analysis using species-specific probes further indicated that HUCB cells can give rise to insulin-producing cells by fusion-dependent and -independent mechanisms. The number of HUCB cells that transdifferentiated and the rate of such an event are critical aspects. The proportion of HUCB-derived insulin-producing cells per total number of islet cells [et al.[In vitro and in vivo. Moreover, they indicated that UC-MSCs seem to be the preferential source of stem cells to convert into IPCs, because of the large potential donor pool, its rapid availability, no risk of discomfort for the donor, and low risk of rejection.Human umbilical cord blood (HUCB) is another source of stem cells with the potential to develop into insulin-producing cells. A few ne study , transplne study , transplne study  has focuet cells  was lesset cells . Howeveret cells  and HUCBet cells , it shous [et al. successfIn vitro. The proteins included coagulation factors VIII [in vivo to treat acquired and inherited disorders. As far as type 1 diabetes is concerned, insulin gene therapy using MSCs is an alternative treatment.MSCs are a promising target population for cell-based gene therapy against a variety of different diseases . The appors VIII , IX [129ors VIII , human gors VIII , human eors VIII  and so oet al.[i) the large capacity to accommodate a construct; (ii) the ability of the virus to infect primary and second cell lines In vitro; (iii) although the virus enters the nucleus it does not integrate with the host DNA and is therefore not likely to unmask oncogenes, it functions separate to the host DNA as an episome; (iv) most patients have already had contacts with the herpes I virus, which normally resides in a quiescent state in neurological tissue; (v). immune reaction against the virus is relatively mild; (vi) established antiviral treatment against the herpes virus is available. In consequence, the modified herpes I virus could serve as a new vector for human insulin gene delivery into MSCs. , HSV type 1 protein VP22 and HIV-1 transactivator TAT protein. The mechanism of PTD-mediated protein transduction is mainly via endocytosis followed by passage from the vesicle into the cytoplasm [New technology, known as protein transduction technology, has been recently developed. A variety of peptides, known as protein transduction domains (PTDs) or cell-penetrating peptides (CPPs), have been characterized for their ability to translocate into live cells. Proteins and peptides can be directly internalized into cells when synthesized as recombinant fusion proteins or covalently cross-linked to PTDs. There are numerous examples of biologically active full-length proteins and peptides that have been delivered to cells both ytoplasm .et al. demonstrated that PDX-1 [et al.[In vitro. In another research, Gräslund's group [It has been suggested that protein transduction technology is useful for the treatment of diabetes, because this technology facilitates the differentiation of stem cells into insulin-producing cells. First, PDX-1 protein and BETA2/NeuroD protein, two pancreatic endocrine transcription factors, both have a PTD sequence in their structure. Noguchi at PDX-1  or BETA2at PDX-1  protein 1 [et al. showed t's group  reportedAs mentioned above, insulin-producing cells generated either by transdifferentiation of MSCs or by delivery of insulin gene into MSCs are able to act as replacement β-cells for the transplantation therapy of type 1 diabetes. These MSCs-derived IPCs may solve the donor shortage issue for islet cell transplantation and provide a cure for this disease. Nevertheless, any substitute for primary islets of Langerhans will require some minimum essential properties. The basic requirements for surrogate β-cells are described as follows .6 primary human islets per recipient, equivalent to approximately 2–4 × 109β-cells. As a result, the ability of MSCs to replicate and to differentiate toward pancreatic endocrine phenotype makes them attractive candidates for producing replacement β-cells. Secondly, the replacement cells must have the ability to synthesize, store and release insulin in response to changes in the ambient glycaemia. Understanding β-cell function at the molecular level will likely facilitate to manufacture physiologically competent insulin-producing cells from MSCs. Thirdly, the proliferative capacity of the replacement cells must be tightly controlled to avoid the development of hyperinsulinemic hypogly-caemia as the β-cell mass expands in vivo. Excluding proliferative cells from the transplant material will help to overcome this problem. In the case of insulin gene transferred MSCs, the possibility of tumour formation has to be considered. Finally, the transplanted cells must avoid destruction by the recipient's immune system. Two major mechanisms are involved in the immune attack against replacement β-cells, one is transplant rejection and the other is recurrence of autoimmunity. In addition to appropriate immunosuppressive treatment, autologous transplantation of MSCs-derived IPCs will circumvent the immune rejection dilemma. On the other hand, Burt et al.[In vitro may differ significantly from those in vivo[In vitro differentiation protocols do not generate β-cells, but cells that have somephenotypic and functional similarity to authentic β-cells. Since IPCs generated from MSCs are developmentally and immunologically distinct from primary β-cells, they may escape the recipient's autoimmune assault.First, to make any significant therapeutic impact vast numbers of replacement β-cells will be required. Current transplantation protocols use up to 1 × 10rt et al. indicatee in vivo, and it et al.[It has been demonstrated that endothelial progenitor cells (EPCs) are responsible for postnatal vasculogenesis in physiological and pathological neovascularization . Ischaemet al. providedin vivo[In vitro[et al.[et al.[MSCs have been shown to promote angiogenesis both in vivo and In v[In vitro. Yet thero[et al. showed tl.[et al. demonstrl.[et al., 157. Anl.[et al.. For exal.[et al.. In addil.