Future recruitment into obstetrics and gynaecology: factors affecting early career choice.

Medical students attending a careers talk in obstetrics and gynaecology at Nottingham University were approached in this survey, to identify factors which influenced an early career choice in O&G. We received 60 responses, giving a response rate of 83.3%. The positive factors that encouraged an early career choice of O&G were: a positive undergraduate O&G attachment; consultant and junior doctor role-models; a good mix of medicine and surgery; availability of hands-on opportunities and early career advice. The perception of long working hours was not a negative influence. Male medical students were put-off by the lack of opportunity to undertake pelvic examinations.

In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension.

Changes in tissue protein synthesis in hypertension have usually been measured in vitro in heart from acutely hypertensive rats without consideration of changes in atrial or pulmonary tissue or changes occurring in long-standing hypertension. The objective of the study was to investigate the in vivo changes in cardiopulmonary protein synthesis in three different rat models of chronic hypertension. Hypertension in aortic constriction, the Goldblatt model, and the bromoethylamine model were induced in rats for 30 days. At the end of the experimental period, in vivo rates of protein synthesis were measured with a flooding dose of [3H]phenylalanine (a method which effectively considers precursor pools). Concomitant measurements included quantification of contractile protein and RNA and DNA contents. Indices of protein breakdown were also assessed by selective measurement of protease activities. At the end of 30 days, aortic constriction induced marked increases in protein contents of the left ventricle, septum, left atria, and lungs. Accompanying changes included concomitant increases in RNA and DNA contents. Left ventricular myofibrillary, sarcoplasmic, and stromal protein contents increased in the aortic constriction model. Less marked changes occurred in the Goldblatt model, though the left atria were not significantly affected. In contrast, the bromoethylamine model had no effect on the protein or RNA contents of any region. In all cardiac regions of all three models, fractional rates of protein synthesis were not significantly affected. However, protein synthesis increased in the lungs of both the Goldblatt and bromoethylamine models at 30 days. Protease activities were decreased in the left ventricles of all three models at 30 days, with lysosomal protease activities declining in the aortic constriction model and cytoplasmic protease activities declining in the other two models. The failure of chronic hypertension to increase ventricular synthesis rates may represent inherent limitations in the time frame for measuring protein synthesis in vivo. However, at earlier time points (i.e., 10 days), the aortic constriction model was characterized by marked increases in left ventricular and atrial protein contents, RNA contents, and fractional rates of protein synthesis. This was consistent with the supposition that, in acute phases of hypertrophy, rates of protein synthesis increase, whereas in established hypertrophy, synthesis rates remain unchanged or decrease. The applicability of the aortic constriction model was investigated by examining the effects of the angiotensin converting enzyme inhibitor lisinopril (5 mg/kg/day). After 30 days treatment, lisinopril impeded the increase in left ventricular mixed and myofibrillar proteins. This effect was accompanied by an apparent increase in protein synthesis. In conclusion, although all three chronic models are able to induce hypertension, varying degrees of hypertrophy develop, which are more pronounced in the aortic constriction model. Accompanying changes include hypertrophy in the atria, reduced rates of ventricular proteolytic activity, and altered rates of protein metabolism in the lungs.

Alcohol-induced reductions in cardiac protein synthesis in vivo are not ameliorated by treatment with the dihydropyridine calcium channel blocker amlodipine.

BACKGROUND: Various studies have indicated that acute ethanol dosage perturbs cardiac function and/or structure with concomitant reductions in protein synthesis. Cellular calcium homeostasis is also perturbed, which may contribute to altered protein synthesis. This is supported by the observation that calcium channel blockers can prevent numerous features of alcohol-induced pathology. However, many of these studies have been carried out in vitro, employing supraphysiological levels of alcohol, or have failed to address whether their results obtained in isolated systems have direct relevance in vivo. The aim of the present investigation was to examine the response of cardiac protein synthesis in vivo due to a physiologically relevant dose of ethanol and determine whether a calcium channel antagonist could prevent these effects. METHODS: Changes in cardiac protein synthesis rates in vivo were assessed by measuring the fractional rates of protein synthesis (i.e., ks) using a "flooding dose" of [3H]phenylalanine. Rats were treated either acutely (10 mg/kg body weight, 3 hr) or chronically (10 mg/kg body weight/day, 30 days) with amlodipine, a dihydropyridine-type calcium channel blocker, before dosing with ethanol (75 mmol/kg body weight, 2.5 hr). RESULTS: Ethanol (75 mmol/kg body weight) inhibited cardiac protein synthesis after 1 hr. Similar responses were recorded at 2.5 and 6 hr after ethanol dosage. At 24 hr, ethanol decreased food intakes. However, a direct comparison between pair-fed controls and alcohol-dosed rats also showed a decrease in cardiac protein synthesis after 24 hr. Acute alcohol dosage reduced cardiac protein synthesis in mixed, myofibrillary, and sarcoplasmic protein fractions. Similar results were obtained when data were expressed relative to ribonucleic acid (i.e., kRNA). Neither acute nor chronic treatments with the calcium antagonist amlodipine ameliorated the deleterious actions of ethanol on protein synthesis. CONCLUSIONS: Ethanol may affect cardiac protein synthesis independently of altered calcium entry.

