Amelioration of histological changes and associated metabolic abnormalities by a combination of Morinda lucida and metformin in diabetic rats

This work investigates the ability of Morinda lucida and co-administration of Morinda lucida/metformin in the control of biochemical and histological changes in alloxan-induced diabetic rats. Alloxan diabetic rats were treated with 200 mg/Kg body weight of Morinda lucida leaves extract, 1 mg/Kg BW of metformin or a combination of the two treatments for 28 days. Results of the studies revealed that Morinda lucida leaves extract significantly improved lipid profile and kidney function in diabetic rats. These positive outcomes were enhanced by combined treated with Morinda lucida leaves extract and metformin. Furthermore, the calculated atherogenic index of treated animals were close to those of normal rats as opposed to diabetic rats. Similarly, histological studies showed that Morinda lucida leaves extract and metformin administered together or singly, ameliorated damages in pancreas and kidneys from alloxan diabetic rats. It can therefore be inferred that combined treatment with Morinda lucida leaves extract and merformin could improve the potency of Morinda lucida leaves used in the management of diabetic complications

Disease Outcome and Brain Metabolomics of Cyclophilin-D Knockout Mice in Sepsis

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction resulting from a systemic inflammatory response to infection, but the mechanism remains unclear. The mitochondrial permeability transition pore (MPTP) could play a central role in the neuronal dysfunction, induction of apoptosis, and cell death in SAE. The mitochondrial isomerase cyclophilin D (CypD) is known to control the sensitivity of MPTP induction. We, therefore, established a cecal ligation and puncture (CLP) model, which is the gold standard in sepsis research, using CypD knockout (CypD KO) mice, and analyzed the disease phenotype and the possible molecular mechanism of SAE through metabolomic analyses of brain tissue. A comparison of adult, male wild-type, and CypD KO mice demonstrated statistically significant differences in body temperature, mortality, and histological changes. In the metabolomic analysis, the main finding was the maintenance of reduced glutathione (GSH) levels and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the KO animals following CLP. In conclusion, we demonstrate that CypD is implicated in the pathogenesis of SAE, possibly related to the inhibition of MPTP induction and, as a consequence, the decreased production of ROS and other free radicals, thereby protecting mitochondrial and cellular function.

Understanding Reward Dysfunction in Bipolar Affective Disorder through Behavioural, Cognitive and Neurobiological Changes

Bipolar disorder, like many neuropsychiatric conditions, can be studied from a number of perspectives; from observation of behaviour, to study of cognitive dysfunction, through to changes at the molecular and genetic level. A consequence of this way of working is that there is inadequate communication between different levels of analysis, such that insufficient thought is given to whether a theoretical model derived from behavioural work fits with neurobiological data, and vice versa. Such limitations represent a key limiting factor in successful translation. Therefore, this paper takes a dominant theoretical model of bipolar disorder, based on that by Gray (1994) and developed by Alloy et al., (2015) as a basis to propose that the foundational pathology in bipolar is reward hypersensitivity, and to review how recent diverse neurobiological, cognitive and behavioural findings fit with this understanding. Executive Function deficits, partially derived from heritable structural changes are suggested as a foundation through which reward hypersensitivity develops to disorder, and CANA1C polymorphism-induced hyperactivity, further serves to drive the system towards reward seeking goals, through interaction with dopaminergic systems. This action is supplemented by a genetic predisposition for cognitive regulatory dysfunction, leading to improper modulation of emotive and reward networks. Specifically, deficits in top-down limbic modulation leads to behaviours disproportionally driven by limbic and reward circuitry; this pathology strengths over time through use. This therefore eventually results in substantial regional disconnect, reflected in epigenetic changes to neurotransmitters and observable histological changes.

A comparative study of human glomerular basement membrane thickness using direct measurement and orthogonal intercept methods

Introduction Here we report estimates of glomerular basement membrane (GBM) thickness in the Brazilian population performed using direct (DM) and orthogonal interception methods (OIM), and comment on potential sources of variation among estimates made by different laboratories. Methodology A total of 38 patients, ranging from 3 to 78 years of age, 26 (68%) males and 12 (32%) females, were submitted to kidney biopsy procedures for renal disease diagnosis. Glomeruli were diagnosed with minor histological changes by conventional, immunofluorescence and electron microscopy. GBM thickness was estimated using both DM and OIM methods. Results Estimates of GBM thickness obtained using DM were higher than those obtained by OIM. However, the application of a correction for non-perpendicular membrane sectioning to DM estimates yielded similar results to those obtained under OIM. The estimated GMB thickness using DM after correction was 289 + 44 nm, versus 287 + 48 nm by OIM. No statistically significant differences were detected in GMB thickness, nor with respect to patient age or sex. Conclusions GBM thickness in the studied Brazilian population measured approximately 290 nm. The application of criteria for estimating the shortest distance between the endothelial and podocyte cell membranes with correction for non-perpendicular membrane sectioning can increase the accuracy of GBM thickness estimates using DM and OIM.

