Electromyogram Power Spectrum and Cardiac Function Changes After Combined Aerobic Interval Training and Inspiratory Muscle Training in Chronic Heart Failure Patients.

Exercise intolerance and dyspnea are the major symptoms of patients with chronic heart failure (CHF) and are associated with a poor quality of life. In addition to impaired central hemodynamics, symptoms may be attributed to changes in peripheral skeletal muscles. This study aimed to evaluate the effects of aerobic interval training (AIT) combined with inspiratory muscle training (IMT) on cardiac and skeletal muscle function and on functional capacity and dyspnea in patients with CHF and inspiratory muscle weakness.Left ventricle ejection fraction was improved significantly after AIT and AIT & IMT with a high percentage of amelioration (17%, P < 0.042) in the combined group compared to the control group. Therefore, we showed a significant improvement in maximal voluntary isometric force, isometric endurance time, root mean square, and frequency median in both strength and endurance manipulations in the aerobic and combined group; however, the improvement was superior in the combined group compared to the control group. Significant amelioration was proved in functional capacity and dyspnea after all types of training but was performed at 18% higher in 6 minutes' walk test and 43% lower in dyspnea for the combined group compared to the control group.Combining AIT to IMT had optimized exercise training benefits in reversing the cardiac remodeling process and improving skeletal muscle function, functional capacity, and dyspnea in patients with CHF.

The impact of exposure of diabetic rats to 900 MHz electromagnetic radiation emitted from mobile phone antenna on hepatic oxidative stress.

The excessive exposure of patients with type 2 diabetes mellitus (T2DM) to electromagnetic radiation (EMR) from mobile phones or their base stations antenna may influence oxidative stress and development of diabetic complications. Here, we investigated the effects of exposing type 2 diabetic rats to EMR of 900 MHz emitted from GSM mobile phone antenna for 24 hours/day over a period of 28 days on hyperglycemia and hepatic oxidative stress. Male Sprague-Dawley rats were divided into 4 groups (12 rats/group): control rats, normal rats exposed to EMR, T2DM rats generated by nicotinamide/streptozotocin administration, and T2DM rats exposed to EMR. Our results showed that the exposure of T2DM rats to EMR nonsignificantly reduced the hyperglycemia and hyperinsulinemia compared to unexposed T2DM rats. The exposure of T2DM rats to EMR for 28 days increased the hepatic levels of MDA and Nrf-2 as well as the activities of superoxide dismutase (SOD) and catalase but decreased phosphorylated Akt-2 (pAkt-2) as compared to unexposed T2DM rats. Therefore, the decrease in the hepatic pAkt-2 in T2DM rats after the exposure to EMR may result in elevated level of hepatic MDA, even though the level of Nrf-2 and the activities of SOD and catalase were increased. Abbreviations: BGL: blood glucose level; EMR: electromagnetic radiation; GSM: global system for mobile communication; H2O2: hydrogen peroxide; LSD: least significance difference; MDA:malondialdehyde; Nrf-2: nuclear factor erythroid 2- related factor 2; PI3K: phosphoinositide-3-kinase; pAkt-2: phosphorylated Akt-2; Akt-2: protein kinase; ROS: reactive oxygen species; SEM: standard error of the mean; STZ: streptozotocin; SOD: superoxide dismutase ; O2-: superoxide radical; CT: threshold cycle; T2DM: type 2 diabetes mellitus.

Impact of GSM-EMW exposure on the markers of oxidative stress in fetal rat liver.

