Comparison of the efficacy of 0.9% normal saline with balanced crystalloid (Plasmalyte) in maintaining the metabolic profile in head injury patients undergoing evacuation of acute subdural haematoma - A randomised controlled trial.

Background and Aims: The choice of intravenous fluids is important in patients with traumatic brain injury (TBI), where large volumes may be required for resuscitation. Our study aimed to compare 0.9% normal saline (NS) with balanced crystalloid (Plasmalyte) in TBI patients in terms of metabolic and coagulation profile, brain relaxation score (BRS) and renal functions using serum urea, creatinine and urinary tissue inhibitor of metalloproteinases-2* insulin-like growth factor binding protein-7, [TIMP-2]*[IGFBP7], value to assess the risk of acute kidney injury. Methods: This randomised controlled trial on 90 TBI patients undergoing emergency craniotomy and subdural haematoma evacuation was conducted in a tertiary care institute. The patients were randomised to receive either NS (Group NS) or Plasmalyte (Group P) as the intraoperative maintenance fluid. The primary outcome measures included the potential of hydrogen (pH), base excess (BE) and chloride values from an arterial blood gas. The secondary outcomes were the coagulation profile, BRS and urinary [TIMP-2]*[IGFBP7]. The two groups' metabolic profile differences were analysed using two-way repeated analysis of variance. BRS was analysed using the Mann-Whitney U test. A P value < 0.05 was considered to be statistically significant. Results: The pH and chloride values were significantly higher, and the BE values were significantly lower in Group P compared to Group NS (P < 0.001). Brain relaxation and coagulation profiles were comparable between the two groups. Serum creatinine (P = 0.002) and urinary [TIMP-2]*[IGFBP7] (P = 0.042) were significantly higher in the NS group. Conclusion: Plasmalyte maintains a more favourable metabolic profile than NS in TBI patients without affecting brain relaxation adversely.

Candesartan cilexetil ameliorates NOSTRIN-NO dependent portal hypertension in cirrhosis and ACLF.

In decompensated cirrhosis, the severity of portal hypertension (PHT) is associated with increased hepatic endothelial nitric oxide synthase (eNOS) trafficking inducer (Nostrin), but the mechanism remains unclear. AIM: To investigate: (1) Whether in cirrhosis-PHT models, ± superimposed inflammation to mimic acute-on-chronic liver failure (ACLF) modulates hepatic nitric oxide synthase trafficking inducer (NOSTRIN) expression, nitric oxide (NO) synthesis, and/or endothelial dysfunction (ED); and (2) Whether the "angiotensin II type 1 receptor blocker" candesartan cilexetil (CC) affects this pathway. CD-1 mice received intraperitoneal carbon tetrachloride injections (CCl4 15% v/v in corn oil, 0.5 mL/kg) twice weekly for 12 wk to induce cirrhosis. After 12 wk, mice were randomized to receive 2-wk oral administration of CC (8 mg/kg) ± LPS. At sacrifice, plasma (biochemical indicators, cytokines, and angiotensin II) and liver tissues (histopathology, Sirius-red stains, and molecular studies) were analysed. Moreover, Nostrin gene knockdown was tested in human umbilical vein endothelial cells (HUVECs). When compared to naïve animals, CCl4-treated animals showed markedly elevated hepatic Nostrin expression (P < 0.0001), while hepatic peNOS expression (measure of eNOS activity) was significantly reduced (P < 0.05). LPS challenge further increased Nostrin and reduced peNOS expression (P < 0.05 for both) in cirrhotic animals. Portal pressure and subsequent hepatic vascular resistance were also increased in all cirrhotic animals following LPS challenge. In CCl4 ± LPS-treated animals, CC treatment significantly reduced Nostrin (P < 0.05) and increased hepatic cGMP (P < 0.01). NOSIP, caveolin-1, NFκB, and iNOS protein expression were significantly increased in CCl4-treated animals (P < 0.05 for all). CC treatment non-significantly lowered NOSIP and caveolin-1 expression while iNOS and NFκB expression was significantly reduced in CCl4 + LPS-treated animals (P < 0.05 for both). Furthermore, Nostrin knockdown significantly improved peNOS expression and associated NO synthesis and reduced inflammation in HUVECs. This study is the first to indicate a potential mechanistic role for the Nostrin-eNOS-NO pathway in cirrhosis and ACLF development. Moreover, this pathway provides a potential therapeutic target given the ameliorative response to Candesartan treatment.

