Long-lasting partnership between insulin resistance and endothelial dysfunction: role of metabolic memory

Background and Purpose

The persistence of deleterious effects of hyperglycaemia even after glucose normalization is referred to as ‘metabolic memory’. However, similar persistent effects of the metabolic consequences of a high fat diet (HFD) have not been described.

Experimental Approach

Rats were given a normal pellet diet (NPD) or a HFD for 3 months. The animals from the HFD group were then returned to the NPD to observe the long-term effects of insulin resistance. Endothelial dysfunction was assessed by carbachol-mediated vasorelaxation and eNOS phosphorylation.

Key Results

As expected, HFD consumption resulted in insulin resistance and endothelial dysfunction. Phosphorylation of eNOS at S1177 was decreased in HFD rats, compared with that in the NPD group. Rats on 3 months of HFD showed glucose intolerance and impaired insulin sensitivity and were then switched back to NPD (REV group). Levels of cholesterol and triglyceride, and adiposity returned to normal in REV rats. However, endothelium-dependent vascular responses to carbachol which were impaired in HFD rats, continued to be impaired in REV rats. Similarly, decreased eNOS phosphorylation after HFD was not improved after 1 or 6 months of REV.

Conclusions and Implications

Our data indicate that returning to NPD did not improve the insulin sensitivity or the endothelial dysfunction induced by HFD. Although some biochemical parameters responsible for insulin resistance and endothelial dysfunction were normalized, molecular and vascular abnormalities, involving NO, persisted for several months, highlighting the long-lasting effects of metabolic memory.     

Oral contraceptive pills induced hemichorea in an adolescent female with polycystic ovarian disease

Chorea is a neurological adverse effect of oral contraceptive pills (OCPs). The onset of chorea following OCPs usage varies widely from few weeks to several years. We report a rare case of chorea which developed within a week of starting OCPs in an adolescent girl with polycystic ovarian disease.KEY WORDS: Chorea, oral contraceptive pills, polycystic ovarian disease     

Haploidentical Hematopoietic Stem Cell Transplantation in Leukemia’s: Experience from a Cancer Center in India

There has been a surge in haploidentical hematopoietic stem cell transplantation (HSCT) in India recently. However, there is a paucity of data on haploidentical HSCT from India. The report is an analysis of data of haploidentical HSCT performed at our center. Analysis of patients with acute leukemia or chronic myeloid leukemia who underwent haploidentical HSCT during 2014–2019 was performed. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide with Mycophenolate-mofetil and Cyclosporine. All patients were transfused peripheral blood stem cells from donors. Overall survival (OS) was calculated using the Kaplan–Meier method. Twenty-one patients underwent haploidentical HSCT. Fourteen-patients were males. The median age of patients was 15 years. Fludarabine with total body irradiation was the most common conditioning regimen (n = 15, 71.4%). The median duration for neutrophil and platelet engraftment was 14 days. Cumulative incidence of acute and chronic GVHD was 19%, and 38% respectively. The median follow-up was 26 months and the two-year OS was 38%. Twelve (57%) patients died during the study period, 8 patients (38%) died from transplant-related mortality (TRM), and 4 from disease relapse. Sepsis was the cause of death in six of the eight TRM. Nine out of 21 patients (42.8%) are leukemia-free on follow-up. Haploidentical HSCT is a promising modality of treatment in patients who have no suitable matched donors. Though the TRM remains high, good disease control was achieved in 42.8% of patients. Multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries.     

Structural Signaling Regulates Inflammation-Induced Enhanced Restitution and Increased Mib-1 and Bax-Indexes After Superficial Injury in Isolated Guinea Pig Gastric Mucosa

Several growth factors and cytokines are involved in regulation of the immediate repair of gastrointestinal mucosa, a process also called restitution. Few data exist on the effect of inflammation on this process using an explant model, where the folded basal lamina is included. The aim of the present study was to investigate the effect of simulated inflammation on restitution and on concomitant proliferation and apoptosis in isolated guinea pig gastric mucosa. Paired gastric mucosae were mounted in Ussing chambers (37 degrees C) and a superficial injury was induced (1.25 M NaCl/5 min) followed by a 4-hr restitution (pH 7.3-7.5). During perfusion, simulated inflammation was induced (with 0.5 or 5.0 ng/ml IL-1beta or with activated polymorphonuclear [PMN] cells). The PI (proliferative index) and AI (apoptotic index) are expressed as the number of Mib-1- or Bax-immunopositive cells per 300 foveolar cells, respectively. The mean recovery of electrophysiological resistance of tissues (R) after injury and exposure to serosal IL-1beta during restitution was 95.2 +/- 5.3% (mean +/- SD), whereas the value for control tissues was 89.6 +/- 6.9% (P = 0.016; N = 9). The mean recovery of R in tissues exposured to activated serosal PMN cells during restitution was 97.6 +/- 2.7%, whereas the value for unexposed control tissues was 93.8 +/- 2.9 (P = 0.004; N = 9). The enhancing effect of PMN cells was partially eliminated by serosal anti-ICAM, whereas serosal cytochalasin D abolished the process completely. The PI of tissues exposed to serosal PMN cells was 34.6 +/- 17.3, whereas the value for unexposed controls was 24.7 +/- 15.5 (P = 0.04; N = 5). The corresponding AI values were 17.0 +/- 2.8 and 12.0 +/- 5.7, respectively (NS; N = 4). Simulated inflammation either with serosal IL-1beta or with activated PMN cells enhances restitution and proliferation, whereas their effect on AI is only suggestive. Exogenous serosal anti-ICAM modulates restitution, whereas cytochalasin D abolishes it completely, suggesting that the structural signaling system including focal adhesions and cytoskeleton plays a significant role in the regulation of restitution.     