The current study investigated the effects of 24 h/day prenatal exposure to global system for mobile communication electromagnetic fields (GSM-EMFs), 900 MHZ-induced electromagnetic radiation (EMR), on oxidative stress (OS) status, apoptotic, and inflammatory changes in liver of rats during their fetal development period. Fifty-two Sprague-Dawley pregnant rats were equally divided into control and exposed groups. Whole embryos were removed at 7.5 dpc (days post coitus), while liver tissues were extracted from embryos at 11.5, 15.5, and 19.5 dpc. For exposed animals, results showed an increased OS reflected by high levels of malondialdehyde (MDA), a decrease in cytosolic superoxide dismutase (cytoSOD) activity, in mitochondrial superoxide dismutase (mitoSOD) levels and catalase (CAT) mRNA expression but also in hepatic nuclear factor erythroïd 2-related Factor 2 (Nrf-2), protein kinase B (Akt1), and intercellular adhesion molecule-1 (ICAM-1) mRNA expression at 15.5 dpc. Moreover, GSM-EMR exposure was shown to significantly decrease mitoSOD and CAT activities at almost all studied ages. Thus, rat embryos may be protected by their mothers from OS, apoptotic, and pro-inflammatory responses till a sensitive developmental stage, during a continuous prenatal EMR exposure. This protection could be then created from the embryos themselves.

A randomized controlled trial of high-intensity interval training and inspiratory muscle training for chronic heart failure patients with inspiratory muscle weakness.

OBJECTIVES: Chronic heart failure is a major public health problem in which supervised exercise programs are recommended as part of non-pharmacological management. There are various reports of the success of high-intensity aerobic interval training (HI-AIT) and inspiratory muscle training (IMT) in the management of chronic heart failure patients. This study tested the hypothesis that the combination of HI-AIT and IMT could result in additional benefits over the IMT and the HI-AIT alone in terms of inspiratory muscle function, exercise capacity, and quality of life in patients with chronic heart failure and inspiratory muscle weakness. METHODS: Forty patients with ejection fraction ≤45% and inspiratory muscle weakness described by maximal inspiratory pressure <70% predicted, underwent three exercise training sessions per week for 12 weeks. Patients were randomly allocated to one of four groups: the HI-AIT group, the IMT group, the combined (HI-AIT & IMT) group, and the control group. Before and after completing their training period, all patients underwent different tests that are mentioned above. RESULTS: No changes were detected in the control group. However, the combined group, when compared to HI-AIT and IMT groups, respectively, resulted in additional significant improvement in maximal inspiratory training (62%, 24%, 25%), exercise time (62%, 29%, 12%), the 6-minute walk test (23%, 15%, 18%), and the Minnesota Living with Heart Failure Questionnaire (56%, 47%, 36%). CONCLUSION: In patients with chronic heart failure and inspiratory muscle weakness, the combination of the HI-AIT and the IMT resulted in additional benefits in respiratory muscle function, exercise performance, and quality of life compared to that of HI-AIT or IMT alone.Trial Registration number: NCT03538249.

Effects of continuous prenatal and postnatal global system for mobile communications electromagnetic waves (GSM-EMW) exposure on the oxidative stress biomarkers in female rat liver.

In light of the increased use of communication technologies, the harm caused by continuous exposure to emitted radiation on pregnancy and developing newborns is among the public concerns. Using Sprague-Dawley rats, our study investigates the effects of 24 h/day prenatal and postnatal 900 MHz radiofrequency electromagnetic radiation (RF-EMR) exposure of female rats on liver oxidative stress (OS) and other hepatic parameters at postnatal days (PND) 1, 9, and 21. Our results showed that RF-EMR exposure led to an increase in oxidative stress status as indicated by a significant elevation in MDA level at PND9 and PND21, a decrease in catalase (CAT) activity at all ages, a reduction (PND1 and PND9) in catalase amounts and mRNA expression, in addition to a decrease in GPx activity at PND21 in the exposed group. Current findings also showed a significant increase in cytoSOD at PND9 and 21 and a reduction in mitoSOD at PND21 in the exposed groups compared to the control groups. However, significant increases in glutathione peroxidase (GPx) level and mitoSOD activity were observed at all studied ages. Furthermore, cytoSOD activity showed a significant reduction in PND1, whereas in PND9 the value of this parameter increased compared to the non-exposed group. Moreover, while SOD1 mRNA expression increased at PND1, it decreased at PND9 and 21. However, GPx1 expression was shown to be always decreased in the exposed group. In addition, at PND1 and 9, exposed rats showed a similar response on Akt1, nuclear factor erythroïd 2-related factor 2 (Nrf-2), and intercellular adhesion molecule-1 (ICAM-1) expression. Therefore, an increased oxidative stress status produced from a continuous (24 h/day) GSM-modulated 900 MHz radiofrequency electromagnetic radiation (RF-EMR) exposure during the prenatal and postnatal periods may result in adverse health effects during future life stages.

