Cardiovascular disease risk stratification in the Pakistani population with and without metabolic syndrome: A single centre cross-sectional study.

Existing atherosclerotic cardiovascular disease (ASCVD) risk stratification algorithms are predominantly validated only for Western populations, and do not include parameters of metabolic syndrome (MetS) which may increase the relative risk for cardiovascular disease in South Asians. This study aimed to compare the differences between 10-year ASCVD risk by the Framingham Risk Score (FRS), Pooled Cohort Risk Equations (PCE), and QRISK3 calculators in a cohort of apparently healthy Pakistani adults and stratify the ASCVD risk by MetS status.A cross-sectional study recruited 179 subjects between the ages of 40 to 74 years from the outpatient department of the Aga Khan University Hospital between May 2019 to November 2022. Anthropometry, demography, and blood samples were collected from each subject after informed consent. The IDF criteria were used to categorize subjects as MetS positive (n = 122) and MetS negative (n = 57). The mean age of study participants was 51.07±7.38 years. The average 10-year ASCVD risk (%) for our cohort was calculated to be 15.34 ± 11.60, 9.66 ± 10.87, and 17.02 ± 14.66 using the FRS algorithm, PCE calculator, and QRISK3 calculator respectively. MetS status did not show a statistically significant association with the risk categories determined by any of the calculators, although numerical ASCVD risk estimates were significantly higher in the MetS positive group for all calculators.Although ASCVD risk is a useful way to reduce CVD burden by identifying asymptomatic individuals at the highest risk of developing ASCVD, a high proportion of individuals with MetS may still be identified as low risk by the current risk stratification algorithms in South Asians. Powered validation studies with larger sample sizes and longitudinal follow-up are needed in South Asians to modify existing calculators to make them more applicable to South Asian populations.

Covid-19 pandemic-prevalence of depression, anxiety and insomnia during Covid-19 lockdown and its associated factors in Karachi, Pakistan.

We aimed to determine the frequency of depression, anxiety and insomnia; identify associated factors; and compare these outcomes amongst a privileged and underprivileged class of Pakistan. A cross-sectional online and face to face survey was conducted in Karachi from April 2020 to May 2020. Validated depression (World Health Organization self-reporting questionnaire), anxiety (general anxiety and depression scale) and insomnia (insomnia severity index) scales were used. Out of 447 participants, the majority were less than 30 years (63.8%) and females (57.7%); 20.8% study participants belonged to poor or very poor socioeconomic status; 17% respondents were from lower middle status and 38% belonged to the higher middle or rich class. Depression, anxiety and insomnia were identified in 30%, 30.63% and 8.5% of participants, respectively. The prevalence of depression, anxiety and insomnia among privileged people was 37.8%, 16.6% and 11.3% respectively whereas among underprivileged were 17.8%, 16.6% and 4.1% respectively. There were significant differences in frequencies of depression (p<0.001), anxiety (p<0.001) and insomnia (p=0.009) among the privileged and underprivileged classes. We found a high prevalence of depression, anxiety and insomnia among both the privileged and underprivileged Pakistani population and a policy needs to be devised to ensure the mental health of Pakistani population.

Systematic Review of Polyherbal Combinations Used in Metabolic Syndrome.

Background: Metabolic syndrome (MetS) is a multifactorial disease, whose main stay of prevention and management is life-style modification which is difficult to attain. Combination of herbs have proven more efficacious in multi-targeted diseases, as compared to individual herbs owing to the "effect enhancing and side-effect neutralizing" properties of herbs, which forms the basis of polyherbal therapies This led us to review literature on the efficacy of herbal combinations in MetS. Methods: Electronic search of literature was conducted by using Cinnahl, Pubmed central, Cochrane and Web of Science, whereas, Google scholar was used as secondary search tool. The key words used were "metabolic syndrome, herbal/poly herbal," metabolic syndrome, clinical trial" and the timings were limited between 2005-2020. Results: After filtering and removing duplications by using PRISMA guidelines, search results were limited to 41 studies, out of which 24 studies were evaluated for combinations used in animal models and 15 in clinical trials related to metabolic syndrome. SPICE and SPIDER models were used to assess the clinical trials, whereas, a checklist and a qualitative and a semi-quantitative questionnaire was formulated to report the findings for animal based studies. Taxonomic classification of Poly herbal combinations used in animal and clinical studies was designed. Conclusion: With this study we have identified the potential polyherbal combinations along with a proposed method to validate animal studies through systematic qualitative and quantitative review. This will help researchers to study various herbal combinations in MetS, in the drug development process and will give a future direction to research on prevention and management of MetS through polyherbal combinations.