Placental expression of striatin & endothelial nitric oxide synthase in women with & without pre-eclampsia.

Background & objectives: Striatin is a multi-domain scaffolding protein essential for activating endothelial nitric oxide synthase (eNOS). However, its role in pre-eclampsia remains use explored. Hence, this study aimed to investigate the association between striatin and eNOS in regulating nitric oxide (NO) production in the placenta of women with and without pre-eclampsia. Methods: Forty pregnant women each without (controls) and with pre-eclampsia (cases) were enrolled in the study. Blood striatin and NO concentrations were detected by the ELISA. Protein expression of striatin, phosphorylated eNOS (peNOS), inducible NOS (iNOS) and phosphorylated NF-κB were measured in the placental tissues by Western blot. Twenty four hour urinary protein and serum urea, uric acid and creatinine were analyzed as an autoanalyzer. Placental histology was analyzed by haematoxylin and eosin staining. Results: Compared to normotensive pregnant women, the levels of serum NO and striatin were decreased in pre-eclamptic women. The protein expression of striatin and peNOS was significantly reduced (P<0.05) while p65NF-κB and iNOS were upregulated considerably (P<0.05) in the placenta of cases compared to controls. Interpretation & conclusions: Our results show for the first time that decreased striatin expression was associated with decreased peNOS protein expression in the placental tissue of pre-eclamptic women. Interestingly, no significant difference was found in blood striatin or NO levels between controls and cases. Thus, therapies that improve placental striatin expression are attractive possibilities, both for prevention as well as treatment of endothelial dysfunction in pre-eclampsia.

Correlation among Poincare plot and traditional heart rate variability indices in adults with different risk levels of metabolic syndrome: a cross-sectional approach from Southern India.

OBJECTIVES: Heart rate variability (HRV) is an important marker of cardiac autonomic modulation. Metabolic syndrome (MetS) can alter cardiac autonomic modulation, raising the risk of cardiovascular disease (CVD). Poincaré plot analysis (PPA) is a robust scatter plot-based depiction of HRV and carries similar information to the traditional HRV measures. However, no prior studies have examined the relationship between PPA and traditional HRV measures among different risk levels of MetS. We evaluated the association between the Poincare plot and traditional heart rate variability indices among adults with different risk levels of MetS. METHODS: We measured anthropometric data and collected fasting blood samples to diagnose MetS. The MetS risk was assessed in 223 participants based on the number of MetS components and was classified as control (n=64), pre-MetS (n=49), MetS (n=56), and severe MetS (n=54). We calculated the Poincaré plot (PP) and traditional HRV measures from a 5 min HRV recording. RESULTS: Besides the traditional HRV measures, we found that various HRV indices of PPA showed significant differences among the groups. The severe MetS group had significantly lower S (total HRV), SD1 (short-term HRV), SD2 (long-term HRV), and higher SD2/SD1. The values of S, SD1, SD2, and SD2/SD1 were significantly correlated with most traditional HRV measures. CONCLUSIONS: We found gradual changes in HRV patterns as lower parasympathetic and higher sympathetic activity alongside the rising number of MetS components. The HRV indices of PPA integrating the benefits of traditional HRV indices distinguish successfully between different risk levels of MetS and control subjects.

Association between metabolic syndrome components and cardiac autonomic modulation in southern Indian adults with pre-metabolic syndrome: hyperglycemia is the major contributing factor.

