A novel secreted glycoprotein that regulates bone resorption has been identified. The protein, termed Osteoprotegerin (OPG), is a novel member of the TNF receptor superfamily. In vivo, hepatic expression of OPG in transgenic mice results in a profound yet nonlethal osteopetrosis, coincident with a decrease in later stages of osteoclast differentiation. These same effects are observed upon administration of recombinant OPG into normal mice. In vitro, osteoclast differentiation from precursor cells is blocked in a dose-dependent manner by recombinant OPG. Furthermore, OPG blocks ovariectomy-associated bone loss in rats. These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity.

We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow-derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

Summary Various bacterial species accumulate intracellular polyhydroxyalkanoates (PHAs) granules as energy and carbon reserves inside their cells. PHAs are biodegradable, environmentally friendly and biocompatible thermoplastics. Varying in toughness and flexibility, depending on their formulation, they can be used in various ways similar to many nonbiodegradable petrochemical plastics currently in use. They can be used either in pure form or as additives to oil‐derived plastics such as polyethylene. However, these bioplastics are currently far more expensive than petrochemically based plastics and are therefore used mostly in applications that conventional plastics cannot perform, such as medical applications. PHAs are immunologically inert and are only slowly degraded in human tissue, which means they can be used as devices inside the body. Recent research has focused on the use of alternative substrates, novel extraction methods, genetically enhanced species and mixed cultures with a view to make PHAs more commercially attractive.

The DALI Lifestyle Study Context: Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results. Objective: The aim of this study was to compare the effectiveness of three lifestyle interventions (Healthy eating (HE), Physical activity (PA) and both HE and PA (HE+PA)) with usual care (UC) in reducing GDM risk. Design: Multicentre Randomised Controlled Trial 2012-2014: The Dali Lifestyle Study Setting: Antenatal clinics across 11 centres in 9 European countries Patients: Consecutive pregnant women <20 weeks gestation with a BMI≥29 kg/m 2 and without GDM by IADPSG criteria (n=436).Intervention: Women were randomized, stratified by site, to Control, HE, PA or HE+PA. Women received 5 face-to-face and up to 4 telephone coaching sessions, based on the principles of motivational interviewing. Gestational weight gain (GWG) <5kg was targeted. Coaches received standardized training and an intervention toolkit tailored to their culture/language. Main outcome measures: GWG at 35-37 weeks, fasting glucose and insulin sensitivity (HOMA-IR) at 24-28 weeks. Results: We randomized 108 women to HE&PA, 113 to HE, 110 to PA and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially less GWG than controls by 35-37 weeks . Despite this reduction there were no improvements in fasting or post-load glucose or,insulin concentrations or HOMA-IR. Birthweight, large and small for gestational age rates were similar. Copyright 2016 DOI: 10.1210/jc.2016 Conclusions: The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycaemia. Lifestyle change alone is unlikely to prevent GDM among women with a BMI≥29 kg/m 2 .PRECIS: We studied pregnant women in a large European multi-centre RCT of physical activity and/or healthy eating and found no effect on GDM risk in spite of significant gestational weight gain limitation INTRODUCTIONGestational diabetes mellitus (GDM), high pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are independently associated with an increased risk of adverse perinatal outcomes, including macrosomia, operative delivery and shoulder dystocia (1). In GDM, such complications have a continuous relationship with maternal glucose concentrations during the oral glucose tolerance test (OGTT) (2). With the increasing prevalence of obesity in pregnancy and GDM (3), it has become increasingly important to develop evidence based clinical interventions that prevent the development of GDM and minimise excess GWG. The development of type 2 diabetes through intensive lifestyle interventions can be reduced by 58% over 4 years in non-pregnant women who have previously had GDM (4). However, whether GDM can be prevented through antenatal lifestyle interventions, even with limitation in excess GWG, is disputed (5). RCTs have provided variable evidence that lifestyle interventions 'work' (6); likely because of different intervention protocols and study populations. Furthermore, at the moment, no studies are available that assessed, ...

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Chronic Helicobacter pylori disease is reduced with Allium vegetable intake. This study was designed to assess the in vivo anti-H. pylori potential of a variety of garlic substances. The garlic materials all showed substantial but widely differing anti-H. pylori effects against all strains and isolates tested. The MICs (range, 8 to 32 g/ml) and minimum bactericidal concentrations (MBCs) (range, 16 to 32 g/ml) of undiluted garlic oil (GO) were smaller than those of garlic powder (GP) (MIC range, 250 to 500 g/ml; MBC range, 250 to 500 g/ml) but greater than the MIC of allicin (4.0 g/ml) ( Table 2) present in GP. Allicin (MIC, 6 g/ml; MBC, 6 g/ml) was more potent than diallyl disulfide (MIC range, 100 to 200 g/ml; MBC range, 100 to 200 g/ml), its corresponding sulfide, but of a strength similar to that of diallyl tetrasulfide (MIC range, 3 to 6 g/ml; MBC range, 3 to 6 g/ml). Antimicrobial activity of the diallyl sulfides increased with the number of sulfur atoms. Time course viability studies and microscopy showed dose-dependent anti-H. pylori effects with undiluted GO, GP, allicin, and diallyl trisulfide after a lag phase of ca. 1 to 2 h. Substantial in vitro anti-H. pylori effects of pure GO and GP and their diallyl sulfur components exist, suggesting their potential for in vivo clinical use against H. pylori infections.

