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To determine the serum concentration of TSP-2 in HIV-associated preeclampsia, archived serum samples from normotensive (n=36) and preeclamptic (n=36) pregnant groups, which were further subdivided by HIV status, were used to measure TSP-2 levels, using MilliPlex immunoassays. A statistical difference was noted for gestational age, systolic blood pressure, diastolic blood pressure and baby weight (p < 0.0001). Based on pregnancy type (normotensive vs preeclamptic), no significant difference in TSP-2 levels was observed regardless of HIV status (26.61 ng/ml; 95% CI: 17.52-34.67 vs 25.35ng/ml; 95% CI: 18.32-37.49). Based on HIV status, a significant increase of TSP-2 levels (p = 0.04) was observed in HIV-positive (29.66 ng/ml; 95% CI: 21.99-38.01) vs HIV-negative (24.34 ng/ml; 95% CI: 16.24-31.48) women. Based on pregnancy type and HIV status, TSP-2 levels were statistically significant between the P+ve and N-ve; and P+ve and P-ve groups (p = 0.01) respectively. The significant TSP-2 elevation noted in preeclamptic versus normotensive pregnancies, may account for the defective trophoblast cell invasion in preeclampsia. Based on HIV status, TSP-2 levels was significantly upregulated, which may be attributed to the action of HIV tat protein. TSP-2 may be a potential biomarker for the early detection of preeclampsia development. [ABSTRACT FROM AUTHOR]

Background. Africa has the highest rate of HIV infection, and HIV-associated nephropathy (HIVAN) is one of the most frequent kidney diseases observed in children. HIVAN in children usually presents as a form of nephrotic syndrome, predominantly focal segmental glomerulosclerosis (FSGS) on histopathology, that often leads to chronic kidney failure. Objective. This study determined the urinary concentrations of ß-2-microglobulin (ß2M) and cystatin C proteins in children with HIVAN and primary FSGS. Methods. The study group comprised 34 children; 14 with HIVAN and 20 with primary FSGS. The control groups were 20 HIV-positive and 20 HIV-negative children with no kidney disease. Urine samples collected from these 74 children were stored at -80°C. Bio-Plex technology was used to analyse the urinary protein concentration of cystatin C and ß2M. Results. A significant increase in urinary ß2M levels was observed in the HIVAN group compared with the HIV-negative group (p=0.0240). No other statistically significant differences in urinary ß2M concentrations were noted across the study groups. Urinary cystatin C levels were significantly increased in primary FSGS children compared with both HIV-negative (p=0.0041) and HIV-positive controls (p=0.0256). Urinary cystatin C displayed a significant increase in the primary FSGS compared with the HIVAN group (p=0.0150). No significant differences in urinary cystatin C levels were noted in the HIVAN group compared with the HIV-negative and HIV-positive control groups. Conclusion. Urinary cystatin C has promising prognostic value to predict primary FSGS from HIVAN. [ABSTRACT FROM AUTHOR]

Background: Dysregulated production or secretion of adipokines from adipose tissue may contribute to the pathogenesis of obesity-linked complications such as diabetes mellitus (DM). Although adipokines have anti-inflammatory activity it is also capable of causing inflammation. Human immunodeficiency virus (HIV) infection predisposes an individual to the development of diabetes. Notwithstanding the side effects of antiretroviral therapy (ART), these may also exacerbate adipokine release and thereby promoting metabolic abnormalities. Aim: This study reviews adipokines in the synergy of diabetes comorbid with HIV infection. It also examines the ameliorative action of ART on adipokines in diabetes. Method: Multiple databases were used to search for each of the adipokines listed in the study. The role and expression of these adipokines were highlighted in its relationship to DM and HIV. Relevant articles were identified, selected and used to write this review article. Results: This narrative review compares adipokine levels among HIV-infected and uninfected patients who are diabetic and have insulin resistance (IR). It also addresses the side effect of ART and its contribution to DM in HIV-infected patients. Adipokines are dysregulated in diabetes and IR, as well as in patients receiving ART. Conclusion: ART, particularly protease inhibitors and non-nucleoside reverse transcriptase inhibitors, promotes IR and metabolic abnormalities. Nonetheless, obesity, physical inactivity, immune dysregulation and inflammation are also contributing factors to IR and DM in HIV-infected patients. Finally, circulating levels of adipokines are dysregulated in DM and further investigations are necessary. [ABSTRACT FROM AUTHOR]