Effects of Essential Oils of Elettaria cardamomum Grown in India and Guatemala on Gram-Negative Bacteria and Gastrointestinal Disorders.

The present study examined the chemical composition and antimicrobial and gastrointestinal activity of the essential oils of Elettaria cardamomum (L.) Maton harvested in India (EC-I) and Guatemala (EC-G). Monoterpenes were present in higher concentration in EC-I (83.24%) than in EC-G (73.03%), whereas sesquiterpenes were present in a higher concentration in EC-G (18.35%) than in EC-I (9.27%). Minimum inhibitory concentrations (MICs) of 0.5 and 0.25 mg/mL were demonstrated against Pseudomonas aeruginosa in EC-G and EC-I, respectively, whereas MICs of 1 and 0.5 mg/mL were demonstrated against Escherichia coli in EC-G and EC-I, respectively. The treatment with control had the highest kill-time potential, whereas the treatment with oils had shorter kill-time. EC-I was observed to be more potent in the castor oil-induced diarrhea model than EC-G. At 100 and 200 mg/kg, P.O., EC-I exhibited 40% and 80% protection, respectively, and EC-G exhibited 20% and 60% protection, respectively, in mice, whereas loperamide (10 mg/kg, i.p., positive control) exhibited 100% protection. In the in vitro experiments, EC-I inhibited both carbachol (CCh, 1 µM) and high K+ (80 mM)-induced contractions at significantly lower concentrations than EC-G. Thus, EC-I significantly inhibited P. aeruginosa and E. coli and exhibited more potent antidiarrheal and antispasmodic effects than EC-G.

Multiple Pathway-Mediated Gut-Modulatory Effects of Maerua subcordata (Gilg) DeWolf.

BACKGROUND: Gastrointestinal disorders are often poorly managed, especially in developing countries, where there are limited resources and therapeutic options. Despite the rich diversity of medicinal plants that offer effective treatment options with fewer side effects, studies that provide scientific verification are lacking. Maerua subcordata (Gilg) DeWolf is among the plants claimed to have wide traditional medicine, use, including as a remedy against gastrointestinal problems. Therefore, this work aimed to evaluate the gut-modulatory effects of a crude leaf extract of M. subcordata (MSL.Cr), as well as its possible mechanism of action. METHODS: A castor oil (10 mL/kg)-induced diarrheal mouse model was used to evaluate the antidiarrheal effect of MSL.Cr, and the spasmodic/antispasmodic effect of the extract was assessed using isolated rabbit jejunum with and without addition of standard cholinergic agonists/antagonists to predict the possible mechanism of action. RESULTS: MSL.Cr exhibited 40% and 80% protection against castor oil-induced diarrhea in mice at doses of 500 and 1,000 mg/kg, respectively. In isolated rabbit jejunum, the extract increased spontaneous contractions at low doses (0.01-0.1 mg/mL), and was sensitive to atropine, whereas it showed complete inhibition at higher doses (0.3-1 mg/mL). It was shown that the relaxant effect was possibly mediated by the involvement of phosphodiesterase-enzyme inhibition and K+-channel activation. The extract potentiated the control concentration-response curve of carbachol, shifting it to the left, similarly to the control drug papaverine. The potassium-channel opening-like activity of MSL.Cr was possibly mediated by the involvement of aspecific K+-channels inhibition, since tetraethylammonium, anunselective antagonist of K+ channels, significantly reversed its inhibitory effect. CONCLUSION: This study showed that the M. subcordata leaf extract demonstrated gut-modulatory effects, possibly mediated by a combination of muscarinic-receptor stimulation, phosphodiesterase inhibition, and aspecific K+-channel activation.

