Ethnopharmacological studies on chrozophora prostrata in perspective of its folkloric reputation as purgative

This study was undertaken to validate the medicinal use of Chrozophora prostrata in constipation. The crude extract of C prostrata produced laxative effect in mice at 100 and 300 mg/kg, similar to carbachol and castor oil. In spontaneously contracting rabbit jejunum tissues, C. prostrata (0.01-3 mg/mL) exhibited atropine-sensitive spasmogenic effect, which was reproducible in guinea-pig ileum. Interestingly, at high concentrations, C. prostrata showed concentration-dependent inhibitory effect on rabbit jejunum, suggesting the presence of accompanied spasmolytic activity. When tested on induced contractions, C. prostrata completely relaxed low K+-induced contraction, while partially inhibited high K+, similar to cromakalim. Tetraethylammonium pretreatment abolished the relaxant effect of C. prostrata on low K+-induced contractions while glibenclamide caused partial inhibition, suggesting the involvement of some non-specific and ATP-dependent K+ channels. These data show that C. prostrata possesses laxative effect at low doses mediated through cholinergic action followed by the spasmolytic activity at high doses mediated possibly through K+ channel activation

Surgical Outcome of Otogenic Brain Abscess in Chronic Suppurative Otitis Media

Objective: To determine the surgical out come of otogenic brain abscess in chronic suppurative otitis media.Material and Methods: This descriptive study was conducted at the departments of ENT, Head, Neck Surgery and Neurosurgery Postgraduate Medical Institute (PGMI) Lady Reading Hospital Peshawar from June 2004 to May 2009 with a total duration of five years. The diagnostic criteria were detailed history, thorough Neuro-otological examination and radiological investigations. These patients were admitted into ENT Department and they were put on quadruple therapy. CT scans were performed on emergency basis and as the patients were diagnosed as having otogenic brain abscess urgent evacuation of abscess was done by neurosurgeon. All the patients with established brain abscess were included in this study while those patients having small multiple abscesses, early cereberitis and non otogenic brain abscesses were excluded from study. A well informed consent was taken from patient explaining the procedure, its risks, benefits and associated complications. The abscesses were primarily treated by neurosurgeons and the ears were later on treated by ENT surgeons. There was neither intra operative nor postoperative complication.Results: This study included 22 patients in the age range of 12-51 years with mean age 25 years. Sixteen were male and six were female, with female to male ratio 1 : 2.6. These patients presented with history of discharging ear, headache, vomiting and disorientation. The signs of disease in these patients were granulation tissues/ cholesteatoma in ear and papilloedema. CT scans were performed in all 22 cases (100%) while MRI in 10 cases (45.45%). There were single brain abscess in 14 cases (63.63%) while 8 cases (44.45%) having multiple brain abscesses. Mainly abscess were found in temporal region followed by cerebellar. The patients with chronic ear disease were treated by radical mastoidectomy and modified radical mastoidectomy after treating the brain abscess by Neurosurgeon. The Neurosurgical procedures performed were capsulotmies in 13 cases (59.09%), Bur hole aspiration in 7 cases (31.81%) and Trans mastoid excision in 2 cases (9.09%). These patients were followed for 3 monthly having CT scan with contrast with bone window.Conclusion: We concluded from our study that otogenic brain abscess is a life threatening complication, so early identification with help of CT scan and prompt surgical intervention with appropriate treatment of middle ear (primary disease) is essential for better outcom

Essential Oils Based Nano Formulations against Postharvest Fungal Rots

Postharvest phytopathogenic rot fungi affect the quality and quantity of perishable fruits and vegetables. About 30–40% peaches deteriorate annually after harvest in world whereas 40–50% losses are reported from Pakistan. Our research envisages importance of an eco-friendly plant essential oils based nano formulations as a management strategy against postharvest deteriorating fungal rots by enhancing their shelf-life and to attenuate reliance on synthetic fungicides. Plant essential oils mode of action against fungal postharvest rots is responsible of rupturing plasma membrane of fungal cell wall. The natural ripening process of perishable commodities does not get affected by the presence of antifungal packaging in the form of plant essential oil nano formulations as no significant alteration in weight loss of produce was recorded. Challenges in applying EOs for microbial suppression in postharvest systems include optimizing their positioning in commercial fruit storage containers. Several innovative approaches are analyzed in terms of work environment and implementation regarding disease management along with future perspectives in concerning field

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Estimation of peripheral dose from Co beam in water phantom measured in Secondary Standard Dosimetry Laboratory, Pakistan