Novel Missense and Splice Site Mutations in USH2A, CDH23, PCDH15, and ADGRV1 Are Associated With Usher Syndrome in Lebanon.

The purpose of this study was to expand the mutation spectrum by searching the causative mutations in nine Lebanese families with Usher syndrome (USH) using whole-exome sequencing. The pathogenicity of candidate mutations was first evaluated according to their frequency, conservation, and in silico prediction tools. Then, it was confirmed via Sanger sequencing, followed by segregation analysis. Finally, a meta-analysis was conducted to calculate the prevalence of USH genes in the Lebanese population. Three missense mutations, two splice site mutations, and one insertion/deletion were detected in eight of the families. Four of these variants were novel: c.5535C > A; p.(Asn1845Lys) in exon 41 of CDH23, c.7130G > A; p.(Arg2377Gln) in exon 32 of ADGRV1, c.11390-1G > A in USH2A, and c.3999-6A > G in PCDH15. All the identified mutations were shown to be likely disease-causing through our bioinformatics analysis and co-segregated with the USH phenotype. The mutations were classified according to the ACMG standards. Finally, our meta-analysis showed that the mutations in ADGRV1, USH2A, and CLRN1 are the most prevalent and responsible for approximately 75% of USH cases in Lebanon. Of note, the frequency USH type 3 showed a relatively high incidence (23%) compared to the worldwide prevalence, which is around 2-4%. In conclusion, our study has broadened the mutational spectrum of USH and showed a high heterogeneity of this disease in the Lebanese population.

Prevalence, Laboratory Findings and Clinical Characteristics of Campylobacteriosis Agents among Hospitalized Children with Acute Gastroenteritis in Lebanon.

PURPOSE: Campylobacter species are currently the most common cause of bacterial gastroenteritis. In Lebanon, Campylobacter infection occurrence is underdiagnosed owing to the lack of specific culture and rapid test kits, particularly among children. This study aimed to evaluate the prevalence, laboratory findings, and clinical characteristics of Campylobacter infection in hospitalized children with acute gastroenteritis in South Lebanon. METHODS: We conducted a 6-month retrospective cohort study between January and June 2018, including 291 children aged between 1 month and 12 years, who were admitted to a tertiary healthcare center in South Lebanon. The medical files of the patients were reviewed to retrieve the required clinical information, including clinical and laboratory data. RESULTS: The prevalence of campylobacteriosis agents in pediatric patients with acute gastroenteritis is 12.02%. Patients infected with Campylobacter had more severe acute gastroenteritis than Campylobacter-negative patients and often presented with high-grade fever, diarrhea episodes more than six times per day, diarrhea lasting for more than five days, and dehydration. Indeed, children with high-grade fever (≥38.5°C) were five times more likely to test positive for Campylobacter than those with low-grade fever. In addition, the results showed a higher Vesikari score for the majority of Campylobacter-positive patients with severe acute gastroenteritis compared to a moderate profile for Campylobacter-negative patients. CONCLUSION: The present study findings highlight that Campylobacter infection is frequent among children with acute gastroenteritis. Therefore, the detection of Campylobacter should be carried out for the diagnosis of human gastroenteritis in Lebanon, along with the detection of routine enteropathogens.

Does the perigestational exposure to chlorpyrifos and/or high-fat diet affect respiratory parameters and diaphragmatic muscle contractility in young rats?

