Search

Snake venoms are natural sources of biologically active molecules that are able to act selectively and specifically on different cellular targets, modulating physiological functions. Thus, these mixtures, composed mainly of proteins and peptides, provide ample and challenging opportunities and a diversified molecular architecture to design and develop tools and agents of scientific and therapeutic interest. Among these components, peptides and small proteins play diverse roles in numerous physiological processes, exerting a wide range of pharmacological activities, such as antimicrobial, antihypertensive, analgesic, antitumor, analgesic, among others. The pharmaceutical and cosmetic industries have recognized the huge potential of these privileged frameworks and believe them to be a promising alternative to contemporary drugs. A number of natural or synthetic peptides from snake venoms have already found preclinical or clinical applications for the treatment of pain, hypertension, cardiovascular diseases and aging skin. A well-known example is captopril, whose natural peptide precursor was isolated from Bothrops jararaca snake venom, which is a peptide-based drug that inhibits the angiotensin-converting enzyme, producing an anti-hypertensive effect. The present review looks at the main peptides (natriuretic peptides, bradykinin-potentiating peptides and sarafotoxins) and low mass proteins (crotamine, disintegrins and three-Finger toxins) from snake venoms, as well as synthetic peptides inspired by them, describing their biochemical, structural and physiological features, as well as their applications as research tools and therapeutic agents.

A 6.5 kDa serine protease inhibitor was purified by anion-exchange chromatography from the crude extract of the Inga umbratica seeds, containing inhibitor isoforms ranging from 6.3 to 6.7 kDa and protease inhibitors of ∼19 kDa. The purified protein was characterized as a potent inhibitor against trypsin and chymotrypsin and it was named I. umbratica trypsin and chymotrypsin inhibitor (IUTCI). MALDI-TOF spectra of the IUTCI, in the presence of DTT, showed six disulfide bonds content, suggesting that this inhibitor belongs to Bowman-Birk family. The circular dichroism spectroscopy indicates that IUTCI is predominantly formed by unordered and -sheet secondary structure. It was also characterized, by fluorescence spectroscopy, as a stable protein at range of pH from 5.0 to 7.0. Moreover, this inhibitor at concentration of 75 M presented a remarkable inhibitory activity (60) against digestive serine proteases from boll weevil Anthonomus grandis, an important economical cotton pest.

Using a combination of in situ FTIR spectroscopy and detailed surface analysis, we find that TMGa decomposes at the same rate in either hydrogen or nitrogen forT< 300° C. Although ammonia does not decompose under these conditions, mixing TMGa with ammonia increases the rate of methane formation. Reacting perdeutroammonia with TMGa shows that hydrogen from the ammonia is incorporated into the product methane (whereas deuterium in the gas phase is not incorporated into the gaseous product). TMGa and ND3do react; however, nitrogen incorporation in the growing film is temperature dependent. Further, although the decomposition of TMGa occurs in the gas phase, the last steps of the decomposition/reaction occur on the substrate surface.

We present preliminary results of long-slit spectroscopic observations of the extended emission line region (hereafter, EELR) in NGC 4388. We detect broad emission lines in the line complexes Hα+[NII] and [SII] which can be modelled by the superposition of several narrow components. Multicomponent line profiles appear at positions very close to the ionization cone axis. There is also some correspondence with the radio emission, which suggests that there is interaction between the radio jets and the ionized gas. We do not confirm the claim of a broad Hα component (FWZI=4000 km/s) by Shields and Filippenko (1996).

ABSTRACTRavuconazole (RCZ) was evaluated for efficacy in comparison to fluconazole (FCZ) and itraconazole (ITZ) in murine models of disseminated histoplasmosis. All regimens tested prolonged survival (P< 0.05 to 0.0001). At equivalent doses of 50 mg/kg of body weight, RCZ and ITZ were equally effective and RCZ was more effective than FCZ (P= 0.02). Clearance of fungal burden from the livers and spleens of mice showed RCZ and ITZ at doses of 50 mg/kg to be efficacious but not curative. These data indicate that RCZ should be studied further.