Metabolic syndrome (MetS) involves multi-factorial conditions linked to an elevated risk of type 2 diabetes mellitus and cardiovascular disease. Pre-metabolic syndrome (pre-MetS) possesses two MetS components but does not meet the MetS diagnostic criteria. Although cardiac autonomic derangements are evident in MetS, there is little information on their status in pre-MetS subjects. In this study, we sought to examine cardiac autonomic functions in pre-MetS and to determine which MetS component is more responsible for impaired cardiac autonomic functions. A total of 182 subjects were recruited and divided into healthy controls (n=89) and pre-MetS subjects (n=93) based on inclusion and exclusion criteria. We performed biochemical profiles on fasting blood samples to detect pre-MetS. Using standardized protocols, we evaluated anthropometric data, body composition, baroreflex sensitivity (BRS), heart rate variability (HRV), and autonomic function tests (AFTs). We further examined these parameters in pre-MetS subjects for each MetS component. Compared to healthy controls, we observed a significant cardiac autonomic dysfunction (CAD) through reduced BRS, lower overall HRV, and altered AFT parameters in pre-MetS subjects, accompanied by markedly varied anthropometric, clinical and biochemical parameters. Furthermore, all examined BRS, HRV, and AFT parameters exhibited an abnormal trend and significant correlation toward hyperglycemia. This study demonstrates CAD in pre-MetS subjects with reduced BRS, lower overall HRV, and altered AFT parameters. Hyperglycemia was considered an independent determinant of alterations in all the examined BRS, HRV, and AFT parameters. Thus, hyperglycemia may contribute to CAD in pre-MetS subjects before progressing to MetS.

Role of zonula occludens in gastrointestinal and liver cancers.

A growing body of evidence suggests that tight junction (TJ) proteins play a crucial role in the pathogenesis of various diseases, including gastrointestinal (GI) cancer and hepatocellular carcinoma (HCC). TJ proteins primarily maintain the epithelial and endothelial cells intact together through integral proteins however, recent reports suggest that they also regulate gene expression necessary for cell proliferation, angiogenesis, and metastasis through adapter proteins such as zonula occludens (ZO). ZO proteins are membrane-associated cytosolic scaffolding proteins that modulate cell proliferation by interacting with several transcription factors. Reduced ZO proteins in GI cancer and HCC are correlated with tumor development and poor prognosis. Pubmed has searched for using the keyword ZO and gastric cancer, ZO and cancer, and ZO and HCC for the last ten years to date. This review summarized the role of ZO proteins in cell proliferation and their expression in GI cancer and HCC. Furthermore, therapeutic interventions targeting ZO in GI and liver cancers are reviewed.

Nimbolide attenuates gut dysbiosis and prevents bacterial translocation by improving intestinal barrier integrity and ameliorating inflammation in hepatocellular carcinoma.

Gut microbiota imbalance plays a key pathological role in hepatocellular carcinoma (HCC) progression; however, the mechanism is poorly understood. We previously showed nimbolide impede tumor development by improving hepatic tight junction (TJ) proteins expression and attenuating inflammation in HCC mice. Here, we aimed to study the role of nimbolide in regulating gut microbiota imbalance and bacterial translocation (BT) through modulating intestinal TJ proteins in an experimental hepatocarcinogenesis. Nimbolide (6 mg/kg) was administered orally for 4 weeks following induction of HCC in mice at the 28th week. Nimbolide treatment attenuated the gut microbiota imbalance by decreasing 16 s rRNA levels of Escherichia coli, Enterococcus, Bacteroides and increasing Bifidobacterium, and Lactobacillus in the intestinal tissue, which was otherwise altered in HCC mice. Furthermore, nimbolide improved intestinal barrier integrity in HCC mice by upregulating TJ proteins such as occludin and ZO-1 expression and subsequently prevented hepatic BT and decreased BT markers such as LBP, sCD14, and procalcitonin in the plasma of HCC mice. Moreover, nimbolide ameliorated intestinal and hepatic inflammation by downregulating TLR4, MyD88, and NF-κB protein expression in HCC mice. Thus, nimbolide represents a novel therapeutic drug for HCC treatment by targeting the gut-liver axis, which plays an imperative role in HCC pathogenesis.

