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Dosing in neonates: Special considerations in physiology and trial design.
Determining the right dose for drugs used to treat neonates is critically important. Neonates have significant differences in physiology affecting drug absorption, distribution, metabolism, and elimination that makes extrapolating dosages from adults and older children inappropriate. In spite of recent legislative effo...
Diabetes-associated changes in the fetal insulin/insulin-like growth factor system are organ specific in rats.
Background:Diabetes in pregnancy affects fetal growth and development. The insulin/IGF system comprising insulin, insulin-like growth factors, their receptors and binding proteins, has been implicated in fetal growth regulation. This study tested the hypothesis that maternal diabetes alters the fetal insulin/IGF system...
Abnormal Calcium Handling and Exaggerated Cardiac Dysfunction in Mice with Defective Vitamin D Signaling.
AIM: Altered vitamin D signaling is associated with cardiac dysfunction, but the pathogenic mechanism is not clearly understood. We examine the mechanism and the role of vitamin D signaling in the development of cardiac dysfunction. METHODS AND RESULTS: We analyzed 1alpha-hydroxylase (1alpha-OHase) knockout (1alpha-OHa...
Whole Exome Analysis Identifies Frequent CNGA1 Mutations in Japanese Population with Autosomal Recessive Retinitis Pigmentosa.
OBJECTIVE: The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP) in the Japanese population. METHODS: In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP) were recruited in this study and ophthalmic e...
Aurora Kinases as Targets in Drug-Resistant Neuroblastoma Cells.
Aurora kinase inhibitors displayed activity in pre-clinical neuroblastoma models. Here, we studied the effects of the pan-aurora kinase inhibitor tozasertib (VX680, MK-0457) and the aurora kinase inhibitor alisertib (MLN8237) that shows some specificity for aurora kinase A over aurora kinase B in a panel of neuroblasto...
Urotensin II Inhibits Doxorubicin-Induced Human Umbilical Vein Endothelial Cell Death by Modulating ATF Expression and via the ERK and Akt Pathway.
BACKGROUND AND PURPOSE: Regulation of the homeostasis of vascular endothelium is critical for the processes of vascular remodeling and angiogenesis under physiological and pathological conditions. Urotensin II (U-II), a potent vasoactive peptide, participates in vascular and myocardial remodeling after injury. We inves...
The Indolinone MAZ51 Induces Cell Rounding and G2/M Cell Cycle Arrest in Glioma Cells without the Inhibition of VEGFR-3 Phosphorylation: Involvement of the RhoA and Akt/GSK3beta Signaling Pathways.
MAZ51 is an indolinone-based molecule originally synthesized as a selective inhibitor of vascular endothelial growth factor receptor (VEGFR)-3 tyrosine kinase. This study shows that exposure of two glioma cell lines, rat C6 and human U251MG, to MAZ51 caused dramatic shape changes, including the retraction of cellular p...
Readmissions after Hospitalization for Heart Failure, Acute Myocardial Infarction, or Pneumonia among Young and Middle-Aged Adults: A Retrospective Observational Cohort Study.
BACKGROUND: Patients aged >/=65 years are vulnerable to readmissions due to a transient period of generalized risk after hospitalization. However, whether young and middle-aged adults share a similar risk pattern is uncertain. We compared the rate, timing, and readmission diagnoses following hospitalization for heart f...
Development and Validation of a Harmonized TaqMan-Based Triplex Real-Time RT-PCR Protocol for the Quantitative Detection of Normalized Gene Expression Profiles of Seven Porcine Cytokines.
Dysregulation of cytokine responses plays a major role in the pathogenesis of severe and life-threatening infectious diseases like septicemia or viral hemorrhagic fevers. In pigs, diseases like African and classical swine fever are known to show exaggerated cytokine releases. To study these responses and their impact o...
The individual N- and C-lobes of calmodulin tether to the Cav1.2 channel and rescue the channel activity from run-down in ventricular myocytes of guinea-pig heart.
The present study examined the binding of the individual N- and C-lobes of calmodulin (CaM) to Cav1.2 at different Ca2+ concentration ([Ca2+]) from approximately free to 2 mM, and found that they may bind to Cav1.2 Ca2+-dependently. In particular, using the patch-clamp technique, we confirmed that the N- or C-lobes can...
L Protease from Foot and Mouth Disease Virus Confers eIF2-Independent Translation for Mrnas Bearing Picornavirus Ires.
The leader protease (Lpro) from foot-and-mouth disease virus (FMDV) has the ability to cleave eIF4G, leading to a blockade of cellular protein synthesis. In contrast to previous reports, our present findings demonstrate that FMDV Lpro is able to increase translation driven by FMDV IRES. Additionally, inactivation of eI...
Ambrisentan improves the outcome of rats with liver transplantation partially through reducing nephrotoxicity.
