Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy.

Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.

Dose-response relationship of photobiomodulation therapy and oxidative stress markers in healing dynamics of diabetic neuropathic ulcers in Wistar rats.

Purpose: Diabetic foot ulcers are reported to be the most expensive complications of diabetes, with high morbidity and mortality rates. If the necessary care is not provided for the wound to heal, the individual may end up amputating the affected feet. Photobiomodulation therapy is a promising non-pharmacological treatment option for wound healing. The objective of the present study is to establish a dose-response relationship between photobiomodulation therapy and oxidative stress markers in the healing dynamics of diabetic neuropathic ulcers in Wistar rats. Methodology: Diabetic neuropathy was induced in 126 Albino Wistar rats. An excisional wound of an area of 2cm2 was made on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12, and 15 J/cm2 of wavelengths 655 and 808 nm was irradiated. The control group animals were kept un-irradiated. The outcome measures were assessed during wound healing's inflammatory, proliferative and remodelling phases. Results: In the experimental group, animals treated with photobiomodulation therapy at doses of 4, 6, and 8 J/cm2 showed better wound healing dynamics. Photobiomodulation therapy modulated the reactive oxygen species and antioxidant levels, thereby improving the oxidative status of the wound. Conclusion: Photobiomodulation therapy of dosages 4, 6, and 8 J/cm2 is effective and is a promising adjuvant modality in treating diabetic neuropathic ulcers. There was a strong dose-response relationship in the experimental groups treated with 4, 6 and 8 J/ cm2. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01157-2.

Effect of photobiomodulation therapy on inflammatory cytokines in healing dynamics of diabetic wounds: a systematic review of preclinical studies.

CONTEXT: Delayed wound healing in diabetes mellitus (DM) is due to the overlapping phases of the healing process. The prolonged inflammation and altered levels of inflammatory cytokines lead to deformed cell proliferation. Photobiomodulation alleviates the expression of inflammatory cytokines and promotes tissue repair, thereby restoring the wound healing process. OBJECTIVE: To find out the effect of photobiomodulation therapy (PBMT) in the healing dynamics of diabetic wounds with particular emphasis on interleukin-6, interleukin-1ß, and tumour necrosis factor-α. METHODS: Scientific databases searched using keywords of the population: DM, intervention: PBMT, and outcomes: inflammatory cytokines. RESULTS: We have included five preclinical studies in the present systematic review for qualitative analysis. These studies evaluated the effect of PBMT at different wavelengths, dosage, and time on wound healing in DM. CONCLUSIONS: The systematic review concludes that PBMT regulates inflammatory cytokines levels, enhances cell proliferation, and migration, thereby improving the wound healing properties.

Dose-Response Relationship of Photobiomodulation Therapy on Matrix Metalloproteinase in Healing Dynamics of Diabetic Neuropathic Ulcers-An in vivo Study.

Individuals with diabetic foot ulcers have overlapped the inflammatory, proliferative and remodeling phase, making the tissue vulnerable to delayed healing responses. We aimed to establish the dose-response relationship of photobiomodulation therapy of different doses and matrix metalloproteinases in the healing dynamics of diabetic neuropathic ulcers. Diabetes was induced in 126 Albino Wistar rats, and neuropathy was induced to the hind paw by a sciatic nerve injury method. An excisional wound was created on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12 and 15 J cm-2 and wavelength 655 nm and 808 nm was irradiated. Photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 showed better wound healing properties with optimized levels of matrix metalloproteinases-1 and 8. We observed a strong dose response in the experimental group treated with 6 and 8 J cm-2 . The findings from the present study conclude that photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 is suggestive of usefulness in diabetic neuropathic ulcer healing. Markers like matrix metalloproteinases may give a clear direction on response to the therapy. Based on the findings from the present study, we recommend to validate the findings for safety and efficacy in future through human prospective randomized controlled clinical trials.