BackgroundPaediatric ulcerative colitis (UC) patients would be well-served by a non-steroidal drug to control mucosal inflammation, without long-term and costly commitment to biologics. Vamorolone is a first-in-class alternative to glucocorticoids (GCs), under development for children with Duchenne muscular dystrophy (DMD); preliminary findings demonstrate improved safety compared with GCs1,2. We sought to define NFkB-regulated, GC-responsive serum biomarkers for use in a proof-of-concept pilot trial of vamorolone in UC, focusing on TFF3 (produced by intestinal epithelia, GC-responsive in UC), and CCL22 (produced by macrophages, GC-responsive in UC and other inflammatory diseases)3,4.MethodsSera from 10 children with IBD (7 UC, 3 CD) were tested pre and post prednisone/prednisolone (1 mg/kg/day, max 40 mg, 1–4 weeks); 210 proteins responsive to GCs in UC 3were analyzed using SOMAscan. Proteins that showed significant change over time were correlated with change in Paediatric Ulcerative Colitis Activity Index (PUCAI) (p < 0.05 significance). Percent change in circulating CCL22 was compared with percent change in DMD patients treated with vamorolone (2 and 6 mg/kg/day, 2 weeks)2. Immunoassays were utilized to validate SOMAscan data.ResultsCCL22 and TFF3 validated as decreased by GCs in IBD (p=0.005, p < 0.001). Decrease in TFF3 correlated with decrease in PUCAI (r=0.741, p=0.022); decrease in CCL22 did not correlate with change in PUCAI. Magnitude of CCL22 decrease in GC-treated UC patients was comparable to that seen in DMD patients treated with 6 mg/kg of vamorolone (47% vs. 33%). SOMAscan findings in UC validated by immunoassays.ConclusionDecreases in serum CCL22 likely reflect effect on innate immune response, while decreases in serum TFF3 may reflect intestinal-specific effects of GCs in UC. CCL22 and TFF3, measured by immunoassays, may be useful as objective secondary outcomes reflective of NFkB inhibition and anti-inflammatory activity in a proof-of-concept trial of vamorolone in paediatric UC.ReferencesHoffman EP, et al. Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes. Steroids. 2018 Jun;134:43–52.Conklin LS, et al. Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. Pharmacol Res. 2018 Oct;136:140–150.Heier CM, et al. Identification of pathway-specific serum biomarkers of response to glucocorticoid and infliximab treatment in children with inflammatory bowel disease. Clin Transl Gastroenterol. 2016 Sep 15;7(9): e192.Conklin LS, et al. Serum biomarkers of glucocorticoid response and safety in anti-neutrophil cytoplasmic antibody-associated vasculitis and juvenile dermatomyositis. Steroids. 2018 Dec; 140:159–166.Disclosure(s)LSC, JNvdA, and EPH are employees of ReveraGen BioPharma. LSC and JNvdA own stock options of ReveraGen. EPH is a co-founder of ReveraGen and owns founder shares.

This article presents information on dieting practices among high school students or has been on a diet in the recent past. Dieting behaviors are likely to be unhealthy, particularly during the adolescent years. Dieting in this age group is concerning because the risk of nutrient deficiencies. The goal of a recent study was to determine the patterns and frequency of dieting behaviors in a high school population in a metropolitan area. The survey instrument consisted of demographic questions including students' self-reported heights and weights and questions regarding dieting practices. Weights were classified according to the body mass index (BMI). A total of 146 student surveys were included in this analysis.

Submicron heterojunction bipolar transistors (HBTs) with maximum frequency of oscillation, fMAX, of 91 GHz have been fabricated using a self-aligned technique and a very heavily carbon-doped (1020cm-3) base layer. Since the quenching of photoluminescence (PL) intensity in heavily-doped GaAs is mainly due to nonradiative recombination in the bulk material, while contribution from surface recombination is negligible, the use of a heavily carbon-doped base layer in AlGaAs/GaAs HBTs minimizes the influence of surface recombination in the extrinsic base region. Thus, for HBTs with a heavily doped base layer, the "emitter size effect" (degradation of HBT current gain) is greatly reduced when the emitter width is scaled down to submicron (0.6 µm) dimensions.

In 1995, the first Venezuelan equine encephalitis (VEE) outbreak in Colombia in 22 years caused an estimated 75,000 human cases, 3000 with neurologic complications and 300 fatal, in La Guajira State. Of the state's estimated 50,000 equines, 8% may have died. An epizootic IC virus, probably introduced from Venezuela, was rapidly amplified among unvaccinated equines. Record high rainfall, producing high densities of vector Aedes taeniorhynchus, led to extensive epidemic transmission (30% attack rate) in the four affected municipalities. Native Wayuu Indians, constituting 24% of the state's population, were at increased risk of infection (risk ratio, 3.3; 95% confidence interval, 2.2–5.3). Epidemiologic studies found no evidence of human-to-human transmission. A higherthan- expected number of abortions during the outbreak confirmed a previously suspected abortifacient role of VEE infection. Pesticide applications and a mass equine vaccination program contributed to preventing the outbreak's spread south of La Guajira.