Serological Positivity against Selected Flaviviruses and Alphaviruses in Free-Ranging Bats and Birds from Costa Rica Evidence Exposure to Arboviruses Seldom Reported Locally in Humans

Arboviruses have two ecological transmission cycles: sylvatic and urban. For some, the sylvatic cycle has not been thoroughly described in America. To study the role of wildlife in a putative sylvatic cycle, we sampled free-ranging bats and birds in two arbovirus endemic locations and analyzed them using molecular, serological, and histological methods. No current infection was detected, and no significant arbovirus-associated histological changes were observed. Neutralizing antibodies were detected against selected arboviruses. In bats, positivity in 34.95% for DENV-1, 16.26% for DENV-2, 5.69% for DENV-3, 4.87% for DENV-4, 2.43% for WNV, 4.87% for SLEV, 0.81% for YFV, 7.31% for EEEV, and 0.81% for VEEV was found. Antibodies against ZIKV were not detected. In birds, PRNT results were positive against WNV in 0.80%, SLEV in 5.64%, EEEV in 8.4%, and VEEV in 5.63%. An additional retrospective PRNT analysis was performed using bat samples from three additional DENV endemic sites resulting in a 3.27% prevalence for WNV and 1.63% for SLEV. Interestingly, one sample resulted unequivocally WNV positive confirmed by serum titration. These results suggest that free-ranging bats and birds are exposed to not currently reported hyperendemic-human infecting Flavivirus and Alphavirus; however, their role as reservoirs or hosts is still undetermined.

Long-term surveillance of liver histological changes in chronic hepatitis C patients completing pegylated interferon-α plus ribavirin therapy: an observational cohort study

Background: For chronic hepatitis C (CHC) patients completing pegylated interferon (PegIFN)-α/ribavirin therapy, long-term liver histological changes remain largely unexplored. Methods: This observational cohort study included 85 CHC patients completing PegIFN-α/ribavirin therapy with liver biopsies performed at baseline and the end of surveillance (EOS). Median years between paired biopsies were 6.75 (interquartile range: 5.63–7.54). Results: In patients with baseline METAVIR fibrosis stages (F) <4 (able to undergo fibrosis progression; n = 77), cases achieving sustained virological response (SVR) ( n = 52) had a significantly lower rate of fibrosis progression than non-SVR cases ( n = 25) (3.8% versus 24.0%, p = 0.012). Among the entire cohort ( n = 85), the rate of activity response [METAVIR activity grades (A) decreasing or maintaining at A0] in SVR cases ( n = 59) was significantly higher than that in non-SVR cases ( n = 26) (94.9% versus 65.4%, p = 0.001). For SVR cases among the entire cohort, independent predictors of fibrosis clearance included baseline F <2 [odds ratio (OR) = 7.877, p = 0.042] and aspartate transaminase (AST) levels declining by >70% at EOS compared with baseline (OR = 9.013, p = 0.038). For non-SVR cases among the entire cohort, baseline AST levels >80 U/l and glucose levels ⩽ 105 mg/dl independently predicted significant fibrosis (F2/F3/F4) at EOS (OR = 12.558, p = 0.049) and activity response (OR = 17.741, p = 0.047), respectively. Conclusions: Among CHC patients completing PegIFN-α/ribavirin therapy, SVR lowers the risk of liver histological progression but does not guarantee fibrosis clearance. For SVR cases, those with baseline F ⩾ 2 or without significantly declined follow-up AST levels should be specifically monitored. As for non-SVR cases, those with a higher baseline AST or glucose level should preferentially receive retreatment.

Histological Changes of Wistar Rats' Hippocampus and Entorhinal Cortex After Prenatal Exposure to Mosquito Coil Smoke

Background: The structural integrity of the hippocampus and the entorhinal cortex appears to be a prerequisite for normal acquisition of information about relational and contextual representation. Increased exposures to pyrethroids by pregnant women and children have raised concerns over their potentials as developmental neurotoxicants. Objectives: We studied the histological changes on the hippocampus and entorhinal cortex of adolescent Wistar rats prenatally exposed to mosquito coil smoke (MCS). Methods: 30 adult Wistar rats (20 females, 10 males) were used for the study. Mating was induced, and pregnancy was confirmed. Pregnant animals were grouped into four, 3 animals per group. Group I was exposed to fresh air. Groups II, III, and IV were exposed to mosquito coil smoke for 4, 6 and 8 hours daily respectively throughout gestation period. On Post-natal day (PND) 29, experimental animals were humanely sacrificed and regions of the hippocampus and entorhinal cortex were processed for histological studies using H & E stain. Results and Conclusion: Our results showed that prenatal exposure to mosquito coil smoke caused neuronal degeneration, distortion in cytoarchitecture of cellular layers and vacuolations in the hippocampus and entorhinal cortex of prenatally exposed groups.