The perinatal period is characterized by developmental stages with high sensitivity to environmental factors. Among the risk factors, maternal High-Fat Diet (HFD) consumption and early-life pesticide exposure can induce metabolic disorders at adulthood. We established the effects of perigestational exposure to Chlorpyrifos (CPF) and/or HFD on respiratory parameters, sleep apnea and diaphragm contractility in adult rats. Four groups of female rats were exposed starting from 4 months before gestation till the end of lactation period to CPF (1 mg/kg/day vs. vehicle) with or without HFD. Sleep apnea and respiratory parameters were measured by whole-body plethysmography in male offspring at postnatal day 60. Then diaphragm strips were dissected for the measurement of contractility, acetylcholinesterase (AChE) activity, and gene expression. The perigestational exposure to CPF and/or HFD increased the sleep apnea index but decreased the respiratory frequency. The twitch tension and the fatigability index were also increased, associated with reduced AChE activity and elevated mRNA expression of AChE, ryanodine receptor, and myosin heavy chain isoforms. Therefore, the perigestational exposure to either CPF and/or HFD could program the risks for altered ventilatory parameters and diaphragm contractility in young adult offspring despite the lack of direct contact to CPF and/or HFD.

Data on dysfunctional muscle contraction and genes contractile expression associated with chlorpyrifos exposure in slow twitch skeletal muscle.

Chlorpyrifos (CPF) is a toxic organophosphate commonly used worldwide. Its residues are being detected in different environmental matrixes and hence in the food chain. Repeated CPF exposure might pose health risk for the general population on long term. This data article contains the data of contractility impairment further to dietary exposure to CPF on a hind limb skeletal muscle; soleus, a typical slow twitch skeletal muscle. Thirty adult male rats Sprague Dawley are divided into three groups receiving the following daily diet for 6 weeks: Group 1 (vehicle), Group 2: CPF1 (CPF 1mg/kg/day) and Group 3: CPF5 (CPF 5 mg/kg/day). Soleus twitch tension and fatigability index are determined at the end of the treatment. The activity of acteylcholinesterase enzyme is assessed in the tissues homogenate. Additionally, we examined the expression levels of ryanodine type 1 receptor (RyR1), ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 1 (Atp2a1), ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2 (Atp2a2) and nicotinic acetylcholine receptor (nAChR) in CPF-exposed skeletal muscle tissue using quantitative real time polymerase chain reaction. CPF exposure at two different doses induced an increase in twitch contraction in soleus muscle along with an increase in fatigability index. These increases are accompanied by low level of acetylcholinesterase enzyme activity as well as modification in genes level expression of nAChR, RyR1, Atp2a1 and Atp2a2 involved in contractility.

Next Generation Sequencing Identifies Five Novel Mutations in Lebanese Patients with Bardet-Biedl and Usher Syndromes.

AIM: To identify disease-causing mutations in four Lebanese families: three families with Bardet-Biedl and one family with Usher syndrome (BBS and USH respectively), using next generation sequencing (NGS). METHODS: We applied targeted NGS in two families and whole exome sequencing (WES) in two other families. Pathogenicity of candidate mutations was evaluated according to frequency, conservation, in silico prediction tools, segregation with disease, and compatibility with inheritance pattern. The presence of pathogenic variants was confirmed via Sanger sequencing followed by segregation analysis. RESULTS: Most likely disease-causing mutations were identified in all included patients. In BBS patients, we found (M1): c.2258A > T, p. (Glu753Val) in BBS9, (M2): c.68T > C; p. (Leu23Pro) in ARL6, (M3): c.265_266delTT; p. (Leu89Valfs*11) and (M4): c.880T > G; p. (Tyr294Asp) in BBS12. A previously known variant (M5): c.551A > G; p. (Asp184Ser) was also detected in BBS5. In the USH patient, we found (M6): c.188A > C, p. (Tyr63Ser) in CLRN1. M2, M3, M4, and M6 were novel. All of the candidate mutations were shown to be likely disease-causing through our bioinformatic analysis. They also segregated with the corresponding phenotype in available family members. CONCLUSION: This study expanded the mutational spectrum and showed the genetic diversity of BBS and USH. It also spotlighted the efficiency of NGS techniques in revealing mutations underlying clinically and genetically heterogeneous disorders.

Impacts of prolonged chlorpyrifos exposure on locomotion and slow-and fast- twitch skeletal muscles contractility in rats.

