Studies on goitrogenic agents in food III. Goitrogenic action of some glycosides isolated from edible nuts

The inclusion of arachidoside and anacardioside, the pigments isolated from the outer skin-covering of groundnuts and cashewnuts respectively, in the diet of rats, at a level of 20 mg per rat per day for 7 weeks results in goitre. Incorporation of potassium iodide in the diet counteracts partially the goitrogenic action of the anthocyanins. Results of studies on the distribution of radioactive iodine in the thyroid glands of the rats suggest that the pigments inhibit the organic binding of radioactive iodine. An anthocyanin pigment and a catechin have been isolated from almonds and areca nuts respectively. In vitro experiments employing the tissue slice as well as homogenate technique reveal that all of the above 4 test compounds interfere with the organic binding of radioactive iodine. The test compounds form stable iododerivatives which, however, do not possess any significant inhibitory effect on the organic binding of radioactive iodine. The implications of the results are discussed

The cohesive element approach to dynamic fragmentation: The question of energy convergence

The cohesive element approach is getting increasingly popular for simulations in which a large amount of cracking occurs. Naturally, a robust representation of fragmentation mechanics is contingent to an accurate description of dissipative mechanisms in form of cracking and branching. A number of cohesive law models have been proposed over the years and these can be divided into two categories: cohesive laws that are initially rigid and cohesive laws that have an initial elastic slope. This paper focuses on the initially rigid cohesive law, which is shown to successfully capture crack branching mechanisms in simulations. The paper addresses the issue of energy convergence of the finite-element solution for high-loading rate fragmentation problems, within the context of small strain linear elasticity. These results are obtained in an idealized one-dimensional setting, and they provide new insight for determining proper cohesive zone spacing as function of loading rate. The findings provide a useful roadmap for choosing mesh sizes and mesh size distributions in two and three-dimensional fragmentation problems. Remarkably, introducing a slight degree of mesh randomness is shown to improve by up to two orders of magnitude the convergence of the fragmentation problem

Development and validation of a clinical and computerised Decision Support System for Management of Hypertension (DSS-HTN) at a Primary Health Care (PHC) setting

Background: Hypertension remains the top global cause of disease burden. Decision support systems (DSS) could provide an adequate and cost-effective m

C24 Sphingolipids Govern the Transbilayer Asymmetry of Cholesterol and Lateral Organization of Model and Live-Cell Plasma Membranes

Mammalian sphingolipids, primarily with C24 or C16 acyl chains, reside in the outer leaflet of the plasma membrane. Curiously, little is known how C24 sphingolipids impact cholesterol and membrane microdomains. Here, we present evidence that C24 sphingomyelin, when placed in the outer leaflet, suppresses microdomains in giant unilamellar vesicles and also suppresses submicron domains in the plasma membrane of HeLa cells. Free energy calculations suggested that cholesterol has a preference for the inner leaflet if C24 sphingomyelin is in the outer leaflet. We indeed observe that cholesterol enriches in the inner leaflet (80%) if C24 sphingomyelin is in the outer leaflet. Similarly, cholesterol primarily resides in the cytoplasmic leaflet (80%) in the plasma membrane of human erythrocytes where C24 sphingolipids are naturally abundant in the outer leaflet. We conclude that C24 sphingomyelin uniquely interacts with cholesterol and regulates the lateral organization in asymmetric membranes, potentially by generating cholesterol asymmetry

The timing of death in patients with tuberculosis who die during anti-tuberculosis treatment in Andhra Pradesh, South India

Background: India has 2.0 million estimated tuberculosis (TB) cases per annum with an estimated 280,000 TBrelated deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i) treatment outcomes including the number who died while on treatment, ii) the month of death and iii) characteristics associated with “early” death, occurring in the initial 8 weeks of treatment. Methods: This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs) in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children) registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results: There were 8,240 TB patients (5183 males) of whom 492 (6%) were known to have died during treatment. Case-fatality was higher in those previously treated (12%) and lower in those with extra-pulmonary TB (2%). There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with “early death”. Conclusion: In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i) the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii) co-morbidities, such as HIV/ AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed

Does 3-Day Course of Oral Amoxycillin Benefit Children of Non-Severe Pneumonia with Wheeze: A Multicentric Randomised Controlled Trial

WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2-59 months of age, who received either oral amoxycillin (31-54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.ClinicalTrials.gov NCT00407394

HIV-1 Inhibits Phagocytosis and Inflammatory Cytokine Responses of Human Monocyte-Derived Macrophages to P. falciparum Infected Erythrocytes

HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1Ba-L infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0–28) versus (34 (27–108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352–3,387) versus 1,552 (889–6,331); pg/mL; p = 0.0078) and IL-1β (16 (7–21) versus 33 (27–65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals

Impaired immune function in Gulf War Illness

<p>Abstract</p> <p>Background</p> <p>Gulf War Illness (GWI) remains a serious health consequence for at least 11,000 veterans of the first Gulf War in the early 1990s. Our understanding of the health consequences that resulted remains inadequate, and this is of great concern with another deployment to the same theater of operations occurring now. Chronic immune cell dysfunction and activation have been demonstrated in patients with GWI, although the literature is not uniform. We exposed GWI patients and matched controls to an exercise challenge to explore differences in immune cell function measured by classic immune assays and gene expression profiling.</p> <p>Methods</p> <p>This pilot study enrolled 9 GWI cases identified from the Department of Veterans Affairs GWI registry, and 11 sedentary control veterans who had not been deployed to the Persian Gulf and were matched to cases by sex, body mass index (BMI) and age. We measured peripheral blood cell numbers, NK cytotoxicity, cytokines and expression levels of 20,000 genes immediately before, immediately after and 4 hours following a standard bicycle ergometer exercise challenge.</p> <p>Results</p> <p>A repeated-measures analysis of variance revealed statistically significant differences for three NK cell subsets and NK cytotoxicity between cases and controls (p < 0.05). Linear regression analysis correlating NK cell numbers to the gene expression profiles showed high correlation of genes associated with NK cell function, serving as a biologic validation of both the <it>in vitro </it>assays and the microarray platform. Intracellular perforin levels in NK and CD8 T-cells trended lower and showed a flatter profile in GWI cases than controls, as did the expression levels of the perforin gene PRF1. Genes distinguishing cases from controls were associated with the glucocorticoid signaling pathway.</p> <p>Conclusion</p> <p>GWI patients demonstrated impaired immune function as demonstrated by decreased NK cytotoxicity and altered gene expression associated with NK cell function. Pro-inflammatory cytokines, T-cell ratios, and dysregulated mediators of the stress response (including salivary cortisol) were also altered in GWI cases compared to control subjects. An interesting and potentially important observation was that the exercise challenge augments these differences, with the most significant effects observed immediately after the stressor, possibly implicating some block in the NK and CD8 T-cells ability to respond to "stress-mediated activation". This has positive implications for the development of laboratory diagnostic tests for this syndrome and provides a paradigm for exploration of the immuno-physiological mechanisms that are operating in GWI, and similar complex syndromes. Our results do not necessarily elucidate the cause of GWI, but they do reveal a role for immune cell dysfunction in sustaining illness.</p