[et al.. Thus, tIn the past few years, there has been dramatic progress in our understanding of the biology of MSCs. Data in the literature concerning cell expansion, phenotypic characterization of MSCs as well as their multi-potency and immunomodulatory properties, are vast and sometimes contradictory. Although the precise identity of MSCs remains a challenge, this has not hampered the beginning of considerable investigation aiming at their potential clinical applications. It is generally accepted that type 1 diabetes is now curable by islet transplantation therapy, and MSCs offer a starting material for generating the large numbers of surrogate β-cells required. The most difficult and yet unsolved issue are how to manufacture physiologically functional insulin-producing cells from MSCs. Moreover, the angiogenic effect of MSCs could also be utilized for diabetes treatment. In conclusion, the prospect of MSCs in treating type 1 diabetes seems to be very promising. However, we should realize that much work needs to be done before pushing the MSC-based therapy from bench to bedside.


The output power produced by high-concentration solar thermal and photovoltaic systems is directly related to the amount of solar energy acquired by the system, and it is therefore necessary to track the sun's position with a high degree of accuracy. Many systems have been proposed to facilitate this task over the past 20 years. Accordingly, this paper commences by providing a high level overview of the sun tracking system field and then describes some of the more significant proposals for closed-loop and open-loop types of sun tracking systems. Such systems are based on a solar collector, designed to collect the sun's energy and to convert it into either electrical power or thermal energy. The literature contains many studies regarding the use of solar collectors to implement such applications as light fixtures, window covering systems, cookers, and so forth -6. In ge° – 1°. Several years later, Semma and Imamru used a simple microprocessor to adaptively adjust the positions of the solar collectors in a photovoltaic concentrator such that they pointed toward the sun at all times [In 1975, one of the first automatic solar tracking systems -13 was pll times ,15.With rapid advances in the computer technology and systems control fields in recent decades, the literature now contains many sophisticated sun tracking systems designed to maximize the efficiency of solar thermal and photovoltaic systems. Broadly speaking, these systems can be classified as either closed-loop or open-loop types, depending on their mode of signal operation . The rem2.et al. [° to be achieved. In 1992, Agarwal [° (0.2 mrad). Kalogirou [Closed-loop types of sun tracking systems are based on feedback control principles. In these systems, a number of inputs are transferred to a controller from sensors which detect relevant parameters induced by the sun, manipulated in the controller and then yield outputs (i.e. sensor-based). In 1986, Akhmedyarov et al.  first inet al.  develope Agarwal  presente Agarwal  developealogirou  presentealogirou  presentealogirou  comparedet al. [et al. [°. Urbano et al. [et al. [In 1998, Khalifa and Al-Mutawalli  developeet al.  proposed [et al.  presenteo et al.  presenteo et al.  construc [et al.  presenteet al. [et al. [In 2004, Roth et al. , 32 desi [et al.  develope° to the north. Al-Mohamad [Abdallah  investig-Mohamad  used a pet al. [et al. [Aiuchi et al.  presente [et al.  designed [et al.  presente3.An open-loop type of controller computes its input into a system using only the current state and the algorithm of the system and without using feedback to determine if its input has achieved the desired goal . The system is simpler and cheaper than the closed-loop type of sun tracking systems. It does not observe the output of the processes that it is controlling. Consequently, an open-loop system can not correct any errors so that it could make and may not compensate for disturbances in the system. Open-loop control algorithms of sun tracking systems utilize some form of solar irradiation geometry model .In 1983, Al-Naima and Yaghobian  developeet al. [et al. [Blanco-Muriel et al.  argued tet al. . Overallet al. . In 2003 [et al.  presente° towards the south.In 2004, Abdallah and Nijmeh  develope° (In the same year, Reda and Andreas  presente° .et al. [1, S2, S3 and S4 (L is the average length of the square aperture, h is the distance between the mask and the detector plane, and a is the width of the slit. However, in M and N vary nonlinearly with the inputs α and β, respectively, i.e. the sensitivity of the sensor depends upon the incident angle of the sunlight. To resolve this problem, the authors replaced the conventional aperture with that shown in ° over the entire field of view of ± 62° for both axes.In 2007, Chen et al. ,48 prese3 and S4 , is dire° [° (°, but was sufficient for most solar engineering applications and could be obtained at a fraction of the computational cost.In a recent study, Grena  presente° . It was ° [° , was higet al. [et al. [Recently, Chen et al. -51 and C [et al. -53 prese4.Advances in the algorithms of sun tracking systems have enabled the development of many solar thermal and photovoltaic systems for a diverse variety of applications in recent years. Compared to their traditional fixed-position counterparts, solar systems which track the changes in the sun's trajectory over the course of the day collect a far greater amount of solar energy, and therefore generate a significantly higher output power. This paper has presented a review of the major algorithms for sun tracking systems developed over the past 20 years. It has been shown that these sun tracking algorithms can be broadly classified as either closed-loop or open-loop types, depending on their mode of control. The control / computational principles of each method have been reviewed and their performance and relative advantages / disadvantages systematically discussed. Overall, the results presented in this review confirm the applicability of sun tracking system for a diverse range of high-performance solar-based applications.


