Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine

Objective-To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M-2) antagonist, methoctramine, in anesthetized horses.Animals-6 horses.Procedure-Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 mug/kg, IV) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 mug/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period.Results-Methoctramine was given at a total cumulative dose of 30 mug/kg to 4 horses, whereas 2 horses received 10 mug/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups.Conclusions and Clinical Relevance-Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M-2 antagonists may represent a safe alternative for treatment of horses with intraoperative bracycardia.

Food restriction promotes downregulation of myocardial L-type Ca2+ channels

Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca2+ channels. Male 60-day-old Wistar rats were fed a control or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca2+ channels was determined by using a pharmacological Ca2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca2+ channels.

Involvement of L-Type Calcium Channel and SERCA2a in Myocardial Dysfunction Induced by Obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca2+) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca2+ channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca2+ channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca2+ channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca2+ channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca2+ protein levels. J. Cell. Physiol. 226: 2934-2942, 2011. (C) 2011 Wiley-Liss, Inc.

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) µU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/µU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/µU) and during glucose infusion (0.15 vs 0.15 ng/µU). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

Magnetic resonance imaging in the diagnosis of type 1 dermoid sinus in two Rhodesian ridgeback dogs

Two cases of type 1 dermoid sinus in Rhodesian ridgebacks are described, with emphasis on the use of magnetic resonance imaging (MRI) in the diagnosis and delineation of the lesions. Magnetic resonance imaging was useful in identifying fluid-filled structures, fibrous capsules, and sinus tracts, but was not able to identify the termination of the tracts.

Auditory evaluation in patients with type 1 diabetes

Objectives: We performed a prospective clinical study of the cochleovestibular symptoms and the risk cofactors and characteristics of hearing loss in patients with type 1 diabetes.Methods: Group I consisted of 40 patients with type I diabetes, and group 2 consisted of 20 control subjects without diabetes. All participants answered a questionnaire, and their medical records were reviewed. They also were submitted to otorhinolaryngological examinations and to auditory tests (pure tone audiometry and acoustic immitance and auditory brain stem response [ABR] tests).Results: Dyslipidemia, hypertension, retinopathy, and diabetic neuropathy were not frequent in the patients of group 1, but incipient nephropathy was present in 47.5% of them. The most frequent cochleovestibular symptoms were tinnitus and hearing loss. Sensorineural hearing loss was found in 4 patients of group I and was predominantly bilateral, symmetric, and affecting the high frequencies, coexisting with normal vocal discrimination. These patients had a longer time from diabetes diagnosis and had poor glycemia control. A delay of ABR interpeak latency I-III was observed in 11.25% of the group I ears. All patients of group 2 presented normal audiograms and ABR tests.Conclusions: In group 1, the most frequent cochleovestibular symptoms were tinnitus and hearing loss. The sensorineural hearing loss was mild, symmetric, and predominantly high-frequency. A delay of ABR interpeak latencies was detected in the patients of group I who had normal audiometric thresholds.

Cutaneous pyogranuloma in a cat caused by virulent Rhodococcus equi containing an 87 kb type I plasmid

A 2-year-old intact male domestic shorthaired cat presented with a chronic, nodular, ulcerated, cutaneous lesion on the right thoracic limb. Histological and cytological examination revealed a pyogranulomatous inflammation with basophilic organisms in the macrophages. A virulent form of Rhodococcus equi containing an 87 kb type I (VapA) virulence plasmid was identified from cultures of biopsy samples. This report describes the clinicopathological features, plasmid profile and virulence of this case of R equi infection.

Cell-free antigens from precocious Paracoccidioides brasiliensis culture induce a typical delayed-type hypersensitivity reaction

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-Type, Nonclinical Toxicity Studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. (J Toxicol Pathol 2010; 23: 171-181)

Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotypic characterization of Toxoplasma gondii in sheep from Brazilian slaughterhouses: New atypical genotypes and the clonal type II strain identified

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Age-related changes in muscle fiber type frequencies and cross-sectional areas in straightbred and crossbred rabbits

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Muscle fiber type characterization and myosin heavy chain (MyHC) isoform expression in Mediterranean buffaloes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)