Low,fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation

Objective/background

Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25 mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD.

The risk of lymph node metastasis in colorectal polyps with invasive adenocarcinoma

One hundred fifty-one patients with colorectal polyps containing invasive adenocarcinoma treated by resection were studied to determine the incidence of lymph node metastasis and whether lymph node metastasis was related to the depth of invasion. Other variables evaluated included size and configuration of the polyp, grade of adenocarcinoma, presence or absence of lymphovascular invasion, and degree of differentiation. In patients with sessile polyps, the incidence of lymph node metastasis was 10 percent. Eighty percent of these lesions had lymphovascular invasion. For pedunculated polyps, the overall incidence of lymph node metastasis was 6 percent. However, there was no incidence of lymph node metastasis when the depth of invasion was limited to the head, neck, and stalk of the polyp (Levels 1, 2, and 3). Only when the depth of invasion reached to the base of the stalk (Level 4) was the risk of lymph node metastasis high (27 percent). The other risk factors were not associated with lymph node metastasis. We concluded that the most significant risk factor for lymph node metastasis in patients with invasive carcinoma in a polyp was invasion into the submucosa of the bowel wall (Level 4).Presented in part at the Tripartite Meeting, Birmingham, United Kingdom, June 19–21, 1989.     

GC-FID,Antioxidants Analysis and Antimicrobial,Anti-Inflammatory,Anti-Diabetic Activities of Tisanes Derived from Underutilized Lemon Grass Cymbopogon khasianus (Hack.)

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Cymbopogon khasianus (Hack.) is widely distributed and an underutilized plants in tropical and subtropical...     

Ultrasonographic estimation of fetal gestational age by fetal kidney length

Introduction: Fetal kidney length vs biparietal diameter (BPD) and femur length (FL) were comparatively evaluated and the role of fetal kidney length in estimating gestational age was determined in the second and third trimesters. Materials and methods: The study was carried out on 199 women with singleton uncomplicated pregnancies attending the outdoor patient department (OPD) for routine ultrasound fetal biometry. Fetal kidney length was measured biweekly, between 18 weeks and 38 weeks of gestation. Linear regression models for estimation of gestational age were derived from biometric indices (BPD and FL) and kidney length. Result: The earliest age at which fetal kidney could be seen sonographically was the 18th week of gestation with the mean kidney length of 12 ± 1.31 mm. The mean sonographic kidney length at the 38th week of gestation was 40.4 ± 1.71 mm, indicating that the mean fetal kidney length increases as pregnancy progresses from 18 weeks to 38 weeks of gestation. Conclusion: The best linear regression model for estimating fetal gestational age is femur length, kidney length, and biparietal diameter in that order, with standard error of ±3.85 days, ±8.04 days, and ±8.75 days, respectively.     

Healthy aging is associated with increased neural processing of positive valence but attenuated processing of emotional arousal: an fMRI study

Arousal and valence play key roles in emotional perception, with normal aging leading to changes in the neural substrates supporting valence processing. The objective of this study was to investigate normal age-related changes in the neural substrates of emotional arousal processing. Twenty-three young and 23 older, healthy women underwent functional magnetic resonance imaging as they viewed images which were neutral or positive in valence and which varied in arousal level from low to high. Using a parametric modulation approach, we examined how the blood oxygen-level dependent signal varied with single trial subjective ratings of valence and arousal, and whether this differed with age. In accordance with previous studies we found that the older group showed greater activation in response to positive valence, in the left amygdala, left middle temporal gyrus and right lingual gyrus. In contrast however, they showed reduced reactivity to emotional arousal, in occipital and temporal visual cortices bilaterally, the left inferior parietal cortex, and the supplementary motor area bilaterally. This study represents the first of its kind to clearly dissociate how aging affects the neural correlates of emotional arousal and valence. The changes in arousal processing may in part be mediated by the functional reorganization evident in the aging brain, such as reduced activation of the posterior cortices as described by the posterior-anterior shift in ageing (PASA) effect.