In neonatal rodents, the beta-cell mass undergoes a phase of remodeling that includes a wave of apoptosis. Using both mathematical modeling and histochemical detection methods, we have demonstrated that beta-cell apoptosis is significantly increased in neonates as compared with adult rats, peaking at approximately 2 weeks of age. Other tissues, including the kidney and nervous system, also exhibit neonatal waves of apoptosis, suggesting that this is a normal developmental phenomenon. We have demonstrated that increased neonatal beta-cell apoptosis is also present in animal models of autoimmune diabetes, including both the BB rat and NOD mouse. Traditionally, apoptosis has been considered a process that does not induce an immune response. However, recent studies indicate that apoptotic cells can do the following: 1) display autoreactive antigen in their surface blebs; 2) preferentially activate dendritic cells capable of priming tissue-specific cytotoxic T-cells; and 3) induce the formation of autoantibodies. These findings suggest that in some circumstances physiological apoptosis may, in fact, initiate autoimmunity. Initiation of beta-cell-directed autoimmunity in murine models appears to be fixed at approximately 15 days of age, even when diabetes onset is dramatically accelerated. Taken together, these observations have led us to hypothesize that the neonatal wave of beta-cell apoptosis is a trigger for beta-cell-directed autoimmunity.

The antimicrobial effects of aqueous garlic extracts are well established but those of garlic oil (GO) are little known. Methodologies for estimating the antimicrobial activity of GO were assessed and GO, GO sulfide constituents, and garlic powder (GP) were compared in tests against human enteric bacteria. Test methodologies were identified as capable of producing underestimates of GO activity. Antimicrobial activity was greater in media lacking tryptone or cysteine, suggesting that, as for allicin, GO effects may involve sulfhydryl reactivity. All bacteria tested, which included both gram-negative and -positive bacteria and pathogenic forms, were susceptible to garlic materials. On a weight-of-product basis, 24 h MICs for GO (0.02 to 5.5 mg/ml, 62 enteric isolates) and dimethyl trisulfide (0.02 to 0.31 mg/ml, 6 enteric isolates) were lower than those for a mixture of diallyl sulfides (0.63 to 25 mg/ml, 6 enteric isolates) and for GP, which also exhibited a smaller MIC range (6.25 to 12.5 mg/ml, 29 enteric isolates). Viability time studies of GO and GP against Enterobacter aerogenes showed time-and dose-dependent effects. Based upon its thiosulfinate content, GP was more active than GO against most bacteria, although some properties of GO are identified as offering greater therapeutic potential. Further exploration of the potential of GP and GO in enteric disease control appears warranted.Garlic (Allium sativum) has traditional dietary and medicinal applications as an anti-infective agent (11,17). In vitro evidence of the antimicrobial activity of fresh and freeze-dried garlic extracts against many bacteria (5, 16), fungi (1), and viruses (20) supports these applications.Early steps involved in identifying the active constituents of garlic were the discovery that the compound allicin (allyl 2-propene thiosulfinate) is formed when garlic cloves are crushed (5, 6, 7) and that its formation depends upon the action of the enzyme alliinase of the bundle sheath cells upon the alliin of mesophyll cells (19). Methyl and allyl sulfide derivatives of allicin are formed by the steam distillation of mashed garlic (13) to produce garlic oil (GO), which is used in many medicinal garlic products.The classic studies of Cavallito and coworkers (5, 6, 7) attributed the antibacterial properties of garlic clove homogenates to allicin. These properties were confirmed against Escherichia coli and Staphylococcus aureus for garlic clove homogenates plus related garlic compounds and commercial supplements (9). In Cavallito's studies, antimicrobial activity was found neither with aqueous garlic extracts lacking allicin nor following the addition of GO or diallyl sulfides (5) and no allyl sulfides were found in freshly prepared aqueous garlic clove extracts (6). Also, an early gas chromatographic study (4) indicated that the relatively rapid decomposition of allicin present in aqueous garlic extracts (14) involved transformation mainly to diallyl sulfides. For these reasons it was concluded that GO and its constituent sulfides lack antimi...