Effect of Photobiomodulation Therapy on Oxidative Stress Markers in Healing Dynamics of Diabetic Neuropathic Wounds in Wistar Rats.

BACKGROUND: Prolonged and overlapping phases of wound healing in diabetes are mainly due to the redox imbalance resulting in the chronicity of the wound. Photobiomodulation therapy works on the principle of absorption of photon energy and its transduction into a biological response in the living tissue. It alleviates the cellular responses, thereby improving the mechanism of wound healing in diabetes. OBJECTIVE: To find out the effect of photobiomodulation therapy of dosage 4 J/cm2 in the healing dynamics of diabetic neuropathic wounds in Wistar rats and its relation with oxidative stress markers. METHODOLOGY: Diabetes was induced using Streptozotocin of 60 mg/kg of body weight to eighteen female Wistar rats. Neuropathy was induced by the sciatic nerve crush injury followed by an excisional wound of 2 cm2 on the back of the animal. Experimental group animals were treated with dosage 4 J/cm2 of wavelength 655 and 808 nm, and control group animals were kept unirradiated. The biomechanical, histopathological, and biochemical changes were analysed in both groups. RESULTS: There was a reduction in mean wound healing time and an increased rate of wound contraction in the experimental group animals compared to its control group. The experimental group showed improved redox status, and histopathological findings revealed better proliferative cells, keratinisation, and epithelialization than un-irradiated controls. CONCLUSIONS: Photobiomodulation therapy of dosage 4 J/cm2 enhanced the overall wound healing dynamics of the diabetes-induced neuropathic wound and optimised the oxidative status of the wound, thereby facilitating a faster healing process.

Implementation and assessment of a module to enhance prescribing competency in undergraduate medical students.

BACKGROUND: Enhancing the prescribing competency of medical students will help them evaluate each case based on their knowledge. It will help them prescribe independently and they will also be able to empathize and counsel patients effectively. In view of this, it was planned to implement a module on prescribing competency and assess the same for undergraduate medical students. METHODS: Faculty training to implement the module was conducted by eminent faculty in this area. After a pre-test, a workshop was conducted for students, wherein they were trained on rational prescribing based on WHO guide to good prescribing followed by small group discussions to identify P (personal) drugs for bronchial asthma and later with comorbidities. Students had to write a prescription and practice communicating the same to a standardized patient. The module was evaluated using a check list (from the WHO guide) and compared with a pre-test. A feedback was provided to the students at the end of the assessment. RESULTS: The scores (median and interquartile values) for prescribing significantly improved from 5 (2, 7) to 25 (24, 27), maximum score being 30. The scores for the communication also increased from 17.5 (14, 24.25) to 53 (52, 55), maximum score being 60, in the post-test. The differences were statistically significant p < 0.01(Wilcoxon Signed Ranks Test). The students expressed that their critical thinking and problem solving capabilities had increased and more importantly 'they felt like a doctor'. CONCLUSION: More such modules need to be prepared and prescribing competency needs reinforcement during the clinical years of the medical curriculum for its effective implementation communicating the same to a standardized patient. The module was evaluated using a check list (from the WHO guide) and compared with a pre-test. A feedback was provided to the students at the end of the assessment.

Sodium Valproate Induced Alopecia: A Case Series.

Drug induced alopecia may range from a barely detectable shedding to an irreversible baldness. Alopecia associated with valproate is a dose-dependent and reversible side effect. We hereby report, three cases of alopecia that occurred in patients who received sodium valproate for various neurological conditions. In all three cases, long term exposure of valproate therapy led to the development of alopecia which eventually resolved after dose reduction or discontinuation. The Naranjo's causality assessment scale indicated valproate as the probable cause of the alopecia in all our patients.

Adverse drug reaction profile of microtubule-damaging antineoplastic drugs: A focused pharmacovigilance study in India.

OBJECTIVES: The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. MATERIALS AND METHODS: Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. RESULTS: A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. CONCLUSIONS: This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society.

