An appraisal of vascular endothelial growth factor (VEGF): the dynamic molecule of wound healing and its current clinical applications.

Angiogenesis is a critical step of wound healing, and its failure leads to chronic wounds. The idea of restoring blood flow to the damaged tissues by promoting neo-angiogenesis is lucrative and has been researched extensively. Vascular endothelial growth factor (VEGF), a key dynamic molecule of angiogenesis has been investigated for its functions. In this review, we aim to appraise its biology, the comprehensive role of this dynamic molecule in the wound healing process, and how this knowledge has been translated in clinical application in various types of wounds. Although, most laboratory research on the use of VEGF is promising, its clinical applications have not met great expectations. We discuss various lacunae that might exist in making its clinical application unsuccessful for commercial use, and provide insight to the foundation for future research.

Avian gut experiments: an alternative approach for teaching the properties of intestinal smooth muscles.

Experiments on isolated mammalian gut are essential components of the physiology curriculum worldwide. Over the years, these routine experiments have been largely replaced by simulation modules, to reduce the euthanization of animals for understanding established facts and mechanisms in gut physiology. However, a medical undergraduate needs hands-on training to handle a living tissue to have a better understanding of physiology. The present sourcebook update describes the use of avian gut, which is usually discarded in abattoirs, as an effective replacement of mammalian gut to understand basic gut smooth muscle physiology. The avian gut can be used to study the effect of various drugs and ions as used in mammalian gut experiments. The experiment protocol described in the update can be performed by students of basic sciences and medical students using minimal laboratory set up and at low cost, producing results comparable to mammalian gut experiments. Ethical permissions may not be necessary; however, the disposal of tissue waste has to follow proper guidelines.

Toxic Chemical from Plastics Attenuates Phenylbiguanide-induced Cardio-respiratory Reflexes in Anaesthetized Rats.

Bisphenol A (BPA) attenuated phenylbiguanide (PBG)-induced cardio-respiratory reflexes involving decreased vagal afferent activity. BPA leaches out from plastics thus it is expected that chronic exposure to plastic boiled (PBW) water will also produce similar changes. Therefore, the present study was undertaken to evaluate the effects of chronic ingestion of PBW on PBG evoked reflexes and were compared with BPA. Adult female rats were ingested BPA containing pellets (2 µg/kg body weight)/PBW/tap water (ad libitum) for 30 days. On day 30, the animals were anaesthetized and BP, ECG and respiratory excursions were recorded. Further, PBG was injected intravenously to evoke cardio-respiratory reflexes and at the end lungs were excised for histopathological examination. BPA concentration in PBW was 6.6 µg/ml estimated by HPLC. In rats receiving tap water, PBG produced bradycardia, hypotension and tachypnoea. In PBW/BPA treated groups, PBG-induced reflexes were attenuated significantly along with emphysematous and consolidative changes in lungs. The present results indicate that PBW attenuates the protective cardio-respiratory reflexes and also produces histopathological changes in lungs.

Acute Exposure to Bisphenol S Decreases In Vitro Right Atrial Contractility in Rats.

AIM/OBJECTIVE: Bisphenols are widely used in the manufacturing of polycarbonate material and epoxy resins which constitute the essential component of plastic. Bisphenol A (BPA) has been reported to produce toxicity on organs in both animal and human studies. Therefore, plastic manufacturers are replacing BPA with other analogues that are considered to be safe, and BPA-free products are now available in the market. However, some studies have reported that bisphenol-S (BPS) also possesses toxic properties. It has been reported to depress ventricular contraction as well as produce ventricular arrhythmia on acute exposure. The present study was performed to examine the effect of BPS on in vitro spontaneously-beating right atria in rats. METHODS: In the present study, in vitro spontaneous contractions of right atria obtained from adult female rats of the Wistar strain were recorded. The atria were exposed to BPS (10-6-10 mM) and its effects on atrial contractions were recorded in the form of cumulative-concentration response with and without administration of antagonists namely atropine, L-NAME, and methylene blue. RESULTS: BPS decreased the rate as well as the force of atrial contractions. The changes produced in the rate and force of atrial contractions were not attributed to ethanol, which was used to prepare BPS solutions. The decrease in right atrial contractility produced by BPS was blocked by L-NAME; however, atropine and methylene blue were not able to antagonize the effects of BPS on atria. CONCLUSIONS: The present study indicates the involvement of NO-dependent but cGMP independent pathway responsible for BPS-induced cardio-toxicity.