Risk loci identified through genome-wide association studies have explained about 25% of the phenotypic variations in nonsyndromic orofacial clefts (nsOFCs) on the liability scale. Despite the notable sex differences in the incidences of the different cleft types, investigation of loci for sex-specific effects has been understudied. To explore the sex-specific effects in genetic etiology of nsOFCs, we conducted a genome-wide gene × sex (GxSex) interaction study in a sub-Saharan African orofacial cleft cohort. The sample included 1,019 nonsyndromic orofacial cleft cases (814 cleft lip with or without cleft palate and 205 cleft palate only) and 2,159 controls recruited from 3 sites (Ethiopia, Ghana, and Nigeria). An additive logistic model was used to examine the joint effects of the genotype and GxSex interaction. Furthermore, we examined loci with suggestive significance (P < 1E-5) in the additive model for the effect of the GxSex interaction only. We identified a novel risk locus on chromosome 8p22 with genome-wide significant joint and GxSex interaction effects (rs2720555, p2df = 1.16E-08, pGxSex = 1.49E-09, odds ratio [OR] = 0.44, 95% CI = 0.34 to 0.57). For males, the risk of cleft lip with or without cleft palate at this locus decreases with additional copies of the minor allele (p < 0.0001, OR = 0.60, 95% CI = 0.48 to 0.74), but the effect is reversed for females (p = 0.0004, OR = 1.36, 95% CI = 1.15 to 1.60). We replicated the female-specific effect of this locus in an independent cohort (p = 0.037, OR = 1.30, 95% CI = 1.02 to 1.65), but no significant effect was found for the males (p = 0.29, OR = 0.86, 95% CI = 0.65 to 1.14). This locus is in topologically associating domain with craniofacially expressed and enriched genes during embryonic development. Rare coding mutations of some of these genes were identified in nsOFC cohorts through whole exome sequencing analysis. Our study is additional proof that genome-wide GxSex interaction analysis provides an opportunity for novel findings of loci and genes that contribute to the risk of nsOFCs. [ABSTRACT FROM AUTHOR]

The effect of the industrial solvent n-hexane on liver function was investigated by studying the livers of rats injected subcutaneously with 0.1 ml n-hexane for seven consecutive days. The results showed that n-hexane causes fatty changes in liver. As compared to the control group, rats injected with the solvent had lower perfusate glucose concentrations. Perfusate lactate levels and lactate:pyruvate ratios were greater.

Women with a history of pre-eclampsia (PE) tend to have a higher risk of developing cardiovascular and neurological diseases later in life. Imbalance in oxidative markers and purinergic enzymes have been implicated in the pathogenesis of neurological disease. This study investigated the effect of PE on oxidative imbalance, purinergic enzyme inhibitory activity, acetylcholinesterase and chymotrypsin activities in the brain of PE rat model at post-partum/post-natal day (PP/PND) 60. Pregnant rats divided into early-onset and late-onset groups were administered with N ω-nitro- l -arginine methyl through drinking water at gestational days 8–17. Rats were allowed free access to water throughout the pregnancy and allowed to deliver on their own. The mother and the pups were euthanized at PP and PND 60, respectively, the cortex and the cerebellum excised, homogenized and stored for analyses of the enzymes. Results showed an increase in nitric oxide and malondialdehyde with a concomitant decrease in reduced glutathione and superoxide dismutase, an indication of oxidative damage. Also, there was an increase in acetylcholinesterase activity with a decrease in chymotrypsin, adenylpyrophosphatase and ecto-nucleoside triphosphate diphosphohydrolase activities in both the cortex and the cerebellum of the mother and the pups at PND 60. These results indicate the involvement of oxidative stress, increased cholinergic activity and depleted proteolytic and purinergic activities in PE-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Iron and folic acid supplementation plays a major role in the prevention and control of iron-deficiency anaemia in pregnancy. Therefore, this study assesses adherence to prophylactic iron supplementation during the antenatal period in South Africa. Methods: An observational study was conducted in a regional hospital from January to December 2016. HIV-uninfected (n = 100) and HIV-infected (n = 100)] women were enrolled and subdivided into three groups: (a) ≤ 34 weeks (n = 33), (b) 34–36 weeks (n = 34) and (c) ≥ 37 weeks (n = 33) gestational age respectively. A structured questionnaire was used for data collection. Data were coded and statistically analysed using SPSS software. Pill count and self-reported data from women (n = 24) at ≤ 34 weeks and 34–36 weeks reflected < 50% adherence and 46% non-adherence, being higher in the HIV-infected women (75%). Nausea was the commonest side effect across all trimesters (79. 2%). Adherence (27.8%) and non-adherence (72.1%) to iron, folic acid and calcium supplementation were found in 88% of women. Conclusion: This study found that adherence to micronutrient supplementation is low in pregnancy, albeit higher in HIV-infected women receiving antenatal care at a regional hospital in Durban, South Africa. Abbreviations: Haemoglobin (Hb), Human Immune Deficiency Virus (HIV), antiretroviral therapy (ARV), zidovudine (ZDV), tuberculosis (TB), low to middle- income countries (LMICs), World Health Organization (WHO), antenatal clinic (ANC). [ABSTRACT FROM AUTHOR]

