Inhibitory effect of salmon calcitonin on bone resorption: Morphological study of the tibial growth plate in rats

Summary Salmon calcitonin (sCT) at doses of 100 and 50 UI given subcutaneously to growing rats produced in vivo evidence of osteoclastic activity inhibition. Histological assessment was carried out by measuring the perichondrial ring of Lacroix height, and a dose-correlated effect was found. These aspects were coupled with an increase in the osteoclast number and suggested that in studies with bone resorption inhibitors, morphological evaluation based on osteoclasts count is not reliable. The changes of the metaphysis suggested also that sCT affects the activity of hypertrophic chondrocytes of the growth plate. Plasma calcium levels did not differ significantly between treated rats and controls; an increased phosphatemia was observed in sCT-treated animals.     

Risk factors for acquisition of multidrug-resistant Pseudomonas aeruginosa producing SPM metallo-beta-lactamase

To evaluate risk factors for colonization or infection due to multidrug-resistant Pseudomonas aeruginosa (MDRPa) carrying the bla(SPM) gene (SPM-MRDPa) among hospitalized patients, we undertook a case control study at a 480-bed, tertiary-care university hospital. Two different case definitions were used. In the first definition, a case patient (SPM case patient) was defined as a patient who had at least one isolate of SPM-MDRPa (14 patients). In the second, a case patient (non-SPM case patient) was defined as a patient who had at least one isolate of non-SPM-MDRPa (18 patients). For each case patient, we selected two controls, defined as a patient colonized and/or infected by a non-MDRPa isolate during the same study period and with the closest duration of hospitalization until the isolation of P. aeruginosa as cases. The use of quinolones was the single independent predictor of colonization and/or infection by bla(SPM) MDRPa (odds ratio [OR] = 14.70, 95% confidence interval [95% CI] = 1.70 to 127.34, P = 0.01), whereas the use of cefepime was the single predictor of colonization and/or infection by non-bla(SPM) MDRPa (OR = 8.50, 95% CI = 1.51 to 47.96, P = 0.01). The main risk factor for MDRPa was a history of antibiotics usage. Stratification of risk factor analysis by a precise mechanism of resistance led us to identify a specific antibiotic, a quinolone, as a predictor for SPM-MDRPa.     

Role of endothelin-1 and thromboxane A2 in the pulmonary hypertension induced by heparin-protamine interaction in anesthetized dogs

This study aimed to study the role of thromboxane A2 (TXA2) and endothelin-1 (ET-1) in the pulmonary hypertension induced by interaction of heparin-protamine in anesthetized dogs. The effect of inhaled nitric oxide (NO) was also investigated in this model. Dogs were anesthetized and instrumented for acquisition of mean arterial blood pressure, mean arterial pulmonary pressure (MPAP), and pulmonary pressure gradient (PPG). Cardiac index (CI), heart rate, and index of systemic vascular resistance were also obtained. Intravenous administration of heparin (500 IU/kg) 3 minutes before protamine (10 mg/kg) caused marked pulmonary hypertension, as evaluated by the increase in MPAP and PPG. This was accompanied by systemic hypotension, CI decrease, and tachycardia. Indomethacin (10 mg/kg), dazoxiben (10 mg/kg), or tezosentan (10-mg/kg bolus plus 10-mg/kg/h infusion) significantly reduced the increase in MPAP and PPG, but had no effect on the systemic hypotension. Similar results were obtained with inhaled NO (3 ppm). Plasma TXB2 levels were markedly elevated during the pulmonary hypertension, and this was abolished in indomethacin-treated dogs. Our study shows that interaction of heparin-protamine in anesthetized dogs lead to TXA2- and ET-1-mediated pulmonary hypertension. Drugs that interfere with the synthesis of these mediators as well as inhaled NO may be of beneficial value to control this disorder.     

