Oxidation of low density lipoprotein by ferritin at lysosomal pH and its possible role in atherosclerosis

Atherosclerosis leading to coronary heart disease and thrombotic stroke is the leading cause of death worldwide. Oxidised low density protein is considered important by many in this disease. Our laboratory has shown that LDL can be oxidised by iron in the lysosomes of macrophages. Others have demonstrated the presence of oxidised products similar to those formed in vitro by catalytically active iron in advanced atherosclerotic lesions. Ferritin is the body’s main iron storing protein. The role of ferritin in lysosomal LDL oxidation and explored the possible consequences for atherosclerosis were investigated. Ferritin oxidised LDL effectively at lysosomal pH (pH 4.5), much faster than at pH 7.4, as shown by increased formation of oxidised lipids (HPLC and tri-iodide assay) and conjugated dienes (automated spectrophotometry). Ferritin spontaneously released iron at lysosomal pH and iron chelators supressed the oxidation of LDL by ferritin. The degradation of apolipoproteinB-100 and cholesteryl esters of LDL speeded up the oxidation of LDL by ferritin. The lysosomotropic antioxidant cysteamine was shown to be a more appropriate antioxidant to effectively inhibit LDL oxidation by ferritin compared to ascorbate, α-tocopherol and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) and N, N′- diphenyl 1,4-phenylenediamine (DPPD). The role of ferritin in lysosomal LDL oxidation within macrophages and macrophage function were accessed. Incubation with ferritin and LDL led to increased intracellular lipid, ceroid and lipid peroxidation in lysosomes. Ferritin and LDL treatment increased glycolysis and THP-1 macrophage-like cells became metabolically activated, as shown by a Seahorse analyser. Ferritin-oxidised LDL induced reactive oxygen species formation and apoptosis in macrophages, suggesting LDL oxidation by ferritin in lysosomes might be atherogenic

Pattern of respiratory diseases seen among adults in an emergency room in a resource-poor nation health facility

Background: There is a paucity of information on utilisation of emergency medical services in Nigeria. This study was conducted to determine the pattern of respiratory diseases seen among adults in an emergency room(ER) and their mortality within twenty- four hours in a health facility in Nigeria. Methods: We carried out a retrospective study on adult patients that presented with respiratory condition from November 2004 to December 2010 at the emergency room of Federal Medical Centre Ido-Ekiti, south western, Nigeria. Results: A total of 3671 cases were seen, 368 were respiratory cases accounting for 10.2 % of the total emergency room visitations. The male to female patients ratio was 1.2:1 and their mean was 49 9 ± 20.3 years. Pneumonia (34.5%) was the most common cases seen in the ER, followed PTB (29.4%), acute asthma (24.5%) , acute exacerbation of COPD (10.3%), upper airway tract obstruction and malignant pleural effusion were 0.5% respectively. Fourteen of the PTB cases (3.8%) were complicated by cor-pulmonale, 9(2.5%) by pleural effusion, 4(1.1%) by massive haemoptysis and 2(0.5%) by pneumothorax. Twenty-four hours mortality was 7.4% and 44.4% of the death was due to PTB, 37.0% was due to pneumonia and 14.8% due to acute asthma attack. The overall mortalities also had a bimodal age group distribution as the highest death was recorded in ages 30-39 and ≥70 years. Conclusion: Pneumonia and PTB were the leading respiratory diseases among adults causing of emergency room visit and early mortality in this health facility in Nigeria.Key words: Disease pattern, Respiratory Disease, Resource-poor country, Emergency Room, Nigeri

A community survey of the pattern and determinants of household sources of energy for cooking in rural and urban south western, Nigeria