OBJECTIVE: Tacrolimus is a potent immunosuppressive agent mainly used for allogeneic solid organ transplantation. Although usage of tacrolimus led to a significant increase in short-term allograft survival, the long-term morbidity remains high. Endothelin-1 (ET-1) is reported to be associated with increased vascular re...
Interventional treatment strategies of thoracic aortic pathologies.
Chronic and acute diseases of the thoracic aorta, including aortic dissection and aortic aneurysm are attracting increasing attention both in the light of an ageing Western and Oriental population and with the proliferation of modern diagnostic imaging modalities. While classical surgical strategies still dominate the ...
Correlation between the embolism area and pulmonary arterial systolic pressure as an indicator of pulmonary arterial hypertension in patients with acute pulmonary thromboembolism.
OBJECTIVE: We tested whether correlation between embolism area and pulmonary arterial pressure may serve as an indicator of pulmonary arterial hypertension in patients with acute pulmonary thromboembolism. PATIENTS AND METHODS: In total, 204 patients who underwent spiral computed tomography (CT) pulmonary angiography a...
Usnic acid inhibits ER stress activation through AMPK signaling pathway in rat cardiomyocytes.
OBJECTIVE: In the present study, we investigated the effects of usnic acid (UA) on the endoplasmic reticulum (ER) stress processes in rat cardiomyocytes. MATERIALS AND METHODS: Gene expression of pro-inflammatory cytokines and activation of ER stress signaling were analyzed. Besides, levels of phosphorylated AMPK were ...
Vacuum Assisted Closure (VAC) therapyTM as a swiss knife multi-tool for enteric fistula closure: tips and tricks: a pilot study.
OBJECTIVE: Enterocutaneous fistulas (ECFs) are an uncommon surgical problem, but they are characterized by a difficult management. Vacuum-assisted closure (VAC) therapy is a method utilized for chronic and traumatic wound healing. At first, VAC therapy had been contraindicated in the treatment of intestinal fistulas, b...
Qualitative motor assessment allows to predict the degree of motor disturbances.
OBJECTIVE: Early diagnosis is necessary in order to determine neurological integrity and the potential risk of improper development, and also to undertake possible early intervention. The quantitative assessment consists of observation of motor development, and provides information about whether a child performs an act...
Bickerstaff's brainstem encephalitis (BBE) in childhood: rapid resolution after intravenous immunoglobulins treatment.
Three young patients with Bickerstaff's brainstem encephalitis (BBE) are reported. Some weeks following an upper tract infection, the children after a short period of recovery, showed acute onset of symmetric weakness of the lower limbs with difficulty in standing by and walking. The distal muscle weakness had a rapid ...
Effects of different antihypertensive drugs on blood pressure variability in patients with ischemic stroke.
OBJECTIVE: Blood pressure variation is one of the factors that affects the risk of stroke recurrence and prognosis. This study investigates the effects of calcium channel blockers and beta-blockers on blood pressure variability in severe ischemic stroke patients. PATIENTS AND METHODS: The clinical data of 24 patients w...
Prevalence of sleep disturbance in chronic pain.
OBJECTIVE: Sleep is a vital function for human beings, which can be affected by several factors. Chronic pain is one of these factors where it is the most frequent cause for seeking medical care in combination with insomnia. The aim of this study is to examine the prevalence and relationship between sleep disturbance a...
Agents for refractory/relapsed acute lymphocytic leukemia in adults.
Although treatment results for adult acute lymphoblastic leukemia (ALL) have improved considerably in the past decades, treating adult patients with relapsed/refractory acute lymphocytic leukemia (ALL) is still difficult. Adults with refractory/relapsed acute lymphocytic leukemia (ALL) processed to death rapidly associ...
Efficacy of intratumoral chemotherapy using arsenic trioxide (As2O3) sustained release tablets for the treatment of neurogliocytoma in nude mice.
OBJECTIVE: This study aimed to investigate the inhibiting effect of arsenic trioxide (As2O3) on neurogliocytoma in nude mice and the mechanism responsible for this effect. MATERIALS AND METHODS: Neurogliocytoma implantation models were constructed in nude mice, which were assigned to three groups: the control group, th...
Saikosaponin-d inhibits proliferation of human undifferentiated thyroid carcinoma cells through induction of apoptosis and cell cycle arrest.
OBJECTIVE: Saikosaponin-d is a triterpene saponin derived from Bupleurum falcatum. L and has been reported to exhibit a variety of pharmacological activities such as anti-bacterial, anti-virus and anti-cancer. The aim of the present study was to explore the effect of saikosaponin-d on the proliferation and apoptosis of...
Wortmannin enhances cisplatin-induced apoptosis in human ovarian cancer cells in vitro.
