Evaluation of chemopreventive effect of Fumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats

AbstractObjectiveTo investigation the chemopreventive potential of Fumaria indica (F. indica) extract (FIE) on N-nitrosodiethylamine and CCl4-induced hepatocarcinogenesis in Wistar rats.MethodsThe experimental animals were divided into six groups (n=6). Hepatocellular carcinoma was induced by single intraperitoneal injection of N-nitrosodiethylamine (NDEA) in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl4(3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The percentage of nodule incidence and liver cancer markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen were estimated along with histopathological investigation in experimental groups of rats.ResultsObtained results demonstrated that the cotreatment with FIE significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA. The treatment with FIE significantly reduced the nodule incidence and nodule multiplicity in the rats after NDEA administration. The levels of liver cancer markers such as AST, ALT, ALP, γ-glutamyl transferase, TBL, AFP and carcinoembryonic antigen were substantially increased by NDEA treatment. However, FIE treatment significantly reduced the liver injury and restored the entire liver cancer markers. Histological observations of liver tissues too correlated with the biochemical observations.ConclusionsThese finding powerfully supports that F. indica exert chemopreventive effect by suppressing the tumor burden and restoring the activities of hepatic cancer marker enzymes on NDEA and CCl4-induced hepatocarcinogenesis in Wistar rats

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Pharmacognostical studies and evaluation of total phenolic and flavonoid contents of traditionally utilized fruits of <i style="">Solanum torvum</i> Sw.

218-224The fruits of Solanum torvum Sw., commonly known as Shoo-shoo bush, Devil’s fig, Wild egg, are pungent in taste, edible, used as a vegetable and are regarded as an essential ingredient in Thai cuisine. In Tripura and West Bengal fruits are crushed or cooked with dry fish (sidhol) and taken with warm rice to cure rheumatic pain. The fruit has been used ethnomedicinally as a tonic and haematopoietic, anti-microbial agent and for the treatment of pain. A decoction of fruits is given for cough ailments and is considered as useful in liver and spleen enlargement. The fruit has sedative, diuretic and digestive in action. In view of the traditional and medicinal importance, the present study deals with pharmacognostical evaluation of fruit including morphological and histological studies. Determination of physicochemical constants, fluorescence analysis and phytochemical profile including TLC fingerprint and estimation of total phenolic and flavonoid contents has also been done

Stability-indicating assay of repaglinide in bulk and optimized nanoemulsion by validated high performance thin layer chromatography technique

A sensitive, selective, precise and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for analysis of repaglinide both as a bulk drug and in nanoemulsion formulation was developed and validated. The method employed TLC aluminum plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform/methanol/ammonia/glacial acetic acid (7.5:1.5:0.9:0.1, v/v/v/v). This system was found to give compact spots for repaglinide (R f value of 0.38 ± 0.02). Repaglinide was subjected to acid and alkali hydrolysis, oxidation, photodegradation and dry heat treatment. Also, the degraded products were well separated from the pure drug. Densitometric analysis of repaglinide was carried out in the absorbance mode at 240 nm. The linear regression data for the calibration plots showed good linear relationship with r 2 = 0.998 ± 0.032 in the concentration range of 50-800 ng. The method was validated for precision, accuracy as recovery, robustness and specificity. The limits of detection and quantitation were 0.023 and 0.069 ng per spot, respectively. The drug undergoes degradation under acidic and basic conditions, oxidation and dry heat treatment. All the peaks of the degraded product were resolved from the standard drug with significantly different R f values. Statistical analysis proves that the method is reproducible and selective for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. Moreover, the proposed HPTLC method was utilized to investigate the degradation kinetics in 1M NaOH

Pharmacognostical studies and evaluation of total phenolic contents of trunk bark of Spondias mangifera Willd.

146-150Spondias mangifera Willd., commonly known as Wild mango or Hog plum (Hindi- Amara) is an important medicinal plant. The dry bark is silver brown coloured with mucilaginous astringent characters. It is traditionally used in North-East regions of India as refrigerant, aromatic, tonic and for the treatment of dysentery, diarrhoea and rheumatism. This study deals with the pharmacognostical evaluation of its dried trunk bark which includes macro and microscopic studies, determination of physicochemical parameters of the extract using TLC fingerprinting

Stress relaxant and antioxidant activities of acid glycoside from Spondias mangifera fruit against physically and chemically challenged albino mice

Aim: Stress relaxant and antioxidant activities of ethanolic extract of fruit Spondias mangifera (EEFSM) and its isolated compound (Sm-01) were evaluated. The structure of Sm-01 was also elucidated. Materials and Methods: EEFSM at two different doses of 100 and 200 mg/kg (bw)/day and Sm-01 at dose of 10 mg/kg (bw)/day were screened for in vivo stress relaxant activity using anoxia stress tolerance, swimming endurance and cyclophosphamide-induced immune suppression model and in vitro antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) model. The levels of Hb, red blood cell (RBC) and white blood cell (WBC) along with organ and body weights suppressed by cyclophosphamide were estimated. The structure of Sm-01 was elucidated by spectroscopy (ultraviolet, infrared, 1H-nuclear magnetic resonance [NMR], 13C-NMR and mass spectrometry) and chemical analyses. Results: Sm-01 was structurally elucidated as propan-1,2-dioic acid-3-carboxyl-β-D-glucopyranosyl-(6'→1")-β-D-glucofuranoside. It was found that EEFSM and Sm-01 significantly increased the anoxia stress tolerance, swimming endurance and duration of stay on rotarod and normalized the levels of Hb, RBC, and WBC along with altered organ and body weights suppressed by cyclophosphamide. EEFSM and Sm-01 also exhibited significant antioxidant activity against DPPH free radical at the concentrations of 0.05, 0.5, and 1.0 mg/mL with obtained IC50of 0.32 and 0.15 mg/mL, respectively. Conclusions: These findings demonstrated that extract and Sm-01 both possess significant stress relaxant and antioxidant activities favoring its use as adaptogens. The activities of the extract may be due to the Sm-01

Marine natural products: A lead for Anti-cancer

27-39Various active anticancer agents are derived from plants and terrestrial microorganisms. Isolation of C-nucleosides from the Caribbean sponge, Cryptotheca crypta, four decades ago, provided the basis for the synthesis of cytarabine, the first marine derived anticancer agent to be developed for clinical use. Cytarabine is currently used in the routine treatment of patients with leukaemia and lymphoma. Gemcitabine, one of its fluorinated derivatives, has also been approved for use in patients with pancreatic, breast, bladder, and non-small-cell lung cancer. Over the past decade, several new experimental anticancer agents derived from marine sources have entered preclinical and clinical trials. Present study address anticancer drug discovery from an evolutionary perspective and present a series of case studies that demonstrate that the rate of anticancer drug discovery can be increased greatly by targeted screening of natural compounds from marine sources

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable