Atopic Dermatitis

The aetiology of atopic dermatitis is multi-faceted and affects our first line host defence, the skin. Atopic dermatitis has a significant influence on a patient’s social and occupational functioning and can have long-lasting effects. The signs and symptoms of AD includes pruritus, erythema, fissuring, and lichenification – these are reduced by the use of moisturizing agents.  Guidelines on how to manage atopic dermatitis aims to improve symptoms and achieve long-term disease control. Patient education remains as important as other treatment strategies and the pharmacist plays an integral role in educating patients on the management of their condition and adherence to therapy.Keywords: Atopic dermatitis, pruritus, filaggrin, FLG gene, microbiome, Th2 cell

Effect of micronutrient fortified beverage on nutritional anaemia during pregnancy

(East African Medical Journal: 2002 79 (11): 598-603

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

EFFECT OF MICRONUTRIENT FORTIFIED BEVERAGE ON NUTRITIONAL ANAEMIA DURING PREGNANCY

Objective: To evaluate the efficacy of a multiple micronutrient fortified beveragecontaining eleven nutrients at physiological levels in prevention of anaemia andimproving iron and vitamin A status during pregnancy.Design: A randomised double blind placebo controlled study.Setting: Mpwapwa and Kongwa Districts in Dodoma Region of Tanzania.Subjects: Five hundred and seventy nine pregnant women were screened for entry intothe study and 439 women who met the study criteria were enrolled.Interventions: Study participants received either a fortified (F) or non-fortified (NF)orange flavoured drinks identical in appearance, provided in two self administeredservings per day for an eight week period.Main outcome measures: Comparison of haemoglobin (Hb), serum ferritin (SF) andserum retinol (SR) at baseline and follow up.Results: After eight weeks of supplementation, the F group (n=129) had a significantlyhigher Hb increase of 0.86g/dL compared to 0.45g/dL in the NF group (n=130) p<0.0001.Gestational age at entry into the study, moderated the effect on Hb of the fortifieddrink. Women at earlier gestational age upon entry, had a higher rise in Hb than womenof late gestational age (0.8g/dL versus 0.04 g/dL rise respectively, p=0.038, n=188). Therisk of being anaemic at the end of the study for those in the F group was reducedby 51% (RR=0.49, CI=0.28 to 0.85). Iron stores (by serum ferritin levels) increasedby 3µg/L in the F group (p=0.012) and a decrease of 2µg/L in the NF group (p=0.115).The follow up ferritin concentration depended on initial ferritin level. Regardless oftreatment group, serum retinol concentrations were significantly higher in mothers whohad delivered. Mothers who had adequate levels at entry benefited more from thesupplement than those with low levels (0.26 µmol/L versus no significant difference).Conclusions: The multiple micronutrient-fortified beverage given for eight weeks topregnant women improved their haemoglobin, serum ferritin and retinol status. Therisk for anaemia was also significantly reduced. The important predictors of Hb increaseat follow up were the fortified beverage, baseline Hb, serum retinol, baseline ferritinand gestational age at entry into study. Anthropological research showed that thebeverage was highly acceptable and well liked

Why do adult women in Vietnam take iron tablets?

BACKGROUND: Conducting iron supplementation programs has been a major strategy to reduce iron deficiency anemia in pregnancy. However, only a few countries have reported improvements in the anemia rate at a national level. The strategies used for control of nutrition problems need regular review to maintain and improve their effectiveness. The objective of this study was to analyze the factors in compliance with taking iron tablets, where daily doses of iron (60 mg) and folic acid (400 μg) were distributed in rural Vietnamese communes. METHODS: A cross sectional survey was conducted in Nghe An province, Vietnam in January, 2003. The study population was adult women aged less than 35 years who delivered babies between August 1(st )2001 and December 1(st )2002 (n = 205), of which 159 took part in the study. Data for the study were collected from a series of workshops with community leaders, focus group discussions with community members and a questionnaire survey. RESULTS: Improvements in the rate of anemia was not given a high priority as one of the commune's needs, but the participants still made efforts to continue taking iron tablets. Two major factors motivated the participants to continue taking iron tablets; their experience of fewer spells of dizziness (50%), and their concern for the health of their newborn baby (54%). When examining the reasons for taking iron tablets for at least 5–9 months, the most important factor was identified as 'a frequent supply of iron tablets' (OR = 11.93, 95% CI: 4.33–32.85). CONCLUSION: The study found that multiple poor environmental risk factors discouraged women from taking iron tablets continuously. The availability (frequent supply) of iron tablets was the most effective way to help adult women to continue taking iron tablets

Effect of universal testing and treatment on HIV incidence — HPTN 071 (PopART)

Background A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. Methods In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. Results The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P=0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P=0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. Conclusions A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.