Background. HIV-associated nephropathy (HIVAN) in sub-Saharan Africa remains a significant cause of morbidity and mortality in children. Early detection of kidney injury is essential for injury-specific interventions that may avert permanent kidney damage and delay progression of kidney injury. Kidney biopsy is presently the gold standard for diagnosis of related kidney disease; however, it is pervasive with attendant complications, and may not be representative owing to sampling error. Serum creatinine is an insensitive and non-specific marker for the diagnosis of various kidney diseases, particularly in HIV-infected patients, who usually have varying degrees of muscle wasting. Therefore, a non-invasive approach using additional biomarkers for early detection of HIV-related kidney diseases, particularly HIV-associated nephropathy (HIVAN), is urgently needed. Objective. To determine the urinary concentrations of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and glutathione-Stransferase- p (GST-p) in children with idiopathic focal segmental glomerulosclerosis (FSGS) and HIVAN. Methods. The study group comprised 34 children: 13 with HIVAN and 21 with idiopathic FSGS. The control groups were 19 HIV-positive and 16 HIV-negative children with no kidney disease. Urine samples collected from these 69 children were stored at -80°C. Urinary concentrations of KIM-1, IL-18 and GST-p were quantified using Bio-Plex assay. Results. A significant increase in urinary KIM-1 levels was observed in the HIVAN group compared with the HIV-positive (p=0.0039) and HIV-negative (p=0.0438) control groups. There was no significant increase in KIM-1 levels on comparison of the idiopathic FSGS group with the control groups (HIV-positive and HIV-negative children) (p=0.0737 and p=0.1757, respectively). No statistically significant differences were noted in urinary IL-18 and GST-p levels across all study groups. Conclusion. Urinary KIM-1 levels are significantly elevated in children with HIVAN and may be a useful biomarker to detect kidney disease in HIV-1-infected children. [ABSTRACT FROM AUTHOR]

Objective: To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission.Design: Cross-sectional immunohistochemical analysis of target receptor expression.Setting: Laboratory-based study of primigravidae attending a district hospital in South Africa.Population or Sample: Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group).Method: Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5 (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for image acquisition and analysis.Main Outcome Measures: Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV.Results: Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159  = 6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F1,159  = 8.803, P = 0.003). p24 was present in both placentae and umbilical cords of babies that were HIV-negative at 6 weeks. ICAM-2 immunostaining was observed in the syncytiotrophoblast across study groups and was significantly higher in the HIV-negative pre-eclamptic group (χ2 (3)  = 45.3; P < 0.001).Conclusion: Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral entry routes across the placental barrier. ICAM-2 expression may influence HIV passage across the placenta or restoration of risk of pre-eclampsia in HAART-treated mothers. HIV was found in fetal circulation regardless of antiretroviral treatment. Further confirmatory ultrastructural and molecular work is warranted.Tweetable Abstract: CD4, CCR5 and ICAM-2 on syncytiotrophoblast may facilitate HIV infection of passage across the placenta. [ABSTRACT FROM AUTHOR]