Cut-off values and clinical efficacy of body roundness index and other novel anthropometric indices in identifying metabolic syndrome and its components among Southern-Indian adults.

CONTEXT: Abdominal obesity (AO) is a definitive link between cardiometabolic complications and metabolic syndrome (MetS). Many traditional and novel anthropometric indices have been identified to determine AO, and their relationship to MetS has been investigated. However, whether these indices are useful in a clinical setting is unknown. Moreover, the cut-off points for these indices to determine MetS have yet to be defined among Southern-Indian adults. AIMS: We aimed to evaluate the cut-off values and clinical efficacy of novel anthropometric indices in identifying MetS and its components. MATERIALS AND METHODS: Subjects (n = 202) were recruited and then grouped into cases (MetS = 106) and controls (healthy = 96). We measured anthropometric data and assayed glycemic and lipid profiles. Using these, we computed a-body shape index (ABSI), abdominal volume index (AVI), body adiposity index (BAI), body roundness index (BRI), conicity index (CI), lipid-accumulation product (LAP), visceral adiposity index (VAI) and waist-triglyceride index (WTI) from published equations. RESULTS: Compared to the control group, all the novel anthropometric indices were noticeably higher in both male and female subjects of the MetS group. The area under the curve values (AUCs) demonstrated that BRI, CI, AVI, and WTI had superior detection power in identifying MetS, and the AUCs varied upon stratification by gender. BRI was strongly associated with the highest odds of having MetS (OR 66.03). CONCLUSIONS: The optimal cut-off and AUC values attained for BRI, CI, AVI, and WTI have a clinical approach in identifying MetS and its components. The efficacy of these indices to identify MetS differed by gender.

Liver Injury in COVID-19: A Direct Hit or Collateral Damage?

SARS-CoV-2 is a novel coronavirus that has been identified, in December 2019, in Wuhan, China, and since it has become a worldwide pandemic, it has imposed far-reaching impacts on global human health and socio-economic activity. Worldwide, over 4 million Covid-19 related deaths were reported until September 2021. Recently published case studies have reported that Covid-19 patients develop different degrees of liver dysfunction. Inevitably, in hospitalized Covid-19 patients who develop acute liver derangement, there are a plethora of potential pathogenic causes such as direct-viral, immune-driven, and drug-induced and/or ischaemic liver injury. Patients with advanced chronic liver diseases (e.g., cirrhosis) and/or autoimmune liver disease have a poor immune function and associated poorer outcomes compared to other critically ill cohorts. However, largely any immediate liver derangement tends to be relatively mild, and as such, any de novo liver injury may not be a significant feature of Covid-19. There is an immediate necessity, therefore, to better understand the liver-specific pathophysiology of COVID-19. This review focuses on the up-to-date information regarding Covid-19 and associated indices for liver dysfunction, possible mechanisms, and potential drug targeted therapies in Covid-19 patients with and without liver dysfunction. PubMed database was used to perform an extensive literature search using the keywords liver and SARS-CoV-2, liver and Covid-19, Covid 19 and treatment, etc.

The Burden of Peripheral Neuropathy in Nondiabetic Chronic Kidney Disease and the Role of Ghrelin Isoforms in its Development.