OBJECTIVE: The PI3K/Akt signaling pathway is constitutively activated in some ovarian cancers; when activated, it promotes invasion and inhibits chemotherapy-mediated apoptosis in cancer cells. The fungal metabolite wortmannin is the currently known inhibitors that show fairly high specificity for PI3K.We examined whet...
The role of gut microbiota in the pathogenesis and management of allergic diseases.
This article has been withdrawn.
Autologous pericardium annuloplasty: a "physiological" mitral valve repair.
AIM: Autologous pericardium annuloplasty (APA) is an alternative to prosthetic ring implantation for mitral valve (MV) repair, avoiding the use of foreign material and preserving the mitral annulus' physiological motion. However, data on durability are questionable. Therefore, we analyzed long-term outcomes of treating...
BRAF alterations in brain tumours: molecular pathology and therapeutic opportunities.
PURPOSE OF REVIEW: To summarize the current knowledge on v-RAF murine sarcoma viral oncogene homologue B1 (BRAF) aberrations in tumours of the central nervous system. RECENT FINDINGS: BRAF alterations are found in variable frequencies across a wide spectrum of diverse central nervous system neoplasms. BRAF V600 point m...
Prognostic Scoring Models for Patients Undergoing Sorafenib Treatment for Advanced Stage Hepatocellular Carcinoma in Real-Life Practice.
BACKGROUND:: The purpose of this study was to build prognostic models capable of estimating the outcomes of individual sorafenib-treated advanced stage hepatocellular carcinoma (HCC) patients based on specific patient and tumor factors. METHODS:: A parametric model for time-to-event data was used to construct scoring s...
Hepatocellular Carcinoma Management in Nonalcoholic Fatty Liver Disease Patients: Applicability of the BCLC Staging System.
BACKGROUND/AIMS:: Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatmen...
Late Toxicity and Outcomes in High-risk Prostate Cancer Patients Treated With Hypofractionated IMRT and Long-term Androgen Suppression Treatment.
OBJECTIVE:: To assess late toxicity and outcomes in high-risk prostate cancer patients treated with hypofractionated radiation treatment with androgen suppression therapy. METHODS:: Sixty high-risk prostate cancer patients were enrolled. IMRT prescription was 68 Gy/25 fractions (2.7 Gy/fraction) to the prostate and pro...
Galangin suppresses HepG2 cell proliferation by activating the TGF-beta receptor/Smad pathway.
Galangin can suppress hepatocellular carcinoma (HCC) cell proliferation. In this study, we demonstrated that galangin induced autophagy by activating the transforming growth factor (TGF)-beta receptor/Smad pathway and increased TGF-beta receptor I (RI), TGF-betaRII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Sm...
Comparison of Propofol, Etomidate, and Thiopental in Anesthesia for Electroconvulsive Therapy: A Randomized, Double-blind Clinical Trial.
OBJECTIVES: This study aimed to compare the effects of propofol, thiopental, and etomidate, which are routinely used in anesthesia for electroconvulsive therapy (ECT), on the cardiovascular system, seizure variables, recovery, cognitive functions, and response to treatment. METHODS: Male patients hospitalized at the Se...
Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.
In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-a...
Utility of galectin-3 as a prognostic biomarker in heart failure: where do we stand?
BACKGROUND: Heart failure (HF) continues to be an illness of daunting proportions with a four- year mortality touching 50%. Biomarkers for prognosticating patients with heart failure have generated immense interest. Several studies have been conducted on a novel biomarker, galectin-3 to assess its prognostic effect in ...
The Yale-Brown Obsessive Compulsive Scale: A Reliability Generalization Meta-Analysis.
The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the most frequently applied test to assess obsessive compulsive symptoms. We conducted a reliability generalization meta-analysis on the Y-BOCS to estimate the average reliability, examine the variability among the reliability estimates, search for moderators, and p...
The Effectiveness of the Personality Assessment Inventory With Feigned PTSD: An Initial Investigation of Resnick's Model of Malingering.
Malingered posttraumatic stress disorder (PTSD) poses a formidable clinical challenge because of the apparent ease in feigning PTSD. As an additional confound, some patients with genuine PTSD produce elevated profiles on feigning indicators that are difficult to distinguish from feigned PTSD. The current study utilized...
Renal Sulfatides: Sphingoid Base-Dependent Localization and Region-Specific Compensation of CerS2-Dysfunction.
Mammalian kidneys are rich in sulfatides. Especially papillary sulfatides contribute to renal adaptation to chronic metabolic acidosis. Due to differences in their ceramide anchors, the structural diversity of renal sulfatides is large. However, the underling biological function of this complexity is not understood. As...
Phase II Study of Concurrent Chemoradiotherapy with S-1 in Patients with Stage II (T2N0M0) Squamous Cell Carcinoma of the Pharynx or Larynx.
