No abstract

It was concluded from the present trial that serial 1% tretinoin peel is a well tolerated and as effective a therapy for melasma in dark-skinned individuals as a standard and well-tried chemical peel, 70% glycolic acid, although larger trials over longer periods may be necessary to substantiate such findings.

Takeda G protein-coupled receptor 5 (TGR5) agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L cells, a potentially therapeutic action against metabolic diseases such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and Type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects, including inhibition of gallbladder emptying. Here, we characterize RDX8940, a novel, orally administered TGR5 agonist designed to have minimal systemic effects and investigate its activity in mice fed a Western diet, a model of NAFLD and mild insulin resistance. Agonist activity, binding selectivity, toxicity, solubility, and permeability of RDX8940 were characterized in standard in vitro models. RDX8940 pharmacokinetics and effects on GLP secretion, insulin sensitivity, and liver steatosis were assessed in C57BL/6 mice fed normal or Western diet chow and given single or repeated doses of RDX8940 or vehicle, with or without dipeptidyl peptidase-4 (DPP4) inhibitors. Gallbladder effects were assessed in CD-1 mice fed normal chow and given RDX8940 or a systemic TGR5 agonist or vehicle. Our results showed that RDX8940 is minimally systemic, potent, and selective, and induces incretin (GLP-1, GLP-2, and peptide YY) secretion. RDX8940-induced increases in plasma active GLP-1 (aGLP-1) levels were enhanced by repeated dosing and by coadministration of DPP4 inhibitors. RDX8940 increased hepatic exposure to aGLP-1 without requiring coadministration of a DPP4 inhibitor. In mice fed a Western diet, RDX8940 improved liver steatosis and insulin sensitivity. Unlike systemic TGR5 agonists, RDX8940 did not inhibit gallbladder emptying. These results indicate that RDX8940 may have therapeutic potential in patients with NAFLD/NASH. NEW & NOTEWORTHY Takeda G protein-coupled receptor 5 (TGR5) agonists have potential as a treatment for nonalcoholic steatohepatitis and nonalcoholic fatty liver disease (NAFLD) but have until now been associated with undesirable side effects associated with systemic TGR5 agonism, including blockade of gallbladder emptying. We demonstrate that RDX8940, a potent, selective, minimally systemic oral TGR5 agonist, improves liver steatosis and insulin sensitivity in a mouse model of NAFLD and does not inhibit gallbladder emptying in mice.

No abstract

We report a rare case of chromoblastomycosis caused by a non-sporulating species of Rhytidhysteron (Order Patellariales, Ascomycota) which was identified by molecular methods. The patient was a post-renal transplant recipient male aged 50 years and a resident of Delhi. The diagnosis was made by direct microscopy, histopathology and isolation of multiple colonies of the dematiaceous mould in pure culture. The samples used to recover the organism were obtained from a biopsy of one of the lesions occurring on his left foot and extending to the shin and thigh. The lesions comprised necrotic granulation tissue with indurated and thickened margins. After 2 weeks of therapy with itraconazole, 100 mg twice daily, the lesions partially retracted. However, the patient developed complications of acute abdominal pain with respiratory distress, necessitating admission to a tertiary-care hospital where he died due to multiple organ failure within 48 h. All attempts to induce sporulation of the fungal isolate on various mycological culture media were unsuccessful. Thereafter, sequencing of the 18S rRNA gene of the isolate and its comparison with GenBank database revealed that the fungus belonged to the genus Rhytidhysteron. As far as we are aware, this is the first case of human infection caused by a fungus of the Order Patellariales. The case underlines the relevance of molecular techniques as valuable tools for identification of non-sporulating opportunistic pathogenic fungi.

Certain linkage positions in oligosaccharides can be discerned by collision-activated dissociation mass spectrometry, rationalized by molecular modelling. Previous work on synthetic oligosaccharides has suggested that daughter ion patterns can distinguish among intact compounds which terminate in alpha-L-fucose and have a penultimate amino sugar. The current study indicates that these observations can be extended to oligosaccharides terminating in beta-D-galactose. In addition, we have observed that protonated, ammoniated and lithiated molecular ions all produce linkage-specific daughter ion spectra in these two sets of oligosaccharides. Sodiated molecular ions could be fragmented usefully under high collision energy offset conditions; potassiated ions were stable and not dissociable under conditions available in a triple-quadrupole instrument. We also show linkage discernment among the permethylated set of these six synthetic oligosaccharides. Methylated derivatives of this set of compounds give more useful product ions, including a 3-linkage specific ion. A novel relationship was noted by a plot of collision energy against (daughter ion/parent ion) ratio, which gave a unique slope for each of the non-reducing terminal linkage positions 3, 4 and 6 in the set of six compounds. The slope of this plot is related to the ability of each linkage position in the oligosaccharide to absorb collisional energy. Rotational freedom of the individual glycosidic linkage is hypothesized to play a role in this phenomenon.

BACKGROUND. Chemical peels have become a popular method for treating melasma. Although daily topical 0.05 and 0.1% tretinoin have been used for melasma, the therapy takes at least 4 to 6 months to produce clinically significant lightening. In a recent trial, 1% tretinoin peel has shown good clinical and histologic results after biweekly applications in 2.5 weeks only in the treatment of melasma. OBJECTIVE. Because there is a paucity of studies evaluating the efficacy and safety of 1% tretinoin peel in the treatment of melasma in dark-skinned Asian population, we conducted a pilot study to evaluate the efficacy and side effects of this potentially new peeling agent versus a standard peeling agent, 70% glycolic acid, in the treatment of melasma in Indian women. METHODS. Ten female patients of melasma, after written consent, were taken up for an open left-right comparison pilot study of 12 weeks. One percent tretinoin peel was applied on one-half of the face, whereas 70% glycolic acid was applied on

Hi-MELASQOL is a reliable and validated tool to measure the quality of life in Indians with melasma.