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Biomedical subjects

R R Jenkins

Publications and source records attributed to R R Jenkins.

13 recordsLinked to original sources

The effect of beta blocking drugs on lipid peroxidation in rat heart in vitro.

Beta-adrenergic receptor blocking drugs include a structurally related class of drugs that are employed clinically to treat a variety of cardiovascular disorders. Since these drugs exert additional nonspecific effects including membrane stabilization, representative samples including atenolol, dilevolol, labetalol, metoprolol and propranolol were studied to determine their influence on lipid peroxidation. Homogenates or liposomes of adult rat hearts were incubated in the presence of various concentrations of propranolol or equivalent concentrations of dilevolol, labetalol, metoprolol or atenolol. Lipid peroxidation was stimulated with 50 microM FeSO4, 5 microM t-butyl hydroperoxide (homogenates) or 0.2 mM citrate FeSO4 (liposomes) plus O2. Lipid peroxidation, as assessed by both the thiobarbituric acid reaction and chemiluminescence, was reduced in a dose-dependent manner as the propranolol concentration was increased from 1 to 10 mM. The five beta-adrenergic receptor blocking drugs reduced lipid peroxidation both in crude homogenates and in liposomes; their effectiveness was related to their lipophilicity. Dilevolol, propranolol, labetalol and metoprolol at a concentration of 20 mM reduced lipid peroxidation by 45%, 37%, 35% and 28%, respectively. The hydrophilic blocker atenolol was ineffective in reducing lipid peroxidation even at elevated concentrations. Lipophilic beta-blocking drugs apparently are capable of exerting an antioxidant effect in protecting membrane lipids against peroxidation.

Adrenergic beta-Antagonists

Elevated muscle vitamin E does not attenuate eccentric exercise-induced muscle injury.

The purpose of this study was to evaluate the effect of elevated muscle vitamin E content on skeletal muscle damage from eccentric exercise. Sixty Sprague-Dawley rats were put on a normal (40 IU vitamin E/kg food) or supplemented (10,000 IU vitamin E/kg food) diet for 5 wk. Injury in soleus muscle was determined using several criteria: reductions in maximal tetanic force and number of intact fibers per square millimeter and elevations in muscle glucose 6-phosphate dehydrogenase activity and plasma creatine kinase activity, either immediately (0 h) or 2 days (48 h) after a downhill walking protocol. Sedentary animals were also tested but did not exercise. Muscle vitamin E levels were significantly elevated (approximately 3- to 4-fold), and susceptibility of the muscles to oxidant stress was decreased, after supplementation. However, vitamin E supplementation did not attenuate injury by any of the criteria employed. Maximal tetanic force decreased approximately 20% at 0 and 48 h after exercise in both groups. The number of intact fibers per square millimeter decreased approximately 30-35% in both groups at 0 and 48 h. Glucose 6-phosphate dehydrogenase activity increased approximately 50-100% in both groups at 48 h, and plasma creatine kinase activity was elevated approximately 2- to 2.5-fold at 0 h in both groups. These findings do not support a major role for free radical damage to muscle membranes in the initiation of injury from eccentric exercise, although they do not disprove free radical involvement in the etiology.

Animals

Myosin isozyme expression in response to stretch-induced hypertrophy in the Japanese quail.

When skeletal muscle is subjected to stretch it undergoes a rapid increase in muscle mass. However, the effect of stretch on the native myosin isozyme content of muscle has received attention only recently. Using the Japanese quail to investigate stretch-induced hypertrophy, we demonstrated an increase in the expression of fast myosin in the predominantly slow anterior latissimus dorsi muscle (ALD). The fast myosin content of the control quail ALD is not sufficient to be quantified on native myosin pyrophosphate gels. After 33 days of stretch, the fast myosin content (N = 10) averaged 16 +/- 11% in the stretched muscles and reached a maximum of 40%. Mean hypertrophy in the stretched muscle, as indicated by muscle weight, was 247 +/- 91% (range, 168-378%). Fast myosin was consistently expressed in muscles with hypertrophy greater than 250%. Muscle fiber size from the stretched muscles contained a greater number of fibers with small cross-sectional areas than was observed in controls. These results indicate that substantial remodeling occurs in the stretched ALD muscle of the Japanese quail.

Animals

Effects of beta-adrenergic blockade on training-induced structural adaptations in rat left ventricle.

The study was designed to evaluate the effects of eight weeks of exercise training or training-beta-adrenergic blockade combination on gross and microscopic alterations of rat cardiac muscle and microvascular bed. Rats were randomly assigned to either sedentary control (C), trained (T), metoprolol-trained (MT), or propranolol-trained (PT) groups. The training protocol involved treadmill running for 8 weeks at 0.5 ms-1, 20% grade. Earlier experiments by us showed this training protocol to be effective in producing significant changes in selected skeletal muscle enzyme activities in all trained groups. In the current study an absolute reduction in left ventricular (LV) weight was observed in the PT compared to the C group (0.91 +/- 0.02 vs. 1.04 +/- 0.04 g, P less than 0.05). LV weight in the T and MT groups was no different from C so that LV to BW ratio (mg.g-1) was significantly increased (P less than 0.05) due to a similar reduction in body weight (BW) in all three training groups. Morphometric analysis of LV myocardium revealed no significant differences in myocyte mean cross-sectional area (micron 2) in any of the groups (289 +/- 16-C, 332 +/- 20-T, 281 +/- 44-MT, and 273 +/- 12-PT). Capillary density independently calculated by light and electron microscopy was unchanged by training or training-beta-blockade combination. It was concluded that training of sufficient intensity and duration to produce skeletal muscle enzyme adaptations does not necessarily produce myocyte hypertrophy or alter LV capillarity. Additionally functioning beta-adrenergic receptors appear to play a role in both the central and peripheral adaptations to endurance exercise training.