Comparing the efficacy and influence on the quality of life of three classes of drugs used in bronchial asthma - a prospective study.

OBJECTIVES: To compare the efficacy of formoterol, montelukast and acebrophylline when used in combination with budesonide in patients with bronchial asthma and to determine their role in the improvement of the quality of life of patients. MATERIALS AND METHODS: A total of 75 patients were divided into 3 groups based on treatment given - formoterol 6 mcg/puff + budesonide 100 mcg/puff combination inhaler, 2 puffs twice daily; oral montelukast 10 mg once daily + budesonide 100 mcg/puff, 2 puffs twice daily and oral acebrophylline 100 mg twice daily + budesonide 100 mcg/puff, 2 puffs twice daily. The patients were followed-up for 4 wk after initiating treatment. Spirometry values - forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR), before and after treatment were recorded. The quality of life was assessed before and after treatment using Asthma Quality of Life Questionnaire (AQLQ). Analysis was done using repeated measures ANOVA followed by Bonferroni's post-hoc test. RESULTS: As compared to baseline values, FEV1, PEFR and Quality of Life showed significant improvement in all 3 groups after 4 wk of treatment (p-value < 0.01). Three patients in acebrophylline-treated group reported gastric irritation while no adverse effects were reported in the other groups. CONCLUSION: Formoterol, montelukast or acebrophylline combined with inhaled corticosteroids have similar efficacy in the treatment of asthma.

Knowledge, attitude and practices related to dietary supplements and micronutrients in health sciences students.

OBJECTIVES: Little is known about supplement users and their dietary behavior in India. This study was conducted with the following objectives: 1. To determine the usage of dietary supplements in health sciences students. 2. To determine their knowledge, attitudes and beliefs regarding micronutrients. MATERIALS AND METHODS: Cross-sectional, questionnaire based study conducted at a University in south India, which included second year students pursuing medical, dental and nursing courses. Data was analysed using SPSS version 19. RESULTS: The commonest reasons for consuming supplements were to maintain good health (136, 40.1%) and ensure adequate nutrition (125, 36.9%). The respondents' opinions about dietary supplements were generally between 'unsure' and 'agree'. Medical students scored the highest percentage (44.84%) in their knowledge about micronutrients as compared to nursing (43.17%) and dental (37.8%). There was a significant difference between the scores of medical and dental students (p=0.005) while the scoring of students of medical and nursing did not vary significantly. There was no significant difference between the scoring percentage of males and females in medical and dental groups while in the nursing group female students scored a better percentage as compared to males (p=0.036). CONCLUSION: Although, the usage of dietary supplements in health sciences students is high, there is a dearth of knowledge, especially regarding role of micronutrients in health and disease. Hence, it is crucial this information must be highlighted in the health sciences curriculum with the objective of producing well-informed professionals who can later on have a positive impact on the health of society.

Effect of ethanolic extract of Acacia auriculiformis leaves on learning and memory in rats.

BACKGROUND: The effects and benefits of Acacia auriculiformis on health are not well established. This study was planned to evaluate the effect of ethanolic extract of Acacia auriculiformis leaves on learning and memory in rats. MATERIALS AND METHODS: Learning and memory were evaluated using passive avoidance paradigm and rewarded alternation test (T-maze) after the oral administration of two doses (200mg/kg and 400mg/kg) of ethanolic extract of Acacia auriculiformis with rivastigmine as positive control. Forty eight rats were divided into 4 groups in each study model. Estimation of brain cholinesterase activity was done to substantiate the results of the above mentioned tests. Data was analyzed using one way Analysis of Variance (ANOVA) followed by Tukey's post-hoc test using GraphPad InStat software, version 3.06. RESULTS: The extract produced a dose-dependent improvement in the memory score namely the step through latency in passive avoidance model (P < 0.001) and the percentage of correct responses in rewarded alternation test (P < 0.05). Dose-dependent inhibition of brain cholinesterase activity (P < 0.001) was also noted. CONCLUSION: The acetylcholinesterase inhibiting property of Acacia auriculiformis contributes to its memory enhancing potential. Further large scale studies are required to elucidate its benefits on cognitive function. This may offer a promising new option for the treatment of dementia and other cognitive deficits.

