INHIBITION OF TUMOUR NECROSIS FACTOR (TNF) ACTIVITY BY A NEW ERGOSTANE STEROID FROM CLEOME DROSERIFOLIA

Objective: To isolate steroidal compound from Cleome droserifolia and explore its activity against tumour necrosis factor (TNF) using molecular docking studies.Methods: Extraction of the plant material was carried using two successive solvents and three compounds were isolated using column chromatography. The isolated compounds were identified using different spectroscopic data such as 1D, 2D nuclear magnetic resonance (NMR), ultraviolet-visible spectroscopy (UV-Visible), fourier transform infrared spectroscopy (FT-IR) and electrospray ionization mass spectroscopy (ESI-MS). Molecular docking was carried in order to investigate the activity of the ergostane derivative as tumour necrosis factor inhibitor.Results: Two steroidal compounds were isolated and identified as ergost-5,7,9,24 (28)-tetraen-3-one (1) and β-sitosterol glucoside (3) by means of spectroscopic measurement. 1-dodecanol (2) was also isolated. The ergostane derivative showed several binding sites with TNF-αConclusion: The new ergostane derivative isolated from the aerial parts of Cleome droserifolia is introduced to serve as a potential tumour necrosis factor inhibitor and may be used as a lead compound for the treatment of rheumatoid arthritis

EFFECT OF RENNIN INHIBITORS AND ANGIOTENSIN II RECEPTOR ANTAGONISTS ON LEFT VENTRICULAR HYPERTROPHY IN RENOVASCULAR HYPERTENSIVE RATS

Objective: Left ventricular (LV) hypertrophy involves numerous structural adaptations that may lead to ventricular dysfunction and eventually, heart failure. Particular emphasis is placed on the molecular mechanisms that govern the development of hypertrophy and may lead to maladaptive structural changes resulting in adverse cardiac events. This study investigates the effectiveness of Valsartan (Val) which is an angiotensinII receptor antagonist and Aliskiren (Ali) which is a direct rennin inhibitor in the treatment of cardiac remodeling resulted from renovascular hypertension, particularly left ventricular hypertrophy, and to address the molecular mechanisms underlying them.Methods: 24 male albino rats were randomly divided into 4 main groups (n=6 each), normal control rats (N), hypertensive control rats (HC), Val treated hypertensive rats (Val, 8 mg/kg/day orally) and Ali treated hypertensive rats (Ali, 25 mg/kg/day orally).Results: At the end of 4 weeks HC rats showed enhanced hypertrophic response (higher heart weight/body weight ratio) and dyslipidemia (lower high density lipoprotein "HDL-c" and higher triacyl glycerol "TAG") and a significant deletion of antioxidant enzymes in comparison with N group. The β myosin heavy chain "βMHC", regulator of calcineurin-1 "RCAN1", nuclear factor kappa B "NFκB" and inducible nitric oxide synthase "iNOS" was markedly elevated. While, α myosin heavy chain "αMHC" was markedly decreased as compared with N group. On the other hand Val treated hypertensive rats and Ali treated hypertensive rats showed a significant decrease in heart weight/body weight ratio, improved lipogram pattern and higher levels of antioxidant enzymes. While, cardiac β-MHC, RCAN-1, NFκB and iNOS were significantly decreased as compared with HC group. Both Val treated hypertensive rats and Ali treated hypertensive rats showed a significant increase in α-MHC, compared with HC groupConclusion: The results reported in this study suggested that chronic untreated hypertension induced a pathological hypertrophy. Administration of the Val or Ali individually exerted beneficial effects regarding the improved lipogram pattern and anti-oxidant enzymes levels, as well as cardiac hypertrophy and highlights the role of Val and Ali as a promising therapeutic strategy for hypertension and LV hypertrophy.Â

Evaluation of Antimicrobial bioactive compounds from Endophytic Fungi Isolated from Moringa oleifera

Endophytic fungi are microorganisms that inhabit the living tissues of their host plants without causing any host loss. They are considered as a continuous natural source of novel bioactive secondary metabolites with potential application in medicine, which are almost same to their host plant. In this study a total of nine endophytic fungal isolates were collected from leaves and stems of Moringa oleifera. Based on the colonization frequency (CF) results, the highest number of isolates was obtained from plant stem, while the least was from leaves. The nine isolates were identified by keeping track of morphological and microscopic observations. Identification of the two antimicrobial potent strains was confirmed by 18S rDNA-based molecular analysis. The nine isolates were found belonging to Chaetomium, Alternaria, Fusarium, Aspergillus, Mycelia, Penicillium and Nigrospora taxa. Among them, Chaetomium taxon was included the highest CF) 40% (. Evaluation of antimicrobial activity documented ethyl acetate fungal extract as the highest effective inhibitor against Gram-negative and Gram-positive bacteria, and Aspergillus fumigatus. Minimum inhibitory concentration (MIC) was examined for the two most potent antimicrobial effective extracts, from Chaetomium laterale and Chaetomium interruptum; it was ranged from 12.5 to 0.39 mg/ml

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

Comparing the effect of acupressure and ginger on chemotherapy gastrointestinal side-effects in children with leukemia

The biosocial data of 90 children with acute lymphoblastic leukemia, were collected along with assessment of gastrointestinal side-effects of chemotherapy using visual analogue scale. Ginger lozenges has more effect than acupressure in alleviating nausea and vomiting. Acupressure alleviate the nausea best in the group aged 13–15 years. Ginger helped more the other two groups (7–12 years, 69 % of the group didn’t suffer from nausea), versus 50 % aged 13–15). Both acupressure and ginger affected girls more than boys in alleviating nausea. The acupressure effect on vomiting incidence didn’t differ in both males and males, whilst ginger helped the males more

Synthesis and anticancer activity of new [(Indolyl)pyrazolyl]-1,3,4-oxadiazole thioglycosides and acyclic nucleoside analogs

<p>New [(Indolyl)pyrazolyl]-1,3,4-oxadiazole compounds and their derived thioglycosides as well as the corresponding sugar hydrazones were synthesized. The acyclo <i>C</i>-nucleoside analogs of the oxadiazoline base system were also prepared by reaction of acid hydrazides with aldehydo sugars followed by one pot process encompassing acetylation and cyclization of the synthesized hydrazones. The anticancer activity of the newly synthesized compounds was studied against colorectal carcinoma (HCT116), breast adenocarcinoma (MCF7) and prostate cancer (PC3) human tumor cell lines and a number of compounds showed moderate to high activities.</p

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit