High Blood Pressure Induced by Audiovisual Stimulation in Young Rats: Effect of Antihypertensive Agents

ABSTRACT

High systolic blood pressure (BP) was induced in young Wistar rats by daily exposure for 30 mins to environmental stimuli consisting of intense (100 dB) sound of 7500 cps and flashing light (0.3 cps). Maximal BP enhancement was obtained after the application of both these stimuli for 3 consecutive days. Such a hypertensive response was detected 24 hrs, but not 1 hr after the trial. High BP backed to normal 72 hrs after discontinuation of the audiovisual stimulation trials. Clinically effective antihypertensive agents (clonidine, prazosin, propranolol, practolol and metoprolol) as well as a new compound under investigation (cicletanine) were proved active in this model. Normotensive nonstressed rats run in parallel did not show any variation in their BP after administration of the same dose of the drugs assayed. This experimental model of hypertension may be a useful tool not only to test new antihypertensive agents but also to study the intriguing question of the role of stress in the development and maintenance of essential hypertension.     

Development of anti-neutrophil cytoplasmic antibody-associated vasculitis in a patient with Graves’ disease independent of anti-thyroid drug therapy

Abstract

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients with Graves’ disease (GD) is linked with the use of anti-thyroid drugs (ATDs). We report the co-occurrence of AAV and GD in a patient that was independent of ATD therapy. A 38-year-old white male presented with systemic symptoms, palpitations, tremors, purpuric skin lesions, and digital pain. Physical examination and biological tests confirmed GD. He quickly developed multiple digital gangrenes and testicular pain/mass. Skin and testicular biopsies showed granulomatous vasculitis of the small- and medium-sized vessels, while his serum contained anti-proteinase-3 antibody.     

降压药物在妊娠期高血压疾病中应用的争议与发展

妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是产科最重要合并症之一,严重影响母婴健康。然而,何时采用降压治疗、如何正确应用降压药物在HDP的治疗中始终存在争议,并在争议中不断发展。循证医学显示,肼苯哒嗪和硝苯地平已不再是HDP降压治疗的一线药物,而拉贝洛尔、尼卡地平也许是更好的选择。     

Preclinical Safety and Pharmacology of Hematide™, a Peptidic Erythropoiesis Stimulating Agent (ESA), in Rats and Monkeys

The pharmacology, toxicokinetics, and safety of Hematide^TM, a synthetic peptidic erythropoiesis-stimulating agent (ESA), were characterized. Hematide was given intravenously (0, 0.5, 5, and 50 mg/kg) weekly for five weeks with a 6- (rat) and 12-week (monkey) recovery period. The pharmacological action of Hematide resulted in polycythemia. Histopathology consistent with drug-induced exaggerated pharmacology was observed primarily in rats. Secondary sequelae resulting from pronounced polycythemia was considered the cause of deaths in rats and a single high-dose monkey. Toxicokinetic analysis indicated prolonged exposure. In conclusion, Hematide is a potent ESA and the safety and efficacy profile support clinical development.     

Gemcitabine Hydrochloride-Loaded Functionalised Carbon Nanotubes as Potential Carriers for Tumour Targeting

The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of −10−1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride.     

Genotoxic assessment and toxicity evaluation of peginesatide in CByB6F1 hybrid mice

Peginesatide is a PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA) that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. Clinical use of peginesatide is anticipated to result in chronic dosing in chronic kidney disease (CKD) patients, and the nonclinical data to support development should include an evaluation of carcinogenic potential evaluation. Peginesatide was not mutagenic or clastogenic in a standard genotoxicity battery of tests. Doses for a rasH2 transgenic mouse carcinogenicity assay were defined in a 28-day study in the wild-type littermates of the rasH2 transgenic mouse strain, using intravenous doses of 1–25?mg/kg on days 1 and 22. The findings were consistent with exaggerated pharmacology, including polycythemia, with associated increases in hemoglobin level and extramedullary hematopoiesis and bone marrow hypercellularity.     

Patient Blood Management: Use of Topical Hemostatic and Sealant Agents

Patient blood management is the scientific use of safe, effective medical and surgical techniques designed to conserve blood, prevent anemia, decrease bleeding, and optimize coagulation in an effort to improve patient outcomes. Perioperative and primary care nurses play a vital role in promoting and making the best use of patient blood management and can play a key role in implementing effective strategies that decrease or eliminate patient exposure to allogeneic blood. The fast and effective minimization of intraoperative bleeding is integral in an effective blood management program. Topical hemostatic and sealant agents can be used to improve blood conservation, reduce overall procedure time, and contribute to faster patient recovery based on specific clinical situations. The proper selection of hemostatic agents can greatly influence the patient’s clinical outcomes.     

The Influence of Beta-Blocking Agents on Plasma Volume and Extracellular Volume in Ischaemic Heart Disease

Plasma volume and extracellular volume (sodium space) were found to be unchanged during treatment with propranolol (nine patients) and practolol (four patients) for well-compensated ischaemic heart disease. The volumes were determined before treatment and 2 days and 3 months after optimal dose for each patient was reached.     

Efflux of Prostaglandins in Right Lymphatic Duct Lymph Following Induced Intravascular Coagulation and Inhibited Fibrinolysis in the Dog

Intravascular coagulation and inhibited fibrinolysis were induced in 10 dogs by infusion of thrombin and tranexamic acid (AMCA). Lymph fluid from the right lymphatic duct, draining the main parts of the lungs, was examined for the presence of smooth-muscle-stimulating activity. The treatment was followed by increased lymph flow due to interstitial pulmonary oedema and efflux of smooth-muscle-stimulating material. The presence of prostaglandin E₁ and E₂ (PGE₁ and E₂) and prostaglandin F-compounds as well as ‘slow reacting substance’ (SRS) in the lymph fluid was demonstrated by bioassay in combination with chromatography. Histamine was not detected in the lymph fluid.