Perioperative stress and anesthesia are risk factors for exacerbation of Multiple Sclerosis (MS) attacks. Infection, emotional labiality and hyperpyrexia are also known to increase the risk of postoperative MS attacks. Appropriate preoperative evaluation, administration of a good premedication, control of fever, selection of the anesthetic agents and effective postoperative pain control can prevent problems after prolonged major surgery in patients with MS diagnosed. This report presents the anesthetic technique in a patient who was a known case of MS for past nine years and presented with renal tumor to undergo laparoscopic nephrectomy under general anesthesia. Multiple sclerosis (MS) is the most common immune demyelinating disorder of the central nervous system which predominantly affects females and play a major role which is involved in genetic factors . Periope2-air-sevoflurane (2%). After intubation, a remifentanil infusion of 0.25 mcg/kg/min was administered. Body temperature ranged between 36.5 ºC and 35.7 ºC during the surgery. A total of 80 mg atracurium besylate was used as a neuromuscular blocking agent and the surgery lasted 7.5 hours. The dose of non-depolarizing muscle relaxant was chosen initially 0.5 mg/kg atracurium and repeated according to clinical signs and capnography. Two units of erythrocyte suspension were transfused during the surgery. After uneventful perioperative period. The patient was given meperidine via patient controlled analgesia (PCA) and intravenous paracetamol after every six hours during the postoperative 24 hours. The patient was discharged from the hospital 10 days later and had no MS attacks during the three-month follow up period.A 57 years old female patient (weight 59 kg) who was a known case of MS for nine years presented with renal tumor to undergo laparoscopic nephrectomy. The patient’s history revealed that she initially had visual impairment and weakness of the legs which resolved with treatment. She has been using Copaxone (glatiramer acetate) therapy for six years and she had no attacks of MS during the last six years. Preanesthetic evaluation showed that she had no other medical diagnosis except MS. She had normal physical examination, PA chest radiograph, ECG and blood tests. She was premedicated with diazepam 5 mg orally the night before the operation. After routine monitoring and intravenous (iv) access were established, anesthetic induction was achieved with the intravenous administration of 60 mg of lidocaine, 180 mg of propofol, 100 μgr of remifentanil and 30 mg of atracuruim besylate. Anesthesia was maintained with O2O and O2. The authors concluded that, given that no spike was observed by pEEG monitoring during surgery, sevoflurane anesthesia was safe and can be used in the exacerbation stage in MS. In the case presented here, sevoflurane was used in the anesthetic procedure. In a study by Kono Y et al. (2 and air in a patient with MS undergoing emergency laparotomy and no postoperative exacerbation of the symptoms was observed. In a study by Inoue et al. (2O and fentanyl, and vecuronium was used as neuromuscular blockers, and postoperative pain was managed with IV infusion of fentanyl instead of neural block with local anesthetics and no MS attacks were noted in a patient with a two year history of MS for gynecologic surgery. Lee KH et al. (All anesthetic techniques used in patients with MS may lead to the exacerbation of MS symptoms. In a study by Barbosa et al. , subaracY et al.  fentanyle et al. , anestheH et al.  reportedH et al. . HoweverH et al. . We usedH et al. , 11. On H et al.  perioper