Objective: To assess the umbilical cord centrality, placental morphometrics, and functional efficiency in preeclampsia.Methods: Placental morphometry of normotensive (n = 69) and preeclamptic (n = 69) patients was evaluated.Results: There was a significant reduction in mean placental surface area (p = 0.0001), length (p = 0.0001), thickness (p = 0.016), and volume (p = 0.0001) in the preeclamptic than in the normotensive groups. Umbilical cord insertion was predominantly eccentric with marginal in early (29%) and late-onset preeclampsia (16%). Placental and birth weight was lower (p = 0.0001) in preeclampsia than in the normotensive group. Placental efficiency was reduced in early-onset preeclampsia.Conclusion: This study demonstrates reduced placental morphometrics with impaired placental efficiency in preeclampsia. [ABSTRACT FROM AUTHOR]

Background. While haemophilia is a disease phenotype in males only, it has an effect on females too. In South Africa, there is no documentation on the views and experiences of haemophilia carrier mothers regarding the disease, or about their response to carrier testing for daughters or other female members of their families. The burden of child care may fall entirely on the mother in some cultures, and having a son with haemophilia may make coping difficult. Knowing their carrier status would allow daughters of carrier mothers to be aware of the chances of themselves having a son with haemophilia. Knowing their own factor levels may also be useful in understanding possible excessive bleeding in themselves. Objectives. To record the experiences of haemophilia carrier mothers in KwaZulu-Natal and their attitudes and opinions on carrier testing for female members of their families. Methods. Forty mothers of haemophiliac sons were interviewed using a structured questionnaire specifically designed and tested for this study. Results. From this cohort, there were 21 potential carrier daughters and 25 potential carrier sisters who would be eligible for further testing and counselling. All the study participants expressed their desire to have carrier testing available for female family members. They also expressed their concerns regarding raising a son with haemophilia, including some culture-specific issues. Conclusion. A diagnosis of haemophilia carriership is seen by mothers of haemophiliac sons as important for female members of their families. A protocol for the care of haemophilia carrier women is therefore necessary. [ABSTRACT FROM AUTHOR]

Background. Knowledge of the pH level of soaps and cleansers used by patients with atopic eczema and sensitive skin is crucial, as high-alkalinity products are irritants and impair the normal skin barrier, so interfering with the adequate control of atopic eczema. Objectives. The aim of this study was to assess the pH of various bar soaps and cleansers that are usually recommended and used by patients with atopic diseases and dry, sensitive skin in South Africa. Methods. Forty-nine commercial soap bars and cleansers were randomly selected for pH analysis. The samples were prepared as 8% emulsions in tap water. Nine undiluted liquid facial cleansers were also evaluated. Deionised water was used as a negative control. The pH of each emulsion or liquid cleanser was recorded in duplicate using a Metrohm pH meter model 827 (Metrohm, Herisau, Switzerland). Results. Of the 49 samples analysed, 34 (69.4%) were alkaline with a pH ranging from 9.3 - 10.7. Two samples (4.1%) were within the acceptable range of (5.4 - 5.9), and 2 samples (4.1%) had pH levels of below 5. In total, 5 samples (10.2 %) had a pH of 4 - 6. Conclusion. The majority of soaps and cleansers analysed in this study were alkaline, with only 2 falling in the acceptable pH range of 5.4 - 5.9 and 5 within the pH range of 4 - 6, thus raising concerns regarding the optimal management of atopic eczema patients. [ABSTRACT FROM AUTHOR]

