Changes in lipid metabolism in diet-induced obesity

Mature male Sprague-Dawley rats fed a powdered Purina Chow diet containing corn oil and condensed milk (CM) were compared to rats fed a Purina Chow diet (control). CM rats gained more weight and consumed more calories over a 73-day period than the control rats. The increased weight gain and body fat in CM rats was accompanied by increased cell number in retroperitoneal and inguinal but not epididymal fat pads while cell size was unchanged in all three pads. After obesity had developed there was an increase in insulin levels, lipolysis, hepatic fatty acid synthesis, and fatty acid oxidation. While CM rats demonstrated hyperinsulinemia and hyperglycerolemia, they maintained normal glucagon and glucose levels. They demonstrated higher rates of fatty acid synthesis in isolated hepatocytes but not in vivo, suggesting that a greater potential for fatty acid synthesis in CM rats was masked in vivo by the inhibitory action of dietary lipids. Beta-oxidation of (1-14C) palmitate in vivo and in vitro, and in vivo ketogenesis were greater in CM than in chow fed rats. These studies demonstrate that, after the development of obesity, CM rats, like genetically obese Zucker rats, are hyperinsulinemic and have elevated levels of fatty acid synthesis. However, unlike obese Zucker rats, CM rats displayed an increase in beta-oxidation. These studies suggest that increased insulin levels and hepatic fatty acid synthesis may contribute to dietary obesity (as they do to genetic obesity), whereas increased fatty acid oxidation in dietary obesity may be a compensatory response to maintain a lower body weight.     

Relationship between the extent of the hypoperfused zone of the myocardium and the occurrence of ventricular fibrillation

Ventricular fibrillation and subsequent death frequently occur so soon after coronary artery occlusion that infarct size cannot be determined; thus the systematic study of their relationship is impossible. Recently, however, a technique has been developed that permits the assessment, in vivo, of the extent of the myocardial hypoperfused zone (HZ). Accordingly, in 55 open-chest dogs, 99mTc-labeled (8 mCi) albumin microspheres (15 microns in diameter) were injected into the left atrium 1 minute after coronary artery occlusion. The zone of hypoperfusion was analyzed in 28 dogs that had ventricular fibrillation (group A) and 27 dogs that had no ventricular fibrillation (group B). In group B, the HZ was 26.3 +/- 1.7% of the left ventricle vs 31.6 +/- 1.3% of the left ventricle in group A (p less than 0.05), showing that ventricular fibrillation occurred in dogs with larger zones of hypoperfusion.     

Training and Education Requirements for Authorized Users of Therapeutic Radiopharmaceuticals: Changes Under Consideration for 10CFR35.390 and Their Potential Impact

The US Nuclear Regulatory Commission (NRC) and 38 Agreement States have the regulatory authority to promulgate and enforce regulations related to the use of radioisotopes for medical purposes. Elements of these regulations include training and experience (T&E) requirements for individuals authorized to use the agents. These regulations are specified in 10CFR35.390. At this time, the NRC is considering significant revisions to the T&E requirements. This article describes current regulations and concerns related to the proposed changes and details the ACR organizational response.     

Captopril (SQ 14,225) (d-3-mercapto-2-methylpropanoyl-l-proline): A novel orally active inhibitor of angiotensin-converting enzyme and antihypertensive agent

Relatively potent and specific in vitro and in vivo (oral or intravenous) inhibition of angiotensin-converting enzyme by a nonpeptidic compound, captopril (SQ 14,225; d-3-mercapto-2-methylpropanoyl-l-poline), was demonstrated in excised guinea pig ileum and in rats, rabbits, cats, dogs, and monkeys. The design of captopril was based on a hypothetical model of the active site of the enzyme. Captopril, in vitro or in vivo, was about ten times as potent as teprotide. Inhibition of angiotensin-converting enzyme was evaluated in vitro and in vivo by inhibition of the contractile or vasopressor activity of angiotensin I or by augmentation of the contractile or vasodepressor activity of bradykinin. Acute of subacute dosage with captopril moderately to markedly lowered the blood pressure of the renin-dependent aorticligated and the conscious two-kidney Goldblatt hypertensive rat; in the latter, the effect was intensified by concomitant dosage with a thiazide diuretic. Furthermore, the life-prolonging effects of captopril in renal hypertensive rats were augmented by a thiazide diuretic. In the two-kidney Goldblatt rat, acute captopril (p.o.) was about ten times as potent as teprotide (s.c.) in lowering blood pressure. Acute or subacute oral doses of captopril moderately reduced the blood pressure of the spontaneously hypertensive Wistar-Kyoto rat; chronic dosage almost normalized blood pressure. Captopril produced little or no hypotension in the saltreplete normotensive Wistar-Kyoto rat. Bilateral nephrectomy virtually abolished the hypotensive activity of captopril in the spontaneous hypertensive rat. The results suggest that captopril acts in large part by inhibiting the renin-angiotensin-aldosterone system to reduce elevated blood pressure, especially in renindependent models of hypertension; the roles of the kallikrein-kinin-prostaglandin systems and sodium balance remain to be elucidated. Captopril also lowers blood pressure in apparently non-renin-dependent types of hypertension by mechanisms that are as yet undefined.     

Toxicologic evaluation of modified gum acacia: mutagenicity, acute and subchronic toxicity.

Modified gum acacia, produced from acacia gum by a process analogous to the production of modified food starch, was tested for mutagenicity in the microbial reverse mutation assay. The assay employed a wide range of dose levels, both with and without metabolic activation. Test results gave no indication that modified gum acacia possessed any mutagenic potential. The acute oral toxicity of modified gum acacia was determined in two studies employing Sprague-Dawley rats, and the LD50 values were found to be >2000 mg/kg. The primary dermal irritation potential of modified gum acacia was evaluated in rabbits by the Draize method. Test results indicated that modified gum acacia was slightly irritating by the Environmental Protection Agency (EPA) classification but not a primary irritant by Consumer Product Safety Commission (CPSC) guidelines. The subchronic toxicity of modified gum acacia was examined in Sprague-Dawley rats fed diets containing 0%, 1%, 2.5%, and 5% modified gum acacia for 13 weeks. No dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. Results of these studies indicate that modified gum acacia does not possess mutagenic potential and that animals are not adversely affected by acute or subchronic exposure to modified gum acacia.     

Guide to CAT scanning in hospital psychiatry : Overview of clinical practice and criteria for use

Advances in imaging techniques have resulted in increasing use of computed axial tomography (CAT) in clinical psychiatry. Treatable brain lesions predominantly manifesting as emotional and behavioral symptoms can be detected with relative ease and safety by CAT scanning. Criteria to select these high-risk psychiatric patients for CAT exam are vague and sparse compared to more abundant guidelines for scanning neurologic and medical patients with focal signs of physical abnormality. The few existing surveys of inpatient psychiatry CAT scanning reveal a 65–70% range of normal findings. As more and more patients are scanned, such an obviously large group of “normals” should not be exposed to current CAT exam costs and risks; at the same time, it is necessary to ensure that those psychiatric patients warranting the procedure are not neglected in referral. This article highlights clinical aspects of CAT brain imaging, summarizes the existing literature on inpatient psychiatry CAT scanning, and recommends initial criteria for CAT brain examination of hospitalized patients.