AIM: Investigate the effect of dietary exposure to chlorpyrifos on locomotion and contraction of soleus andextensor digitorum longus (edl) involved in locomotion. Methods: Rats were fed diets containing 1 or 5 mg kg-1 of chlorpyrifos for six weeks. Locomotion has been assessed weekly using beam walking and beam balance tests. Soleus and edl were removed to study contractile properties, myofibrillar protein content and myosin heavy chain isoforms. RESULTS: Animals treated with 5 mg kg-1 chlorpyrifos had a decrease body weight. An increase by 28% and 24% in latency time assessed by beam walking test and a decrease by 9% and 13% in the beam balance time was reported after 6 weeks of 1 and 5 chlorpyrifos exposure respectively. The contractile properties in soleus showed an increase in twitch amplitude by 25% and 63% in 1 and 5 doses respectively, without modification in the contraction time and half relaxation time. edl treated with 1 mg kg-1 showed a decrease by 35%, 42% and 22% in twitch amplitude, contraction time and half relaxation time respectively. edl treated with 5 mg kg-1 showed an increase of 23% in twitch amplitude without modification of the other parameters. These changes were associated with modification of myofibrillar protein content in all treated groups. Myosin heavy chain isoforms were altered in both skeletal muscles treated with 1 mg kg-1. CONCLUSION: Exposure to chlorpyrifos can alter the locomotion and produce physiological changes in a dose and muscle type related manner.

Novel Missense Mutations in BEST1 Are Associated with Bestrophinopathies in Lebanese Patients.

To identify Bestrophin 1 (BEST1) causative mutations in six Lebanese patients from three families, of whom four had a presumed clinical diagnosis of autosomal recessive bestrophinopathy (ARB) and two showed a phenotype with a single vitelliform lesion, patients were subjected to standard ophthalmic examinations. In addition, BEST1 exons and their flanking regions were amplified and sequenced by Sanger sequencing. Co-segregation and detailed bio-informatic analyses were performed. Clinical examination results were consistent with ARB diagnosis for all index patients showing multifocal vitelliform lesions and a markedly reduced light peak in the electrooculogram, including the two patients with a single vitelliform lesion. In all cases, most likely disease-causing BEST1 mutations co-segregated with the phenotype. The ARB cases showed homozygous missense variants (M1, c.209A>G, p.(Asp70Gly) in exon 3, M2, c.1403C>T; p.(Pro468Leu) in exon 10 and M3, c.830C>T, p.(Thr277Met) in exon 7), while the two patients with a single vitelliform lesion were compound heterozygous for M1 and M2. To our knowledge, this is the first study describing mutations in Lebanese patients with bestrophinopathy, where novel biallelic BEST1 mutations associated with two phenotypes were identified. Homozygous mutations were associated with multifocal lesions, subretinal fluid, and intraretinal cysts, whereas compound heterozygous ones were responsible for a single macular vitelliform lesion.

Best mode of inspiratory muscle training in heart failure patients: a systematic review and meta-analysis.

Objectives The objective of this study was to evaluate the effects of inspiratory muscle training on inspiratory muscle strength, functional capacity and dyspnoea for patients with chronic heart failure, by summarising the published research on the effects of inspiratory muscle training. To identify the best mode of intervention in terms of: the load of maximal inspiratory pressure; the frequency of sessions; and the total duration of intervention. Methods A relevant literature research using the PubMed database, Cochrane and references of published studies, from 1998 to 2016, was conducted. Out of 65 randomised controlled trials, seven were considered as potentially relevant and were retrieved for detailed analysis. The methodological quality of each randomised controlled trial was rated using the physiotherapy evidence database scale. Results The included seven studies contained data on 203 patients. Typical training protocols involved training three, six or seven times per week with intensity ranging from 30% to 60% and for a duration ranging from 6 to 12 weeks. Maximal inspiratory pressure, walking distance and dyspnoea were improved in all studies and especially in those who set a load of 60% in their maximal inspiratory pressure, and have trained patients six times per week for 12 weeks. Conclusion In chronic heart failure patients, inspiratory muscle training results in a marked improvement in inspiratory muscle strength, walking distance and dyspnoea, notably when training patients at 60% of maximal inspiratory pressure, six times per week and for 12 weeks. A small number of studies and heterogeneity among studies may limit the findings of the present study.

