Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is the frontline chemotherapeutic drug used against various cancers due to its superior anticancer activity. It has recently been redeveloped for the purpose of treating cytokine storm in COVID-19 patients. Podophyllotoxin and its naturally occurring congeners have low bioavailability and almost all these initially discovered compounds cause systemic toxicity and development of drug resistance. Moreover, the production of synthetic derivatives that could suffice for the clinical limitations of these naturally occurring compounds is not economically feasible. These challenges demanded continuous devotions towards improving the druggability of these drugs and continue to seek structure-optimization strategies. The discovery of renewable sources including microbial origin for podophyllotoxin is another possible approach. This review focuses on the exigency of innovation and research required in the global R&D and pharmaceutical industry for podophyllotoxin and related compounds based on recent scientific findings and market predictions.
Populus ciliata Wall ex. Royle has folkloric repute to treat various cardiovascular ailments and related disorders. The current study was designed to evaluate the toxic profile, cardioprotective and hypotensive effects of Populus ciliata (Wall. ex Royle). Populus ciliata crude ethanolic extract (Pc. Cr) and its aqueous (Pc. Aq) & organic (Pc. Dcm) fractions were tested on isolated aorta of rat and rabbit having intact and non-intact endothelium respectively. Pc. Cr & Pc. Aq relaxed the contractions induced by PE (1 µM)-induced and K+ (80 mM)-induced on aorta, possibly by mediating endothelium derived relaxing factor (EDRF) in intact endothelium and voltage dependent L-type calcium channels blocking (CCB) mechanism in non-intact endothelium. Pc. Cr showed anti-hypertensive & cardioprotective activity by decreasing force of contraction & heart rate on isolated rabbit paired atria and reduced blood pressure in anesthetized rat. Cardioprotective effect of Pc. Cr was assessed in isoproterenol induced acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) in Sprague Dawley rats. In LVH, Pc. Cr exerted positive effects by decreasing angiotensin II & renin and increasing cGMP & nitric oxide (NO) with reduced cardiac fibrosis, necrosis and cardiac cell size. In AMI, Pc. Cr responded effectively by decreasing cardiac markers creatinine kinase (CK), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LD) in blood associated with less edema and necrosis. Presence of catechin, vinallic acid, P-coumeric acid and quercitin identified through HPLC support the effectiveness of Pc. Cr in hypertension, AMI and LVH. Pc. Cr showed no significant adverse effects in Sprague Dawley albino rats after acute & sub-acute treatment in histopathological investigation. Extract of Populus ciliata showed vasorelaxant, hypotensive and cardioprotective effect in Sprague Dawley albino rats and white albino rabbit by mediating EDRF and voltage dependent L-type CCB mechanism respectively.
This project is an observational, descriptive study evaluating frequencies of rotavirus disease in hospitalized children aged less than 5 years old between 2015 and 2021 in the Pediatric Hospital of Brasov, Central Romania. The study compares socio-demographic (age, sex, place of living and ethnicity), clinical, and treatment aspects between community-acquired rotavirus gastroenteritis (CARG) and hospital-acquired rotavirus gastroenteritis (HARG). During that period, 1913 hospitalized children had a rapid positive immunichromatographic rotavirus test from stool specimens. Among them, 1620 (84.6%) were CARG and 293 (15.4%) were HARG. CARG conditions represented 28.5% of all acute hospitalized gastroenteritis (n = 5673) whereas HARG represented 5.2%. Around the same percentage of urban children were seen in CARG as in HARG (58.5% (n = 948) for CARG and 56.3% (n = 164) for HARG). About 64.9% (n = 1052) of CARG cases were from Roma population, and 66.5% (n = 195) in HARG. The age group with the highest frequency of the disease was 12 to 24 months old for both CARG and HARG. The average hospital duration was 5.09 days for CARG and 7.62 days for HARG. Diarrhea was the principal symptom in both CARG and HARG (92.6% (n = 1500) for CARG and 93.9% (n = 275) for HARG). Most CARG patients (61% (n = 989)) were treated for symptomatic management with iv fluids. Most HARG (60.4% (n = 177)) were treated for symptomatic management with iv fluids and antibiotics. A significant seasonal shift to a later period in the year was observed during the last registration year of 2021, possibly due to the COVID-19 epidemic. The seasonal disease burden of rotavirus infection in children remains high in hospital care in Romania, which may justify the systematic introduction of rotavirus vaccination across the whole country.
Background/Objectives: Viral gastroenteritis leads to a broad range of hospitalization costs globally in children, depending on the region. To our knowledge, no recent studies have examined the hospitalization cost associated with viral gastroenteritis in Romania. The aim of this study is to determine the direct hospitalization cost of community-acquired viral gastroenteritis (rotavirus, adenovirus and norovirus) in children admitted to Children’s Clinical Hospital of Brașov, Romania, for one year. Methods: All children aged 0–60 months hospitalized for a stool sample positive for rotavirus, adenovirus or norovirus during January 2023 and December 2023 were included in this study. Hospital-acquired gastroenteritis, gastrointestinal coinfections or children with acute coinfection were excluded. The stool specimens were tested using the immunochromatography method. Results: Out of the total of 282 children, 218 children presented rotavirus gastroenteritis, 35 children presented adenovirus gastroenteritis and 29 children presented norovirus gastroenteritis. Regarding patient characteristics, a higher proportion of boys than girls was observed in all three comparison groups, the average age for children with rotavirus was 22.2 months vs. norovirus and adenovirus, and children presented an average age of 16.4 months. Average hospitalization length of stay for rotavirus was 4.64 (±1.95) days, for adenovirus it was 4.54 (±1.52) days and for norovirus it was 4.75 (±1.93) days. Direct hospitalization costs did not differ between rotavirus, adenovirus, and norovirus infections (Kruskal–Wallis H(2) = 0.145, p = 0.930). Conclusions: In this single-center study, rotavirus remained the most frequent cause of viral gastroenteritis requiring hospitalization in young children, followed by adenovirus and norovirus. Although the average length of stay was similar across groups, hospitalization costs varied, with rotavirus-associated cases showing the highest mean expenses and widest cost variability.