Tuberculosis, Anaemia and Erythropoietin: a study evaluating the role of erythropoietin in the pathophysiology of the anaemia of tuberculosis

Although it is more than 100 years since Robert Koch discovered the tubercle bacillus, and more than 40 years since effective chemotherapy became available, tuberculosis remains a major cause of morbidity and mortality in the world to-day. A major contributor to the morbidity is anaemia. This anaemia falls under the classification of anaemia of chronic disorders, the pathogenesis of which has not been fully elucidated. With the advent of recombinant human erythropoietin (Epo ), it has become evident that a blunted Epo response to the anaemia plays a major role. The mechanism (s) involved still have to be elucidated. The aims of, this study were to evaluate serum Epo levels and iron parameters in anaemic patients with active pulmonary tuberculosis (PTB) and investigate the effect of tumour necrosis factor alpha (TNFa) produced by activated macrophages in PTB patients on Epo production in vitro. Furthermore, the mechanism involved in Epo gene expression was investigated. Haematological and biochemical parameters (including serum iron and Epo) were I studied prospectively in four groups each of 1 O subjects. Group I comprised newly diagnosed non-pregnant individuals with pulmonary tuberculosis (PTB), haemoglobin below 110 g/L, and having no apparent dissemination or other I associated systemic illnesses. Group II were age and sex matched PTB patients with haemoglobin levels greater than 130 g/L. Group III ·consisted of otherwise healthy ' people with demonstrated absolute iron deficiency anaemia with haemoglobin corresponding to those in Group I. Group IV consisted of 10 healthy non-anaemic volunteers. For matching degrees of anaemia, the serum Epo was significantly lower in Group I than in Group III patients. In PTB, therefore, the Epo response to anaemia is attenuated. With anti-tuberculous therapy there was a significant increase in the Hb and serum iron levels in the Group I patients which correlated with a fall in the levels of the inflammatory marker C-reactive protein (CRP). This argues for the degree of inflammation being casually related to the anaemia. To further investigate the effect of inflammation on Epo production, blood samples were collected. from individuals in Groups I, II and III and the peripheral blood mononuclear cells (I>BMC) were assayed for the cytokine TNFa. The incubation of supernatant fractions (SNF) of the anaemic PTB group with HepG2 cells resulted in a marked inhibition of Epo production by these cells. Dose response studies showed that increasing concentration of SNF resulted in a progressive reduction in Epo production, which could be reversed by the presence of anti-TNFa antibodies in the: medium. Thus TNFa is capable of inhibiting Epo production and may play a role in the blunted Epo response to anaemia seen in patients with PTB. In order to characterize the mechanisms involved in oxygen sensing, the murine Epo gene was studied to define the sequences within the enhancer involved in oxygen sensing and Epo gene expression. To this end, transfection experiments of deleted, mutated and re-iterated enhancer sequences located 3' to the poly (A) signal sequence were carried out in HepG2 cells and in the non-Epo producing lung fibroblastoid cell line a23. Transcription factor binding to the enhancer was investigated by DNA I footprint analysis and revealed that at least three sites within a 96 nucleotide sequence 0f the Epo enhancer were critical. Oxygen regulated operation was dependent on sites ' ' within the first 25 nucleotides. In both HepG2 and a23 cell lines the same two critical sites in the 5' region of the enhancer were necessary for function. Sequences located 3' to this region modulated enhancer function but did not themselves convey oxygen regulated operation. This study has contributed to the understanding of the pathophysiology of the I anaemia of tuberculosis in that in this disease, TNFa released from activated macrophages was capable of inhibiting Epo production in vitro. This may explain the attenuated Epo response to anaemia in PTB patients. Furthermore, three critical sites on the Epo enhancer were shown to be essential for oxygen sensing and Epo gene expression. It can be postulated, therefore, that TNFa may disrupt the interaction of transcription factors with critical sites of oxygen sensing on the enhancer and prevent the increased production of Epo. Further work is required to clarify this postulate

