The Transient Receptor Potential Ion Channel TRPV6 Is Expressed at Low Levels in Osteoblasts and Has Little Role in Osteoblast Calcium Uptake

Background: TRPV6 ion channels are key mediators of regulated transepithelial absorption of Ca2+ within the small intestine. Trpv6-/- mice were reported to have lower bone density than wild-type littermates and significant disturbances in calcium homeostasis that suggested a role for TRPV6 in osteoblasts during bone formation and mineralization. TRPV6 and molecules related to transepithelial Ca2+ transport have been reported to be expressed at high levels in human and mouse osteoblasts. Results: Transmembrane ion currents in whole cell patch clamped SaOS-2 osteoblasts did not show sensitivity to ruthenium red, an inhibitor of TRPV5/6 ion channels, and 45Ca uptake was not significantly affected by ruthenium red in either SaOS-2 (P = 0.77) or TE-85 (P = 0.69) osteoblastic cells. In contrast, ion currents and 45Ca uptake were both significantly affected in a human bronchial epithelial cell line known to express TRPV6. TRPV6 was expressed at lower levels in osteoblastic cells than has been reported in some literature. In SaOS-2 TRPV6 mRNA was below the assay detection limit; in TE-85 TRPV6 mRNA was detected at 6.90±1.9 × 10−5 relative to B2M. In contrast, TRPV6 was detected at 7.7±3.0 × 10−2 and 2.38±0.28 × 10−4 the level of B2M in human carcinoma-derived cell lines LNCaP and CaCO-2 respectively. In murine primary calvarial osteoblasts TRPV6 was detected at 3.80±0.24 × 10−5 relative to GAPDH, in contrast with 4.3±1.5 × 10−2 relative to GAPDH in murine duodenum. By immunohistochemistry, TRPV6 was expressed mainly in myleocytic cells of the murine bone marrow and was observed only at low levels in murine osteoblasts, osteocytes or growth plate cartilage. Conclusions: TRPV6 is expressed only at low levels in osteoblasts and plays little functional role in osteoblastic calcium uptake

Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemia mice with cachexia

Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia

The impact of formative testing on study behaviour and study performance of (bio)medical students: a smartphone application intervention study.

BACKGROUND: Formative testing can increase knowledge retention but students often underuse available opportunities. Applying modern technology to make the formative tests more attractive for students could enhance the implementation of formative testing as a learning tool. This study aimed to determine whether formative testing using an internet-based application ("app") can positively affect study behaviour as well as study performance of (bio)medical students. METHODS: A formative testing app "Physiomics, to the next level" was introduced during a 4-week course to a large cohort (n = 461) of Dutch first year (bio)medical students of the Radboud University. The app invited students to complete 7 formative tests throughout the course. Each module was available for 3-4 days to stimulate the students to distribute their study activities throughout the 4-week course. RESULTS: 72% of the students used the app during the course. Study time significantly increased in intensive users (p < 0.001), while no changes were observed in moderate (p = 0.07) and non-users (p = 0.25). App-users obtained significantly higher grades during the final exam of the course (p < 0.05). Non-users more frequently failed their final exam (34%, OR 3.6, 95% CI: 2.0-6.4) compared to moderate users (19%) and intensive users (12%). Students with an average grade <6.5 during previous courses benefitted most from the app, as intensive (5.8 ± 0.9 / 36%) and moderate users (5.8 ± 0.9 / 33%) obtained higher grades and failed their exam less frequently compared to non-users (5.2 ± 1.1 / 61%). The app was also well appreciated by students; students scored the app with a grade of 7.3 ± 1.0 out of 10 and 59% of the students indicated that they would like the app to be implemented in future courses. CONCLUSIONS: A smartphone-based application of formative testing is an effective and attractive intervention to stimulate study behaviour and improve study performance in (bio) medical students

Pilot study evaluating the effects of an intervention to enhance culturally appropriate hypertension education among healthcare providers in a primary care setting

Background: To improve hypertension care for ethnic minority patients of African descent in the Netherlands, we developed a provider intervention to facilitate the delivery of culturally appropriate hypertension education. This pilot study evaluates how the intervention affected the attitudes and perceived competence of hypertension care providers with regard to culturally appropriate care.Methods: Pre- and post-intervention questionnaires were used to measure the attitudes, experienced barriers, and self-reported behaviour of healthcare providers with regard to culturally appropriate cardiovascular and general care at three intervention sites (N = 47) and three control sites (N = 35).Results: Forty-nine participants (60%) completed questionnaires at baseline (T0) and nine months later (T1). At T1, healthcare providers who received the intervention found it more important to consider the patient's culture when delivering care than healthcare providers who did not receive the intervention (p = 0.030). The intervention did not influence ex

Parallel assessment of male reproductive function in workers and wild rats exposed to pesticides in banana plantations in Guadeloupe

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations.</p> <p>Methods</p> <p>A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans.</p> <p>Results</p> <p>No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats.</p> <p>Conclusion</p> <p>Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.</p

Bone resorption inhibitor alendronate normalizes the reduced bone thickness of TRPV5(-/-) mice.