Effects of the dihydropyridine calcium channel blocker amlodipine on ventricular and atrial protein synthesis in an aortic constriction model of hypertension and, following chronic treatment, in the left ventricle of SHR rats.

The dihydropyridine calcium channel blocking agent amlodipine is an effective anti-hypertensive agent and its use (in doses of 5 or 10 mg/day/kg body weight) was investigated in male Wistar rats with hypertension induced by aortic constriction. Controls were sham-operated and pair-fed. At the end of the study, rates of protein synthesis were measured with radiolabelled phenylalanine to calculate fractional rates of protein synthesis (ks), absolute rates of protein synthesis (Vs) and synthesis rates relative to RNA (kRNA). After 30 days of aortic constriction, weights of the left ventricle and left atrium were significantly increased by hypertension. The weights of the right ventricle and right atrium were relatively unaffected. Hypertension was accompanied by significant increases in the protein and RNA contents of the left ventricle and left atrium. The contractile and non-contractile protein contents were also increased in the left ventricles of hypertensive rats as were total proteins and total RNA. In the myofibrillary fraction, ks decreased. The right ventricle and right atrium were generally unaffected except for a decline in mixed protein ks. Many of these changes in hypertension were ameliorated by treatment with amlodipine, particularly at the higher dose (i.e. 10 mg/kg body weight/day) implicating an effect on protein metabolism. In the left ventricle these included amelioration of the increases in mixed and contractile proteins, total RNA contents, mixed Vs and Vs for sarcoplasmic and stromal proteins. The ameliorating effects of amlodipine were moderate in the left atrium. Furthermore, amlodipine also retarded the hypertension-induced reduction in right ventricule rates of protein synthesis. Although the preceding study emphasises the preventative aspects of amlodipine's efficacy, an additional study was carried out in SHR rats to ascertain the applicability for regression per se. Amlodipine (10 mg/kg/body weight) therapy for 30 weeks caused regression of LV mass, total protein, RNA and DNA contents. We conclude that amlodipine, is an efficient agent in ameliorating the hypertension-induced changes in protein metabolism in an aortic constriction model.

Effects of acute ethanol on ventricular myofibrillary protein synthesis in vivo in normotensive and hypertensive rats.

The acute inhibitory effects of ethanol (75 mmol/kg body weight; i.p.; 2.5 hour) on the synthesis of the myofibrillary and other protein fractions in normotensive and hypertensive rats were investigated. Male Wistar rats were subjected to 30 days aortic constriction to induce hypertension. Controls were sham-operated and subjected to controlled feeding so that both groups of rats received identical food intakes. At the end of the study the left ventricles were analysed. Hypertension was associated with a significant increase in the content of myofibrillary and non-contractile proteins with slightly reduced protein synthesis. A marked decrease in the rates of contractile and non-contractile protein synthesis occurred in response to ethanol dosage in sham-operated control rats. The decline in myofibrillary protein synthesis was greater in the hypertensive animals. A reduction in the synthesis of contractile proteins will compromise the formation of new contractile elements and contribute to the impaired contractility of hypertensive ethanol misusers.

Protein synthesis during regression of left ventricular hypertrophy with lisinopril in abdominal aortic constriction model of hypertension.

The use of lisinopril was assessed in inducing regression of established left ventricular hypertrophy. Left ventricular hypertrophy was achieved by aortic constriction in the rat. Lisinopril was administered in drinking water (5 mg/kg body weight/day) to aortic constricted rats starting from Day 30 for a period of further 30 days. At the end of 60 days the rates of protein synthesis were measured using the flooding dose technique. Lisinopril reduced the mixed protein contents of the regressed left ventricle from 223 +/- 7 mg to 175 +/- 10 mg/left ventricle in the aortic constricted rats; P < 0.01, all data are means +/- SEM, n = 5-8. The regression of left ventricular mass occurred along with simultaneous decrease in the rate of protein synthesis (i.e., 6.56 +/- 0.33 in aortic constricted rats versus 4.40 +/- 0.44%/day, in lisinopril treated left ventricles, P < 0.05). However, the expanded cardiocyte fiber thickness remained unchanged despite lisinopril treatment (i.e., 20.4 +/- 0.7 in aortic constricted rats versus 19.5 +/- 0.6 microm in regressed left ventricles, P > 0.05). The results indicate that regression of pressure overloaded hypertrophy with lisinopril primarily occurs by a decrease in protein synthesis in the connective tissue components of the left ventricle, although cytoskeletal components may be unaffected.

