Comparison of the efficacy, safety, and tolerability of the FDC of telmisartan + bisoprolol with telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: A double-blind, multicentric, phase-III clinical study.

AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.

Indian Clinician's Perspective on the Approach to the Management of Hypertension: A Cross-Sectional Study.

Introduction Hypertension (HTN) is considered one of the most frequent life-threatening noncommunicable illnesses. Because HTN has a significant public health impact on cardiovascular health status and healthcare systems in India, it is critical to study Indian clinicians' approaches to HTN management. Methodology This was a cross-sectional, multicentric, non-interventional, and single-visit study that aimed to gather data from across India and examine sociodemographic characteristics and clinician treatment choices in the management of HTN in Indian individuals. As a result, building an information platform about HTN is critical to preventing and controlling this growing burden. Results A total of 5298 patients were recruited in the study from 1061 study centers across India. Among the study patients, 66.67% were females with a mean age of 53.95 ± 14.4, and 66.28% of hypertensive patients presented comorbidities. Among the known risk factors for HTN, 2227 (44.5%) were smokers, while 2587 (51.7%) had sedentary lifestyles. A family history of HTN in either one or both parents was seen in 1076 (21.50%) patients. In management, 40.40% of patients were on anti-hypertensive monotherapy. Amlodipine (41.8%) in monotherapy and amlodipine + metoprolol (32.34%) in combination therapy were the most commonly prescribed antihypertensive. Conclusion Management of HTN can be improved by imparting patient education and awareness about the need for medication compliance, lifestyle modifications, and regular follow-up clinic visits.

May Measurement Month Blood Pressure Screening Program: A Pan India Study.

Background: High blood pressure (BP) is the largest contributor to the global burden of disease and mortality. This Blood Pressure screening program was initiated in conjunction with the May Measurement Month to increase the awareness of the importance of BP and also designed to understand the problems of real time clinical situations. Methodology: This was a cross sectional, multicentric, non-interventional, observational and single visit study. The study was conducted in the Outpatient department of many clinics/ institutions. The convenience sampling technique was used to select the centers in this study and obtain the geographical distribution of India. Results: A total of 1,36,095 BP screening forms were considered for analysis. A total of 37,017 subjects (27.2%) had BP of >130/80 mm Hg. Among participants, 44.5% of men in age group of 51 ­ 60 years had high BP. 31.2 % of the women in the age group of 41-50 years had high BP. Among 37017 subjects, 14066 subjects (38%) were newly diagnosed subjects with hypertension. In the subset (N=22,951) of known cases of hypertension, Men were 14, 127 (Urban, N=7488 and Rural, N=6639) and 8824 were women (Urban, N=4588 and Rural, N=4236). The common comorbidities were dyslipidemia, cardiovascular disorders and diabetes. Conclusion: Despite the advances in hypertension management and emphasis on patient education, our study shows that hypertension continues to be a significant health burden. Improving patient compliance to lifestyle modifications, medication and regular follow-up clinic visits by imparting patient education and awareness can provide better results in Hypertension management.

Multifunctional aspects of Piriformospora indica in plant endosymbiosis.

Piriformospora indica (Hymenomycetes, Basidiomycota) is an endophytic fungus that colonises plant roots, and was originally isolated from Rajasthan desert. It is comparable to Arbuscular Mycorrhizal (AM) fungi in terms of plant growth promotional effects. P. indica has been used as an ideal example to analyse the mechanisms of mutualistic symbiosis. Major benefit of P. indica over AM fungi is that it is axenically cultivable in different synthetic and complex media. A preliminary attempt was made to scrutinise the role of P. indica co-cultivation on seedling vigour of common vegetables like Cucumis sativus L., Abelmoschus esculentus (L.) Moench, Solanum melongena L. and Capsicum annuum L. The positive effect of P. indica co-culture on seedling performance was compared to the effects of growth hormones like indole acetic acid and benzyl amino purine when supplemented to the MS medium at a concentration of 0.1 mg ml-1. An exogenous supply of auxin resulted in enhanced production of roots and cytokinin supplement favoured shoot production, whereas P. indica co-culture favoured simultaneous production of shoot and root over the control. P. indica colonisation inside the roots of C. sativus L. was also successfully established. These preliminary results indicate the prospective role of P. indica in vegetable farming through its favourable effect on plant growth.