Surveillance Study of Acute Gastroenteritis Etiologies in Hospitalized Children in South Lebanon (SAGE study).

PURPOSE: Acute gastroenteritis (AGE) is a major cause of morbidity and remains a major cause of hospitalization. Following the Syrian refugee crisis and insufficient clean water in the region, this study reviews the etiological and epidemiological data in Lebanon. METHODS: We prospectively analyzed demographic, clinical and routine laboratory data of 198 children from the age of 1 month to 10 years old who were admitted with the diagnosis of AGE to a private tertiary care hospital located in the district of Nabatieh in south Lebanon. RESULTS: Males had a higher incidence of AGE (57.1%). Pathogens were detected in 57.6% (n=114) of admitted patients, among them single pathogens were found in 51.0% (n=101) of cases that consisted of: Entamoeba histolytica 26.3% (n=52), rotavirus 18.7% (n=37), adenovirus 6.1% (n=12) and mixed co-pathogens found in 6.6% (n=13). Breast-fed children were significantly less prone to rotavirus (p=0.041). Moreover, children who had received the rotavirus vaccine were significantly less prone to rotavirus (p=0.032). CONCLUSION: Our findings highlight the high prevalence of E. histolytica infection as the major cause of pediatric gastroenteritis in hospitalized children, during the summer period likely reflecting the insanitary water supplies and lack of hygiene. Moreover the 42.4% of unidentified causative pathogens should prompt us to widen our diagnostic laboratory arsenal by adopting new diagnostic technologies.

Dataset on significant role of Candesartan on cognitive functions in rats having memory impairment induced by electromagnetic waves.

Rapid growing of mobile phones users has raised about the possible effects of these electromagnetic waves (EMW) on human health. Many studies have examined the role of these EMW on biological systems, but the results are still contradictory and controversial. In addition to EMW, over-activation of angiotensin type 1 receptor (AT1R) has been associated with cognitive decline, incidence and progression of neurodegenerative diseases. Candesartan, an AT1R blocker, is well recognized for treatment of hypertension. However, its role on cognitive functions such as spatial and recognition memory remains elusive. Thus, young rats were divided into 3 groups: control, exposed to radiofrequency electromagnetic waves (EMW), and exposed to EMW during Candesartan treatment (EMW+Cand). Spatial memory performance was assessed using the object recognition test and recognition memory performance using Morris water maze test. Significant differences where found between EMW exposed rats and EMW+Cand exposed rats treated with Candesartan compared to control, EMW group impaired learning, spatial and short term memory along with unaffected sensorimotor function whereas EMW+Cand group improved learning, spatial memory and short term memory deficit induced by EMW in addition to absence of its role on sensorimotor function. Although our data provides evidences of the protective role of Candesartan against EMW-induced cognitive decline, more future studies are still needed to confirm these findings which can provide new fields in treatment of EMW-induced damage by Candesartan.

Impact of chronic exposure to the pesticide chlorpyrifos on respiratory parameters and sleep apnea in juvenile and adult rats.

The widely used organophosphorus pesticide chlorpyrifos (CPF) is often detected in food. CPF inhibits acetylcholinesterase and can modify muscle contractility and respiratory patterns. We studied the effects of chronic exposure to CPF on respiratory parameters and diaphragm contractility in 21- and 60-days old rats. Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups vs vehicle: controls) from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle) thereafter. Two developmental time points were studied: weaning (day 21) and adulthood (day 60). Whole-body plethysmography was used to score breathing patterns and apnea index during sleep. Then, diaphragm strips were dissected for the assessment of contractility and acetylcholinesterase activity. Results showed that the sleep apnea index was higher in CPF-exposed rats than in controls. In adult rats, the expiratory time and tidal volume were higher in CPF-exposed animals than in controls. At both ages, the diaphragm's amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that chronic exposure to CPF is associated with higher sleep apnea index and diaphragm contractility, and modifies respiratory patterns in sleeping juvenile and adult rats.