Protein synthesis in the hypertrophied heart of spontaneously hypertensive rats and a comparison of the effects of an ACE-inhibitor and a calcium channel antagonist.

The aim of the investigation was to assess and compare the effects of a calcium channel antagonist, (i.e. amlodipine) and an ACE-inhibitor (i.e. lisinopril) in reducing chronic left ventricular hypertrophy in 15-week old spontaneously hypertensive rats (SHR). Changes in cardiac hypertrophy were assessed after 8 weeks by measuring the fractional rates of protein synthesis using a 'flooding dose' of [3H]-phenylalanine for 10 min. Blood pressure was monitored throughout the treatment period in both SHR and Wistar-Kyoto control rats (WKY). The results showed a decrease in blood pressure by amlodipine after 1 week of treatment which was further reduced at 4 to 8 weeks. Lisinopril caused immediate and sustained reductions in blood pressure (190 mmHg to 130 mmHg, P < 0.001). After 8 weeks of treatment in SHR rats, amlodipine had no significant effect on left ventricular weight (P > 0.05), whereas lisinopril caused a marked reduction. The protein content and RNA were also not changed by amlodipine. In contrast, lisinopril significantly lowered the tissue protein, RNA and DNA content (P < 0.001). The changes in the left ventricles of lisinopril-treated SHR rats were accompanied by an increase in the fractional synthesis rate of left ventricular myofibrillar proteins (+12 per cent, P < 0.025). The synthesis rate per unit RNA was also increased in right ventricular tissue of lisinopril-treated SHR rats. However, amlodipine had no effect on the fractional synthesis rates of any of the left-ventricular fractions of SHR rats (P > 0.05). The cellular efficiency in the right ventricle was also increased in amlodipine-treated SHR rats, indicating a moderate effect on protein metabolism. In conclusion, amlodipine had minimal effects in the reduction of established left ventricular hypertrophy (LVH), despite reducing the blood pressure, whereas lisinopril caused regression of LVH. These events were associated with small changes in protein synthesis rates, with the contractile protein showing an increase.

Ethanol toxicity and cardiac protein synthesis in vivo.

Long- and short-term alcohol consumption induce a variety of cardiovascular changes, including alterations in hemodynamic variables and tissue biochemistry. In many instances some of the perturbations may be considered as compensatory adjustments, and indeed, there is some controversy that moderate long-term consumption may cause alterations in plasma lipid profiles, conferring cardiovascular protection by reducing the incidence of coronary artery disease. In the long term, however, ethanol misuse may induce a specific disease entity, namely alcoholic heart muscle disease, and short-term ethanol exposure may also perturb tissue contractility and hemodynamic indices. The mechanisms of these changes are unknown, but central to many of the metabolic and functional disturbances are alterations in tissue protein synthesis, perhaps precipitated or exacerbated by free radial formation or by the formation of protein-acetaldehyde adducts. Methods for measuring protein synthesis in vivo are reviewed, and their application to elucidating the mechanisms involved in cardiac abnormalities is described, including the effects of ethanol. Our results demonstrate that the effects of alcohol toxicity also occur at the subcellular level, and the synthesis of mitochondrial proteins are reduced in vivo, perhaps even contribution to defects in energy generation, the normal function of which is required to maintain contractility.

The deleterious effects of alcohol on the heart: involvement of protein turnover.

Ethanol ingestion can induce a variety of metabolic changes in the heart, and recent studies have even suggested that moderate ethanol intake confers cardio-protective effects in reducing mortality due to coronary artery disease. However, in this review we explore the consequences of excessive ethanol intake or alcohol misuse. We investigate the epidemiology of alcohol misuse, and thereafter present evidence supporting the existence of a specific alcoholic heart muscle disease (AHMD). The prevalence of AHMD is described and the contributing mechanisms are discussed. These include the involvement of free radicals, defects in intermediary metabolism and the formation of acetaldehyde adducts. Special attention has been paid to ethanol-induced changes in protein turnover. Our studies show that ethanol impairs the protein synthetic pathways, affecting the contractile proteins per se, as well as the subcellular organelles as exemplified by the mitochondria. Acetaldehyde appears to be a particularly potent toxin. The experiments described in this review emphasize the need for investigative studies in intact models. The mechanisms inherent in the pathogenesis of AHMD may be applicable to other heart muscle disorders.