Termination of Pregnancy in Zimbabwe: a Medico Legal Problem

A Zimbabwe Law Review ( ZLR ) article on abortion as a medical and legal problem

Association of Rural Setting With Poorer Disease Outcomes for Patients With Rheumatic Diseases : Results From a Systematic Review of the Literature

This work was conducted within the Versus Arthritis and Medical Research Council Centre for Musculoskeletal Health and Work although there was no specific financial support for this project. The authors have no conflict of interest to report. We acknowledge the work of Svenja Kleiser from the Faculty of Biology, Albert-Ludwigs-University Freiburg, Germany who conducted the literature search during an internship at the Epidemiology Group, University of Aberdeen, United Kingdom.Peer reviewedPostprin

Internally displaced persons and COVID-19: a wake-up call for and African solutions to African problems – the case of Zimbabwe

In this paper we engage with the situation of internally displaced persons (IDPs) residing in two informal settlements in Zimbabwe, within the context of the COVID-19 pandemic. We draw on an ongoing collaborative, interdisciplinary and impact-oriented project that seeks to help IDPs to be more prepared to protect themselves from the COVID-19 pandemic. We start by providing an analysis of the existing COVID-19 preventative messages and their applicability to the IDPs situation, and further argue for the need to adopt Transformative Public Health Education (TPHE), to allow co-creation and co-production with IDPs in order to produce messages and interventions that suit their lived realities. We then move on to show the importance of leveraging local low cost COVID-19 solutions, drawing on the example of the innovations that the project adapted in order to meet the needs of the IDPs residing in the two informal settlements

Effects of topical mometasone furoate therapy on local and systemic macrophage migration inhibitory factor levels in allergic rhinitis patients

Amaç: Bu çalışmada mometazon furoat nazal sprey (MFNS) ile tedavi ettiğimiz alerjik rinitli hastalarda tedavi öncesi (TÖ) / tedavi sonrası (TS) serumda ve nazal lavaj sıvılarında makrofaj migrasyon inhibitör faktör (MİF) düzeylerini araştırdık. Ayrıca, tedavinin naza lmukozadaki eozinofil düzeyine etkilerini irdeledik. Gereç ve Yöntem: İlk muayene sırasında alerjik rinit yakınmalarının en az ikisine sahip olan 22 hastanın semptomları skorlandı, muayene bulguları kaydedildi; serumda ve nazal lavaj sıvısında MİF değerleri saptandı. Hastalara günde bir kez 100 g MFNS (Nasonex®) başlandı. TS dördüncü haftada semptomlar ve muayene bulguları yeniden değerlendirildi, nazal lavaj/serum MİF değerleri ELISA metodu ile ölçüldü. Nazal mukoza impresyonsitolojisimateryallerinde eozinofillerin diğer hücrelere göre oranları hesaplandı. Bulgular: TÖ/TS nazal lavaj MİF ortalaması (sırasıyla 503,53 294,50 pg/ml ve 1422.35 1097,98 pg/ml, P0.05) bulundu. Nazal mukozanın impresyon sitolojisinde eozinofil yüzdesi TÖve TS, sırasıyla 51.86 28,94 ve 25.64 23,60 idi. Eozinofil yüzdeleri arasındaki fark istatistiksel olarak anlamlıydı (p<0.001). Semptomskorları ortalaması TÖve TS sırasıyla 16,95 4,27 ve 9,24 3,38 idi. Skor ortalamalarındaki fark istatistiksel olarak anlamlıydı (P<0.001). Sonuç: HastalarımızdaTSda anlamlı klinik bir düzelme görüldü.TS semptomskorları ve nazalmukoza eozinofil yüzdeleri belirgin şekilde azaldı. TSda lokal MİF düzeylerinde ise artış izlendi. MFNS tedavisini takiben MİF değerlerinde izlenen anlamlı değişikliğin klinik düzelmeyle ilişkisinin daha ayrıntılı incelenmesi gerekmektedir.Background: In this study we aimed to investigate the systemic and local levels of macrophagemigration inhibitory factor (MIF) before and after topically applied mometasone furoate therapy in patients with allergic rhinitis. We also investigated the effects of therapy on local eosinophil accumulation. Material and Methods: Twenty-two patients (8 males and 14 females; median of 46 years ranging, from 17 to 68 years) with AR were subjects of this study. Percentages of eosinophils in nasal smears were calculated. MIF levels in serum and nasal lavage were measured by an enzyme-linked immunosorbent assay. Results: Topical glucocorticoid treatment significantly inhibited total symptom score (TSS) (16,95 4,27 and 9,24 3,38, respectively, p<0.001). After therapy, mean percentages of eosinophils decreased significantly (51.86 28,94 and 25.64 23,60 respectively, p<0.001) by impression cytology. MIF levels both in serum (782,55 759,43pg/ml and 917.10 1080,37 pg/ml, respectively) and nasal lavage (503,53 294,50 pg/ml and 1422.35 1097,98 pg/ml, respectively) increased after mometasone therapy. However, only the change in nasal lavage samples was statistically significant (p<0.001). Conclusions: TSS and nasal eosionophil numbers in nasal mucosa decreased following therapy. Further investigations are needed to evaluate the relations between clinical improvement and the significant changes in MIF levels following MFNS treatment