Introduction:The use of solid fuels for cooking is associated with indoor pollution and lung diseases. The objective of the study was to determine the pattern and determinants of household sources of energy for cooking in rural and urban South Western, Nigeria. Methods: We conducted a cross sectional study of households in urban (Ado-Ekiti) and rural (Ido-Ekiti) local council areas from April to July 2010. Female respondents in the households were interviewed by trained interviewers using a semi-structured questionnaire. Results: A total of 670 households participated in the study. Majority of rural dwellers used single source of energy for cooking (55.6%) and urban dwellers used multiple source of energy (57.8%). Solid fuel use (SFU) was higher in rural (29.6%) than in urban areas (21.7%). Kerosene was the most common primary source of energy for cooking in both urban and rural areas (59.0% vs.66.6%) followed by gas (17.8%) and charcoal (6.6%) in the urban areas, and firewood (21.6%) and charcoal (7.1%) in the rural areas. The use of solid fuel was strongly associated with lack of ownership of dwellings and larger household size in urban areas, and lower level of education and lower level of wealth in the rural areas. Kerosene was associated with higher level of husband education and modern housing in urban areas and younger age and indoor cooking in rural areas. Gas was associated with high income and modern housing in the urban areas and high level of wealth in rural areas. Electricity was associated with high level of education, availability of electricity and old age in urban and rural areas respectively. Conclusion: The use of solid fuel is high in rural areas, there is a need to reduce poverty and improve the use of cleaner source of cooking energy particularly in rural areas and improve lung health. Pan African Medical Journal 2012; 12:

A comparative assessment of the awareness of danger signs and practice of birth preparedness and complication readiness among pregnant women attending rural and urban general hospitals in Lagos State

Background: Nigeria still experiences a high burden of unsafe motherhood. The knowledge of obstetric danger signs and the effective application of the principles of birth preparedness and complication readiness (BPACR) have the potential to significantly reduce the high maternal and perinatal morbidity and mortality rates. However, rural-urban differences may exist in the knowledge and practice of  BPACR among women, and these may limit its potential benefit. We set out to assess and compare the knowledge of obstetric danger signs and practice of BPACR among pregnant women attending Rural (Agbowa) and Urban (Gbagada) Hospitals in Lagos State. Materials and Methods: In this cross-sectional comparative study, pregnant women attending antenatal clinics in each health facility were recruited into the study using a systematic sampling method. A structured interviewer administered questionnaire adapted from the safe motherhood John Hopkins Program for International Education in Gynecology and Obstetrics prototype questionnaire was used for data collection. Data were analyzed using SPSS version 17.0. Results: Awareness of obstetric danger signs during pregnancy was good among rural and urban study participants accounting for 62.4% and 68.4%, respectively. The most commonly identified danger sign in pregnancy, labor, and after delivery was bleeding from the genital tract. The awareness of danger signs during labor and after delivery identified by the women was low in both settings, though relatively higher in the urban area. The level of BPACR was low in both groups of women but was higher among women attending the urban center (31.6%) compared with the rural center (13.2%) P-value < 0.001. Conclusion and Recommendations: Activities aimed at improving birth preparedness practices particularly among rural women should be considered

Magnitude of missed opportunities for prediabetes screening among non-diabetic adults attending the family practice clinic in Western Nigeria: Implication for diabetes prevention

Background: Prediabetes in primary care patients is often unrecognised, with a resultant loss of opportunity for diabetes prevention. A paucity of information about the magnitude of missed opportunities for prediabetes screening in Nigeria and other African countries exists.Methods: A cross-sectional study was conducted amongst 417 primary care participants aged ≥ 18 years. A questionnaire was administered and respondents were assessed for a missed opportunity for prediabetes screening using seven risk factors identified from guidelines. The fasting blood glucose (FBG) test was performed with capillary blood using a glucometer (Accucheck Advantage, Roche Diagnostics, Mannheim, Germany). Prediabetes was defined as an FBG of 5.6 mmol/L – 6.9 mmol/L according to the American Diabetes Association (ADA) guidelines.Results: The incidences of missed prediabetes and diabetes diagnoses were 8.8% and 1.0%, respectively. The proportion of respondents who had various risk factors that met screening guidelines but missed the opportunities for prediabetes screening was between 2.2% and 44.1%. Approximately 80% of the respondents had at least one of the seven guideline-recommended risk factors but were not screened by the clinic doctors. The higher the number of risk factors in the respondents, the higher the proportion of respondents with a missed prediabetes diagnosis.Conclusion: There were missed opportunities for prediabetes screening and consequent diabetes prevention identified in this study. The finding that high-risk patients with prediabetes in our setting often missed the opportunity to be detected through screening suggests that primary care physicians in our setting need to improve on the practice of prediabetes screening.Keywords: prediabetes; diabetes; missed opportunity; missed diagnosis; primary care; primary care physicians; family practice clinic

Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019

Background: Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings: In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation: Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Funding: Bill & Melinda Gates Foundation