Multiple Mechanisms of Flaxseed: Effectiveness in Inflammatory Bowel Disease.

MATERIALS AND METHODS: Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage parameters of the hematoxylin and eosin-stained and periodic acid-Schiff-alcian blue-stained sections of the colon were scored to be assessed. Possible antispasmodic mechanism was studied on isolated rabbit jejunum, while antibacterial activity was assessed in vitro for microbes implicated in IBD. RESULTS: In AA-induced colitis, Flaxseed oil was found to be more effective in reducing mortality and colonic ulcers than Fs.Cr at 500 mg/kg dose. Fs.Cr was more efficacious in increasing mucin content as compared to oil, exhibiting slightly greater anti-inflammatory effect (50% vs 35%) and reducing depth of lesion (55% vs 42.31%, respectively). Antispasmodic activity of Fs.Cr (0.03 and 0.1 mg/ml) was mediated by phosphodiesterase inhibitors (PDEI, possibly PDE-4 subtype) with a resultant increase in cAMP levels. Flaxseed oil PDEI activity was mild (1 and 3 mg/ml). Fs.Cr (0.1 and 0.3 mg/ml) was potent in exhibiting anticholinergic activity, similar to dicyclomine, whereas Flaxseed oil showed anticholinergic effect at 1 and 3 mg/ml. Flaxseed oil (9 and 14 µg/ml) was bactericidal against enteropathogenic E.coli (EPEC), enterotoxigenic E.coli (ETEC), and enteroaggregative E.coli (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100 µg/ml. CONCLUSIONS: Results of this study, taken together with previous studies, suggest that Flaxseed possesses anti-inflammatory, antibacterial, and antispasmodic action through multiple pathways and thus offers promising potential to be developed for IBD.

Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms.

New treatments for inflammatory bowel disease are of interest due to high rate of remission failure. Natural products have been effective in IBD therapeutics as they have multiple constituents. The aim of the present study was to evaluate the effect of Flaxseed extract (Fs.Cr) on ulcerative colitis and identify the possible mechanisms involved. Colitis was induced by intrarectal administration of 6% AA in BALB/c mice. Colonic mucosal damage was assessed after 24h by calculating disease activity index (DAI), macroscopic and histological damage scores, biochemical measurement of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total glutathione activities. Since cytokines are involved in exacerbating inflammatory cascade with emerging role of innate immune cytokines in IBD therapeutics, we hence assessed the effect on the levels of TNF-α, IFN-γ and IL-17, at 6, 12 and 24h by ELISA. Fs.Cr ameliorated the severity of AA colitis as evident by improved DAI, macroscopic damage and the histopathological scores along with restoration of goblet cells. Fs.Cr decreased MDA and MPO activities and enhanced antioxidant activity compared to the AA group. Finally, Fs.Cr in doses (300 and 500mg/kg) decreased TNF-α and IFN-γ levels at all time points with simultaneous increase in IL-17 levels at 24h as compared to the AA group. These results suggest that Fs.Cr ameliorates the severity of AA colitis by reducing goblet cell depletion, scavenging oxygen-derived free radicals, reduce neutrophil infiltration that may be attributed due to decreasing IFN-γ and TNF-α and increasing IL-17 levels.