A prospective study on the role of foot evertor muscle activity in recurrence of clubfoot.

BACKGROUND: Even after corrective casting and bracing, clubfoot recurrence is challenging throughout childhood, with around 14-40 % recurrence rates. Most of the literature on recurrence was attributed to various factors, and minimal research was conducted to know the role of foot evertor muscle activity and its stimulation benefits. This study aimed to assess the role of foot evertor muscle activity in idiopathic congenital clubfoot recurrence by using clinical, sonographic, and electromyographic parameters. METHODS: A prospective cohort study was conducted at our tertiary care hospital from 2020 to 2022. The patient's demographic data, Pirani, Dimeglio, Clinical Evertor Muscle Activity scores, sonographic cross-sectional areas of leg muscle, and evertor motor activity using surface electromyography were recorded in adherence to the pre-defined intervals. RESULTS: In total, 51 patients (51 feet) were included in the study, and the overall recurrence rate was 27.5 % (14/51). In this study, around 47 % (24/51) of children had mild or poor clinical evertor activity; among them, 58 % (14/24) children had a recurrence, and the insufficient clinical evertor activity and recurrence were strongly correlated (p = 0.01). Evertor muscle cross-sectional area ratio, motor unit potentials, and recruitment were comparatively less in the recurred group; however, only the cross-sectional area ratio was statistically significant (p = 0.02). CONCLUSION: Early detection of evertor muscle weakness can help to individualize the treatment plans by predicting recurrence. Therefore, it should be included in routine clinical evaluations. Further research is required to determine the advantages of evertor muscle-strengthening activities in preventing idiopathic clubfoot deformity. LEVEL OF CLINICAL EVIDENCE: A prospective cohort study, Level of evidence-II.

Acute toxicity of bisphenol A in rats.

Bisphenol A (BPA), an estrogenic compound, is used in manufacturing plastics and is known to produce toxic effects on various systems in man and animals. Since the use of plastics in day-to-day life is increasing, exposure to BPA will also increase. Therefore, this study was undertaken to determine the median lethal dose (LD50) of BPA via intraperitoneal and intravenous route in adult rats (by Dixon's up and down method) and also to know the acute systemic changes (in blood pressure, respiration and ECG) produced by lethal dose of BPA. Adult female albino rats of Charles Foster strain were used in the study. LD50 of BPA was 841 and 35.26 mg/kg body weight for ip and iv route, respectively. Injection of lethal dose of BPA (40 mg/kg body weight) produced acute toxicity manifesting as immediate respiratory arrest and hypotension after the injection of BPA followed by bradycardia. The animals died within 7.3 +/- 0.7 min. Volume of ethanol (vehicle; 0.1 mL) present in the lethal dose of BPA was not lethal and had no effect on respiration, blood pressure and heart rate. The results provide evidence that the acute exposure to BPA produces lethality with a very narrow range of lethal and survival dose for iv route. Further, the lethality appears to be due to respiratory arrest and hypotension.

Plastic bottle feeding produces changes in biochemical parameters in human infants - A pilot study.

BACKGROUND: Plastic bottles are widely used by people to feed their infants when breastfeeding is not possible. Bisphenol A (BPA), an endocrine disruptor is widely used in the manufacturing of plastic wares and is leached out from these plastic wares on exposure to high temperature, changed pH, or cleaning the plastic wares by harsh detergents. PURPOSE: Feeding through plastic bottles over prolong duration is expected to expose the infants to leached BPA. Hence the present study was taken up to compare the effects of breastfeeding and plastic bottle feeding on biochemical parameters in infants and also detect for the presence of free BPA or its metabolite in the infants. METHODS: Biochemical tests like lipid profile, liver function tests, creatine-kinase-MB (CK-MB), serum urea, serum electrolytes were performed on blood samples obtained from infants who were breastfed and plastic bottle fed. Further, plasma and urine samples of the infants were subjected to Liquid chromatography-mass spectrometry analysis for detecting free BPA and BPA glucuronide. RESULTS: Biochemical changes in form of raised triglycerides, cholesterol, low-density lipoproteins, very low-density lipoproteins and increase in CK-MB, serum urea were observed in plastic bottle fed infants. BPA glucuronide was also detected in the urine of these infants. Free BPA was not detected in plasma or urine samples of the infants except in one plasma sample from bottle-fed group. CONCLUSION: Plastic bottle feeding may lead to toxic changes in the functioning of organs which manifest as altered biochemical parameters.

