Benzofuran Iboga-analogs Modulate Nociception and Inflammation in an Acute Mouse Pain Model.

Pain management following acute injury or post-operative procedures is highly necessary for proper recovery and quality of life. Opioids and non-steroidal anti-inflammatory drugs (NSAIDS) have been used for this purpose, but opioids cause addiction and withdrawal symptoms whereas NSAIDS have several systemic toxicities. Derivatives of the naturally occurring iboga alkaloids have previously shown promising behavior in anti-addiction of morphine by virtue of their interaction with opioid receptors. On this frontier, four benzofuran analogs of the iboga family have been synthesized and their analgesic effects have been studied in formalin induced acute pain model in Swiss albino mice at 30 mg/kg of body weight dose administered intraperitoneally. The antioxidant, anti-inflammatory and neuro-modulatory effects of the analogs were analyzed. Reversal of tail flick latency, restricted locomotion and anxiogenic behavior were observed in iboga alcohol, primary amide and secondary amide. Local neuroinflammatory mediators' substance P, calcitonin gene related peptide, cyclooxygenase-2 and p65 were significantly decreased whereas the depletion of brain derived neurotrophic factor and glia derived neurotrophic factor was overturned on iboga analog treatment. Behavioral patterns after oral administration of the best analog were also analyzed. Taken together, these results show that the iboga family of alkaloid has huge potential in pain management.

Corneal Confocal Microscopy Abnormalities in Children and Adolescents With Type 1 Diabetes.

OBJECTIVE: Utility of corneal confocal microscopy (CCM) in children and adolescents with type 1 diabetes mellitus (T1DM) without neuropathic symptoms or signs and minimal abnormality in large and small nerve fiber function tests remains largely undetermined. This study aimed to evaluate the performance of CCM in comparison to thermal detection thresholds (TDT) testing and nerve conduction studies (NCS) for detecting neuropathy in children with T1DM. METHODS: A cohort of children and adolescents with T1DM (n = 51) and healthy controls (n = 50) underwent evaluation for symptoms and signs of neurological deficits, including warm detection threshold, cold detection threshold, vibration perception threshold, NCS, and CCM. RESULTS: Children with T1DM had no or very minimal neuropathic symptoms and deficits based on the Toronto Clinical Neuropathy Score, yet NCS abnormalities were present in 18 (35%), small fiber dysfunction defined by an abnormal TDT was found in 13 (25.5%) and CCM abnormalities were present in 25 (49%). CCM was abnormal in a majority of T1DM children with abnormal TDT (12/13, 92%) and abnormal NCS (16/18, 88%). CCM additionally was able to detect small fiber abnormalities in 13/38 (34%) in T1DM with a normal TDT and in 9/33 (27%) with normal NCS. CONCLUSION: CCM was able to detect corneal nerve loss in children with and without abnormalities in TDT and NCS.

Occupational Health in Practice: Heart Rate Profile of the Lathe Machine Workers.

Context: Lathe machine work is an important unorganized sector in India. However, to date, no work physiological studies have been conducted among these workers to evaluate the physical strain involved in this work. Aim: The present study aims to determine the workload in different lathe machine tasks from working heart rates (HRs) and certain cardiac indices. Settings and Design: A cross-sectional study was conducted among 38 full-time male workers aged between 21 and 60 years. Methods and Materials: The HR was measured directly during the productive work phase, additional work phase, and work pauses. Two cardiac strain indices, viz., net cardiac cost and relative cardiac cost were derived. The workload was also judged according to some standard acceptable criteria of physical strain. Statistical Analysis Used: Mean and standard deviation were obtained for different categories of HR. Intergroup comparisons were conducted through one-way analysis of variance and the t-test. Results: The mean working HR was found to be 99 beats per minute. A maximal working HR of 105 ± 6.1 beats per minute with a corresponding relative cardiac cost of 26% was obtained during the additional work phase. Conclusions: The overall workload appeared to be moderate in nature. An acceptable criterion of cardiac cost of 30% appeared to be the most sensitive index in detecting workers experiencing a higher level of physical strain.

Ameliorative effects of clindamycin - nanoceria conjugate: A ROS responsive smart drug delivery system for diabetic wound healing study.

BACKGROUND: Increased incidence of antibiotic-resistant species calls for development of new types of nano-medicine that can be used for healing of bacteria-caused wounds, such as diabetic foot ulcer. As diabetic patients have inefficient defense mechanism against reactive oxygen species (ROS) produced in our body as a by-product of oxygen reduction, the process of wound healing takes longer epithelialisation period. Ceria nanoparticles (CNPs) are well-known for their antibacterial and ROS-scavenging nature. Yet till now no significant effort has been made to conjugate ceria nanoparticles with drugs to treat diabetic wounds. METHODS: In this experiment, CNPs were synthesized in-house and clindamycin hydrochloride was loaded onto it by physical adsorption method for reactive oxygen species responsive drug delivery. Various physico-chemical characterisations such as Transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Energy dispersive X-ray, Thermogravimetric study etc. were performed to affirm the formation of both nanoceria along with drug encapsulated nanoceria. RESULTS: Both of these as-prepared formulations inhibited the growth of Gram-positive as well as Gram-negative bacteria confirmed by Disk diffusion study; exhibiting their antibacterial effect. In-vitro drug release study was carried out in physiological environment both in absence and presence of hydrogen peroxide solution to test the reactive ROS-responsiveness of the drug loaded nanocomposites. It also exhibited faster wound healing in diabetes-induced rats. Therefore, it could successfully lower the amount of serum glucose level, inflammation cytokines, hepatotoxic and oxidative stress markers in diabetic rats as confirmed by various ex vivo tests conducted. CONCLUSION: Thus, drug loaded ceria nanoparticles have the potential to heal diabetic wounds successfully and can be considered to be useful for the fabrication of appropriate medicated suppositories beneficial for diabetic foot ulcer treatment in future.

PEG-Induced Osmotic Stress Alters Root Morphology and Root Hair Traits in Wheat Genotypes.

Wheat crop in drought-prone regions of Bangladesh suffers from osmotic stress. The objective of this study was to investigate the response of wheat genotypes with respect to root morphology and root hair traits under polyethylene glycol (PEG)-induced osmotic stress. A total of 22 genotypes of wheat were grown hydroponically and two treatments-0% and 10% PEG-were imposed at 14 days after germination. Plant growth was reduced in terms of plant height, number of live leaves per tiller, shoot dry weight, number of root-bearing phytomers, and roots per tiller. Notably, PEG-induced osmotic stress increased root dry weight per tiller by increasing length of the main axis and lateral roots, as well as the diameter and density of both lateral roots and root hairs of the individual roots. A biplot was drawn after a principal component analysis, taking three less-affected (high-yielding genotypes) and three highly affected (low-yielding genotypes and landrace) genotypes under 10% PEG stress, compared to control. Principal component 1 separated PEG-treated wheat genotypes from control-treated genotypes, with a high and positive coefficient for the density of lateral roots and root hairs, length and diameter of the main axis, and first-order lateral roots and leaf injury scores, indicating that these traits are associated with osmotic stress tolerance. Principal component 2 separated high-yielding and tolerant wheat genotypes from low-yielding and susceptible genotypes, with a high coefficient for root dry weight, density of root hairs and second-order lateral roots, length of the main axis, and first-order lateral roots. An increase in root dry weight in PEG-stress-tolerant wheat genotypes was achieved through an increase in length and diameter of the main axis and lateral roots. The information derived from this research could be exploited for identifying osmotic stress-tolerant QTL and for developing abiotic-tolerant cultivars of wheat.