OBJECTIVE: The goals of treatment for head and neck cancer are cure and organ-function preservation. For organ preservation, primary treatment via radiotherapy alone is thought to be insufficient for Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx. The objective of the present study was to inv...
Efficacy and safety of triple combination therapy with artesunate-amodiaquine-methylene blue for falciparum malaria in children: a randomised controlled trial in Burkina Faso.
BACKGROUND: Methylene blue (MB) has been shown to be safe and effective against falciparum malaria in Africa and to have pronounced gametocytocidal properties. METHODS: Three days treatment with artesunate (AS)-amodiaquine (AQ)-MB was compared to AS-AQ in a randomised controlled phase IIb study in 221 children aged 6-5...
Innate Inflammation Induced by the 8-Oxoguanine DNA Glycosylase-1-KRAS-NF-kappaB Pathway.
8-Oxoguanine-DNA glycosylase-1 (OGG1) is the primary enzyme for repairing 7,8-dihydro-8-oxoguanine (8-oxoG) via the DNA base excision repair pathway (OGG1-BER). Accumulation of 8-oxoG in the genomic DNA leads to genetic instability and carcinogenesis and is thought to contribute to the worsening of various inflammatory...
Mast Cells Control the Expansion and Differentiation of IL-10-Competent B Cells.
The discovery of B cell subsets with regulatory properties, dependent on IL-10 production, has expanded our view on the mechanisms that control inflammation. Regulatory B cells acquire the ability to produce IL-10 in a stepwise process: first, they become IL-10 competent, a poised state in which B cells are sensitive t...
Neutrophils Counteract Autophagy-Mediated Anti-Inflammatory Mechanisms in Alveolar Macrophage: Role in Posthemorrhagic Shock Acute Lung Inflammation.
Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome after hemorrhagic shock (HS) resulting from major surgery and trauma. The increased susceptibility in HS patients to the development of ALI suggests not yet fully elucidated mechanisms that enhance proinflammatory responses and/or suppr...
Inflammasome Activation by Campylobacter jejuni.
The Gram-negative pathogen Campylobacter jejuni is the most common cause of bacterial foodborne disease worldwide. The mechanisms that lead to bacterial invasion of eukaryotic cells and massive intestinal inflammation are still unknown. In this study, we report that C. jejuni infection of mouse macrophages induces upre...
Variation and Genetic Control of Gene Expression in Primary Immunocytes across Inbred Mouse Strains.
To determine the breadth and underpinning of changes in immunocyte gene expression due to genetic variation in mice, we performed, as part of the Immunological Genome Project, gene expression profiling for CD4+ T cells and neutrophils purified from 39 inbred strains of the Mouse Phenome Database. Considering both cell ...
A Novel Method Using Blinatumomab for Efficient, Clinical-Grade Expansion of Polyclonal T Cells for Adoptive Immunotherapy.
Current treatment of chronic lymphocytic leukemia (CLL) patients often results in life-threatening immunosuppression. Furthermore, CLL is still an incurable disease due to the persistence of residual leukemic cells. These patients may therefore benefit from immunotherapy approaches aimed at immunoreconstitution and/or ...
Progression of Relapsing-Remitting Demyelinating Disease Does Not Require Increased TCR Affinity or Epitope Spread.
In this study, we investigate the basis of T cell recognition of myelin that governs the progression from acute symptoms into disease remission, relapse, and chronic progression in a secondary progressive model of demyelinating disease. Until now, the frequency and affinity of myelin-reactive CD4 T cells that elicit re...
Spontaneous clearance of hepatitis C virus in a patient co-infected with hepatitis C virus and human immunodeficiency virus: a case report.
The effect of highly active antiretroviral therapy (HAART) on hepatitis C virus (HCV) infection remains unclear. Spontaneous HCV clearance with initiation of HAART in non-cirrhotic HCV patients co-infected with human immunodeficiency virus (HIV) has been reported. We describe an HIV/HCV patient with decompensated cirrh...
A potential treatment of non-alcoholic fatty liver disease with SIRT1 activators.
Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulato...
Pathophysiological and clinical approach to cirrhotic cardiomyopathy.
Hyperdynamic circulation, systolic and diastolic left ventricular dysfunction and certain electrophysiological abnormalities have been associated with cirrhosis and known for a long time. These clinical features have been introduced as cirrhotic cardiomyopathy (CCM), which is characterized by blunted myocardial contrac...
What non-alcoholic fatty liver disease has got to do with obstructive sleep apnoea syndrome and viceversa?
Non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnoea syndrome (OSAS) are common conditions, frequently encountered in patients with obesity and/or metabolic syndrome. NAFLD and OSAS are complex diseases that involve an interaction of several intertwined factors. Several lines of evidence lend credence...