Introduction: Peripheral neuropathy is one of the most common complications in chronic kidney disease (CKD). The neuroprotective role of ghrelin is being explored recently. Here we aim to determine the burden of neuropathy in nondiabetic CKD and to find the association of peripheral nerve function with plasma ghrelin levels in these patients. Methods: This was a cross-sectional study conducted in nondiabetic CKD patients on conservative management to determine the magnitude of neuropathy. The association of ghrelin isoforms with nerve functions was assessed between three groups, namely CKD with neuropathy, CKD without neuropathy, and healthy volunteers, with 20 participants in each group. Results: The proportion of neuropathy in nondiabetic CKD was 78% (n = 78), of which 51% (n = 40) were asymptomatic. Des acyl ghrelin (DAG) and total ghrelin (TG) levels were 1545.5 ± 487.4 and 1567.4 ± 485.3 pg/mL, respectively, in CKD patients with neuropathy and were found to be elevated compared to those without neuropathy, who had 1000.4 ± 264.2 and 1019.7 ± 264.3 pg/mL of DAG and TG, respectively (P < 0.001). Assessment of correlation between nerve conduction parameters and DAG levels showed positive correlation between DAG levels and common peroneal latency (r = 0.69; P < 0.01), median sensory latency (r = 0.45; P < 0.05), and sural latency (r = 0.51; P < 0.05). We found negative correlation between median velocity (r =-0.56; P < 0.05), common peroneal velocity (r = -0.64; P < 0.01), median sensory velocity (r =-0.49; P < 0.05), and sural velocity (r = -0.54; P < 0.05). There was no statistically significant difference in acyl ghrelin levels among the groups. Conclusion: The prevalence of peripheral neuropathy in CKD is significantly higher with almost half of them being asymptomatic. Impaired renal clearance in CKD leads to the accumulation of DAG, which subsequently inhibits the neuroprotective functions of AG leading to neuropathy in CKD.

Prevalence and determinants of sarcopenia in Indian patients with chronic kidney disease stage 3 & 4.

OBJECTIVES: There is limited literature on the prevalence and determinants of sarcopenia in the Indian predialysis chronic kidney disease (CKD) population. The current study attempts to characterize sarcopenia in CKD stages 3 & 4 using 3-compartment model dual-energy X-ray absorptiometry (DXA). METHODS: This is secondary data from a randomized trial on bicarbonate supplementation for preserving muscle mass. A 3-compartment DXA was done to assess body composition in 188 subjects aged 18 to 65, with stable kidney function. Sarcopenia was defined by Asian Working Group criteria - appendicular skeletal mass index < 5.4 kg/m2 in women and < 7 kg/m2 in men. RESULTS: Sarcopenia was present in 69.1% (n = 130). There was no difference in the prevalence of sarcopenia in CKD stage 3 (n = 62; 72.1%) vs CKD stage 4 (n = 68, 66.7%); P = 0.434. A lower body mass index (BMI) (OR 1.69; 95% CI 1.43, 2.01) and lower bicarbonate levels (OR 1.22; 95% CI 1.02, 1.47), and age (OR 0.95; 95% CI 0.91, 0.98) was independently associated with the muscle mass. A BMI cut-off of 18 failed to identify sarcopenia in 78.4% (n = 102) subjects (Kappa statistic 0.396). The receiver operating characteristic curve for mid-arm muscle circumference for identifying sarcopenia was 0.651 (95% CI 0.561, 0.740). CONCLUSIONS: Sarcopenia is highly prevalent in CKD 3 and 4. Sarcopenic individuals are older, with a low BMI and lower bicarbonate levels. The anthropometric parameters and biochemical parameters did not help identify sarcopenia in the predialysis population.

Nimbolide inhibits tumor growth by restoring hepatic tight junction protein expression and reduced inflammation in an experimental hepatocarcinogenesis.