Pharmacological basis for the medicinal use of Linum usitatissimum (Flaxseed) in infectious and non-infectious diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Linum usitatissimum, commonly known as Flaxseed has traditionally been used for the management of diarrhea and gastrointestinal infections. This study was planned to assess pharmacological basis for the medicinal use of Flaxseed in infectious and non-infectious diarrhea. MATERIALS AND METHODS: The crude aqueous-methanolic extract of Flaxseed was studied using the in vivo castor oil-induced diarrhea, gut motility and enteropooling assays. Mechanistic basis was further elucidated by testing the inhibitory effect on spontaneously contracting isolated rabbit jejunum preparations, suspended in a 10ml tissue bath containing Tyrode׳ solution, maintained at 37°C and aerated with carbogen. Antibacterial efficacy of the Flaxseed extract was tested against different enteric and non-enteric pathogenic bacteria using in vitro antibacterial assays. RESULTS: Flaxseed extract reduced the diarrheal score in mice, by 39%, 63.90% and 68.34% at the respective doses of 100, 300 and 500mg/kg. Intestinal secretions were reduced by 24.12%, 28.09% and 38.80%, whereas the intestinal motility was reduced by 31.66%, 46.98% and 56.20% at respective doses of 100, 300 and 500mg/kg. When tested on isolated rabbit jejunum preparations, Flaxseed extract produced a dose-dependent inhibition of both spontaneous and high K(+) (80mM)-induced contractions, and shifted the concentration-response curves of Ca(++) to the right with suppression of the maximum response, similar to that caused by verapamil. Flaxseed extract was found to possess bactericidal activity at the tested concentrations of 12.5mg/ml, against vancomycin-resistant Enterococcus faecalis (100%), Escherichia coli K1 (88.88%), methicillin-resistant Staphylococcus aureus (98.76%), Bacillus cereus (92.64%), Pseudomonas aeruginosa (76.83%) and Salmonella typhi (26.91±3.35%). The concentration of 10mg/ml showed bactericidal effects against all the aforementioned pathogens except Escherichia coli K1, whereas for Pseudomonas aeruginosa and Salmonella typhi, it was bacteriostatic at this concentration. CONCLUSIONS: Our results indicate that Linum usitatissimum (Flaxseed) extract exhibits antidiarrheal and antispasmodic activities by virtue of its antimotility and antisecretory effects which are mediated possibly through inhibition of Ca(++) channels, though additional mechanism(s) cannot be ruled out. Flaxseed extract proved effective against both enteric and non-enteric pathogens causing diarrhea, thus ensuring wide coverage and rationalizing its medicinal use in both the infectious and non-infectious diarrhea.

Over prescription of antibiotics for adult pharyngitis is prevalent in developing countries but can be reduced using McIsaac modification of Centor scores: a cross-sectional study.

BACKGROUND: Although Group A beta hemolytic streptococcus (GABHS) can cause bacterial pharyngitis, the most common etiology is viral; despite this viral etiology, antibiotics are commonly prescribed for this infection in industrialized countries. We investigated the prevalence of GABHS in adult pharyngitis patients from lower socioeconomic settings in Karachi, Pakistan, how often antibiotics are prescribed for pharyngitis and if appropriate agents were used in a developing world setting. Finally, we wanted to see the usefulness of modified McIsaac scores in predicting positive cultures. METHODS: Adult patients were recruited from three local hospital outpatient dispensaries (OPDs). All patients aged 14-65 years who were suspected of having bacterial pharyngitis had throat swabs taken. Laboratory results for GABHS pharyngitis were then compared with their prescriptions. Appropriateness (using the World Health Organization's definition) and type of antibiotic prescribed were assessed. RESULTS: Of 137 patients, 30 patients each were studied for scores of 0, 1, 2 and 3; 17 patients were studied for score 4. Although 6 (4.4%) patients were GABHS+, for a prevalence of 43.8 per 1000 population, antibiotics were prescribed to 135 patients (98.5%). Of these, only 11.1% received appropriate antibiotics while 88.9% received inappropriate antibiotics. Penicillins were prescribed most (34.1%), especially amoxicillin/clavulanate; followed by macrolides (31.1%), especially the second-generation agents, and fluoroquinolones (14.8%). McIsaac scores were found to be 100% sensitive and 68.7% specific, giving a positive predictive value (PPV) of 12.7% and a negative predictive value (NPV) of 100%. CONCLUSIONS: Antibiotics were prescribed irrationally to adult pharyngitis patients, as most cultures were negative for bacterial infection. McIsaac modification of Centor scores related directly to culture results. We would therefore highly recommend its use to help family physicians make treatment decisions for adult pharyngitis patients.