Malaria and obesity: obese mice are resistant to cerebral malaria

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Metabolic Regulation in Progression to Autoimmune Diabetes

Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes

Bilateral cyclic cheek lesions related to premenstrual syndrome: a multifactorial pathogenesis?

Introduction Cheek biting is a chronic, usually innocuous, self-inXicted injury that often occurs as a parafunctional habit. Case report We report an unusual case of bilateral cyclic cheek lesions in a 34-year-old woman characterized by hyperkeratinization near the biting edges of the teeth and hematic lesions accompanied by a cheek swelling sensation, without pain and burning. The lesions coincided with a premenstrual syndrome, characterized by Xuid retention Introduction Cheek biting is a chronic, usually innocuous, self-inXicted injury that often occurs as a parafunctional habit. Case report We report an unusual case of bilateral cyclic cheek lesions in a 34-year-old woman characterized by hyperkeratinization near the biting edges of the teeth and hematic lesions accompanied by a cheek swelling sensation, without pain and burning. The lesions coincided with a premenstrual syndrome, characterized by Xuid retentionrelated symptoms, such as leg swelling, breast tenderness, bloatedness with abdominal girth variation and weight gain. Conclusions We concluded that the excessive water retention caused a little widespread swelling, present at cheeks level also, that associated with a temporary bruxism (perhaps related to psychological stress typical of premenstrual syndrome) was probably responsible for the cyclic cheek lesions. Therefore, an oral exam by the womens health care provider may be valuable in cases of premenstrual syndrome

Sulfur-containing cyclic ketimines and imino acids. A novel family of endogenous products in the search for a role.

Aminoethylcysteine, lanthionine, cystathionine and cystine are mono-deaminated either by l-amino-acid oxidase or by a transaminase exhibiting the properties described for glutamine transaminase. The deaminated products cyclize producing the respective ketimines. Authentic samples of each ketimine were prepared by reacting the appropriate aminothiol compound with bromopyruvate, except cystine ketimine which required the interaction of thiopyruvate with cystine sulfoxide. Reduction of the first three mentioned ketimines with NaBH4 yields the respective derivatives with the saturated rings of thiomorpholine and hexahydrothiazepine. The same reduction is carried out enzymically by a reductase extracted from mammalian tissues. Properties of the members of this family of compounds are described. Gas chromatography followed by mass spectrometry permits the identification of most of these products. HPLC is very useful for the determination of the ketimines by taking advantage of specific absorbance at 380 nm obtained by prior derivatization with phenylisothiocyanate. Adaptation of these and other analytical procedures to biological samples disclosed the presence of most of these compounds in bovine brain and in human urine. By using [35S]lanthionine ketimine as a representative member of the ketimine group, the specific, high-affinity, saturable and reversible binding to bovine brain membranes has been demonstrated. The binding is removed by aminoethylcysteine ketimine and by cystathionine ketimine indicating the occurrence in bovine brain of a common binding site for ketimines. The reduced ketimines are totally ineffective in competing with [35S]lanthionine ketimine. Alltogether these findings are highly indicative for the existence in mammals of a novel class of endogenous sulfur-containing cyclic products provided with a possible neurochemical function to be investigated further

Leptin in autoimmunity: many questions, some answers

It has recently become apparent that several molecules involved in the control of metabolism also play an important function in the regulation of immune responses. Among those molecules, the adipocyte-derived cytokine leptin has been shown to significantly influence innate and adaptive immune responses both in normal and in pathological conditions. For example, levels of leptin are typically low in infection and high in autoimmunity, both systemically and at the site of inflammation. Moreover, in addition to its long-known effects on the promotion of T helper 1 immune responses and cell-mediated immunity, leptin has more recently been found capable to constrain proliferation of regulatory T cells. As such, leptin represents not only a link between metabolism and immune responses in general but also a pivotal modulator of the magnitude of selected mechanisms of peripheral immunity in relation to body fat mass. We review here the most recent advances on the role of leptin in the control of immune tolerance and critically discuss how strategies aimed at neutralizing the leptin axis could represent innovative tools for the therapy of autoimmune disorders