BACKGROUND: Altered tight junction (TJ) proteins are correlated with carcinogenesis and tumor development. Nimbolide is a tetranotriterpenoid that has been shown to have antioxidant and anti-proliferative properties; however, its anticancer effects and molecular mechanism in hepatocellular carcinoma (HCC) remains obscure. AIM: To investigate the effect of nimbolide on TJ proteins, cell cycle progression, and hepatic inflammation in a mouse model of HCC. METHODS: HCC was induced in male Swiss albino mice (CD-1 strain) by a single intraperitoneal injection of 100 mg/kg diethylnitrosamine (DEN) followed by 80 ppm N-nitrosomorpholine (NMOR) in drinking water for 28 wk. After 28 wk, nimbolide (6 mg/kg) was given orally for four consecutive weeks in DEN/NMOR induced HCC mice. At the end of the 32nd week, all the mice were sacrificed and blood and liver samples were collected for various analyses. Macroscopic examinations of hepatic nodules were assessed. Liver histology and HCC tumor markers such as alpha-fetoprotein (AFP) and glypican-3 were measured. Expression of TJ proteins, cell proliferation, and cell cycle markers, inflammatory markers, and oxidative stress markers were analyzed. In silico analysis was performed to confirm the binding and modulatory effect of nimbolide on zonula occludens 1 (ZO-1), nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB), and tumor necrosis factor alpha (TNF-α). RESULTS: We found nimbolide treatment at a concentration of 6 mg/kg to HCC mice reduced hepatic tumor size by 52.08% and tumor volume (P < 0.01), and delayed tumor growth in HCC mice with a concomitant reduction in tumor markers such as AFP levels (P < 0.01) and glypican-3 expression (P < 0.05). Furthermore, nimbolide treatment increased tight junction proteins such as ZO-1 and occludin expression (P < 0.05, respectively) and reduced ZO-1 associated nucleic acid binding protein expression (P < 0.001) in HCC mice liver. Nimbolide treatment to HCC mice also inhibited cell proliferation and suppressed cell cycle progression by attenuating proliferating cell nuclear antigen (P < 0.01), cyclin dependent kinase (P < 0.05), and CyclinD1 (P < 0.05) expression. In addition, nimbolide treatment to HCC mice ameliorated hepatic inflammation by reducing NF-κB, interleukin 1 beta and TNF-α expression (P < 0.05, respectively) and abrogated oxidative stress by attenuating 4-hydroxynonenal expression (P < 0.01). Molecular docking studies further confirmed that nimbolide interacts with ZO-1, NF-κB, and TNF-α. CONCLUSION: Our current study showed for the first time that nimbolide exhibits anticancer effect by reducing tumor size, tumor burden and by suppressing cell cycle progression in HCC mice. Furthermore, nimbolide treatment to HCC mice ameliorated inflammation and oxidative stress, and improved TJ proteins expression. Consequently, nimbolide could be potentially used as a natural therapeutic agent for HCC treatment, however further human studies are warranted.

Cut-off Values and Clinical Utility of Surrogate Markers for Insulin Resistance and Beta-Cell Function to Identify Metabolic Syndrome and Its Components among Southern Indian Adults.

BACKGROUND: Insulin resistance (IR) is a collective clinical entity that exacerbates metabolic syndrome (MetS). As the gold-standard test to quantify IR involves intravenous insulin loading and repeated blood glucose monitoring, many indices have been developed for IR assessment for convenience. This study tested the ideal cut-off values and clinical utility of IR indices in identifying MetS. METHODS: We recruited 150 subjects, 75 MetS patients and 75 healthy controls, then obtained written informed consent to participate in this study. We collected fasting blood samples for glucose and lipid profiles and calculated nineteen indices of IR and insulin secretion using validated formulae. We determined the precision of these IR indices using the area under the curve (AUC) in a receiver operating characteristic analysis. RESULTS: Subjects with MetS have significantly higher IR coupled with lower insulin sensitivity and beta-cell function than controls. Among the surrogate markers of IR tested, the homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-adiponectin (HOMA-AD), triglyceride-glucose (TyG) index, HOMA-1%S (insulin sensitivity), quantitative insulin sensitivity check index (QUICKI), McAuley index, single-point insulin sensitivity estimator (SPISE), and HOMA-2%B (beta-cell function) showed the highest AUC values for detecting MetS. CONCLUSION: Our study results suggest that the ideal cut-off and AUC values identified for HOMA-IR, HOMA-AD, the TyG index, HOMA-1%S, QUICKI, the McAuley index, SPISE, and HOMA-2%B offer a clinical approach to the early detection and risk stratification for MetS among people in southern India.

