Biomedical Research Laboratories (United States)

Upacicalcet (formerly SK-1403/AJT240) is a novel non-peptide calcimimetic agent that acts as a calcium-sensing receptor (CaSR) agonist for the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). We compared upacicalcet with other calcimimetics (etelcalcetide or cinacalcet) and examined its in vitro and in vivo characteristics in terms of its human CaSR agonistic activity, its efficacy in normal and CKD rats after a single administration, and its effect on gastric emptying in rats. Upacicalcet activated human CaSR depending on the extracellular calcium (Ca2+) concentration without exhibiting an agonistic action when the extracellular Ca2+ level was below the physiological level. On the other hand, etelcalcetide had an agonistic activity even in the absence of physiological levels of extracellular Ca2+. The intravenous administration of upacicalcet to normal and double-nephrectomized rats dose-dependently (0.03–3mg/kg and 0.3–30mg/kg, respectively) decreased the serum intact parathyroid hormone (iPTH) and serum Ca2+ levels; however, the effect of upacicalcet on the reduction in serum Ca2+ disappeared at extracellular Ca2+ levels below the physiologically range, even when administered at a dose higher (100-fold) than the effective dose. Furthermore, upacicalcet did not affect gastric emptying in normal rats when administered up to a dose of 10mg/kg (300-fold higher than the dose affecting serum iPTH levels), while the administration of cinacalcet significantly slowed gastric emptying by approximately 50%. These findings suggest that upacicalcet has potential as an alternative calcimimetic agent with good pharmacological properties and a lower risk of hypocalcemia and gastrointestinal complications.

In recent days, biological specimens are digitalized and digital images are available in virtual herbarium for teaching and learning process. Now, there is a need to explore possibilities of usage of barcodes and quick response (QR) codes in developing virtual herbarium for quick access as well as study the taxonomy of repository specimens. In order to establish a virtual herbarium for lichens using barcode and QR code techniques, lichen specimens such as Chrysothrix candelaris (L.) J.R.Laundon, Leucodermia leucomelos (L.) Kalb, Heterodernia flabellate (fee) D.D.Awasthi, Parmotrema andinum (Mull.Arg.) Hale, Parmotrema grayanum (Hue) Hale, Parmellinella stuppeum (Taylor) Hale, and Ramalina intermedia (Delise ex Nyl.) Nyl. were collected from the Eastern Ghats and the Western Ghats of Tamil Nadu, India and were identified based on morphological, anatomical and biochemical methods. Moreover, these specimens were preserved in the conventional lichen herbarium as reference materials for future studies. The barcodes and QR codes were generated for all the repository specimens to access the materials as well as to get a complete description of the lichen specimens. The generated barcodes provided the binomial name of lichen specimens along with their accession number. Similarly, the QR codes provided the digital image of lichen specimens along with complete descriptions such as distribution, habit and habitat, growth forms, name of the family, reproductive structure, chemistry, nature of thallus structure and lichen secondary metabolites. From these studies, we standardized a simple, rapid with reproducible protocol to develop a virtual herbarium for lichens to get the digital image and to access the complete descriptions of lichen specimens. This study might be useful for Lichenologists to get information about lichens in digital form and to maintain the lichen wealth for future regenerations without disturbing the lichen biodiversity.

An advanced transient optoelectronic method for time-resolved photoluminescence is developed; it is highly applicable and enables the accurate investigation of charge carrier diffusion in metal halide perovskite thin films.

White lighting-emitting diodes (WLEDs) using binary complementary color phosphors for n-UVLED chips are highly expected to realize a lighting source with high color rendering index and high luminous efficiency.

Functionalization of separation membranes with ion-exchange ligands allows control of the surface mobility of protein molecules facilitating optimized membrane design.

A novel series of RORγ inhibitors was identified starting with the HTS hit 1. After SAR investigation based on a prospective consideration of two drug-likeness metrics, ligand efficiency (LE) and fraction of sp(3) carbon atoms (Fsp(3)), significant improvement of metabolic stability as well as reduction of CYP inhibition was observed, which finally led to discovery of a selective and orally efficacious RORγ inhibitor 3z.

Diagnostic tests for visceral leishmaniasis that are based on antigens of a single Leishmania strain can have low diagnostic performance in regions where heterologous parasites predominate. The aim of this study was to investigate and compare the performance of five serological tests, based on different Leishmania antigens, in three endemic countries for visceral leishmaniasis. A total number of 231 sera of symptomatic and asymptomatic cases and controls from three endemic regions of visceral leishmaniasis in East Sudan, North India and South France were evaluated by following serological tests: rKLO8- and rK39 ELISA, DAT (ITMA-DAT) and two rapid tests of rK39 (IT LEISH) and rKE16 (Signal-KA). Overall, rKLO8- and rK39 ELISA were most sensitive in immunocompetent patients from all endemic regions (96–100%) and the sensitivity was reduced to 81.8% in HIV co-infected patients from France. Sera of patients from India demonstrated significantly higher antibody responses to rKLO8 and rK39 compared with sera from Sudan (p<0.0001) and France (p<0.0037). Further, some Indian and Sudanese patients reacted better with rKLO8 than rK39. Sensitivity of DAT (ITMA-DAT) was high in Sudan (94%) and India (92.3%) but low in France being 88.5% and 54.5% for VL and VL/HIV patients, respectively. In contrast, rapid tests displayed high sensitivity only in patients from India (96.2%) but not Sudan (64–88%) and France (73.1–88.5% and 63.6–81.8% in VL and VL/HIV patients, respectively). While the sensitivity varied, all tests showed high specificity in Sudan (96.7–100%) and India (96.6%).Heterogeneity of Leishmania parasites which is common in many endemic regions complicates the diagnosis of visceral leishmaniasis. Therefore, tests based on homologous Leishmania antigens are required for particular endemic regions to detect cases which are difficult to be diagnosed with currently available tests.

Diet‐related metabolic disorders are on the rise globally, and plant‐derived antioxidants may moderate these conditions. Palm fruit juice (PFJ) contains unique polyphenols with biological impact against various chronic diseases (Brit J Nutr 106:1664, 2011), including type 2 diabetes (T2DM) and metabolic syndrome in the Nile rat (NR). To examine these relationships, 84 male Wildtype NR were fed diabetogenic diets, as lab chow (#5020) or semipurified diets (CHO:fat:protein %En=70:10:20 or 40:43:17), in 4 experiments, with PFJ provided as a drink or mixed into the diet up to 1800ppm (GAE equiv). Body wt as well as random and fasting glucose were assessed for up to 6mo along with terminal organ weights, insulin, and plasma lipids to quantify T2DM. PFJ decreased blood glucose in all 4 experiments, and the anti‐diabetogenic effect correlated with polyphenol intake. PFJ was effective both as a drink and mixed into the diet, exerting positive effects on circulating insulin and liver, kidney and pancreas weight, without any observed negative effects. Data suggest mechanisms of preventing hyperglycemia may include reduced intestinal glucose absorption and/or stimulation of insulin secretion by protecting against ROS to preserve mitochondrial function (see related abstracts).Funding source: Foster Biomed Res Lab and the Malaysian Palm Oil Board