OBJECTIVE: To check the prices, availability, and affordability of the World Health Organization (WHO) key access antibiotics in private sector pharmacies of Lahore, Pakistan.
METHODOLOGY: A survey of WHO key access antibiotics from WHO essential medicine list 2017 was conducted in private sector pharmacies of 4 different regions of Lahore employing adapted WHO/HAI methodology. The comparison of prices and availability between originator brands (OB) and lowest price generics (LPG) were conducted followed by the effect of medicine price differences on patient's affordability. The data were analyzed using a preprogrammed WHO Microsoft excel workbook.
RESULTS: The mean availability of OB products was 45.20% and the availability of LPGs was 40.40%. The OBs of co-amoxiclav, clarithromycin and metronidazole and LPGs of azithromycin and ciprofloxacin were easily available (100%) in all private sector pharmacies. Whereas, antibiotics like chloramphenicol, cloxacillin, nitrofurantoin, spectinomycin, and cefazolin were totally unavailable in all the surveyed pharmacies. The OBs and LPGs with high MPRs were ceftriaxone (OB; 15.31, LPG; 6.38) and ciprofloxacin (OB; 12.42, LPG; 5.77). The median of brand premium obtained was 38.7%, which varied between the lowest brand premium of 3.97% for metronidazole and highest for ceftriaxone i.e. 140%. The cost of standard treatment was 0.5 day's wage (median) if using OB and 0.4 day's wage (median) for LPG, for a lowest paid unskilled government worker. Treatment with OB and LPG was unaffordable for ciprofloxacin (OB; 2.4, LPG; 1.1) & cefotaxime (OB; 12.7, LPG; 8.1).
CONCLUSION: There is dire need to properly implement price control policies to better regulate fragile antibiotic supply system so that the availability of both OB and LPG of key access antibiotics should be increased. The prices could be reduced by improving purchasing efficiency, excluding taxes and regulating mark-ups. This could increase the affordability of patients to complete their antibiotic therapy with subsequent reduction in antimicrobial resistance.
Objective: This study aims to fractionate water extract of Labisia pumila, identify the compound(s) involved and elucidate the possible mechanism(s) of its vasorelaxant effects.
Methods: Water extract of Labisia pumila was subjected to liquid-liquid extraction to obtain ethyl acetate, n-butanol and water fractions. In SHR aortic ring preparations, water fraction (WF-LPWE) was established as the most potent fraction for vasorelaxation. The pharmacological mechanisms of the vasorelaxant effect of WF-LPWE were investigated with and without the presence of various inhibitors. The cumulative dose-response curves of potassium chloride (KCl)-induced contractions were conducted to study the possible mechanisms of WF-LPWE in reducing vasoconstriction.
Results: WF-LPWE produced dose-dependent vasorelaxant effect in endothelium-denuded aortic ring and showed non-competitive inhibition of dose-response curves of PE-induced contraction, and at its higher concentrations reduced KCl-induced contraction. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly inhibited vasorelaxant effect of WF-LPWE. WF-LPWE significantly reduced the release of intracellular calcium ion (Ca2+) from the intracellular stores and suppressed the calcium chloride (CaCal2)-induced contraction. Nω-nitro-L-arginine methyl ester (L-NAME), methylene blue, indomethacin and atropine did not influence the vasorelaxant effects of WF-LPWE.
Conclusion: WF-LPWE exerts its vasorelaxant effect independently of endothelium and possibly by inhibiting the release of calcium from intracellular calcium stores, receptor-operated calcium channels and formation of inositol 1,4,5- triphosphate. WF-LPWE vasorelaxant effect may also mediated via nitric oxide-independent direct involvement of soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathways.
AIM OF THE STUDY: This study is designed to investigate the vasorelaxant effect of Chen pi and to study its pharmacology effects.
MATERIALS AND METHODS: The vasorelaxant effect of water extract of Chen pi (CRW) were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. The fingerprint of Chen pi and the extracts were developed with quantification of hesperidin content by HPTLC.
RESULTS: CRW exhibited the strongest vasorelaxant activity. CRW caused the relaxation of the phenylephrine pre-contracted aortic rings in the presence and absence of endothelium as well as in potassium chloride pre-contracted endothelium-intact aortic ring. The incubation of propranolol (β-adrenergic receptor blocker), atropine (muscarinic receptor blocker), Nω-nitro-L-arginine methyl ester (NO synthase inhibitor), ODQ (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (KV blocker), barium chloride (Kir blocker), and glibenclamide (KATP blocker) significantly reduced the vasorelaxant effects of CRW. CRW was also found to be active in reducing Ca2+ releases from the sarcoplasmic reticulum and suppressing the voltage-operated calcium channels.
CONCLUSION: The vasorelaxant effect of CRW on rat aorta involves NO/sGC, calcium and potassium channels, muscarinic and β-adrenergic receptors.
METHODS: The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders.
FINDINGS: 95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.
INTERPRETATION: Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.
FUNDING: Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.
METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes.
RESULTS: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke.
CONCLUSIONS: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.