Severe acute respiratory syndrome coronavirus-2 infection and the gut-liver axis.

Patients affected by coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, manifest various gastrointestinal and hepatic abnormalities alongside respiratory disorders. The identification of this virus in the feces of more than 50% of infected individuals indicates the possibility of viral shedding and fecal-to-oral transmission. Preliminary reports have also identified alterations in the intestinal microbiota profile in infected individuals. Moreover, COVID-19 patients manifest various degrees of liver injury characterized by alterations in liver enzymes. Digestive symptoms and liver abnormalities correlate with disease severity, the incidence of critical outcomes and patient's recovery. However, the pathogenic mechanisms behind COVID-19-induced abnormalities in the gut-liver axis seem to be multifactorial in origin. This review compiles current knowledge sourced from preclinical and clinical research and summarizes gastrointestinal and hepatic dysfunctions observed following SARS-CoV-2 infection, and also explores the possible mechanisms generating abnormalities in the gut-liver axis. Furthermore, this review sheds light on possible therapeutic targets against these disorders.

Impaired baroreflex sensitivity and cardiac autonomic functions are associated with cardiovascular disease risk factors among patients with metabolic syndrome in a tertiary care teaching hospital of South-India.

BACKGROUND & AIM: Baroreflex sensitivity (BRS) and heart rate variability (HRV) have been proposed to assess early autonomic dysfunction in metabolic syndrome (MetS) patients. Autonomic dysfunction in MetS patients may increase the risk of developing cardiovascular disease (CVD). However, the association of BRS and HRV with CVD risk factors remains elusive in MetS. The primary aim of this study was to assess the BRS and HRV in MetS patients among South-Indian adults and check whether BRS and HRV are associated with CVD risk factors. METHODS: We performed anthropometric indices, body composition, physiological parameters such as BRS, HRV, and other autonomic function tests in 176 subjects divided into MetS patients (n = 88) and healthy controls (n = 88). Fasting blood samples were collected for biochemical profiles and calculated insulin resistance indices, atherogenic index (AI), and rate pressure product (RPP). RESULTS: When compared to controls, we found significantly reduced BRS and an increased ratio of low-frequency (LF) to high-frequency (HF) power of HRV (LF/HF) in the MetS group. We observed significant differences in body composition and biochemical profiles among the MetS group. BRS and LF/HF ratio of HRV have shown a significant association with CVD risk factors in the MetS group. CONCLUSIONS: We observed autonomic dysfunction as low BRS and high LF/HF ratio of HRV in MetS patients. Additionally, the present results emphasize that the association of BRS and LF/HF ratio with anthropometric, glucose, lipid parameters, and other CVD risk factors may increase the susceptibility of MetS patients to higher CVD risk.

Changes in the levels of comet parameters before and after fluoxetine therapy in major depression patients.

Major depression belongs to mood disorders and characterized by worthlessness, no interest or happiness in any activity; lasting for atleast two weeks. Etio-pathological changes of major depression include oxidative stress leading to free radical synthesis which causes damage to carbohydrates, proteins, lipids and nucleic acids. Nucleic acid damage can be identified by either single or double strand breaks and for quantitative estimation of the same, neutral or alkaline comet assay is performed. Fluoxetine is the drug of choice for treatment of major depression having antioxidant function. In the current study eighty drug naïve major depression patients were recruited and comet parameters namely total comet length, head diameter and tail length were measured before starting the treatment and after completion of eight week fluoxetine therapy. The levels of comet parameters were higher in females than males suggesting higher prevalence of major depression among females. On categorizing into three age groups, the numbers of major depression patients belonging to 18-30 year age group were higher than 31-40 and 41-50 year age groups. All the parameters of deoxyribonucleic acid damage were reduced after eight week of fluoxetine therapy indicating that fluoxetine has anti-oxidant action along with its antidepressant properties, which cause reversal of oxidative stress induced damage occurring during major depression.