The rs3957357C>T SNP in GSTA1 Is Associated with a Higher Risk of Occurrence of Hepatocellular Carcinoma in European Individuals.

Glutathione S-transferases (GSTs) detoxify toxic molecules by conjugation with reduced glutathione and regulate cell signaling. Single nucleotide polymorphisms (SNPs) of GST genes have been suggested to affect GST functions and thus to increase the risk of human hepatocellular carcinoma (HCC). As GSTA1 is expressed in hepatocytes and the rs3957357C>T (TT) SNP is known to downregulate GSTA1 mRNA expression, the aims of this study were: (i) to explore the relationship between the TT SNP in GSTA1 and the occurrence of HCC; (ii) to measure GSTA1 mRNA expression in HCCs. For that purpose, we genotyped non-tumor-tissue-derived DNA from 48 HCC patients and white-blood-cell-derived DNA from 37 healthy individuals by restriction fragment length polymorphism (RFLP). In addition, expression of GSTA1 mRNA was assessed by real-time PCR in 18 matching pairs of HCCs and non-tumor livers. Survival analysis was performed on an annotated microarray dataset containing 247 HCC patients (GSE14520). The GSTA1 TT genotype was more frequent in HCC than in non-HCC patients (27% versus 5%, respectively), suggesting that individuals carrying this genotype could be associated with 2-fold higher risk of developing HCCs (odds ratio = 2.1; p = 0.02). Also, we found that GSTA1 mRNA expression was lower in HCCs than in non-tumor livers. HCCs expressing the highest GSTA1 mRNA levels were the smallest in size (R = -0.67; p = 0.007), expressed the highest levels of liver-enriched genes such as ALB (albumin, R = -0.67; p = 0.007) and COL18A1 (procollagen type XVIII, R = -0.50; p = 0.03) and showed the most favorable disease-free (OR = 0.54; p<0.001) and overall (OR = 0.56; p = 0.006) outcomes. Moreover, GSTA1 was found within a 263-gene network involved in well-differentiated hepatocyte functions. In conclusion, HCCs are characterized by two GSTA1 features: the TT SNP and reduced GSTA1 gene expression in a context of hepatocyte de-differentiation.

Thyroxine transfer from cerebrospinal fluid into choroid plexus and brain is affected by brefeldin A, low sodium, BCH, and phloretin, in ventriculo-cisternal perfused rabbits.

BACKGROUND: Thyroxine (T4) hormone is synthesized by the thyroid gland and then released into the systemic circulation where it binds to a number of proteins. Dysfunction in T4 transport mechanisms has been demonstrated in multiple central nervous system (CNS) diseases including Alzheimer's disease. In the presence of different compounds that inhibit potential T4 transport mechanisms, this study investigated the transfer of T4 from cerebrospinal fluid (CSF) into Choroid Plexus (CP) and other brain tissues. The compounds used were brefeldin A, low sodium artificial CSF (aCSF), BCH, phloretin, and taurocholate (TA). METHODS: Radiolabeled T4 ((125)I-T4) was perfused continuously into the CSF and was assessed in several brain compartments with reference molecule (14)C-mannitol and blue dextran, using the in vivo ventriculo-cisternal perfusion (V-C) technique in the rabbit. The aCSF containing the drug of interest was infused after 1 h of perfusion. Drugs were applied independently to the aCSF after 1 h of control perfusion. RESULTS: Of interest, in presence of low sodium or BCH, the percentage recovery of (125)I-T4, was increased compared to controls, with concomitant increase in T4 clearance. Conversely, brefeldin A, phloretin, and TA did not exert any significant effect on the recovery and clearance of (125)I-T4 assessed in aCSF. On the other hand, the uptake of (125)I-T4 into CP was raised by 18 fold compared to controls in the presence of brefeldin A. In addition, low sodium, BCH, or phloretin alone, enhanced the uptake of (125)I-T4 by almost 3-fold, whereas TA did not show any significant effect. Finally, the uptake and distribution of (125)I-T4 into other brain regions including ependymal region (ER) and caudate putamen (CAP) were significantly higher than in controls. CONCLUSION: Our study suggests the involvement of different mechanisms for the transfer of (125)I-T4 from CSF into CP and other brain regions. This transfer may implicate sodium-dependent mechanisms, amino acid "L" system, or organic anion transporting polypeptide (OATP).