Adaptation, Physiological

Free radical chemistry. Relationship to exercise.

Free radicals are molecules or molecular fragments containing an unpaired electron in the valence shell. Radicals interested only a few chemists until 18 years ago when an enzyme was discovered which functioned to remove a specific oxygen-centered radical. That discovery renewed interest in radicals and has already begun to alter thinking on many clinical problems. Free radicals have been shown to be common phenomena that play a role in normal biochemistry but require an elaborate control system to be held in check. Since oxygen-centered radicals are produced in intermediate metabolism, exercise should increase their production and that has been shown to be so. There is also evidence that the consumption of large quantities of ambient oxygen during exercise induces harmful chemistry known as lipid peroxidation. Presently, there are insufficient data available to ascertain how the human body tolerates such increased production of free radicals and lipid peroxidation and how the consequences of that chemistry might relate to the overall well being of exercising humans.

Antioxidants

Microalbuminuria and hypertension in long-term renal donors.

In order to determine whether the proteinuria observed in some renal donors was glomerular or tubular in origin, and to determine whether creatinine clearance was an accurate index of glomerular filtration rate (GFR) in subjects with reduced nephron mass, 29 donors were evaluated 9-18 years after uninephrectomy. Results were compared with those in 31 age-, sex-, and race-matched controls evaluated at the same time. Mean creatinine clearance (Ccreat) in donor was 78% that of controls, which was similar to the 85% ratio of inulin clearance (Cin) in donors compared with that of controls. Furthermore, the ratio of Ccreat/Cin was similar in both donors and controls. One third of the renal donors had an elevated albumin excretion compared with controls (microalbuminuria [12-220 mg/24 hr] in seven patients; 301 and 1084 mg/24 hr in two patients). There was no correlation between albuminuria and blood pressure, nor was there a demonstrable clinical cause for the albuminuria in most patients. In contrast to these results, excretion of beta-2 microglobulin, an index of tubular proteinuria, was normal in all but one patient. The prevalence of hypertension was higher in donors compared with the expected prevalence adjusted for age, sex, and race. These results verify that creatinine clearance is a reliable measure of GFR in long-term renal donors. They also demonstrate an increased frequency of glomerular proteinuria and hypertension in renal donors. Despite these mild abnormalities, GFR is well preserved for up to 18 years postuninephrectomy.

Adult

Effects of beta 1- vs. beta 1- beta 2-blockade on training adaptations in rat skeletal muscle.

The effect of selective vs. nonselective beta-blockade on fast-twitch [extensor digitorum longus (EDL)] and slow-twitch [soleus (SOL)] muscle enzyme activities following endurance training were characterized. Citrate synthase (CS), lactate dehydrogenase (LDH), and beta-hydroxyacyl-CoA dehydrogenase (HAD) activities were compared in SOL and EDL muscles of trained (T), metoprolol-trained (MT), propranolol-trained (PT), and sedentary (C) rats. Following 8 wk of treadmill running (1 h/day, 5 days/wk at approximately 30 m/min), LDH activity was depressed approximately 20% (P less than 0.05) in both SOL and EDL in only the PT rats, indicating inhibition of beta 2-mediated anaerobic glycolysis. EDL CS activity was similarly elevated in all three trained groups compared with sedentary controls. In SOL muscle, however, a drug attenuation effect was observed so that CS activity was increased only in the T (P less than 0.01) and MT (P less than 0.05) groups. HAD enzyme activity was increased somewhat (P less than 0.10) in SOL muscle in only the T group, but more so (P less than 0.05) in EDL in all three trained groups. The above findings suggest a training-induced selectivity effect not only with respect to beta 1-vs. beta 1-beta 2-blockers, but also with respect to muscle fiber type.

3-Hydroxyacyl CoA Dehydrogenases

Prevalence of Trichomonas vaginalis in men at high risk for sexually transmitted diseases.

This study determined the prevalence of Trichomonas vaginalis in young men who were at high risk for sexually transmitted diseases; compared different diagnostic tests for trichomonads; and compared sexual behavior of men with positive and negative trichomonas test results. Men (85) aged 16-22 years inclusive, were recruited from a job-training program to participate in this study. Urethral specimens were obtained after prostatic massage for the isolation of Neisseria gonorrhoeae, Chlamydia trachomatis, and trichomonads. The diagnosis of trichomonas infection was made by urethral culture, urine sediment culture, direct examination of urine sediment, direct specimen test (DFA), and Papanicolaou (PAP) smear of urethral swab. Trichomonas vaginalis was seen in 58% of the men, gonorrhoea in 23.5%, chlamydia in 29%, pediculosis in 6%, and condyloma acuminata in 7%, respectively. There was no statistically significant difference in age of the participants, frequency of intercourse, and number of sexual partners in the last 3 months in men with positive and negative trichomonas test results. After controlling for gonorrhoea, pyuria was significantly associated with trichomonas-positive urine (P = .01). No single test was ideal for the diagnosis of trichomonas infection. Using a combination of urethral culture and urine sediment culture as the "gold standard," DFA was 60% sensitive and 73.0% specific. However, urine sediment culture along with DFA identified 94% of all men with positive trichomonas test results.

Adolescent