Ginkgolide-A attenuates bacterial translocation through activating PXR and improving antimicrobial peptide Reg 3A in experimental cirrhosis.

BACKGROUND AND AIMS: Bacterial translocation (BT) is strongly associated with disease progression and poor outcome in cirrhotic patients. The role of Pregnane X receptor (PXR) in regulating bacterial translocation in cirrhosis is unknown. We previously showed that Ginkgolide-A (GA), a natural PXR ligand, attenuated BT in cirrhotic mice by abrogating inflammation along the gut-liver-axis, and by protecting small intestinal tight junctions (TJ). Here, we aimed to investigate the effect of GA in activating PXR and associated antimicrobial peptides (AMPs) in regulating BT in experimental cirrhosis. METHODS: Male Swiss albino mice were administered CCl4 (0.5 mL/kg body-weight, i.p twice a week) for 12 consecutive weeks. After the 12th week, mice were randomized and administered with GA (100-mg/kg body-weight, oral) every-day for 2 weeks. At termination, blood, gut and liver tissues were collected for molecular studies. RESULTS: GA treatment to cirrhotic mice significantly increased the expression of small intestinal PXR and Regenerating family member 3 alpha (Reg3A), which were otherwise reduced in CCl4 cirrhotic mice. Moreover, compared to naive mice a significantly reduced Lactobacillus, and increased Bacteroides and Enterococcus 16s rRNA levels were observed in the small intestine and liver of cirrhotic mice. Treatment with GA to cirrhotic mice significantly reduced intestinal overgrowth and translocation of Enterococcus and Bacteroides to the liver. Furthermore, GA treatment significantly attenuated intestinal permeability and BT marker soluble-CD14 (sCD14), which were increased in CCl4 cirrhotic mice. CONCLUSION: The study showed for the first time that, GA treatment to cirrhotic rodents attenuates BT, by improving PXR and Reg3A expression.

Reliability of Anthropometry-Based Equations Compared to Dual Energy Absorptiometry for Assessing Body Composition in Predialysis Chronic Kidney Disease-A Longitudinal Study.

OBJECTIVES: Skinfold thickness measurements for assessing body composition are reported to have good reproducibility compared to the reference method of dual energy absorptiometry (DXA). In the current study, we compared the level of agreement between body composition measured with DXA and skinfold thickness (SFT) in CKD Stage 3 and 4, at 2 occasions, 6 months apart. METHODS: Body composition was assessed in 177 Indian patients with CKD Stage 3 and 4 using DXA and anthropometry (SFT). The body fat mass obtained by the 2 methods was compared by paired t-test, intraclass correlation coefficients, regression analysis, and Bland-Altman plots. A linear regression analysis was done to identify the patient-related parameters which would account for the intermethod differences between DXA and SFT. RESULTS: Compared to DXA, SFT underestimated the fat mass at baseline as well as 6 months [DXA vs. SFT at entry: 15.85 kg (95% confidence interval, CI 15.07-16.65) vs. 13.71 kg (95% CI 13.21-14.32), P < .001; at 6 months: 16.13 (95% CI 15.33-16.93) vs. 13.85 (95% CI 13.25-14.45), P < .001]. The intraclass correlation coefficients at entry and 6 months were 0.894 (0.857-0.921) and 0.896 (0.860-0.923), respectively. The intermethod differences between DXA and SFT at baseline and 6 months were comparable: 2.08 kg (95% CI 1.66-2.5) at baseline versus 2.27 kg (95% CI 1.83-2.71) at 6 months, P = 0.200. Gender and body mass index turned out to be the significant predictors of intermethod differences at base line and exit (P < .001). CONCLUSIONS: SFT-based measurements show good reproducibility compared to DXA over a period of 6 months. However, SFT systematically underestimates the fat mass by 2 Kg compared to DXA.