Bisphenol A decreases atrial contractility involving NO-dependent G-cyclase signaling pathway.

Bisphenol A (BPA) is used in manufacturing plastics. Even though BPA is reported to produce reproductive and behavioral toxicity in experimental animals, the direct effect of BPA on the cardiovascular system is not known. The present study was therefore undertaken to evaluate the effect of BPA, on spontaneously beating rat right atrial preparations. In this study, in vitro isometric contractions of right atria were recorded. Cumulative concentration-response of BPA on atrial contractions was obtained in the absence or presence of antagonists. BPA (0.1-100 µ m) decreased the rate and the force of atrial contractions in a concentration-dependent manner. At 100 µ m, the decreases were >90%. The BPA-induced changes were not blocked by atropine (muscarinic receptor blocker). However, pretreatment with N-ω-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) or methylene blue (a guanylyl cyclase inhibitor) blocked the BPA-induced changes in rate and force. Nitroglycerine, an NO-donor, decreased the rate and force of atrial contractions. Further, the BPA-induced changes were not due to the solvent (ethanol) used to dissolve it. The present study therefore indicates that BPA decreases the atrial contractility involving NO-dependent G-cyclase signaling mechanisms.

Online Foundation Course Program for First Year Medical Undergraduates Amidst the COVID-19 Pandemic - A New Learning Experience.

Foundation programs are conducted in medical schools for undergraduate students, since they are naïve and unaware of the medical profession in depth. The program helps them to become familiar with the undergraduate medical training. The present intake of first year medical undergraduates had joined the institute amidst the COVID-19 pandemic and hence the foundation program had to be conducted through an online platform. The present paper is a description of the online program conducted in the institute and is aimed to focus on the pros and cons of using an online platform for conducting the program and the experience gained from it. The online foundation program was conducted over a period of 16 days through the Zoom© platform. The program was tailored to cater for the orientation of 175 students who were admitted for first year MBBS batch 2020-2021. Feedback from students was obtained through Google Forms© at the end of the program. The online program was conducted smoothly due to the dedicated efforts of all the team members. Sessions requiring hands-on training and physical field visits had to be omitted in the present program. Network connectivity issues were reported sometimes. The conduction of the online foundation course program was indeed a learning experience. The team work was well reflected in the feedback from the students, which revealed appreciation for the overall program. Many sessions went very well in the online mode; however, sessions on humanities and extracurricular activities could have been organized in a better way with the physical presence of the students.

Contribution and dilemmas of Medical undergraduate students in combating disease outbreaks: COVID 19 and previous outbreaks.

COVID 19 has brought several challenges for each individual, changing the world's perception of health-care professionals. People are hailing health-care professionals as heroes, worthy of praise and gratitude. However, the pandemic has overburdened the health-care system. In this situation, the undergraduate medical students are being used as a crucial part of the health-care team in various ways. Involvement of medical undergraduates in situations of natural disaster is not new. In fact, a review of history of previous natural disasters reveals that this has been normal every time health systems have been overburdened. In the present situation of COVID 19, these students have a crucial role to play in helping frontline workers combat the crisis. Though the students would like to render their services, they are in a state of dilemma, as their roles are not defined clearly and their training to combat the pandemic is inadequate, as it was in previous outbreaks. This highlights a need to introduce module-based training for medical graduates to contribute effectively in combating future outbreaks.

Exploring Physiology Through Working Model Preparation by Undergraduate Students.

