The role of alpha-adrenoceptor mechanism(s) in morphine-induced conditioned place preference in female mice

It has been shown that the alpha-adrenergic system is involved in some effects of opioids, including analgesia and reward. Gender differences also exist between males and females in response to alpha-adrenergic agents. This study was designed to determine the effects of alpha-adrenoceptor agonists and antagonists on the acquisition or expression of morphine-induced conditioned place preference (CPP) in female mice. The experiments showed that subcutaneous injections of morphine (0.5-8 mg/kg) induced CPP in a dose-dependent manner in mice. Intrapritoneal administration of the alpha-1-adrenoceptor agonist, phenylephrine (0.03, 0.1 and 0.3 mg/kg), and alpha-2 adrenoceptor agonist, clonidine (0.0001, 0.0005 and 0.001 mg/kg), as well as alpha-1-adrenoceptor antagonist, prazosin (0.01, 0.05 and 0.1 mg/kg) or alpha-2 adrenoceptor antagonist, yohimbine (0.005, 0.01 and 0.05 mg/kg) did not induce motivational effects and also did not alter locomotor activity in the animals. In the second set of experiments, the drugs were used before testing on Day 5, to test their effects on the expression of morphine-induced CPP. Intrapritoneal administration of phenylephrine and clonidine decreased the expression of morphine-induced CPP. In contrast, after application of prazosin or yohimbine, the expression of morphine-induced CPP was increased. Administration of lower (0.03 mg/kg) and higher doses of phenylephrine (0.1 and 0.3 mg/kg) during acquisition of morphine CPP decreased and increased the morphine CPP, respectively. Similarly, the administration of prazosin and clonidine decreased while yohimbine increased the morphine CPP. It may be concluded that alpha-adrenoceptor mechanism(s) influence morphine-induced CPP in female mice.     

Effects of nitric oxide on morphine self-administration in rat

Previous studies have reported that morphine exerts its effects in part through the release of nitric oxide (NO). In the present study, the effects of acute and chronic administration of the NO precursor, L-arginine and NO synthase (NOS) inhibitor, L-nitro-amino-methyl-ester (L-NAME) on morphine self-administration in rats were investigated. The animals were initially trained to press a lever using food as reinforcer. Rats were surgically prepared with a chronic Silastic catheter implanted in the external jugular vein. Five days after surgery, they were trained to press a lever for drug self-administration. The present data indicate that L-arginine (0.05, 0.1, and 0.15 mg/kg/injection) but not L-NAME (0.05, 0.1, and 0.15 mg/kg/injection) induced self-administration behavior and increased locomotion. The response induced by L-arginine (0.1 mg/kg/injection) was reduced by pretreatment with L-NAME (5, 10, and 15 mg/kg ip). Both the acute (5, 10, and 15 mg/kg ip) and the chronic (200 mg/kg ip; twice daily for 4 days) administration of L-arginine reduced morphine self-administration. However, acute (5, 10, and 20 mg/kg ip) and chronic (50 mg/kg ip; twice daily for 4 days) administration of L-NAME increased morphine self-administration significantly. It can be concluded that NO may have a role in morphine self-administration.     

The possibility of a universal declaration of biomedical ethics

Statements on issues in biomedical ethics, purporting to represent international interests, have been put forth by numerous groups. Most of these groups are composed of thinkers in the tradition of European secularism, and do not take into account the values of other ethical systems. One fifth of the world''s population is accounted for by Islam, which is a universal religion, with more than 1400 years of scholarship. Although many values are held in common by secular ethical systems and Islam, their inferences are different. The question, “Is it possible to derive a truly universal declaration of biomedical ethics?” is discussed here by examining the value and extent of personal autonomy in Western and Islamic biomedical ethical constructs. These constructs are then tested vis‐à‐vis the issue of abortion. It is concluded that having a universal declaration of biomedical ethics in practice is not possible, although there are many conceptual similarities and agreements between secular and Islamic value systems, unless a radical paradigm shift occurs in segments of the world''s deliberative bodies. The appellation “universal” should not be used on deliberative statements unless the ethical values of all major schools of thought are satisfied.Several well‐known international medical and biomedical bodies, such as the World Medical Association (WMA) and the Unesco''s International Bioethics Committee, have established universal declarations of rights on various aspects of clinical practice.^1,2 These declarations were initiated and authored primarily by secular thinkers, in the European tradition (although not necessarily from Europe). These groups represent only a minority of the world''s population. Muslims represent 20% of the world''s population and 30% (58/191) of the world''s countries.ⁱThe WMA''s membership includes nine Muslim countries.ⁱⁱ Unesco''s International Bioethics Committee, composed of experts from 36 countries, includes six representatives from Muslim countries—16% of the membership body.Three of the six countries, Lebanon, Syria and Turkey, however, have secular or socialist constitution.ⁱⁱⁱHence the need for a broader, more inclusive and truly “universal” framework for such a declaration of rights.Islam has a highly developed legal code, the shar''iah, as well as a distinguished intellectual history of philosophy, jurisprudence and ethics.^3,4,5 With limited exceptions, such as the Islamic Medical Code of Ethics, Muslim organisations have not been active in drafting declarations of biomedical ethics.⁶ Nonetheless, there are many points of confluence between the rights and principles observed in Islamic jurisprudence, occidental philosophy and universal bills of rights such as the WMA.¹ Points of overlap include principles such as the inherent freedom of mankind, autonomy, patients'' right to honest information and the inviolability of the doctor–patient relationship.⁵Even where there appears to be agreement in principle, the conclusions reached are different. This is partly because of differing assumptions and foundational beliefs as points of induction. In addition, Islamic jurisprudence allows for consideration of local customs and the specific needs of the petitioner (personal, familial and psychological), leading to situational ethics.⁵This article seeks to determine whether a truly universal code of bioethics is possible, by examining the commonly held belief in personal autonomy. Autonomy over bodily functions is further examined in the light of the controversial practice of elective abortion, comparing secular and Islamic approaches. If controversial issues cannot be resolved, the feasibility of a truly universal code of ethics would be called into question.     