Susceptibility profile, resistance mechanisms & efficacy ratios of fosfomycin, nitrofurantoin & colistin for carbapenem-resistant Enterobacteriaceae causing urinary tract infections.

Background & objectives: The escalation in carbapenem resistance among Enterobacteriaceae has resulted in a lack of effective therapeutic alternatives. Older antimicrobials, fosfomycin, nitrofurantoin and colistin for urinary tract infections (UTIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) may be effective treatment options. The objectives of this study were to evaluate the utility of fosfomycin, nitrofurantoin and colistin in treating UTI caused by CRE and molecular characterization of the plasmid-mediated carbapenem resistance mechanisms. Methods: Consecutive, non-duplicate isolates of CR Escherichia coli and Klebsiella spp. from urine cultures were included (n=150). Minimum inhibitory concentrations (MIC) were determined by E-test (fosfomycin and nitrofurantoin) and broth microdilution (colistin). Efficacy ratios were derived by dividing susceptibility breakpoints by observed MIC values of the drugs for the isolates. Isolates were screened for genes coding for carbapenemases using multiplex PCR. Fosfomycin, nitrofurantoin and colistin-resistant isolates were screened for plasmid-borne resistance genes fos A3, oqx AB and mcr-1, respectively using PCR. Results: Among E. coli, 98.9, 56 and 95 per cent isolates were susceptible to fosfomycin, nitrofurantoin and colistin, respectively, while 94 and 85 per cent of Klebsiella spp. were susceptible to fosfomycin and colistin, respectively. The efficacy ratios indicated fosfomycin as the drug of choice for UTI caused by CR E. coli and Klebsiella spp., followed by colistin. The blaNDM gene was most common, followed by blaOXA48-like. Plasmid-borne genes encoding resistance to fosfomycin, nitrofurantoin and colistin were absent. Interpretation & conclusions: With increasing resistance against the current treatment options, older drugs may emerge as effective options. Molecular screening of resistant isolates is essential to prevent the spread of plasmid-borne resistance against these drugs.

Comparative study of primary and secondary closure of the surgical wound after removal of impacted mandibular third molars.

AIM: Aim of the study is to compare the primary and secondary healing after surgical removal of impacted mandibular third molars, in terms of swelling, severity of pain, trismus, and periodontal healing between two types of closure. MATERIALS AND METHODS: A total of 60 patients, divided into two groups randomly: group A, with 30 patients in which primary closure was done; group B, with 30 patients in which secondary closure was done. A comparison between two groups was done in terms of postoperative pain, swelling, trismus at first, third, and seventh postoperative days, and periodontal healing near adjacent second molar after 6 months. RESULTS: The swelling and pain in group A were greater than that in group B, with a statistically significant difference (p < 0.05). Mouth opening is greater in group B compared to group A. There is no significant difference in periodontal healing in between two groups after 6 months. Complication like alveolar osteitis was noted in 1 patient (3.3%) in group B. CONCLUSION: We conclude that secondary closure was better than primary closure in terms of postoperative pain, swelling, and trismus. Irrespective of any closure technique, there is no difference in terms of periodontal healing.

Efficacy of a New Topical Nano-hyaluronic Acid in Humans.

BACKGROUND: The aim of this study was to evaluate the efficacy of a new topical low molecular nano-hyaluronic acid preparation in treating wrinkles, skin hydration, and skin elasticity in humans. METHODS: Thirty-three women with an average age of 45.2 were studied for a period of eight weeks to measure the anti-wrinkle efficacy of a new nano-hyaluronic acid. The measurements were performed in the periorbital regions by investigating the three-dimensional structure using a DermaTOP for wrinkles, Corneometer for skin hydration, Cutometer for skin elasticity, and a Chroma Meter for erythema. Thereafter, standardized images were taken and evaluated by six selected and trained raters at the end of the study for reduction of visible wrinkles as well as skin color uniformity and pigmentation. RESULTS: The results of the study showed a statistically significant moisturizing effect of the product range (lotion, serum, and cream, after 2,4, and 8 weeks of treatment. Measurement of skin roughness showed a significantly finer skin structure after two weeks of treatment, and skin elasticity showed a significant improvement after 2 and 8 weeks of treatment. CONCLUSION: The new nano-hyaluronic acid clearly demonstrated a significant benefit in decreasing the depth of wrinkles (up to 40%), and skin hydration (up to 96%) and skin firmness and elasticity were significantly enhanced (up to 55%) at the end of eight weeks.