Carbamazepine and its metabolites in epileptic patients

Carbamazepine is a drug which is now widely used for the treatment of both generalised epilepsy (tonic-clonic seizures) and partial epilepsy (with simple or complex symptomatology). This study was undertaken in an attempt to assess the role of the metabolites of carbamazepine, viz. 10, 11-epoxy-carbamazepine and 10, 11-dihydro-10,11-dihydroxy-carbamazepine, with regard to their therapeutic efficacy and the occurrence of side effects of the parent drug. It was also designed to seek a possible explanation as to why certain patients with optimal levels of carbamazepine in plasma fail to respond to therapy. A total of 23 epileptic patients (11 females and 12 males) suffering from either generalised (tonic-clonic) seizures or partial complex seizures took part in the study. The patients were divided into two groups according to their seizure frequency: Responders - those patients who had no seizures in the month prior to entry into the study (12 patients). Non-Responders - those patients who had a minimum of one seizure a week in the month prior to entry into the study (11 patients). Carbamazepine and its metabolites were monitored between 8 a.m. and 6 p.m. by taking blood samples at two hourly intervals. Cerebrospinal fluid (CSF) was also obtained from seven patients in the non-responder group. The drug and its metabolites were assayed simultaneously by the thin-layer chromatographic (TLC) method of Hundt and Clark (1975). Six of the 23 epileptic patients complained of side effects: nausea and headaches were the most frequently mentioned complaint. Statistical analysis showed, however, that there was no significant difference in the peak levels of carbamazepine and metabolites in patients both with or without side effects. Therefore, it was not possible to define a threshold level of the drug above which side effects were likely to occur. Also, no definite conclusion could be reached as to whether the metabolites play a role in the manifestation of side effects. The area under the curve (AUC) is a measure of the overall plasma concentration of carbamazepine and metabolites (present between 8 a.m. and 6 p.m.) in the individual patients of the two groups. There was no significant difference in the AUC of carbamazepine between responders and non-responders. However, the AUC of the dihydroxy and epoxy metabolites was significantly higher in the non-responders (P<-0.002 and P < 0.02 respectively). Moreover, in the CSF samples of the non-responders, the mean (±SD) ratio of the dihydroxy metabolite to the parent drug was as high as 1.17 (±0,36). The results show a clear association between high levels of metabolites and poor response to carbamazepine therapy. Furthermore, it would seem that either both metabolites are inactive or that if the epoxy metabolite is active as in the rat (Frigerio and Morselli 1975), any likely therapeutic effect is counter-acted by the relatively large concentration of inactive dihydroxy metabolite (Schmutz et al 1979). Moreover, it may follow that non-response to carbamazepine - despite optimal levels of the drug in plasma - may be due to competition by inactive dihydroxy metabolite for the site (s) of action of the parent drug in the brain. Research strategies which might be used to test this hypothesis have been proposed

Cost-effectiveness of ceftriaxone in the treatment of community-acquired pneumonia in adult hospital patients

Objectives. A retrospective analysis was conducted to assess the cost-effectiveness of four intravenous antibiotic treatment regimens in the treatment of severe community-acquired pneumonia (CAP) in adults in a private hospital setting. The study compared some third-generation cephalosporin regimens with a second-generation cephalosporin and an amoxicillin/clavulanic acid (co-amoxiclav) regimen to investigate published South African treatment guidelines from a pharmacoeconomic point of view.Method. A phanmaco-economic model of local costs, from a payer perspective, was based on the results of a meta-analysis of clinical papers from peer-reviewed journals. The study compared intravenous (IV) ceftriaxone (2 g once daily), cefotaxime (IV 2 g 3 times a day), cefuroxime (IV 750 mg 3 times a day, followed by 500 mg orally 3 times a day) and amoxicillin/clavulanic acid (IV 750 mg 3 times a day, followed by 625 mg orally 3 times a day).Results. An analysis of the odds ratios (ORs) of all two-way comparisons indicated that ceftriaxone ensured significantly higher probabilities of successful outcomes than the other antibiotic treatment regimens (ORs in the order of two were indicated). The phanmaco-economic results suggested that the ceftriaxone treatment regimen was the most cost-effective in the hospital treatment of CAP in adult patients. These results proved to be robust across sensitivity analyses for success rates and treatment days. A sensitivity analysis testing the assumption that patients could be discharged once the oral treatment was initiated indicated that the amoxicillin/clavulanic acid and cefuroxime treatment arms were more cost-effective. The clinical validity of such an assumption is questionable.Conclusion. Despite the conservative approach followed in terms of ceftriaxone data, both the clinical results and cost-effectiveness supported the use of ceftriaxone in the treatment of CAP in adults in the hospital setting