Evaluation of the effect of Ferula asafoetida Linn. gum extract on learning and memory in Wistar rats.

OBJECTIVE: Memory loss is universal and is the first symptom to manifest in majority of the patients suffering from Alzheimer's disease. This study is designed to investigate the effect of Ferula asafoetida linn. (F. foetida) extract on learning and memory in rats. MATERIALS AND METHODS: Learning and memory were evaluated using elevated plus maze and passive avoidance paradigm after the oral administration of two doses (200 mg/kg and 400 mg/kg) of F. foetida aqueous extract with rivastigmine as positive control. Brain cholinesterase activity, serum thiols and cholesterol were also estimated. RESULTS: Extract produced significant improvement in memory score i.e. step through latency at 400 mg/kg dose in passive avoidance model (P< 0.05) and dose-dependent improvement of transfer latency in elevated plus maze model (P< 0.001). Dose-dependent inhibition of brain cholinesterase (P< 0.001) and significant improvement in antioxidant levels (P< 0.05) were also noted. CONCLUSIONS: Memory enhancing potential of F. foetida can be attributed to acetylcholinesterase inhibiting and antioxidant properties. Hence, dietary usage of F. foetida is beneficial and can also be employed as an adjuvant to existing anti-dementia therapies.

Hypoglycemic effect of aqueous extract of Trichosanthes dioica in normal and diabetic rats.

BACKGROUND: Trichosanthes dioica is used to treat diabetes mellitus, epilepsy, alopecia, and skin disease in folklore medicine. The leaf extract of the plant is used in diabetes mellitus but there have been no scientific studies reported. AIMS: To study the effect of Trichosanthes dioica on serum glucose level in glucose loaded, normal and hyperglycemic rats. SETTINGS: Kasturba Medical College, Manipal, Karnataka, India. DESIGN: Experimental. MATERIALS AND METHODS: The aqueous extract of leaves of Trichosanthes dioica are compared with glibeclamide for their influence on fasting blood sugar in glucose loaded, normoglycemic and streptozotocin induced (45 mg/kg ip) hyperglycemic rats. STATISTICAL ANALYSIS: The data was analyzed by one way ANOVA followed by Scheffe's post hoc test. RESULTS: In glucose loaded rats, normal rats and hyperglycemic rats the aqueous extract at both the doses (800 mg/kg/p.o and 1600 mg/kg/p.o) reduced blood glucose significantly when compared to control but it was not as effective as glibenclamide. CONCLUSION: The aqueous extract of Trichosanthes dioica has antihyperglycemic action.

Prevalence of menopausal symptoms and quality of life after menopause in women from South India.

OBJECTIVES: This study was carried out to establish the age at onset of menopause and the prevalence of menopause and menopausal symptoms in South Indian women. MATERIALS AND METHODS: Three hundred and fifty-two postmenopausal women attending the outpatient clinics of obstetrics and gynaecology department of Dr TMA Pai Hospital, a tertiary care Hospital in South India, were included in the study. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used in the study. Data were presented as percentages for qualitative variable. RESULTS: The mean age at menopause was 48.7 years. Most frequent menopausal symptoms were aching in muscle and joints, feeling tired, poor memory, lower backache and difficulty in sleeping. The vasomotor and sexual domains were less frequently complained when compared to physical and psychological domains. CONCLUSION: The age at onset of menopause in southern Karnataka (India) is 48.7 years which is four years more than the mean menopause age for Indian women. This could be attributed to better socioeconomic and health-care facility in this region.