“I don’t use a condom (with my regular partner) because I know that I’m faithful, but with everyone else I do”: The cultural and socioeconomic determinants of sexual partner concurrency in young South Africans

Finding ways to reduce the high rates of sexual partner concurrency is increasingly believed to be vital to controlling HIV spread in southern Africa. We describe the frequency and correlates of sexual partner concurrency in a representative sample of 3 324 young South Africans aged 14-25. Of the 2 468 individuals who were sexually active 21% had engaged in concurrent sexual partnerships. Multivariate analysis revealed that concurrency was more common with males, Africans, those who knew their partner had anotherpartner, early age of sexual debut, four or more lifetime sexual partners, alcohol consumption, and self-perception of being at high risk for acquisition of HIV. If the respondent’s partner knew his or her friends (termed high structural embeddedness) this was associated with a 52% reduction in concurrency rates. There are significant differences in both the rates of concurrency and the risk factors underpinning these in the different racial/ethnic groups. Analysis of these underlying determinants suggests that cultural rather than socioeconomic factors predominate, which has important implications for the design and targeting of prevention efforts

Hyaluronan Biology and Regulation in Renal Tubular Epithelial Cells and its Role in Kidney Stone Disease

Renal stone disease is a widespread problem afflicting more and more people throughout the world. Epidemiological studies show an increase in incidence and prevalence rates. In North America and Europe the yearly incidence is estimated to be about 0.5% 1, 2. The prevalence of kidney stones in the USA has risen in two decades from 3.2% to 5.2% 3. The lifetime risk is about 10-15% in the developed world, but can be as high as 20-25% in the middle east 1, 2. Kidney stone disease often presents as an episode of acute renal colic with characteristic severe intermittent pain in the flank or lower abdomen, vomiting and haematuria caused by a calculus obstructing the ureter 4. Renal stone disease has a substantial impact on the health care system. For example, the total annual cost for urolithiasis in the United States in 1995 was estimated to be $1.83 billion 5. Nephrolithiasis is likely to recur and recurrence rates are reported to be 50% in 10 years and 75% in 20 years 1. Apparently the development of minimal invasive techniques for stone removal, such as extracorporal shock-wave lithotripsy (ESWL), ureterorenoscopy (URS) and percutaneous nephrolitholapaxy (PCNL) together with current standards to avoid stone recurrence such as general measures and metabolic therapy have not resolved the increasing problem of (recurrent) stone formation 4, 6, 7. Therefore scientific research is warranted to better understand the etiology of stone disease aimed at preventing kidney stone formation in healthy people or stone recurrence in patients

Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys

Retention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate (CaOx) crystal binding during wound healing. This concept was investigated in vivo by treating rats for 1, 4, and 8 d with ethylene glycol (0.5 and 0.75%) in their drinking water to induce renal tubular cell damage and CaOx crystalluria. Tubular injury was morphologically scored on periodic acid-Schiff-stained renal tissue sections and tissue repair assessed by immunohistochemical staining for proliferating cell nuclear antigen. CaOx crystals were visualized in periodic acid-Schiff-stained sections by polarized light microscopy, and renal calcium deposits were quantified with von Kossa staining. HA was visualized with HA-binding protein and OPN and CD44 immunohistochemically with specific antibodies and quantified with an image analyzer system. Already after 1 d of treatment, both concentrations of ethylene glycol induced hyperoxaluria and CaOx crystalluria. At this point, there was neither tubular injury nor crystal retention in the kidney, and expression of HA, OPN, and CD44 was comparable to untreated controls. After 4 and 8 d of ethylene glycol, however, intratubular crystals were found adhered to injured/regenerating (proliferating cell nuclear antigen positive) tubular epithelial cells, expressing HA, OPN, and CD44 at their luminal membrane. In conclusion, the expression of HA, OPN, and CD44 by injured/regenerating tubular cells seems to play a role in retention of crystals in the rat kidney

Nevirapine-Associated Early Hepatotoxicity: Incidence, Risk Factors, and Associated Mortality in a Primary Care ART Programme in South Africa

BACKGROUND: The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality. CONCLUSIONS: The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria

Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway

Sea spray aerosols (SSAs) have profound effects on our climate and ecosystems. They also contain microbiota and biogenic molecules which could affect human health. Yet the exposure and effects of SSAs on human health remain poorly studied. Here, we exposed human lung cancer cells to extracts of a natural sea spray aerosol collected at the seashore in Belgium, a laboratory-generated SSA, the marine algal toxin homoyessotoxin and a chemical inhibitor of the mammalian target of rapamycin (mTOR) pathway. We observed significant increased expression of genes related to the mTOR pathway and Proprotein convertase subtilisin/kexin type 9 (PCSK9) after exposure to homoyessotoxin and the laboratory-generated SSA. In contrast, we observed a significant decrease in gene expression in the mTOR pathway and of PCSK9 after exposure to the natural SSA and the mTOR inhibitor, suggesting induction of apoptosis. Our results indicate that marine biogenics in SSAs interact with PCSK9 and the mTOR pathway and can be used in new potential pharmaceutical applications. Overall, our results provide a substantial molecular evidence base for potential beneficial health effects at environmentally relevant concentrations of natural SSAs

Colorimetric characterization and classification of the virgin olive oil from the spanish-moroccan mediterranean area

Se han realizado medidas por reflexión del color de 200 muestras de aceite de oliva virgen de las zonas de producción sur de España y zona norte de Marruecos. También se han realizado medidas del grado de acidez de los mismos y se emplea el análisis cluster para el estudio de su clasificación. Los resultados obtenidos muestran que, en general, los aceites marroquíes presentan con respecto a los españoles, tonalidades más verdosas (hº medio de 87,3º frente a 85,1º) y son menos saturados (C* medio de 91,7 frente a 105,3). Por otra parte, el grado de acidez difiere notablemente para ambas zonas geográficas, con valores medios de 0,31 para los aceites españoles y 2,87 para los marroquíes. A partir de estas medidas experimentales el análisis cluster muestra que, es posible clasificar los aceites de oliva según su zona geográfica de producción (hispano-marroquí), en función del grado de acidez ó del ángulo de tono.Colour measurements by reflection of 200 virgin olive oil samples from the southern zone of Spain and the northern one of Morocco were made. Acidity measurements of these oils were made as well, and a cluster analysis was employed for their classification. Results show that, generally, Moroccan oils present a hue more greenish (hº average of 87.3º) than the Spanish ones (85.1º), and those are less saturated (C* average of 91.7 and 105.3, respectively). On the other hand, acidity is remarkably different for these two geographic zones, having average values of 0.31 for Spanish oils and 2.87 for Moroccan ones. From these experimental measurements, the cluster analysis shows that it is possible to classify these oils according to their geographic production zones (Spanish-Moroccan area) depending on the acidity or the hue angle.Esta trabajo ha sido realizado gracias al Proyecto 17PRO/00 financiado por la Agencia Española de Cooperación Internacional (AECI)

Matrix Modulation of the Bioactivation of Estragole by Constituents of Different Alkenylbenzene-containing Herbs and Spices and Physiologically Based Biokinetic Modeling of Possible In Vivo Effects

The alkenylbenzene estragole is a constituent of several herbs and spices. It induces hepatomas in rodents at high doses following bioactivation by cytochrome P450s and sulfotransferases (SULTs) giving rise to the ultimate carcinogenic metabolite 1'-sulfooxyestragole which forms DNA adducts. Methanolic extracts from different alkenylbenzene-containing herbs and spices were able to inhibit SULT activity. Flavonoids including quercetin, kaempferol, myricetin, apigenin, and nevadensin were the major constituents responsible for this inhibition with Ki values in the nano to micromolar range. In human HepG2 cells exposed to the proximate carcinogen 1ʹ-hydroxyestragole, the various flavonoids were able to inhibit estragole DNA adduct formation and shift metabolism in favor of glucuronidation which is a detoxification pathway for 1ʹ-hydroxyestragole. In a next step, the kinetics for SULT inhibition were incorporated in physiologically based biokinetic (PBBK) models for estragole in rat and human to predict the effect of co-exposure to estragole and (mixtures of) the different flavonoids on the bioactivation in vivo. The PBBK-model-based predictions indicate that the reduction of estragole bioactivation in rat and human by co-administration of the flavonoids is dependent on whether the intracellular liver concentrations of the flavonoids can reach their Ki values. It is expected that this is most easily achieved for nevadensin which has a Ki value in the nanomolar range and is, due to its methyl ation, more metabolically stable than the other flavonoid