Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.     

Little Rock Lake (Wisconsin): Perspectives on an experimental ecosystem approach to seepage lake acidification

Ecosystem-level experiments are essential in assessing the effects of environmental perturbations like acidification. To date in North America, such experiments have been rare and geographically limited to drainage lakes in south-western Ontario and to streams in the northeastern US. Seepage lakes, which are the dominant hydrologic type in large regions of the US, have received limited attention from many perspectives, including whole-system manipulation. The Little Rock Lake Acidification Project was initiated to expand insights from previous acidification experiments with whole drainage lakes to a seepage lake system. It involves the gradual acidification of a small (18 ha), seepage lake in northcentral Wisconsin. The lake has been divided into a treatment and reference basin using a flexible, inert barrier; and the treatment basin is being acidified in steps of 0.5 pH units/2 yr period from a starting pH of 6.1 to a final pH of 4.6 (roughly the average pH of rain in this region). The goals are to document the biological and chemical changes which occur, to identify the direct and indirect mechanisms which regulate responses, and to expand insights to a class of lakes previously understudied. In this paper, we describe the history and rationale of the project and we discuss in general terms the utility and constraints of whole-ecosystem manipulations.     

Ghrelin increases food intake in obese as well as lean subjects

OBJECTIVE: To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of ghrelin. DESIGN: Randomised, double-blind, placebo-controlled study of intravenous ghrelin at doses 1 pmol/kg/min and 5 pmol/kg/min. SUBJECTS: In all, 12 healthy lean subjects (mean body mass index (BMI) 20.5+/-0.17 kg/m(2)) and 12 healthy overweight and obese subjects (mean BMI 31.9+/-1.02 kg/m(2)). MEASUREMENTS: Food intake, appetite and palatability of food, ghrelin and other obesity-related hormones, growth hormone. RESULTS: Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only (mean increase 36.6+/-9.4%, P<0.01.) High-dose ghrelin infusion increased energy intake in both groups (mean increase 20.1+/-10.6% in the lean and 70.1+/-15.5% in the obese, P<0.01 in both cases.) Ghrelin infusion increased palatability of food in the obese group. CONCLUSION: Ghrelin increases food intake in obese as well as lean subjects. Obese people are sensitive to the appetite-stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity.     

Syringe possession arrests are associated with receptive syringe sharing in two Mexico-US border cities.

AIMS: To identify factors associated with receptive syringe sharing among injection drug users (IDUs) and elucidate the association between syringe possession arrests and syringe sharing. DESIGN: Cross-sectional study. SETTING: Mexican border cities of Tijuana, Baja California and Ciudad Juarez, Chihuahua. PARTICIPANTS: IDUs in Tijuana (n = 222) and Ciudad Juarez (n = 206) were recruited using respondent-driven sampling (RDS). IDUs were > or = 18 years and had injected illicit drugs in the past month. MEASUREMENTS: An interviewer-administered survey was used to collect quantitative data on socio-demographic, behavioral and contextual characteristics, including self-reported syringe sharing and arrests for syringe possession. Associations with receptive syringe sharing were investigated using logistic regression with RDS adjustment. FINDINGS: Overall, 48% of participants reported ever being arrested for carrying an unused/sterile syringe, even though syringe purchase and possession is legal in Mexico. Arrest for possessing unused/sterile syringes was associated independently with receptive syringe sharing [adjusted odds ratio (AOR) = 2.05; 95% confidence interval (CI): 1.26, 3.35], as was injecting in a shooting gallery (AOR = 3.60; 95% CI: 2.21, 5.87), injecting in the street (AOR = 2.05; 95% CI: 1.18, 3.54) and injecting methamphetamine (AOR = 2.77; 95% CI: 1.41, 5.47) or cocaine (AOR = 1.96; 95% CI: 1.15, 3.36). More than half of participants (57%) had been arrested for possessing a used syringe; in a second model, arrest for used syringe possession was also associated independently with receptive sharing (AOR = 2.87; 95% CI: 1.76, 4.69). CONCLUSIONS: We documented high levels of syringe-related arrests in two Mexican-US border cities and an independent association between these arrests and risky injection practices. Public health collaborations with law enforcement to modify the risk environment in which drug use occurs are essential to facilitate safer injection practices.     

Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA- 5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.     

Regenerative peripheral nerve interfaces for real-time,proportional control of a Neuroprosthetic hand

Introduction

Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control.

Methods

Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs.

Results

Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R²?=?0.758 and R²?=?0.802, respectively).

Conclusion

EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.

     

Economic vulnerability,violence, and sexual risk factors for HIV among female sex workers in Tijuana,Mexico

AIDS and Behavior - Economic vulnerability is often reported to underlie involvement in sex work among female sex workers (FSW), but may also create urgency in women’s work, limiting...     