BACKGROUND: Physiology is a foundation for studying medicine. Student-centred learning methods are needed for a better understanding of the subject. Preparation of working models by students in Physiology is expected to provide better understanding of the subject since they learn by doing these themselves. The present study was designed to understand the effectiveness of a working model making activity for first-year undergraduate medical students. METHODS: The participants were 97 first-year medical undergraduate students. These students were divided into teams. The topics to prepare working models were chosen by the students according to their interests. The models were prepared by using clay, thermocol, batteries, motors, etc. by the students. These models were displayed in an exhibition organized by the department and marks were awarded to the students according to their performance. A feedback questionnaire form was provided to the students, which they had to complete individually. The questionnaires were analyzed to understand the perception of students regarding the activity. RESULTS: Of the students, 35% strongly agreed and 52% agreed that model making was a useful exercise and helped them in understanding Physiology. Of the students, 27% strongly agreed and 50% agreed that their understanding improved with this assignment and 32% of students strongly agreed and 58% agreed that this activity allowed them to analyze the topic and think logically. Of the students, 36% strongly agreed and 50% agreed that they gained confidence in the topic while they were preparing the model and seeing it functioning. Of the students, 37% strongly agreed and 46% agreed that they had the opportunity to work in a team. Of the students, 39% strongly agreed and 47% agreed that faculty had supported them appropriately. Most of the students agreed that they would recommend such activities to their friends studying in medical colleges elsewhere. CONCLUSION: The students found the activity not only interesting but useful and would encourage their friends studying elsewhere to participate in such activities.

Effect of Exposure of Plastic Infant Feeding Bottle Leached Water on Biochemical, Morphological and Oxidative Stress Parameters in Rats.

Bisphenol A (BPA) is leached out from plastic infant feeding bottles that are filled with warm milk/water due to high temperatures, exposing the infants to BPA. The present study aims to understand the effects of ingestion of BPA leached from plastic infant feeding bottle and delineate the underlying mechanisms in rats. In this study, adult rats of Wistar strain were divided into 3 groups. In the first group, the rats consumed normal food and tap water ad libitum. In the second group, the rats ingested BPA (20 µg/kg bodyweight/day, orally). In the third group, the rats drank water leached from plastic infant feeding bottles. After 30days, tests involving biochemical parameters, histopathological examination, and oxidative stress enzyme markers were performed, and the levels of BPA in plastic-leached water were estimated by HPLC analysis. There were significant biochemical changes in the form of increased alkaline phosphatase (ALP), creatine kinase-muscle/brain (CK-MB), and lactate dehydrogenase (LDH) levels in both treated groups as compared to control group, accompanied by structural damage to the vital organs, and lipid peroxidation, glutathione reductase, and catalase activity were also high in the treated groups. Further, the BPA concentration in plastic leached water was estimated to be 0.1 ± 0.02 µg/mL.

Bisphenol A attenuates phenylbiguanide-induced cardio-respiratory reflexes in anaesthetized rats.

Bisphenol A (BPA), a toxic chemical released from plastics, produces respiratory arrest and hypotension after a latency. The latency was similar to the reflex apnoea induced by the vagal C fibre stimulation. Therefore, the present study was undertaken to examine the effects of chronic and acute exposure to BPA on cardio-respiratory reflexes elicited by phenylbiguanide (PBG). Acute and chronic experiments were performed on adult female rats. In chronic experiments, the animals were ingested with pellets containing BPA (2 µg/kg body weight) or without BPA (time-matched control) for 30 days. Subsequently, the animals were anaesthetized and prepared for recording blood pressure, ECG and respiratory excursions. PBG was injected through jugular vein to evoke reflexes in these animals. In acute experiments, the PBG reflexes were obtained before and after injecting BPA/ethanol. Also vagal afferent activity was recorded in some rats. In time-matched control rats, PBG produced bradycardia, hypotension and tachypnoea over a period of time. The maximal changes were around 50-65%. In BPA treated group, the PBG-induced heart rate and respiratory frequency changes were attenuated significantly. Acute exposure of animals to BPA (35 mg/kg body weight) for 30 min also attenuated the PBG-induced responses significantly. The attenuation of the PBG reflex responses by BPA in acute experiments was associated with decreased vagal afferent activity. The present results indicate that BPA attenuates the protective cardio-respiratory reflexes due to decreased vagal afferent activity.