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.     

The relation between bundle branch block and cardiac enlargement

The size of the heart was ascertained at necropsy or by roentgenologic examination in 100 consecutive cases of typical bundle branch block.The clinical diagnoses were: arteriosclerotic heart disease, 58 per cent; coronary artery occlusion, 25 per cent; chronic rheumatic valvular disease, 9 per cent; and miscellaneous conditions, 8 per cent.The heart was enlarged in all cases in which it was examined post mortem; the average cardiac weight was 586 Gm., the lowest, 375 Gm.Of the cases in which there was only a roentgenographic examination, the heart was increased in size in 91 per cent. In three of the six cases in which there was no enlargement, the diagnosis was Graves' disease.Left bundle branch block was present in 90 per cent of the cases. In 71 per cent of these the left ventricle was larger than the right, and in none was the right ventricle preponderant. Hypertensive heart disease was almost invariably associated with left bundle branch block.Of the ten cases of right bundle branch block, the right ventricle was predominant in four, and the left ventricle in one. Both ventricles were enlarged in five cases of coronary artery occlusion.Diffuse myocardial involvement was found in all cases in which a necropsy was performed.It is concluded that, in most instances, chronic bundle branch block is the result of an increase in the size of the heart, and of myocardial damage, with diffuse involvement of the bundle branch system. The type of bundle branch block depends on which ventricle is predominantly enlarged.     

Facteurs de croissance intestinaux

The rate of cell proliferation is under the control of humoral factors, luminal nutrition and intestinal growth factors which maintain mucosal homeostasis by highly complex mechanisms. Among endocrine effectors, growth hormone (GH) has been noted to exert a trophic effect on the small intestine and stimulates the bowel morphologic and proliferative adaptation after resection. These effects may be mediated by IGF-I. The nutrients (lipids > proteins > polysacharids) and polyamines are the main effectors in the control of mucosal proliferation.A number of intestinal growth factors whose expression may be regulated by luminal or hormonal effectors may play an important role in the control of intestinal growth. Milk EGF (Epidermal Growth Factor) has a trophic effect in the suckling rat. In the adult only systemic EGF stimulates intestinal growth after resection, infection or treatment with methotrexate. TGFα (Transforming Growth Factor alpha), a ligand that binds to the same receptor as EGF, exerts the same trophic responses. TGFα may be the more physiologically ligand of the EGF receptor in the adult. In addition TGFα may be implicated in the progression of colonic tumours. IGF-I and IGF-II (Insulin-like Growth Factor), polypeptides structurally homologous to proinsulin, have mitogenic, morphogenic and metabolic properties. The members of the FGF (Fibroblast Growth Factor) family have only a moderate effect on the growth of intestinal epithelial cells and a main role in the repair of damaged tissue. TGFβ (Transforming Growth Factor) is an inhibitor of intestinal epithelial cell growth in the G1 phase of the cell cycle. TGFβ may be the physiological regulator of apoptosis in the colonic epithelium and the loss of this function may favour tumour progression. TGFβ also induces the production of constituents of the extracellular matrix and promotes the healing of wounded tissue.     

Brief Report: Dynamic calcium signals mediate the feeding response of the carnivorous sundew plant

Some of the most spectacular examples of botanical carnivory—in which predator plants catch and digest animals presumably to supplement the nutrient-poor soils in which they grow—occur within the Droseraceae family. For example, sundews of the genus Drosera have evolved leaf movements and enzyme secretion to facilitate prey digestion. The molecular underpinnings of this behavior remain largely unknown; however, evidence suggests that prey-induced electrical impulses are correlated with movement and production of the defense hormone jasmonic acid (JA), which may alter gene expression. In noncarnivorous plants, JA is linked to electrical activity via changes in cytoplasmic Ca²⁺. Here, we find that dynamic Ca²⁺ changes also occur in sundew (Drosera spatulata) leaves responding to prey-associated mechanical and chemical stimuli. Furthermore, inhibition of these Ca²⁺ changes reduced expression of JA target genes and leaf movements following chemical feeding. Our results are consistent with the presence of a conserved Ca²⁺-dependent JA signaling pathway in the sundew feeding response and provide further credence to the defensive origin of plant carnivory.     

Exploring the Utility of Recombinant Snake Venom Serine Protease Toxins as Immunogens for Generating Experimental Snakebite Antivenoms

Snakebite is a neglected tropical disease that causes high rates of global mortality and morbidity. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Despite polyclonal antibody-based antivenoms being the mainstay life-saving therapy for snakebite, they are associated with limited cross-snake species efficacy, as there is often extensive toxin variation between snake venoms, including those used as immunogens for antivenom production. This restricts the therapeutic utility of any antivenom to certain geographical regions. In this study, we explored the feasibility of using recombinantly expressed toxins as immunogens to stimulate focused, pathology-specific, antibodies in order to broadly counteract specific toxins associated with snakebite envenoming. Three snake venom serine proteases (SVSP) toxins, sourced from geographically diverse and medically important viper snake venoms, were successfully expressed in HEK293F mammalian cells and used for murine immunisation. Analyses of the resulting antibody responses revealed that ancrod and RVV-V stimulated the strongest immune responses, and that experimental antivenoms directed against these recombinant SVSP toxins, and a mixture of the three different immunogens, extensively recognised and exhibited immunological binding towards a variety of native snake venoms. While the experimental antivenoms showed some reduction in abnormal clotting parameters stimulated by the toxin immunogens and crude venom, specifically reducing the depletion of fibrinogen levels and prolongation of prothrombin times, fibrinogen degradation experiments revealed that they broadly protected against venom- and toxin-induced fibrinogenolytic functional activities. Overall, our findings further strengthen the case for the use of recombinant venom toxins as supplemental immunogens to stimulate focused and desirable antibody responses capable of neutralising venom-induced pathological effects, and therefore potentially circumventing some of the limitations associated with current snakebite therapies.     

The GIST of Targeted Therapy for Malignant Melanoma

The high response rates to the tyrosine kinase inhibitor imatinib in KIT-mutated gastrointestinal stromal tumors (GIST) has led to a paradigm shift in cancer treatment. In a parallel fashion, the field of melanoma is shifting with the utilization of targeted therapy to treat BRAF-mutated melanoma. We reviewed published literature in PubMed on GIST and melanoma, with a focus on both past and current clinical trials. The data presented centers on imatinib, vemurafenib, and most recently dabrafenib, targeting KIT and BRAF mutations and their outcomes in GIST and melanoma. The BRAF^V600E melanoma mutation, like the KIT exon 11 mutation in GIST, has the highest response to therapy. High response rates with inhibition of KIT in GIST have not been recapitulated in KIT-mutated melanoma. Median time to resistance to targeted agents occurs in ~7 months with BRAF inhibitors and 2 years for imatinib in GIST. In GIST, the development of secondary mutations leads to resistance; however, there have been no similar gatekeeper mutations found in melanoma. Although surgery remains an important component of the treatment of early GIST and melanoma, surgeons will need to continue to define the thresholds and timing for operation in the setting of metastatic disease with improved targeted therapies. Combination treatment strategies may result in more successful clinical outcomes in the management of melanoma in the future.     

Severe Hypoglycemia Due to Cryptic Insulin Use in a Bodybuilder

Background

Bodybuilding is a demanding sport, which requires high-volume, high-resistance weight training and augmented nutritional intake, toward an increase of overall body muscle mass accompanied by an overall decrease of body fat percentage and mass. Among bodybuilders, the use of various legal and illegal supplements is common. These supplements may be naturally occurring or man-made.

Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

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