Summary: Tuberculosis (TB) is mainly a disease of the lungs, but Mycobacterium tuberculosis (Mtb) can establish infection in virtually any organ in the body. Rising rates of extrapulmonary (EP) TB have been largely associated with the HIV epidemic, as patients co-infected with HIV show a four-fold higher risk of EPTB. Spinal TB (Pott's Disease), one of the most debilitating extrapulmonary forms of disease, is difficult to diagnose and can cause deformity and/or neurological deficits. This study examined the histopathology and distribution of immune cells within spinal TB lesions and the impact of HIV on pathogenesis. The overall structure of the spinal granulomas resembled that seen in lung lesions from patients with pulmonary TB. Evidence of efficient macrophage activation and differentiation were detectable within organized structures in the spinal tissue, irrespective of HIV status. Interestingly, the granulomatous architecture and macroscopic features were similar in all samples examined, despite a reversal in the ratio of infiltrating CD4 to CD8 T cells in the lesions from HIV-infected patients. This study provides a foundation to understand the mechanism of tissue destruction and disease progression in Spinal TB, enabling the future development of novel therapeutic strategies and diagnostic approaches for this devastating disease. [Copyright &y& Elsevier]

Recently it has been suggested that TGF-β[sub 1] may play an important role in trophoblast invasion of spiral arteries in pre-eclampsia. This study was designed to investigate TGF-β[sub 1] levels in pre-eclampsia. Platelet depleted plasma TGF-β[sub 1] levels were measured by ELISA in 43 normotensive healthy non-pregnant women, 30 normotensive healthy pregnant and 42 pre-eclamptic women: TGF-β[sub 1] levels were increased significantly in the pre-eclamptics (4·9±0·9 ng/ml) compared to the normotensive pregnant (1·9±0·54 ng/ml; P<0·001) and normotensive non-pregnant groups (2·1±0·41 ng/ml; P<0·0001). There was no significant difference in TGF-β[sub 1] levels between normotensive pregnant and non-pregnant groups (1·9±0·54 vs. 2·1±0·41 ng/ml; P=0·2). There was a highly significant correlation between neonatal weight (r=0·63; P<0·0001) and TGF-β[sub 1] levels. The finding of increased levels of plasma TGF-β[sub 1] suggests an aetiological role of this peptide in pre-eclampsia. [ABSTRACT FROM AUTHOR]

Maternal plasma ET-1 levels and the immunolocalisation of ET-1 in the fetal membranes of pre-eclamptic primigravidae at ≥28 weeks, gestation were studied. The levels of maternal plasma ET-1 and immunoreactive ET-1 were increased in pre-eclampsia. Immunoreactive ET-1 was localised in the amnion, chorion and decidua of normal pregnant women as well as those with pre-eclampsia-eclampsia. Intense labelling was observed in moderate pre-eclampsia (BP 140/90 - 170/110 mmHg) with very intense labelling in severe pre-eclampsia (BP >170/110 mmHg), especially in the amniotic epithelium, chorionic villi, maternal blood vessels, cytotrophoblasts and giant cells of the decidua. The increased ET-1 levels demonstrated in fetal membranes of pre-eclamptic women are probably produced in a paracrine and/or autocrine manner, contributing to the hypertension, vasospasm and fetal growth restriction characteristic of the syndrome. A larger study would be required to show significant change in endothelin production in pre-eclampsia. [ABSTRACT FROM AUTHOR]

C9H6FNO2S, triclinic, P1̄ (no. 2), a = 7.2786(2) Å, b = 8.1014(3) Å, c = 16.1084(5) Å, α = 76.320(1)°, β = 87.918(1)°, γ = 80.784(1)°, V = 911.00(5) Å3, Z = 4, Rgt(F) = 0.0298, wRref(F2) = 0.0857, T = 100(2) K.

C24H33FN2O7, triclinic, P1̅ (no. 2), a = 11.0118(7) Å, b = 11.5684(7) Å, c = 11.7276(7) Å, α = 112.294(1)°, β = 100.557(1)°, γ = 105.775(2)°, V = 1259.56(13) Å3, Z = 2, Rgt(F) = 0.0411, wRref(F2) = 0.1050, T = 173 K.

C8H6BrFO2S, monoclinic, P21/m (no. 11), a = 4.7846(2) Å, b = 9.6099(4) Å, c = 10.3260(4) Å, β = 103.137(1)°, V = 462.36(3) Å3, Z = 2, Rgt(F) = 0.0193, wRref(F2) = 0.0502, T = 100(2) K.