Effect of glycemic status on peripheral nerve conduction in lower limbs in type 2 diabetes mellitus patients

Background: Diabetes mellitus (DM) is one of the most common chronic diseases globally. Diabetic neuropathy is the most common & troublesome complication. But exact pathogenesis is not yet known. Comparatively there are few studies showing relation between glycemic status & diabetic neuropathy. Hence present study was conducted, which was aimed to assess the same in lower limbs in type 2 DM.  Methods: 60 type 2 diabetes mellitus male patients were selected from diabetic OPD. 30 were having glycated hemoglobin (HbA1c) 6%-9% (group B), 30 were having HbA1c > 9% (group C). They were compared with age and sex matched 30 normal healthy controls (group A). Conduction velocity and amplitude of bilateral sural sensory nerve action potential (SNAP) and peroneal compound muscle action potential (CMAP) were recorded. Glycated hemoglobin was measured using ion exchange resin method. Results: Group B and group C had significantly lesser means of conduction velocity and amplitude of sural SNAP (p<0.001) and peroneal CMAP (p<0.05) as compared to group A. Hb A1c had statistically significant negative correlation with conduction velocity and amplitude of sural SNAP (p<0.001) as well as peroneal CMAP (p<0.001). Conclusions: This study shows that diabetic patients with higher blood glucose levels are at increased risk of diabetic neuropathy. Diabetic neuropathy in lower limbs worsens with increasing blood glucose levels. Hence stringent action has to be taken at an early stage to control blood glucose levels. Also, patients should be encouraged for regular follow up and strict glycemic control.

Evaluation of Phytoremediation Potential of Lantana camara for Heavy Metals in an Industrially Polluted Area in Bhopal, India

Soil contamination from industrial effluents and mining activities is a widespread concern all over the world. Generally soil act as the buffer zone between atmosphere and underground water, thus soil contamination creates a serious threat to soil and to the surrounding biosphere. This research program is aimed to make an in-depth investigation about the remediation of contaminated sites from various metal contaminants using specific plants. This study concentrates on the evaluation of phytoremediation potential of Lantana camara for the surroundings of industrial area of Bhopal, which is heavily affected by heavy metal pollution. The aim of our research was to identify some interesting accumulators which may associate an important biomass production with an effective absorption and translocation of heavy metals. The present study is focused on the ability of the native plant to accumulate and tolerate high concentrations of heavy metals on heavy metal supplemented M S medium in tissue culture, which are often associated in polluted areas

Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml(-1) with a limit of detection of 0.16 ng ml(-1)

Body plethysmography in chronic obstructive pulmonary disease patients: A cross-sectional study

Background: Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the world, for which smoking is a common cause. It is preferable to diagnose COPD at an earlier stage and to assess its progression so that mortality and morbidity of the disease could be reduced. Hence, we conducted this study to assess parameters of body plethysmography in Indian population where the data are lacking and to assess whether the use of body plethysmography can detect COPD earlier. Subjects and Methods: The study was approved by the Ethics Committee at B. J Government Medical College, Pune. In this comparative randomized cross-sectional study, healthy control subjects (CN), smokers without COPD diagnosis (SM) who were smoking for more than 5 pack-years and smokers with COPD who were further classified depending upon GOLD criteria as mild COPD (C1), moderate COPD (C2), and severe COPD (C3) (n = 30 each group) were considered. All the participants were males who gave written informed consent. Subject underwent routine spirometry (FEV1, FVC, FEV1/FVC, PEFR, and FEF25-75%) along with body plethysmography where sGaweff, sGawtot, residual volume (RV), total lung capacity (TLC), and inspiratory capacity (IC) were recorded. Statistical Analysis: The differences in lung function were compared between healthy controls and smokers and also between the three groups of COPD severity (GOLD guidelines) employing univariate analysis of variance and Bonferroni's post hoc test. Results: Spirometry could not differentiate between smokers without COPD and healthy controls. However, three parameters on body plethysmography (IC, sGawtot, and sGaweff) were sensitive enough to detect differences between smokers without COPD and healthy controls. Conclusion: Using body plethysmography, the vexed question troubling the clinician, which of the smokers progress to COPD and who do not before they develop irreversible changes can perhaps be answered if further large-scale multicenter studies and long-term follow-up studies confirm the findings in this study