BackgroundPeripheral or scatter dose harms neighbouring normal tissues during administration of dose to cancerous tissues, therefore, knowledge of peripheral dose is an important consideration in radiotherapy.AimIn present study, absorbed dose measurements in a water phantom were performed for three field sizes, 7[[ce:hsp sp="0.25"/]]×[[ce:hsp sp="0.25"/]]7[[ce:hsp sp="0.25"/]]cm2, 10[[ce:hsp sp="0.25"/]]×[[ce:hsp sp="0.25"/]]10[[ce:hsp sp="0.25"/]]cm2 and 15[[ce:hsp sp="0.25"/]]×[[ce:hsp sp="0.25"/]]15[[ce:hsp sp="0.25"/]]cm2.Materials and methodsFor each field size, dose was measured at six depths below the front surface of the water phantom; 2.5–15[[ce:hsp sp="0.25"/]]cm with an interval of 2.5[[ce:hsp sp="0.25"/]]cm. Measurements were made at equal transverse distances along the horizontal axis, from 1[[ce:hsp sp="0.25"/]]cm to 6[[ce:hsp sp="0.25"/]]cm, on both sides of the central beam axis and normalized with central axis dose of each field. All measurements were made at the source to surface distance of 100[[ce:hsp sp="0.25"/]]cm.ResultsVariation of peripheral dose with lateral distance was analysed and an appropriate parametric equation for each field size and depth was constructed.ConclusionsThe peripheral radiation dose showed a strong dependence on field size and distance from field boundary

Studies on Antidiarrheal and Antispasmodic Activities of Lepidium sativum Crude Extract in Rats

This study was aimed to provide the pharmacological basis for the medicinal use of Lepidium sativum in diarrhea using in vivo and in vitro assays. The seed extract of Lepidium sativum (Ls.Cr) at 100 and 300 mg/kg inhibited castor oil-induced diarrhea in rats. In isolated rat ileum, Ls.Cr (0.01-5 mg/mL) reversed carbachol (CCh, 1 mu M) and K(+) (80 mM)-induced contractions with higher potency against CCh, similar to dicyclomine. Preincubation of rat ileum with a lower concentration of Ls.Cr (0.03 mg/mL) caused a rightward parallel shift in the concentration-response curves (CRCs) of CCh without suppression of the maximum response, while at the next higher concentration (0.1 mg/mL), it produced a non-parallel rightward shift with suppression of the maximum response, similar to that of dicyclomine. Ls.Cr shifted the CRCs of Ca(++) to the right with suppression of the maximum response, similar to verapamil. These data suggest that Lepidium sativum seed extract possesses antidiarrheal and spasmolytic activities mediated possibly through dual blockade of muscarinic receptors and Ca(++) channels, though additional mechanism(s) cannot be ruled out and this study explains its medicinal use in diarrhea and abdominal cramps

Prokinetic and laxative activities of Lepidium sativum seed extract with species and tissue selective gut stimulatory actions

Aim of the study: To provide ethnopharmacological basis for the medicinal use of Lepidium sativum seeds in indigestion and constipation. Materials and methods: The in vivo studies were conducted in mice, while isolated tissues of mouse, guinea-pig and rabbit were suspended in tissue bath to measure isotonic contractions. Results: The aqueous-methanolic extract of Lepidium sativum seeds (Ls.Cr) at 30 and 100 mg/kg showed atropine-sensitive prokinetic and laxative activities in mice, which were partially sensitive to atropine. In isolated gut preparations of mouse and guinea-pig, Ls.Cr (0.1-1 mg/mL) caused a concentration-dependent stimulatory effects both in jejunum and ileum, which was blocked in the presence of atropine. In rabbit jejunum, the stimulant effect of Ls.Cr remained unchanged in the presence of atropine, pyrilamine or SB203186, while in rabbit ileum, the stimulatory effect was partially blocked by atropine. The Ls.Cr was more efficacious in gut preparations of rabbit than in guinea-pig or mouse. The phytochemical analysis of the plant extract detected alkaloids, saponins and anthraquinones as plant constituents. Conclusion: This study showed the prokinetic and laxative effects of Lepidium sativum in mice, which were partially mediated through a cholinergic pathway. The in vitro spasmodic effect of the plant extract mediated through a similar mechanism with species and tissue-selectivity, provides a rationale for the medicinal use of the seeds of Lepidium sativum in indigestion and constipation, and suggests studying the plant extracts on more than one species to get the wider picture

Species Differences in the Antidiarrheal and Antispasmodic Activities of Lepidium sativum and Insight into Underlying Mechanisms

The aim of this study was to see if the crude extract of Lepidium sativum (Ls.Cr) exhibits species specificity in its antidiarrheal and antispasmodic activities along with insight into the underlying mechanisms using the in-vivo and in-vitro experiments. Ls.Cr inhibited castor oil-induced diarrhea in mice at doses (300 and 1000 mg/kg) three times higher dose than for rats. In isolated rat ileum and jejunum, Ls.Cr completely inhibited carbachol (CCh), low K+ (25 mM) and high K+ (80 mM)-induced contractions, while in guinea-pig tissues, Ls.Cr caused complete inhibition of only CCh-induced contraction. In rabbit tissues, Ls.Cr completely inhibited CCh and low K+-induced contractions sensitive to K+ channel antagonists. Pretreatment of guinea-pig and rat tissues with Ls.Cr caused a rightward shift in CCh-induced contractions in a pattern similar to dicyclomine, while in rabbit and rat tissues, Ls.Cr shifted isoprenaline curves to the left similar to papaverine. These data indicate that the antidiarrheal and antispasmodic activities of L. sativum are species dependent, mediating its antispasmodic effect through combinations of multiple pathways including activation of K+ channels, and inhibition of muscarinic receptors, Ca++ channels and PDE enzyme. Rat tissues showed the highest potency. Based on the results, we recommend using multiple species to know the real pharmacological profile of medicinal product