DETECTION OF CHRONIC TYPHOID CARRIERS AMONG FOOD HANDLERS IN WAD MEDANI , GEZIRA STATE , SUDAN

Typhoid fever remains a disease of major public health importance in the tropics. This cross sectional prospective descriptive study was carried out between July 2005 to July 2008 in Wad Medani Town. The objective of the study was to identify chronic typhoid carriers among food handlers in Wad Medani. To achieve this objective, Vi agglutination test was used to determine suggested typhoid carriers among food handlers then stool culture was performed on those with a positive Vi agglutination test. A questionnaire was designed to collect data from suggested typhoid carriers about hygienic practices during food handling and processing .&nbsp; The collected data were reviewed and coded. Data were analyzed using SPSS versions 10.0 software for tabulation and statistical analysis. The results showed that, ten percent of the examined food handlers were found positive typhoid carriers by Vi agglutination test, 48.5% of the suspected of typhoid carriers were found positive by stool culture, street vendors were more common among suspected typhoid carriers, all of whom had not received any health education about typhoid disease. The study suggested the following recommendations: Regular health authority inspection visitor food handling personnel specially street vendors to exclude typhoid carriers among them, education and training course in good hygienic practices should be provided to all food handlers specially typhoid carriers by Food Control Department, Ministry of Health, Gezira State

Effect of dryer & drying methods and production time on the quality and safety of dried yoghurt during storage

The main objective of this research is to study the effect of drying, drying methods and production time on the quality &amp; safety of dried yoghurt and effect of storage on it.&nbsp; 4 kg of natural yoghurt freshly produced during the first day of shelf life, and 4 kg after expiration date (day 11), the samples were dried using two method, spray drying process and the traditional method, dried yoghurt samples were stored at room temperature after being packed in an unsealed plastic container for 3 months.&nbsp; The experiment was conducted in Samsung /turkey, in Ondokuz Mayis university, Department of food Engineering labs. Chemical, physical, microbiological and sensory analysis of raw and dried yoghurt &nbsp; samples were performed before and during storage. The results of the study showed that drying significantly affects all properties of yoghurt. The moisture content (1%) was affected by drying as moisture decreased by great rate of more than (70%) (P ≤ 0.05), moisture was also affected by small amount by the storage; Protein content % was significantly increased by drying from (4.020%) in the raw yoghurt produced during production shelf life, and (3.217%) in the yoghurt produced after expiration date to (7.177%) in average, the protein content values were not affected by the storage in the dried samples by the spray drying method. Drying significantly (P ≤ 0.05) affect the values of fat content where the values increased after expiration date to (13%) in average, and the value were not affected by the storage. The non-fatty solids content significantly (P ≤ 0.05) increased by drying, has become an average of (77.00%) after drying. Acidity value ratio increased by drying and storage by meager percentage, the pH value significantly decreased (P ≤ 0.05) by drying and storage at a significantly rate. Total Solids % was significantly affected (P≤0.05) by drying and storage as it increased from (16.42%) in the raw yoghurt (during production shelf life) and (14.69%) in the raw yoghurt (after expiration date) to become more than (90%) by drying. As for the microbial content; the total bacteria value decreased by drying, but were not affected by storage, also lactic acid bacteria values reduced significantly (P ≤ 0.05) by drying, but remained the same during storage. However, the total count of yeast, molds, E-coli bacteria was not found in the raw yoghurt and has not grown during storage. In the sensory evaluation, the panelists preferred a raw yoghurt and dried yoghurt in the first month, and then the rate and values of the sensory evaluation decreased significantly (P ≤ 0.05) during storage. The study concluded that, the validity of yoghurt can be extended by drying, and taking advantages of yoghurt in the last day by drying and storing it