Bilateral adrenal masses: a single-centre experience

Background Bilateral adrenal masses may have aetiologies like hyperplasia and infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may have coexisting hypocortisolism. Bilateral tumours are likely to have hereditary/syndromic associations. The data on clinical profile of bilateral adrenal masses are limited. Aims To analyse clinical, biochemical and radiological features, and management outcomes in patients with bilateral adrenal masses. Methods Retrospective analysis of 70 patients with bilateral adrenal masses presenting to a single tertiary care endocrine centre from western India (2002–2015). Results The most common aetiology was pheochromocytoma (40%), followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%), metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years) compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%). The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas all cases of metastasis had abdominal pain. Mean size of adrenal masses was the largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001). Conclusion In evaluation of bilateral adrenal masses, age at presentation, presenting symptoms, lesion size, and biochemical features are helpful in delineating varied underlying aetiologies

C-Terminal Proline Deletions in KCNC3 Cause Delayed Channel Inactivation and an Adult-Onset Progressive SCA13 With Spasticity

Mutations in the potassium channel gene KCNC3 (Kv3.3) cause the autosomal dominant neurological disease, spinocerebellar ataxia 13 (SCA13). In this study, we expand the genotype-phenotype repertoire of SCA13 by describing the novel KCNC3 deletion p.Pro583_Pro585del highlighting the allelic heterogeneity observed in SCA13 patients. We characterize adult-onset, progressive clinical symptoms of two afflicted kindred and introduce the symptom of profound spasticity not previously associated with the SCA13 phenotype. We also present molecular and electrophysiological characterizations of the mutant protein in mammalian cell culture. Mechanistically, the p.Pro583_Pro585del protein showed normal membrane trafficking with an altered electrophysiological profile, including slower inactivation and decreased sensitivity to the inactivation-accelerating effects of the actin depolymerizer latrunculin B. Taken together, our results highlight the clinical importance of the intracellular C-terminal portion of Kv3.3 and its association with ion channel function

KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia 13 displays aberrant intracellular trafficking

Spinocerebellar ataxia 13 (SCA13) is an autosomal dominant disease resulting from mutations in KCNC3 (Kv3.3), a voltage-gated potassium channel. The KCNC3(R420H) mutation was first identified as causative for SCA13 in a four-generation Filipino kindred with over 20 affected individuals. Electrophysiological analyses in oocytes previously showed that this mutation did not lead to a functional channel and displayed a dominant negative phenotype. In an effort to identify the molecular basis of this allelic form of SCA13, we first determined that human KCNC3(WT) and KCNC3(R420H) display disparate post-translational modifications, and the mutant protein has reduced complex glycan adducts. Immunohistochemical analyses demonstrated that KCNC3(R420H) was not properly trafficking to the plasma membrane and surface biotinylation demonstrated that KCNC3(R420H) exhibited only 24% as much surface expression as KCNC3(WT). KCNC3(R420H) trafficked through the ER but was retained in the Golgi. KCNC3(R420H) expression results in altered Golgi and cellular morphology. Electron microscopy of KCNC3(R420H) localization further supports retention in the Golgi. These results are specific to the KCNC3(R420H) allele and provide new insight into the molecular basis of disease manifestation in SCA13

A <i>KCNC3</i> mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking

<div><p>The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the <i>KCNC3</i>^<i>R423H</i> allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3^R423H in <i>Drosophila</i> triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3^R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in <i>Drosophila</i>, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3^R423H with <i>Drosophila</i> epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3^R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of KCNC3^R423H may be mediated through indirect effects on EGFR signaling in the developing cerebellum. Our results therefore confirm the <i>KCNC3</i>^<i>R423H</i> allele as causative for SCA13, through a dominant negative effect on KCNC3^WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology.</p></div