Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model : promising activity without the risk of hepatic adverse effect

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Influence of Supplementing Parsley and Cilantro Extracts on Sensory Parameters of Soft Cheese with Highlighting on Their Antibacterial Impact

  The study was achieved to show the influence of supplementing different concentrations of parsley and cilantro extracts on sensory and microbiological parameters of soft cheese during 2 weeks of storage. The antibacterial activity of crude extracts and the Minimum Inhibitory Concentration (MIC) of both plants were determined. Also, a study of food poisoning bacteria survival in artificially contaminated soft cheese. The Escherichia coli (E. coli), Salmonella Typhimurium (S. Typhimurium), and Staphylococcus aureus (S. aureus) were sensitive to oil extract (0.5%) of both plants, while E. coli and S. Typhimurium were sensitive to methanol extract (5.0%) of cilantro based on MIC. The oil extract (0.5%) of parsley had a significant (p<0.05) improving effect on the sensory parameters of samples throughout storage. In E. coli and S. Typhimurium contaminated samples, there was a significant difference (p<0.05) between samples with the oil extract (0.25% and 0.5%) of parsley and samples without extracts for pH value at end of the storage period. Based on the survival results, S. Typhimurium could not be isolated from all cheese samples with oil extract (0.5%) of cilantro on days 12 and 14 of storage, while E. coli count was reduced to 2.85 and 2.36 log CFU/g in cheeses with oil extract (0.25%) of parsley and cilantro, respectively. The S. aureus could not be isolated from all cheese samples with oil extract (0.5%) of parsley and cilantro from day eight till the end of the storage period. Results of the study recommended the use of these plants oil extracts to improve soft cheese safety and quality. This trial of the survival of food poisoning bacteria in the soft cheese supplemented by oil and methanol extracts of parsley and cilantro is one of the fewest studies, particularly in the Middle East