Effects of disulfiram on excitation-contraction coupling in rat soleus muscle.

The aim of this study was to analyze whether disulfiram could affect excitation-contraction coupling in rat slow-twitch ( soleus) muscle.In small bundles of intact fibers, the amplitude and the time constant of relaxation of twitch and potassium contractures were dose-dependently and reversibly reduced by disulfiram at concentrations up to 27 microM. At larger concentrations (up to 67.5 microM) these effects were still present but less pronounced. In the presence of disulfiram (27 microM), the relationship between the amplitude of potassium contractures and membrane potential was shifted to more positive potentials whereas, the steady state inactivation curve was unchanged. These observations suggest that disulfiram has no effect on voltage sensors. In saponin-skinned fibers, the amount of Ca(2+) taken up, estimated by using the amplitude of 10 mM of caffeine contracture, was increased by disulfiram (27 microM). By contrast no significant modification was observed in the sensitivity of the ryanodine receptors to caffeine (contractures generated at 5 mM of caffeine) and in the myofibrillar Ca(2+) sensitivity (Triton X-100 skinned fibers). These results indicate that disulfiram induces a dose-dependent reversible effect on the contractile responses of soleus mammalian skeletal muscle by acting mainly on the sarcoplasmic reticulum Ca(2+)-ATPase activity.

Nandrolone decanoate reduces changes induced by hindlimb suspension in voltage-dependent tension of rat soleus muscle.

The effect of 8 weeks of nandrolone decanoate treatment (15 mg kg(-1)/week, 5 weeks under normal conditions followed by 3 weeks of unloading) was tested for the voltage-dependence of activation and steady-state inactivation of contraction in isolated small bundles (2-4 cells) of intact slow-twitch skeletal muscle in rats. Twenty-four male rats were divided into three groups (8 rats/group, weight matched) for 8 weeks: (1) control, (2) unloaded, and (3) unloaded-treated. Compared with age-matched control values (unloaded vs. control), suspension induced a shift in the isometric tension characteristics toward fast-twitch types in the soleus muscle. In contrast, nandrolone decanoate treatment of suspended animals reduced unweighting-induced atrophy in the muscle and maintained: (1) the relative amplitude of twitch tension to the maximal Ca(2+) activated in saponin-treated fibers (control: 3.6 +/- 0.4%, unloaded: 6.9 +/- 1.1% and unloaded-treated: 4.6 +/- 0.2%), (2) the time to peak tension (control: 130 +/- 18 ms, unloaded: 85 +/- 12 ms and unloaded-treated: 110 +/- 11 ms), (3) the time constant of relaxation (control: 320 +/- 12 ms, unloaded: 120 +/- 13 ms and unloaded-treated: 349 +/- 20 ms), (4) the relative amplitude of K(+) contracture tension to the maximal Ca(2+) activated in saponin-treated fibers (control: 82.9 +/- 3.1%, unloaded: 65.1 +/- 2.8%, and unloaded-treated: 91.7 +/- 1.9%), (5) the potential at 50% of the activation curve (control: -40.4 +/- 1.2 mV, unloaded: -35.5 +/- 1.6 mV, and unloaded-treated: -48.4 +/- 1.2 mV), and (6) the potential at 50% of the inactivation curve (control: 42.2 +/- 1.9 mV, unloaded: -34.5 +/- 1.1 mV, and unloaded-treated: -37.9 +/- 1.1 mV). This study clearly shows that treatment with anabolic-androgenic steroids can prevent atrophy and functional changes induced by 3 weeks of unweighting in rat skeletal muscles.