Involvement of thromboxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 mM) was inhibited by PAF receptor blocker (WEB 2086, IC50 = 0.65 mM) and calcium channel blockers, diltiazem (IC50 = 13 mM) and verapamil (IC50 = 18 mM). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 10 mM), a cyclooxygenase inhibitor (indomethacin; IC50 = 0.2 mM) and inhibitor of TLCK, herbimycin A with IC50 value of 5 mM. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 mM. However, the inhibitors of MAP kinase, PD98059 and protein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of thromboxane and tyrosine kinase pathways

Patients' perception and actual practice of informed consent, privacy and confidentiality in general medical outpatient departments of two tertiary care hospitals of Lahore

<p>Abstract</p> <p>Background</p> <p>The principles of informed consent, confidentiality and privacy are often neglected during patient care in developing countries. We assessed the degree to which doctors in Lahore adhere to these principles during outpatient consultations.</p> <p>Material & Method</p> <p>The study was conducted at medical out-patient departments (OPDs) of two tertiary care hospitals (one public and one private hospital) of Lahore, selected using multi-stage sampling. 93 patients were selected from each hospital. Doctors' adherence to the principles of informed consent, privacy and confidentiality was observed through client flow analysis performed by trained personnel. Overall patient perception was also assessed regarding these practices and was compared with the assessment made by our data collectors.</p> <p>Results</p> <p>Some degree of informed consent was obtained from only 9.7% patients in the public hospital and 47.8% in the private hospital. 81.4% of patients in the public hospital and 88.4% in the private hospital were accorded at least some degree of privacy. Complete informational confidentiality was maintained only in 10.8% and 35.5% of cases in public & private hospitals respectively. Informed consent and confidentiality were better practiced in the private compared to the public hospital (two-sample t-test > 2, p value < 0.05). There was marked disparity between the patients' perspective of these ethical practices and the assessment of our trained data collectors.</p> <p>Conclusion</p> <p>Observance of medical ethics is inadequate in hospitals of Lahore. Doctors should be imparted formal training in medical ethics and national legislation on medical ethics is needed. Patients should be made aware of their rights to medical ethics.</p

Functional Role of MicroRNAs in Embryogenesis

This book chapter will provide an overview of the functional role of microRNAs (miRNAs) in embryogenesis. A brief introduction to embryogenesis and emphasis on the importance of miRNAs in gene regulation will be provided. The biogenesis and mechanism of action of miRNAs will be discussed in detail with a focus on the importance of miRNA-mRNA interaction in gene regulation. The chapter will then delve into the role of miRNAs in early embryonic development, including their importance in the establishment of the three germ layers, cell proliferation, differentiation, and apoptosis during embryogenesis. The role of miRNAs in organogenesis and tissue differentiation, specifically the formation of specific organs such as the heart, lung, liver, and brain, will also be discussed. The chapter will conclude by examining the dysregulation of miRNAs in embryonic development and disease, including teratogenicity, developmental disorders, and developmental cancer. The chapter will summarize the functional roles of miRNAs in embryogenesis and will offer future perspectives and potential therapeutic applications of miRNAs in embryonic development and disease

Correlation of Immunoglobulin G With Severity Of Psoriasis

Objectives:  To find the correlation of immunoglobulin G with severity of psoriasis. Methodology: This cross-sectional descriptive study was conducted at Sir Ganga Ram Hospital Lahore/Niazi Teaching Hospital Sargodha. Study duration was six months from January 2020 to June 2020. One hundred patients of psoriasis (confirmed by Dermatologist) were included in the study. Questionnaire based on age, gender, duration of illness, type and severity of problem etc and biochemical test including immunoglobulin G were filled by consented patients. The study comprised into patients and controls groups. Fifty age matched Subjects with no history of skin disease were taken as controls. For immunological assessment, IgG was measured by the technique of ELISA. Results: Mean age of developing of disease was in the range of 36 to 43 years. A few patients have family history with a problem of asthma. High severity of index (59 to 61) in both genders with duration of disease was 4 to 6 years. A direct correlation between level of IgG and disease severity was observed. Conclusion: Increased level of immunoglobulin G and its direct correlation with severity of psoriasis may suggest an activation of 2nd immune defense that try to reduce the severity of disease

Do Anti-Epilepsy Drugs Increase Suicide Ideation Risk In Epilepsy Patients?

Objective: To determine the frequency of suicide risk within first six months after starting anti-epilepsy treatment. Methodology: This Descriptive cross-sectional study conducted at department of Medicine, Jinnah Hospital Allama Iqbal Medical College Lahore Pakistan from January 2019 to January 2020.The Scale of Suicidal Ideation (SCI)consists of 19 items which were used to evaluate patients’ suicidal intentions and to monitor patients’ response tointerventions over time. Patients with diagnosed psychiatric illness such as depression and schizophrenia, past historyof suicidal attempts and patients with poor drug compliance were excluded. After informed consent, 140 epilepticpatients, who had been recently started on anti-epilepsy medicines, aged 20 to 55 years of both gender were enrolled using non-probability consecutive sampling technique. Demographic information and detailed medical history were noted and patients were assessed for suicide risk using the Scale of Suicidal Ideation (SCI). All data was recorded and analyzed using SPSS version 23.0. Results: Mean age was 28.9±6.3 years with 104 (74.3%) males and 36 (25.7%) females. Sixty-eight (48.6%) patients belonged to low socio-economic status whereas 29 (20.7%) and 43 (30.7%) patients were from middle and high Socio-economic Status respectively. Sixty-eight (48.6%) patients were illiterate while 42 (30.0%) and 30 (21.4%) patients had educational status of up to matriculation and graduate or above respectively. In the present study, 46 (32.8%) patients had suicidal ideation with low socio-economic status  (p-value 0.013)  and illiterate educational status (p-value 0.002) having statistically significant association with suicidal ideation. Conclusion: Suicidal ideation was seen in almost one-third epilepsy patients on anti-epileptic drugs with low socioeconomic status and illiterate educational status being significant risk factor

A Shift From Logistic Software to Service Model: A Case Study of New Service-Driven-Software for Management of Emergency Supplies During Disasters and Emergency Conditions by WHO

World Health Organization (WHO) states access to medicine as a priority area for universal health coverage, wherein a well-functioning medicine supply chain is indispensable. Optimization of supply chains to cut losses related to overstocking, expiration, and inefficiencies protect the investments and strengthen health systems to better deliver the health services. This article shares the experience of developing a service-driven-software for pharmaceutical supplies during emergency conditions and disasters, and the advantages gained. In 2005, Logistic Support System (LSS), the updated version of SUMA (Supply Management), was introduced by WHO during the earthquake in Pakistan which had offered valuable but limited services to many countries. Moving from ad hoc to a more organized approach, the medical donations and stockpiles of essential medicinal supplies were inventoried on LSS database for managing the dispatch of medical supplies to the disaster-hit area in a shortest possible time. Post disaster rescue and rehabilitation work further instigated the need for development of a new software, Pharmaceutical Information Management System (PIMS), that was effective in the emergency as well as routine inventory operations. It was used for efficient and improved access of medicines and faster decision making. The new systems proved vital to anticipate over/under stocking through proactive alerts and prompting. The updated information on epidemiological and drug utilization needs were crucial for the effective quantification and ordering throughout the supply chain. Implementation of PIMS demanded appreciable customization including conversion of system from stand-alone to online system with consolidation of information on stocks from all locations. Provision of multi-user option allowed facilitation according to the user authorization, and was equipped with improved-speed, efficiency, and security. PIMS was successfully replicated by the pioneer team of pharmacist from Pakistan in other countries

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research