Cohort profile: the Right to Care Clinical HIV Cohort, South Africa

PURPOSE: The research objectives of the Right to Care Clinical HIV Cohort analyses are to: (1) monitor treatment outcomes (including death, loss to follow-up, viral suppression and CD4 count gain among others) for patients on antiretroviral therapy (ART); (2) evaluate the impact of changes in the national treatment guidelines around when to initiate ART on HIV treatment outcomes; (3) evaluate the impact of changes in the national treatment guidelines around what ART regimens to initiate on drug switches; (4) evaluate the cost and cost-effectiveness of HIV treatment delivery models; (5) evaluate the need for and outcomes on second-line and third-line ART; (6) evaluate the impact of comorbidity with non-communicable diseases on HIV treatment outcomes and (7) evaluate the impact of the switch to initiating all patients onto ART regardless of CD4 count. PARTICIPANTS: The Right to Care Clinical HIV Cohort is an open cohort of data from 10 clinics in two provinces within South Africa. All clinics include data from 2004 onwards. The cohort currently has data on over 115 000 patients initiated on HIV treatment and patients are followed up every 3–6 months for clinical and laboratory monitoring. FINDINGS TO DATE: Cohort data includes information on demographics, clinical visit, laboratory data, medication history and clinical diagnoses. The data have been used to identify rates and predictors of first-line failure, to identify predictors of mortality for patients on second-line (eg, low CD4 counts) and to show that adolescents and young adults are at increased risk of unsuppressed viral loads compared with adults. FUTURE PLANS: Future analyses will inform national models of HIV care and treatment to improve HIV care policy in South Africa

Performance Improvement of Microbial and Rheological Characteristics of Dehydrated Cow-goat Yogurt Powder Based on Their Combination and Drying Methods

Yogurt powder is dehydrated products producing by one of drying methods based on removal moisture or reduces water activity of finally product, which increase the shelf life of food. Rehydration is an importance part in viability of bacteria cells (lactic acid bacteria) in the product of powder fermented. This study is aimed to treatment cow and goat yogurt powder with rehydrate processing to provide suitable rehydration method. Methods of Ibrahim and Pestana were employed to make yogurt and drying by freeze-dryer and spry-dryer, whilst Indonesia National Standards (SNI) with Association of Official Analytical Chemistry International (A O A C), used to analysed the parameters of rehydrated yogurt. T-test were performed to evaluate the difference between data by Microsoft Excel Version 13, and separate between means used Multiple Duncan Test. The rehydration conditions consider was; powder to water ratio (1:3, 1:4, and 1:5), respectively. These results shown there was significant different between rehydrated freeze-dried and spray-dried yogurt on viscosity, pH, titratable acidity and survival bacteria cells, whilst the water to powder ratio had significant effect on features properties of rehydrated yogurt. The study results established that the rehydration water ratio 1:3 by freeze-dryer gave generally better quality compared to fresh yogurt.&nbsp

Economic Growth and Internet Usage Impact on Publication Productivity among ASEAN’s and World’s Best Universities

Measuring the number of papers which are published each year, publication productivity is the factor which shows the reputation of universities and countries. However, the effect of growing economy and using internet on the publication productivity in Asian countries has not been discovered yet. The present research is going to figure out the publication productivity among the elite universities in Asian countries and also ten top universities around the world in the last twenty years (from 1993 to 2012). Furthermore, the current research is aimed to study the relationship among publication, gross domestic product (GDP) and internet usage. It is worth to mention that the publication of the top Ten Malaysian Universities was regarded for the similar period of time. To get the exact numbers of documents like papers, conference articles, review papers and letters which are published by the universities in the last twenty years, the writer of the same paper used the Science Direct database. Moreover, the data for GDP and the number of internet usage was collected through the World Bank database (World Data Bank).To compare all kinds of publications,one-way ANOVA was used and to investigate the impact of economic growth and internet usage on publication productivity, multiple regression analysis was applied.The results showed that the rate of publication growth was 1.9, 20.9, and 65.5 in top universities in the world, ASEAN countries and Malaysia, respectively.The results also showed that there was a positive and significant correlation between GDP and the number of internet users with the number of publications in ASEAN and Malaysian universities. Internet usage had much more influence in comparison with the GDP in predicting the number of publications among these groups except for top ten Malaysian universities from 2003 to 2012. In summary, publication trends in top ten Malaysian and ASEAN universities are promising. However, policy makers and science managers should spend much more percentage of their GDP on Internet facilities and research studies that their outputs lead to more rapid economic growth and internet usage