Cholangiocyte endothelin 1 and transforming growth factor beta1 production in rat experimental hepatopulmonary syndrome

BACKGROUND & AIMS: Hepatic production and release of endothelin 1 plays a central role in experimental hepatopulmonary syndrome after common bile duct ligation by stimulating pulmonary endothelial nitric oxide production. In thioacetamide-induced nonbiliary cirrhosis, hepatic endothelin 1 production and release do not occur, and hepatopulmonary syndrome does not develop. However, the source and regulation of hepatic endothelin 1 after common bile duct ligation are not fully characterized. We evaluated the sources of hepatic endothelin 1 production after common bile duct ligation in relation to thioacetamide cirrhosis and assessed whether transforming growth factor beta1 regulates endothelin 1 production. METHODS: Hepatopulmonary syndrome and hepatic and plasma endothelin 1 levels were evaluated after common bile duct ligation or thioacetamide administration. Cellular sources of endothelin 1 were assessed by immunohistochemistry and laser capture microdissection of cholangiocytes. Transforming growth factor beta1 expression and signaling were assessed by using immunohistochemistry and Western blotting and by evaluating normal rat cholangiocytes. RESULTS: Hepatic and plasma endothelin 1 levels increased and hepatopulmonary syndrome developed only after common bile duct ligation. Hepatic endothelin 1 and transforming growth factor beta1 levels increased over a similar time frame, and cholangiocytes were a major source of each peptide. Transforming growth factor beta1 signaling in cholangiocytes in vivo was evident by increased phosphorylation and nuclear localization of Smad2, and hepatic endothelin 1 levels correlated directly with liver transforming growth factor beta1 and phosphorylated Smad2 levels. Transforming growth factor beta1 also stimulated endothelin 1 promoter activity, expression, and production in normal rat cholangiocytes. CONCLUSIONS: Cholangiocytes are a major source of hepatic endothelin 1 production during the development of hepatopulmonary syndrome after common bile duct ligation, but not in thioacetamide-induced cirrhosis. Transforming growth factor beta1 stimulates cholangiocyte endothelin 1 expression and production. Cholangiocyte-derived endothelin 1 may be an important endocrine mediator of experimental hepatopulmonary syndrome.     

Alcohol-induced increases in insulin-like growth factor binding protein-1 are partially mediated by TNF

BACKGROUND: Alcohol (EtOH) alters the plasma and tissue content of insulin-like growth factor (IGF)-I, an important anabolic hormone. However, the bioavailability and bioactivity of IGF-I can also be modulated by changes in soluble proteins that bind IGF-I (IGFBPs). The purpose of the present study was to determine whether EtOH intoxication in rats alters the plasma concentration and tissue mRNA content of various IGFBPs. Based on initial results subsequent studies were performed to assess potential mechanisms by which EtOH increased IGFBP-1. METHODS: Rats were administered EtOH (75 mmol/kg) and blood and tissues collected at various times thereafter. Separate groups of rats were also pretreated with 4-methylpyrazole (4-MP; alcohol dehydrogenase inhibitor), cyanamide (inhibitor of acetaldehyde metabolism), RU486 (glucocorticoid receptor antagonist) or the tumor necrosis factor (TNF) antagonist (TNF(BP)) prior to EtOH administration. RESULTS: Acute EtOH intoxication did not alter the mRNA content of IGFBP-3, -4 or -5 in liver or kidney. However, EtOH increased IGFBP-1 in blood (5-fold), which was associated with an up-regulation of IGFBP-1 mRNA content in liver and kidney (2- to 3-fold). Likewise, the injection of the nonmetabolizable alcohol -butanol also increased IGFBP-1 in plasma, liver, and kidney. The increased IGFBP-1 in blood and tissues was not prevented by inhibiting alcohol metabolism with 4-MP. However, pretreatment with cyanamide markedly accentuated the EtOH-induced increase in IGFBP-1 in blood (20-fold), liver (3.5-fold), and kidney (12-fold), indicating that accumulation of acetaldehyde can enhance IGFBP-1 synthesis. A time course study indicated that EtOH increased plasma IGFBP-1 levels as early as 0.5-1 hr, and that this response was associated with elevated IGFBP-1 mRNA in liver but not kidney. Pretreatment with RU486 did not prevent or attenuate the EtOH-induced increase in IGFBP-1. However, the alcohol-induced increase in IGFBP-1 was attenuated by TNF(BP). CONCLUSIONS: These data suggest that the acute alcohol-induced increase in IGFBP-1 is mediated, at least in part, by TNF and is independent of EtOH metabolism and increases in endogenous glucocorticoids.