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

BACKGROUND: Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. METHODS: Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. RESULTS: Serum growth hormone levels failed to correlate with age (r(2 )= 3.03) in the entire group of normal subjects (i.e. 20 – 80 years). In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r(2 )= 0.092). Of note, serum growth hormone was positively correlated with age (adjusted r(2 )= 0.269) in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs) or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p < 0.001) in systemic lupus erythematosus patients, but only when compared to the entire group of normal subjects. Serum somatostatin levels differed from normal subjects only in older (i.e. >55 yrs) systemic lupus erythematosus patients. CONCLUSIONS: These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal hyperostosis and hypermobility syndrome where significantly higher serum growth hormone levels were found. Somatostatin levels in elderly systemic lupus erythematosus patients may provide a clinical marker of disease activity in these patients

Regulation of Intestinal Immune Response by Selective Removal of the Anterior, Posterior, or Entire Pituitary Gland in Trichinella spiralis Infected Golden Hamsters

The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been previously reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion and intestinal absorption, as well as increased susceptibility to bacterial and viral infections. However, to our knowledge, no findings have been published concerning the immune response following HYPOX during worm infection, particularly that which is caused by the nematode Trichinella spiralis. The aim of this work was to analyze the effects of total or partial HYPOX on colonization of T. spiralis in the intestinal lumen, together with duodenal and splenic cytokine expression. Our results indicate that 5 days post infection, only neurointermediate pituitary lobectomy (NIL) reduces the number of intestinally recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser confocal microscopy, we observed that the mean intensity of all tested Th1 cytokines was markedly diminished, even in the duodenum of infected controls. In contrast, a high level of expression of these cytokines was noted in the NIL infected hamsters. Likewise, a significant decrease in the fluorescence intensity of Th2 cytokines (with the exception of IL-4) was apparent in the duodenum of control and sham infected hamsters, compared to animals with NIL surgeries, which showed an increase in the expression of IL-5 and IL-13. Histology of duodenal mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located along the lamina propria, which was related to the presence of the parasite. We conclude that hormones from each pituitary lobe affect the gastrointestinal immune responses to T. spiralis through various mechanisms

Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-α and dexamethasone

<p>Abstract</p> <p>Background</p> <p>CD38 is expressed in human airway smooth muscle (HASM) cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-α). CD38 has a role in airway hyperresponsiveness, a hallmark of asthma, since deficient mice develop attenuated airway hyperresponsiveness compared to wild-type mice following intranasal challenges with cytokines such as IL-13 and TNF-α. Regulation of CD38 expression in HASM cells involves the transcription factor NF-κB, and glucocorticoids inhibit this expression through NF-κB-dependent and -independent mechanisms. In this study, we determined whether the transcriptional regulation of CD38 expression in HASM cells involves response elements within the promoter region of this gene.</p> <p>Methods</p> <p>We cloned a putative 3 kb promoter fragment of the human <it>cd38 </it>gene into pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of the putative <it>cd38 </it>promoter region revealed one NF-κB and several AP-1 and glucocorticoid response element (GRE) motifs. HASM cells were transfected with the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-κB and some of the AP-1 sites, or the promoter with mutations of the NF-κB and/or AP-1 sites. Using the electrophoretic mobility shift assays, we determined the binding of nuclear proteins to oligonucleotides encoding the putative <it>cd38 </it>NF-κB, AP-1, and GRE sites, and the specificity of this binding was confirmed by gel supershift analysis with appropriate antibodies.</p> <p>Results</p> <p>TNF-α induced a two-fold activation of the 3 kb promoter following its transfection into HASM cells. In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF-κB and/or AP-1 sites or in the presence of dexamethasone, there was no induction in the presence of TNF-α. The binding of nuclear proteins to oligonucleotides encoding the putative <it>cd38 </it>NF-κB site and some of the six AP-1 sites was increased by TNF-α, and to some of the putative <it>cd38 </it>GREs by dexamethasone.</p> <p>Conclusion</p> <p>The EMSA results and the cd38 promoter-reporter assays confirm the functional role of NF-κB, AP-1 and GREs in the cd38 promoter in the transcriptional regulation of CD38.</p

Impact of glucocorticoid receptor density on ligand-independent dimerization, cooperative ligand-binding and basal priming of transactivation: a cell culture model

Glucocorticoid receptor (GR) levels vary between tissues and individuals and are altered by physiological and pharmacological effectors. However, the effects and implications of differences in GR concentration have not been fully elucidated. Using three statistically different GR concentrations in transiently transfected COS-1 cells, we demonstrate, using co-immunoprecipitation (CoIP) and fluorescent resonance energy transfer (FRET), that high levels of wild type GR (wtGR), but not of dimerization deficient GR (GRdim), display ligand-independent dimerization. Whole-cell saturation ligand-binding experiments furthermore establish that positive cooperative ligand-binding, with a concomitant increased ligand-binding affinity, is facilitated by ligand-independent dimerization at high concentrations of wtGR, but not GRdim. The down-stream consequences of ligand-independent dimerization at high concentrations of wtGR, but not GRdim, are shown to include basal priming of the system as witnessed by ligand-independent transactivation of both a GRE-containing promoter-reporter and the endogenous glucocorticoid (GC)-responsive gene, GILZ, as well as ligand-independent loading of GR onto the GILZ promoter. Pursuant to the basal priming of the system, addition of ligand results in a significantly greater modulation of transactivation potency than would be expected solely from the increase in ligand-binding affinity. Thus ligand-independent dimerization of the GR at high concentrations primes the system, through ligand-independent DNA loading and transactivation, which together with positive cooperative ligand-binding increases the potency of GR agonists and shifts the bio-character of partial GR agonists. Clearly GR-levels are a major factor in determining the sensitivity to GCs and a critical factor regulating transcriptional programs