Calpain and reactive oxygen species targets Bax for mitochondrial permeabilisation and caspase activation in zerumbone induced apoptosis.

Fluorescent protein based signaling probes are emerging as valuable tools to study cell signaling because of their ability to provide spatio- temporal information in non invasive live cell mode. Previously, multiple fluorescent protein probes were employed to characterize key events of apoptosis in diverse experimental systems. We have employed a live cell image based approach to visualize the key events of apoptosis signaling induced by zerumbone, the active principle from ginger Zingiber zerumbet, in cancer cells that enabled us to analyze prominent apoptotic changes in a hierarchical manner with temporal resolution. Our studies substantiate that mitochondrial permeabilisation and cytochrome c dependent caspase activation dominate in zerumbone induced cell death. Bax activation, the essential and early event of cell death, is independently activated by reactive oxygen species as well as calpains. Zerumbone failed to induce apoptosis or mitochondrial permeabilisation in Bax knockout cells and over-expression of Bax enhanced cell death induced by zerumbone confirming the essential role of Bax for mitochondrial permeabilsation. Simultaneous inhibition of reactive oxygen species and calpain is required for preventing Bax activation and cell death. However, apoptosis induced by zerumbone was prevented in Bcl 2 and Bcl-XL over-expressing cells, whereas more protection was afforded by Bcl 2 specifically targeted to endoplasmic reticulum. Even though zerumbone treatment down-regulated survival proteins such as XIAP, Survivin and Akt, it failed to affect the pro-apoptotic proteins such as PUMA and BIM. Multiple normal diploid cell lines were employed to address cytotoxic activity of zerumbone and, in general, mammary epithelial cells, endothelial progenitor cells and smooth muscle cells were relatively resistant to zerumbone induced cell death with lesser ROS accumulation than cancer cells.

Role of community pharmacists in improving knowledge and glycemic control of type 2 diabetes.

OBJECTIVE: To study the role of the community pharmacists in improving knowledge and glycemic control in patients with type 2 diabetes residing in villages of Coimbatore district, Tamil Nadu. MATERIALS AND METHODS: Fifty patients were interviewed, of whom 39 subjects were included in the study. The literate and chronic diabetic patients were included in the study and illiterate, children below 12 years of age, pregnant women, nursing mothers and subjects with any other chronic disorders were excluded from the study. The subjects were interviewed and divided randomly into two groups. There were 20 subjects in the control group and 19 in the intervention group. The study protocol was explained to all the participants, and written informed consent was obtained from them. Before the initiation of the study, the subjects were interviewedfor 20-40 min to educate them about diabetes. Subjects in the intervention group received continuous counselling and medical advice to improve their awareness about the disease and drugs. During the study period, the Diabetes Care Profile (a questionnaire developed by J.J. Fitzgerald of the Michigan Diabetes Research and Training Center, University of Michigan Medical School, Michigan) was performed to each subject. The interval between visits was 2 months. All the values are expressed in mean ± standard deviation. RESULTS: The intervention group showed better progress in the recovery of diabetics because of the continuous counselling and monitoring. There were significant changes in Diabetes Care Profile subscale scores in both the control and the intervention groups at the end of the study, viz. 1.8 ± 4.52 to 2.75 ± 6.62 and 3.10 ± 3.23 to 1.53 ± 2.66. Similarly, the knowledge test score was found to be increased in the intervention group compared with the baseline values (8.53 ± 1.81 to 12.16 ± 1.34). CONCLUSIONS: At the end of the study period, the patients of the intervention group had very good glycemic control. Their health status and understanding of diabetes and its management were better, and they had fewer problems such as episodes of hyperglycemia or hypoglycemia.