Could a simple antenatal package combining micronutritional supplementation with presumptive treatment of infection prevent maternal deaths in sub-Saharan Africa?

BACKGROUND: Reducing maternal mortality is a key goal of international development. Our objective was to determine the potential impact on maternal mortality across sub-Saharan Africa of a combination of dietary supplementation and presumptive treatment of infection during pregnancy. Our aim was to demonstrate the importance of antenatal interventions in the fight against maternal mortality, and to stimulate debate about the design of an effective antenatal care package which could be delivered at the lowest level of the antenatal health system or at community level. METHODS: We collated evidence for the effectiveness of antenatal interventions from systematic reviews and controlled trials, and we selected interventions which have demonstrated potential to prevent maternal deaths. We used a model-based analysis to estimate the total reduction in maternal mortality in sub-Saharan Africa which could be achieved by combining these interventions into a single package, based on a WHO systematic review of causes of maternal deaths. RESULTS: Severe hypertensive disorders, puerperal sepsis and anemia are causes of maternal deaths which could be prevented to some extent by prophylactic measures during pregnancy. A package of pills comprising calcium and iron supplements and appropriate anti-microbial and anti-malarial drugs could reduce maternal mortality in sub-Saharan Africa by 8% (range <1% to 20%). This estimate is based on Cochrane Review estimates for the effectiveness of daily calcium supplements in reducing the risk of death/serious morbidity due to hypertensive disorders (RR = 0.80, 95% CI 0.65-0.97), anti-microbial prophylaxis in reducing the odds of puerperal sepsis/postpartum endometritis (OR = 0.49, 95% CI 0.23-1.06), anti-malarial prophylaxis in reducing the risk of severe antenatal anemia (RR = 0.62, 95% CI 0.50-0.78), and iron supplementation in reducing the risk of iron deficiency anemia at term (RR = 0.33, 95% CI 0.16-0.69). CONCLUSION: Maternal mortality could be reduced by a combination of micronutrient supplementation and presumptive treatment of infection during pregnancy. Such an approach could be adopted in resource-poor settings where visits to antenatal clinics are infrequent and would complement existing Safe Motherhood activities

Efficiency of Purine Utilization by Helicobacter pylori: Roles for Adenosine Deaminase and a NupC Homolog

The ability to synthesize and salvage purines is crucial for colonization by a variety of human bacterial pathogens. Helicobacter pylori colonizes the gastric epithelium of humans, yet its specific purine requirements are poorly understood, and the transport mechanisms underlying purine uptake remain unknown. Using a fully defined synthetic growth medium, we determined that H. pylori 26695 possesses a complete salvage pathway that allows for growth on any biological purine nucleobase or nucleoside with the exception of xanthosine. Doubling times in this medium varied between 7 and 14 hours depending on the purine source, with hypoxanthine, inosine and adenosine representing the purines utilized most efficiently for growth. The ability to grow on adenine or adenosine was studied using enzyme assays, revealing deamination of adenosine but not adenine by H. pylori 26695 cell lysates. Using mutant analysis we show that a strain lacking the gene encoding a NupC homolog (HP1180) was growth-retarded in a defined medium supplemented with certain purines. This strain was attenuated for uptake of radiolabeled adenosine, guanosine, and inosine, showing a role for this transporter in uptake of purine nucleosides. Deletion of the GMP biosynthesis gene guaA had no discernible effect on mouse stomach colonization, in contrast to findings in numerous bacterial pathogens. In this study we define a more comprehensive model for purine acquisition and salvage in H. pylori that includes purine uptake by a NupC homolog and catabolism of adenosine via adenosine deaminase

Gluebodies Offer a Route To Improve Crystal Reliability and Diversity through Transferable Nanobody Mutations That Introduce Constitutive Close Contacts

Design of modular, transferable protein assemblies has broad applicability and in structural biology could help with the ever-troublesome crystallization bottleneck, including finding robustly behaved protein crystals for rapidly characterizing ligands or drug candidates or generating multiple polymorphs to illuminate diverse conformations. Nanobodies as crystallization chaperones are well-established but still unreliable, as we show here. Instead, we show an exemplar of how robust crystallization behavior can be engineered by exploring many combinations (>200) of nanobody surface mutations over several iterations. Critically, what needed testing was crystallization and diffraction quality, since target–nanobody binding affinity is decoupled from crystallizability enhancement. Our study yielded multiple polymorphs, all mediated by the same interface, with dramatically improved resolution and diffraction reliability for some mutants; we thus name them ‘Gluebodies’ (Gbs). We further demonstrate that these Gb mutations do transfer to some other targets, both for achieving robust crystallization in alternative packing forms and for establishing the ability to crystallize a key early stage readout. Since the Gb interface is evidently a favored interaction, it may be broadly applicable for modular assembly; more specifically, this work suggests that Gbs should be routinely attempted for crystallization whenever nanobodies are available