Nitric oxide pathway in the nucleus raphe magnus modulates hypoxic ventilatory response but not anapyrexia in rats

Nucleus raphe magnus (NRM) is one of the cellular groups of the brainstem that is involved in the physiologic responses to hypoxia and contains nitric oxide (NO) synthase. In the present study, we assessed the role of NO pathway in the NRM on the hypoxic ventilatory response (HVR) and anapyrexia (a regulated decrease in body temperature). To this end, pulmonary ventilation (VE) and body temperature (Tb) of male Wistar rats were measured before and after microinjection of N-monomethyl-L-arginine (L-NMMA, a nonselective nitric oxide synthase inhibitor, 12.5 microg/0.1 microl) into the NRM, followed by hypoxia. Control rats received microinjection of saline. Under resting conditions, L-NMMA treatment did not affect pulmonary VE or Tb. Typical hypoxia-induced hyperventilation and anapyrexia were observed after saline treatment. L-NMMA into the NRM reduced the HVR but did not affect hypoxia-induced anapyrexia. In conclusion, the present study indicates that NO in the NRM is involved in HVR, exerts an inhibitory modulation on the NRM neurons but does not mediate hypoxia-induced anapyrexia.     

Phentolamine bioequivalence study

OBJECTIVE: To assess the bioequivalence of 2 tablet formulations of phentolamine (Regitine phentolamine 40 mg tablet formulation by Novartis, Brazil, as test formulation, and Vasomax, phentolamine 40 mg tablet formulation by Schering Plough S.A., Brazil, as reference formulation). METHODS: A single 40 mg oral dose of each formulation was administered to 36 male healthy volunteers. The study was conducted after screening, using an open, randomized, 2-period crossover design, a 7-day interval between doses, and wash-out period of at least 4 weeks. Plasma samples for determination of phentolamine were obtained predose and at intervals over 720 min postdose. Plasma concentrations were quantified by reversed-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM) method. Precision of the method was evaluated using calibration curves and plasma quality control samples. The subjects were monitored throughout the study. Systolic and diastolic blood pressure and pulse rate measurement were taken predose and at intervals up to 720 min. Tolerance of both products was good. No serious adverse reactions were reported. The pharmacokinetic parameters calculated for both compounds included: AUC(0-720 min), AUC(0-infinity), C(max), Ca and k(e). RESULTS: The maximum concentrations reached (C(max)) were compared. Regitine 40 mg formulation C(max) geometric mean ratio was 108.29% (90% CI = 98.58-118.96) of Vasomax 40 mg formulation. The areas under the curve (AUC(0-720 min)) were compared. Regitine 40 formulation (AUC(0-720 min)) geometric mean ratio was 102.33% (90% CI = 97.21-107.72) of Vasomax 40 mg formulation. CONCLUSION: Since the 90% CI for both C(max) and AUC ratio where inside the 80 to 125% interval proposed by the Food and Drug Administration, it is concluded that Regitine 40 mg tablet is bioequivalent to Vasomax for the rate and extent of absorption.     

Hertig and beyond: a systematic and practical approach to the endometrial biopsy

Evaluation of the endometrial biopsy is a challenge to practicing pathologists, largely due to the wide range of morphologic patterns resulting from both normal and abnormal cyclic changes, exogenous hormones, infections, and intrauterine tumors. Successfully addressing these challenges requires that the practitioner (i) understand the clinical questions being asked, (ii) have a realistic expectation for answering these questions, and (iii) have a systematic approach to resolving these questions in the context of these expectations. The approach outlined begins with the subdividing of women with endometrial alterations into three general categories: (i) women in their fourth decade undergoing evaluation for infertility, (ii) women in their fifth decade who experience abnormal uterine bleeding, and (iii) women in their sixth decade and beyond who experience postmenopausal bleeding. The clinical expectations for each group are unique, as are the morphologic patterns most commonly encountered. Algorithms for the laboratory management of cyclic changes, dysfunctional bleeding, and mixed-pattern endometria are provided, as are pitfalls in interpretation and exclusion of neoplasia.