Acute and chronic losartan administration: effect on angiotensin II content and modulation of [3H]norepinephrine release from rat interscapular brown adipose tissue

Summary To determine if acute or chronic (21 days) losartan (10mg/kg, s.c.) regulates the renin-angiotensin system in interscapular brown adipose tissue, angiotensin II (AII) content and [³H]overflow from slices preloaded with [³H]norepinephrine were examined. Acute or chronic losartan administration had no effect on AII content. AII increased evoked [³H]overflow from slices from control rats. Losartan administration did not alter basal [³H]outflow or evoked [³H]overflow. Acute losartan administration inhibited AII-induced enhancement of evoked [³H]overflow. Tolerance developed to the inhibitory effect of losartan following chronic administration.Supported by a grant from the American Heart Association (Local Kentucky Affiliate) and by a gift from DuPont Merck Pharmaceuticals. Portions of this work have been presented in abstract form [The Pharmacologist 34(3): 157, 1992]     

Acute and chronic effects of nornicotine on locomotor activity in rats: altered response to nicotine

Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use. Received: 11 January 1999 / Final version: 25 March 1999     

Clinical Analysis of 57 Patients with Ovarian Dysgerminoma

Objective  Ovarian dysgerminoma is an uncommon ovarian malignancy, Its clinicai features are special and there are many factors affecting its prognosis. If treated properly, the patient can be cured. Otherwise it may endanger the patient’s life. The aim of this study is to investigate the clinical features and factors related to prognosis of ovarian dysgerminoma. Methods  Data from 57 patients with pure ovarian dysgerminoma were analyzed retrospectively. The patients were admitted to the Cancer Center, Sun Yat-sen University from January 1.1964 to December 31, 2000. Results  The main clinical features were abdominal mass (56.1% ), abdominal pain (21.1% ), abdominal swelling (17.5%.), vaginal bleeding (5.3% )and genital tract abnormalities (5.3%). Twenty-six patients had stage I diseases, 8 stage II.9 stage III.1 stage IV and 13 recurrent and persistent diseases. The uterus was involved in 41.2% of patients with stage II -III diseases. Combined modality was given to 52 cases and a single-method treatment to 5 cases. The total overall 5 and 10-year survival rates for stages I-IV was 80.1 % and 70.0% respectively. The 5-year survival rate for stage I was 100%, stage II 55.2%. stage III 55.6% and stage IV 0%; for recurrent and persistent diseases, 72.7%. The stage I group of 12 patients. received adnexectomy and 14 patients underwent hysterectomy and adnexa removal. There was no significant difference between the 5 and 10-year survival rates (all 100%). Of the 23 patients in the stage I group to whom oniy chemotherapy was given after operation, 19 cases received 3 or more courses and were well without recurrence; 4 patients received only one course and one of them recurred 21 months after the operation. In the group of stages II and III cases, the 5-year survival rate was 86.7% for those whose chemotherapy courses were 3≥ 4 and 25.0% for patients who received less than 4 courses of chemotherapy (P<0.05). Conclusions  The prognosis of ovarian dysgerminoma is closely related to the disease stage and treatment modality. A fertility-preserving operation can be considered in early -staged patients, but caution needs to be exercised in the middle to late staged cases. Good results can be achieved with an operation-based combined modality in recurrent patients.     

Establishing and managing a periodontal biobank for research: the sharing of experience

Periodontal bio‐repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad‐based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.     

Acute coronary syndromes

The first 150 words of the full text of this article appear below. Key points Coronary artery disease accounts for >30% ofdeaths in Western society. The diagnosis of myocardial infarctionshould be qualified by size, causation and time from occurrence. Mortalityis reduced by immediate or ‘primary’ percutaneouscoronary intervention or thrombolysis within the first 24 hof onset of ST-segment elevation myocardial infarction. Strategiesto reduce platelet activation (glycoprotein IIb/IIIa receptorantagonists, or clopidogrel) are now recommended in the treatmentof high-risk non-ST-segment myocardial infarction/unstable angina. Elevatedserum troponins may be the result of non-ischaemic myocardialdamage, especially in critical illness.