Bisegmentectomy 7-8 as alternative to more extensive liver resections

BACKGROUND: Preservation of hepatic parenchyma should be attempted whenever possible in order to reduce the risk of liver failure and increase the chance to re-resect the recurrence. STUDY DESIGN: The presence of a lesion in segments 7-8 infiltrating the right hepatic vein is usually an indication for right hepatectomy. If a thick inferior right hepatic vein is seen, a bisegmentectomy 7-8 can be performed. We review our experience with this uncommon liver resection. RESULTS: In 11 of 332 patients with colorectal liver metastases, a lesion was localized in segments 7-8 infiltrating the right hepatic vein. Six underwent resection of segments 7-8. The mean estimated rate of remnant liver volume (segments 2-4 plus caudate lobe) was 23.7%; 4 patients had neoadjuvant chemotherapy. Intraoperative mean blood loss was 200 mL without transfusions; no patients developed postoperative liver failure, and there was no in-hospital mortality. Surgical margin was negative in all patients. Median survival was 25 months, with 3 patients alive and disease-free. One patient with an intrahepatic recurrence underwent re-resection. CONCLUSIONS: Bisegmentectomy 7-8 is an uncommon but safe procedure that allows curative resections without unnecessary sacrifice of functional parenchyma.     

Optimal designs in stability studies

New optimality criteria for stability studies are proposed, and the related optimal designs are investigated. For each optimality criterion, optimal designs are identified within a class of competing designs. The property of the optimal designs for detecting slope differences is discussed.     

Disruption of growth hormone signaling retards early stages of prostate carcinogenesis in the C3(1)/T antigen mouse

Recent epidemiological studies suggest that elevated serum titers of IGF-I, which are, to a large degree, regulated by GH, are associated with an increase in prostate cancer risk. The purpose of the current study was to develop the first animal models to directly test the hypothesis that a normal, functional GH/IGF-I axis is required for prostate cancer progression. The GH receptor (GHR) gene-disrupted mouse (Ghr(-/-)), which has less than 10% of the plasma IGF-I found in GHR wild-type mice, was crossed with the C3(1)/T antigen (Tag) mouse, which develops prostatic intraepithelial neoplasia driven by the large Tag that progress to invasive prostate carcinoma in a manner similar to the process observed in humans. Progeny of this cross were genotyped and Tag/Ghr(+/+) and Tag/Ghr(-/-) mice were killed at 9 months of age. Seven of eight Tag/Ghr(+/+) mice harbored prostatic intraepithelial neoplasia lesions of various grades. In contrast, only one of the eight Tag/Ghr(-/-) mice exhibited atypia (P < 0.01, Fischer's exact test). Disruption of the GHR gene altered neither prostate androgen receptor expression nor serum testosterone titers. Expression of the Tag oncogene was similar in the prostates of the two mouse strains. Immunohistochemistry revealed a significant decrease in prostate epithelial cell proliferation and an increase in basal apoptotic indices. These results indicate that disruption of GH signaling significantly inhibits prostate carcinogenesis.     

Diagnostic value of frozen section examination in thyroid nodule-surgery at the shariati hospital (1997–2000)

Introduction There is controversy regarding the use and accuracy of frozen section (FS) in managing thyroid nodules. We compared the diagnostic value of FS with that of permanent histopathology examination and fine needle aspiration (FNA). Materials and Methods Permanent, FS, and FNA sample reports were compared in 214 patients between 1997 and 2000. FS, FNA, and permanent pathology (gold standard) results were compared using McNemar's test. Results 160 women and 54 men (mean age: 42.3±5.4 yr) took part in the study; 163 patients (76%) had benign and 51 (24%) malignant lesions; 76% of our thyroid cancer cases were papillary, 13.5% follicular, 6% medullary carcinoma, 4% Hürthle cell carcinoma, and 0.5% anaplastic carcinoma. FNA yielded definite results in 150 patients (sensitivity 72%, specificity 96%, and precision 90%). In 64 patients with equivocal FNA, FS was performed (sensitivity 36%, specificity 73%, and precision 85%). The observed difference between FNA and FS was not statistically significant. Discussion When FNA results are inconclusive, FS does not provide any further information. In suspected cases of papillary, undifferentiated, or medullary carcinomas, FS can confirm FNA findings and guide surgical therapy. An erratum to this article is available at .     

A pseudoaneurysm of the left atrium as a rare source of coronary artery embolization

A 67 years old woman with history of surgical Mitral valve replacement underwent transoesophageal echocardiography for evaluation of mild dyspnoea. It revealed a large narrow-necked outpouching from medial portion of the inferior wall of the left atrium (LA) that was extended to the interatrial septum. A diagnosis of the LA pseudoaneurysm was made. It contained a fresh clot. Five days later, the patient presented with an acute inferior ST-elevation myocardial infarction. Coronary angiography revealed an occluded right coronary artery at its distal part by a large thrombus. Thromboaspiration was done and resulted in restoration of a Thrombolysis in Myocardial Infarction Score (TIMI) flow 3 without underlying stenosis.