Lipoprotein(a) as an independent risk factor for coronary artery disease in patients below 40 years of age

Coronary artery disease has assumed alarming proportions in Indians and often affects people at younger age. Traditional risk factors fail to explain the high incidence of disease. Although lipoprotein(a) has been shown to be a powerful risk factor for atherosclerosis, there is very limited data with regard to its significance in premature coronary artery disease. The present study was therefore undertaken to assess lipoprotein(a) levels and its role as a marker of coronary artery disease in patients below the age of 40 years. Lipid profile and lipoprotein(a) levels were estimated in 50 patients of angiographically proven coronary artery disease and an equal number of age-matched healthy controls. There was no significant difference in the family history of coronary artery disease, body mass index and waist-hip ratio between the two groups. Total plasma cholesterol, triglyceride and LDL-cholesterol levels were significantly higher and HDL-cholesterol significantly lower in patients as compared to controls. In patients of coronary artery disease, mean lipoprotein(a) levels, measured by ELISA method, were 35.0 +/- 32.4 mg/dL and the median was 26.7 mg/dL. These values were significantly higher than the mean of 20.3 +/- 17.0 mg/dL (p < 0.002) and the median of 13.8 mg/dL (p < 0.015) in controls. Multiple regression analysis, to assess the influence of various risk factors, showed that low HDL-cholesterol (odds ratio 4.62, 95% CI 1.84-11.60; p < 0.015) and elevated lipoprotein(a) levels (odds ratio 3.06, 95% CI 1.24-7.55; p < 0.001) were independent risk factors, whereas high total cholesterol and triglyceride levels did not have any independent influence on premature coronary artery disease. Our data thus suggest that lipoprotein (a) levels are elevated and constitute an independent risk factor in patients with premature coronary artery disease below 40 years of age.     

Epidemiological profile,management and outcomes of patients with acute coronary syndrome: Single centre experience from a tertiary care hospital in North India

BackgroundCardiovascular disease is the leading cause of death in India. Our aim is to study the clinical, epidemiological profile and in-hospital outcomes of patients presenting with acute coronary syndrome.MethodsWe did a prospective single center observational study of the 1203 patients presenting with ACS to a tertiary referral center in North India over a period of one year (July 2018–June 2019).ResultsThe mean age of study population was 58.4 ± 12.5 years. STEMI and NSTE-ACS accounted for 69.9% and 31.1% respectively. 62.1% of our patients were from rural background. The median time to hospital admission was 600 min for STEMI patients, thrombolysis was performed in 52% of cases. Cardiogenic shock at presentation was noted in 18%. Coronary angiography and percutaneous coronary intervention were done in 1062 (88.3%) and 733 (60.9%) patients respectively. The overall in-hospital mortality was 7.6%. STEMI patients had higher mortality than NSTE-ACS (8.9% vs 4.5% p < 0.001). Female gender (OR?3.306 C.I. 1.87–5.845), severe MR (OR?4.65, C.I.?1.187–18.18), acute kidney injury (AKI) at admission (OR-5.15, C.I.?2.5–10.63), higher Killip class (class III/IV) (OR?3.378,C.I.?1.292–8.849), AF (OR?3.25, C.I.?1,18–8.92), complete heart block (CHB) (OR?4.44,C.I.?2.09–9.43) and right bundle branch block (RBBB) (OR?2.86, C.I.?1.2–6.8) were significant predictors of in hospital mortality.ConclusionsOur study represents the predominance of STEMI as the initial ACS presentation with a considerable delay in first medical contact and higher prevalence of cardiogenic shock (CS). STEMI patients had higher mortality. Female sex, severe MR, AKI, higher Killips class, AF, CHB, RBBB being predictors of high in-hospital mortality in ACS patients.     

Treatment strategies for central nervous system infections: an update

Introduction: Central nervous system infection continues to be an important cause of mortality and morbidity worldwide. Our incomplete knowledge on the pathogenesis of how meningitis-causing pathogens cause CNS infection and emergence of antimicrobial resistance has contributed to the mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis, but early recognition of bacterial meningitis continues to be a challenge.

Areas covered: This review gives an overview on current therapeutic strategies for CNS infection with a focus on recent literature since 2010 on bacterial meningitis. Bacterial meningitis is a medical emergency, requiring early recognition and treatment. The selection of appropriate empiric antimicrobial regimen, after incorporating the epidemiology of bacterial meningitis, impact of vaccination, emergence of antimicrobial-resistant bacteria, role of adjunctive therapy and the current knowledge on the pathogenesis of meningitis and associated neuronal injury are covered.

Expert opinion: Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood–brain barrier, with efficacy in cerebrospinal fluid. Emergence of CNS-infecting pathogens with resistance to conventional antibiotics has been increasingly recognized, but development of new antibiotics has been limited. More complete understanding of the microbial and host factors that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.     

