Snakebites By Bothrops Spp In Children In Campinas, São Paulo, Brazil.

From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y) were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7% as moderate envenoming and 20.6% as severe envenoming. Two patients (2.7%) showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5%), pain (94.5%) ecchymosis (73.9%) and blisters (11%). Local and/or systemic bleeding was observed in 28.8% of the patients. Before antivenom (AV) administration, blood coagulation disorders were observed in 60.7% (incoagulable blood in 39.3%) of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6% of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). The main clinical complications observed were local infection (15.1%), compartment syndrome (4.1%), gangrene (1.4%) and acute renal failure (1.4%). No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75) or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55). The frequency of local infection was significantly greater in severe cases (p < 0.001). Patients admitted more than 6 h after the bite had a higher risk of developing severe envenoming (p = 0.04).43329-3

Antinociceptivna i protuupalna svojstva vodeno-etanolnog ekstrakta pokožice grožđa vrste Vitis labrusca izolirane iz otpada vinske industrije

Research background. Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach. A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions. In all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50% of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution. This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.Pozadina istraživanja. Ekstrakt komine grožđa, kao i vino, ima mnoga biološka svojstva, poput antioksidacijskog i protuupalnog učinka. Nažalost, proizvođači vina odbacuju neiskorišteni trop iako sadržava bioaktivne spojeve s antioksidacijskim i protuupalnim svojstvima. Svrha je ovoga rada bila ispitati antinociceptivna i protuupalna svojstva vodeno-etanolnog ekstrakta pokožice grožđa vrste Vitis labrusca iz agroindustrijskog otpada. Značaj je ovoga istraživanja u tome što se korištenjem otpada daje dodatna ekonomska vrijednost grožđu u uzgojnom lancu. Eksperimentalni pristup. Ekstrakt je dobiven iz pokožica izdvojenih iz reprezentativnog uzorka komine. Udjel fenolnih spojeva određen je praćenjem višestrukih reakcija pomoću masene spektrometrije i metodom Folin-Ciocalteu, uz galnu kiselinu kao standard. Biološka aktivnost ekstrakata ispitana je na miševima koji su hranjeni sirovim ekstraktom u dozama od 30, 100 i 300 mg/kg. Ispitani su sljedeći parametri: mehanička hiperalgezija pomoću von Frey filamenata, toplinska hiperalgezija na vrućoj ploči pri 55 °C, edem šape pomoću pomičnog mjerila i aktivnost mijeloperoksidaze kao pokazatelj aktivacije neutrofila. Nefrotoksičnost i hepatotoksičnost su ispitane biokemijskim pretragama uzoraka krvi miševa hranjenih ekstraktom grožđa vrste Vitis labrusca. Rezultati i zaključci. Maseni udjel pokožica u svim uzorcima otpada vinske industrije iznosio je 75 % mokre tvari i 59 % suhe tvari. Identificirali smo devet različitih antocijanina (3-O-glukozide peonidin, delfinidin, petunidin i malvidin; 3-p-kumaroil-glukozide cijanidin, peonidin, pe¬tunidin i malvidin, te malvidin-3,5-diglukozid), pet flavonoida (apigenin-7-glukozid, luteolin-7-glukozid, kvercetin-3-galaktozid, izorhamnetin-3-glukozid i miri¬cetin-3-rutinozid), a maseni udjel fenolnih spojeva, izražen kao ekvivalent galne kiseline, bio je 26,62 mg/g. Ispitivanja in vivo pokazala su da su ektrakti grožđa vrste Vitis labrusca masenog udjela 100 i 300 mg/kg smanjili mehaničku i toplinsku hiperalgeziju kod miševa nakon injekcije karagenana, reducirali edem šape za 50 % i smanjili broj neutrofila. Osim toga, nije bilo pokazatelja nefrotoksičnosti i hepatotoksičnosti. Ekstrakt dobiven iz otpada vinske industrije ima analgetska i protuupalna svojstva, djelomično zbog toga što sadržava fenolne spojeve, a nije toksičan za tkiva bubrega i jetre. Novina i znanstveni doprinos. Dobiveni se bioproizvod može upotrijebiti kao alternativa sintetičkim protuupalnim agensima, s istim farmakološkim potencijalom a manje nuspojava. Pokazali smo da se vinski otpad grožđa vrste Vitis labrusca može upotrijebiti za proizvodnju antinociceptivnih i protuupalnih proizvoda (nutraceutičkih, farmaceutskih i kozmetičkih) koji nemaju toksični učinak, te na taj način pridonijeti zaštiti okoliša

Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta - regulation by selective estrogen receptor modulators and importance in breast cancer

Estrogens display intriguing tissue-selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer, for menopausal hormone replacement, and for fertility regulation. Certain compounds that act through the estrogen receptor (ER), now referred to as selective estrogen receptor modulators (SERMs), can demonstrate remarkable differences in activity in the various estrogen target tissues, functioning as agonists in some tissues but as antagonists in others. Recent advances elucidating the tripartite nature of the biochemical and molecular actions of estrogens provide a good basis for understanding these tissue-selective actions. As discussed in this thematic review, the development of optimal SERMs should now be viewed in the context of two estrogen receptor subtypes, ERα and ERβ, that have differing affinities and responsiveness to various SERMs, and differing tissue distribution and effectiveness at various gene regulatory sites. Cellular, biochemical, and structural approaches have also shown that the nature of the ligand affects the conformation assumed by the ER-ligand complex, thereby regulating its state of phosphorylation and the recruitment of different coregulator proteins. Growth factors and protein kinases that control the phosphorylation state of the complex also regulate the bioactivity of the ER. These interactions and changes determine the magnitude of the transcriptional response and the potency of different SERMs. As these critical components are becoming increasingly well defined, they provide a sound basis for the development of novel SERMs with optimal profiles of tissue selectivity as medical therapeutic agents