Contains fulltext : 70385.pdf (publisher's version ) (Open Access)TRPV5 is a Ca(2+)-selective channel involved in transcellular Ca(2+) absorption expressed in kidney and in the ruffled border of osteoclasts. Studies in hypercalciuric TRPV5 knockout (TRPV5(-/-)) mice, which display significantly increased vitamin D levels, showed that TRPV5 ablation increases number and size of osteoclasts but impairs osteoclast-mediated bone resorption. The latter is not in line with the observed decreased bone thickness in TRPV5(-/-) mice. Bisphosphonates also inhibit osteoclast-mediated bone resorption. The aim of this study was to evaluate the effect of alendronate on the expression of the Ca(2+) transporters in bone, kidney, and duodenum and, importantly, the bone phenotype in TRPV5(-/-) mice. Wildtype (TRPV5(+/+)) and TRPV5(-/-) mice were treated during 10 wk with 2 mg/kg alendronate or vehicle weekly and housed in metabolic cages at the end of treatment. Urine and blood samples were taken for biochemical analysis, and duodenum, kidney, and femur were sampled. Expression of Ca(2+) transporters and osteoclast ruffled border transporters in bone and cultured osteoclasts was determined by QPCR analysis. Femurs were scanned using muCT, and resorption pit assays were performed in bone marrow cultures isolated from TRPV5(+/+) and TRPV5(-/-) mice. Alendronate treatment enhanced bone thickness in TRPV5(+/+) mice but also normalized the disturbed bone morphometry parameters in TRPV5(-/-) mice. Bone TRPV5 expression was specifically enhanced by alendronate, whereas the expression of Ca(2+) transporters in kidney and intestine was not altered. The expression of the osteoclast ruffled border membrane proteins chloride channel 7 (CLC-7) and the vacuolar H(+)-ATPase did not differ between both genotypes, but alendronate significantly enhanced the expression and PTH levels in TRPV5(-/-) mice. The expression of TRPV5, CLC-7, and H(+)-ATPase in osteoclast cultures was not affected by alendronate. The number of resorption pits was reduced in TRPV5(-/-) bone marrow cultures, but the response to vitamin D was similar to that in TRPV5(+/+) cultures. The alendronate-induced upregulation of TRPV5 in bone together with the decreased resorptive capacity of TRPV5(-/-) osteoclasts in vitro suggests that TRPV5 has an important role in osteoclast function. However, our data indicate that significant bone resorption still occurs in TRPV5(-/-) mice, because alendronate treatment normalized bone thickness in these mice. Thus, TRPV5(-/-) mice are able to rescue the resulting defect in osteoclast-mediated bone resorption, possibly mediated by the long-term hypervitaminosis D or other (non)hormonal compensatory mechanisms

SYMPTOMATOLOGY AND GROWTH IN INFANTS WITH COWS MILK PROTEIN INTOLERANCE USING 2 DIFFERENT WHEY-PROTEIN HYDROLYSATE BASED FORMULAS IN A PRIMARY HEALTH-CARE SETTING

Both growth and the course of allergic symptoms were evaluated in 79 infants with cow's milk protein intolerance, aged three months or younger, diagnosed by standard elimination/provocation and treated with a whey-hydrolysate based infant formula: Nutrilon Pept(R) or Pepti Junior(R). The efficacy of both products, in terms of symptomatology and growth, was compared with each other. The products differ in fat source (Pepti Junior 50% of its fat as MCT, Nutrilon Pepti normal LCT fat blend) and the presence of lactose (Pepti Junior: lactose free; Nutrilon Pepti: 40% of its carbohydrate as lactose). The study was part of a large project that aimed at standardising the approach towards cow's milk protein intolerance in Baby Health Clinics. Nearly 50 Baby Health Clinics participated in this project. In this study, growth and symptomatology (skin, respiratory tract, gastrointestinal tract) were monitored during an intervention period of at least 10 weeks. Infants in both feeding groups showed normal growth, and in at least 80% of the infants an improvement of the overall symptomatology could be seen during the intervention period. Most profound were the decreases in prevalence and severity of eczema and infantile colic. No differences in efficacy were found in this study between the two infant formulas. It was concluded that the exclusive use of either whey hydrolysate based infant formula resulted in an improvement of allergic symptoms and in normal growth in infants diagnosed by elimination/provocation for cow's milk protein intolerance in a Primary Health Care setting