Facility-based active management of the third stage of labour: assessment of quality in six countries in sub-Saharan Africa

Objective

To assess the quality of facility-based active management of the third stage of labour in Ethiopia, Kenya, Madagascar, Mozambique, Rwanda and the United Republic of Tanzania.

Methods

Between 2009 and 2012, using a cross-sectional design, 2317 women in 390 health facilities were directly observed during the third stage of labour. Observers recorded the use of uterotonic medicines, controlled cord traction and uterine massage. Facility infrastructure and supplies needed for active management were audited and relevant guidelines reviewed.

Findings

Most (94%; 2173) of the women observed were given oxytocin (2043) or another uterotonic (130). The frequencies of controlled cord traction and uterine massage and the timing of uterotonic administration showed considerable between-country variation. Of the women given a uterotonic, 1640 (76%) received it within three minutes of the birth. Uterotonics and related supplies were generally available onsite. Although all of the study countries had national policies and/or guidelines that supported the active management of the third stage of labour, the presence of guidelines in facilities varied across countries and only 377 (36%) of 1037 investigated providers had received relevant training in the previous three years.

Conclusion

In the study countries, quality and coverage of the active management of the third stage of labour were high. However, to improve active management, there needs to be more research on optimizing the timing of uterotonic administration. Training on the use of new clinical guidelines and implementation research on the best methods to update such training are also needed.     

Immunolocalization of Musashi1 and Fibronectin Type III Domain Containing 3B in Water Buffalo Mammary Glands

Water buffaloes are the principle source of milk in south Asia and Africa. Mammary gland repeatedly undergoes the cycles of growth and regeneration during pregnancy, lactation and involution. It is assumed that buffalo mammary gland has mammary stem and progenitor cells that regulate gland growth and regeneration. In the present study the authors analyzed percentage of cellular composition, proliferation status and putative mammary stem/progenitor cell population. Identification of putative buffalo mammary stem/progenitor cells was attempted using immunohistochemical staining with Musashi1 (MSI1), an adult stem cell marker and fibronectin type III domain containing 3B (FNDC3B), a mammary stem and cancer cell marker. Immunolocalization of MSI1 and FNDC3B showed nuclear and cytoplasmic staining of alveolar and ductal mammary epithelial cells (MEC) and a few stromal cells. The percentage of MSI1-positive MEC in non-lactating (3.31 ± 1.11 %), lactating (2.73 ± 0.78 %) and mastitic glands (3.30 ± 0.97 %) were equivalent, indicating that the proportion of putative stem/progenitor cell population did not differ during various physiological stages. Likewise, the percentage of FNDC3B-positive MEC in non-lactating (12.40 ± 3.22 %) tended to be higher than lactating (8.19 ± 2.71 %) and mastitic glands (4.88 ± 2.37 %). In some cases, expression of MSI1 and FNDC3B was exceptionally high with high proliferative indices (37.6 ± 2.4 %)-an indication of tumor cells. This is the first report on expression of MSI1 and FNDC3B in buffalo mammary gland. Identification of buffalo mammary stem cells using MSI1 and FNDC3B requires further studies and functional validation.     

Novel immunosuppressive agent caerulomycin A exerts its effect by depleting cellular iron content

Background and Purpose

Recently, we have described the use of caerulomycin A (CaeA) as a potent novel immunosuppressive agent. Immunosuppressive drugs are crucial for long-term graft survival following organ transplantation and treatment of autoimmune diseases, inflammatory disorders, hypersensitivity to allergens, etc. The objective of this study was to identify cellular targets of CaeA and decipher its mechanism of action.

Experimental Approach

Jurkat cells were treated with CaeA and cellular iron content, iron uptake/release, DNA content and deoxyribonucleoside triphosphate pool determined. Activation of MAPKs; expression level of transferrin receptor 1, ferritin and cell cycle control molecules; reactive oxygen species (ROS) and cell viability were measured using Western blotting, qRT-PCR or flow cytometry.

Key Results

CaeA caused intracellular iron depletion by reducing its uptake and increasing its release by cells. CaeA caused cell cycle arrest by (i) inhibiting ribonucleotide reductase (RNR) enzyme, which catalyses the rate-limiting step in the synthesis of DNA; (ii) stimulating MAPKs signalling transduction pathways that play an important role in cell growth, proliferation and differentiation; and (iii) by targeting cell cycle control molecules such as cyclin D1, cyclin-dependent kinase 4 and p21^CIP1/WAF1. The effect of CaeA on cell proliferation was reversible.

Conclusions and Implications

CaeA exerts its immunosuppressive effect by targeting iron. The effect is reversible, which makes CaeA an attractive candidate for development as a potent immunosuppressive drug, but also indicates that iron chelation can be used as a rationale approach to selectively suppress the immune system, because compared with normal cells, rapidly proliferating cells require a higher utilization of iron.