Alteration of cytosine-guanine interactions due to N7 metal cation binding: a structure-activity relationship for cisplatin analogues

Metal cation binding to N7 of guanine (G) and the resulting altered interaction with cytosine (C) were investigated by ab initio quantum chemical calculations for the ions Li+, Na+, B+, Be2+, and Mg2+. It was found that the CG H-bonding interaction becomes more stable and the stacking interaction less stable as the charge density for the ion (ion charge/ionic radius) increases. From this observation a hypothesis is presented for a structure-activity relationship, which is supported by in vivo animal data, that may permit the design of less toxic analogues of the antitumor agent cisplatin.     

Physical activity consultation for people with Type 2 diabetes: evidence and guidelines.

Physical activity is an important, but often underused, therapeutic strategy within diabetes care. To date, little is known about the best way to promote physical activity in diabetes care. Physical activity consultation is an intervention designed to promote physical activity behaviour change. This article provides guidelines on how to conduct a physical activity consultation with people who have Type 2 diabetes, and reviews the evidence surrounding the effectiveness of this intervention in this population. The trans-theoretical model is the underlying theory of behaviour change for the physical activity consultation intervention. The review identifies research which supports the use of this model for understanding physical activity behaviour in people with Type 2 diabetes. The review outlines a number of modifiable variables associated with physical activity behaviour change in this population. How each of these variables is addressed within the guidelines for conducting a physical activity consultation is identified. Finally, limited but consistent research highlights the effectiveness of physical activity consultation for promoting physical activity in people with Type 2 diabetes.     

Long-term follow-up and the role of surgery in adolescents with morbid obesity

PURPOSE: Obesity has become a health-care crisis in the United States. Adolescent obesity is now one of the most common childhood disorders, with 4.7 million American adolescents having a body mass index (BMI) greater than the 95th percentile. Most patients do not respond to diet modification or exercise programs and attention is now turning toward surgery as a source of weight loss in adolescents. Few studies have looked at the overall morbidity and mortality of weight loss surgery in this patient population. METHODS: This is a retrospective study of medical charts of 15 bariatric surgical procedures performed on 14 adolescents without known genetic syndromes associated with severe childhood obesity from 1971 to 2001 at the University of Minnesota. Procedures performed on these patients included vertical banded gastroplasty (n = 7), Roux-en-Y gastric bypass (n = 5), and jejunoileal bypass (n = 3). Jejunoileal bypass procedures were performed from 1971 to 1977, after which time this procedure was abandoned. Patient age ranged from 13 to 17 years (mean, 15.7 years). Mean follow-up time was 6 years, with 9 patients available for long-term follow-up. RESULTS: All procedures were performed using an open technique by 1 surgeon. There were no perioperative deaths; complications included 1 case of wound infection, 2 episodes of dumping syndrome that resolved without revision, 1 episode of hypoglycemia, and 1 case of short-term electrolyte imbalance in a patient who underwent jejunoileal bypass. The average BMI dropped from 58.5 +/- 13.7 to 32.1 +/- 9.7 kg/m(2) (P < .01)--a 45% reduction. CONCLUSIONS: Surgery for morbid obesity is safe and results in significant weight loss in adolescents who fail medical therapy.     

Effects of cocaine, exercise, and resting conditions on plasma corticosterone and catecholamine concentrations in the rat

Cocaine and exercise are both known as stressors, but little is known about the combined effects of these two treatments. In this study, rats under the influence of cocaine (12.5 mg/kg, intraperitoneally [IP]) or saline were exposed to a variety of resting conditions, as well as exercise (running, 26 m/min, 10% grade, for 30 minutes), to evaluate the amount of stress imposed by these conditions as determined by the changes in the plasma concentrations of corticosterone (C) and catecholamines (norepinephrine [NE], epinephrine [E], dopamine [DA]). After injection of saline, resting near the operating treadmill for 30 minutes caused the concentration of C to increase from 0.07 +/- 0.03 to 0.30 +/- 0.05 microgram/mL (P less than .05), compared to the increase to only 0.15 +/- 0.04 micrograms/mL after resting in a cage. This increase due to proximity to the treadmill subsided after 50 minutes. After cocaine, the 30-minute resting values were 0.70 +/- 0.15 (treadmill) and 0.55 +/- 0.13 (cage) (P less than .05), and did not subside after 50 minutes. Cocaine also increased levels of E, NE, and DA above those in saline under all rest conditions. With exercise, the value for C in saline increased to 0.61 +/- 0.18, but, in cocaine, the value went to 0.93 +/- 0.05 (P less than .05). The concentrations of E (946 +/- 74 v 603 +/- 101 pg/mL, cocaine v saline) and NE (1,027 +/- 102 v 440 +/- 153, cocaine v saline) during exercise also were exaggerated by cocaine treatment (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary venous retroperfusion of arterial blood for the treatment of acute myocardial ischemia

Synchronized coronary venous retroperfusion of autologous arterial blood was offered to patients referred for medically refractory unstable angina or evolving myocardial infarction with contraindications to thrombolytic therapy. Primary endpoints of angina, ST segment deviation, and two-dimensional echocardiographic systolic wall motion were followed to determine the efficacy of retroperfusion in patients prior to and then during angioplasty, surgical intervention, or pharmacological management, as the clinical picture warranted. Over a 12 month period, 21 patients were referred and 15 received retroperfusion. All experienced full relief of angina (p = 0·008). ST segment deviations and systolic wall motion of ischemic zones were observed to improve (p = 0·06 ST changes; p = 0·0001 wall motion changes) with synchronized retrograde perfusion. During attempts to remove patients from retroperfusion, statistically significant (p < 0·01) reproducible changes in these same endpoints were documented. Retroperfusion appears to improve acute myocardial ischemia. This technique functions well in the intensive care unit environment with only fluoroscopy as technical imaging support.     

Otitis media in children born to human immunodeficiency virus-infected mothers.

Acute otitis media (AOM) is thought to occur frequently in children infected with human immunodeficiency virus (HIV). We compared experience with AOM of 28 HIV-infected children with that of 33 children who seroreverted to HIV antibody negative status by age 18 months. The mean number of episodes/year of AOM for children who seroreverted decreased from 1.33 in the first year of life to 0.13 in the third year, whereas the mean number of episodes/year in HIV-infected children increased from 1.89 to 2.40. By age 3 years, all HIV-infected children had experienced 1 or more episodes of AOM, and 80% had experienced 6 or more, whereas 75% of children who seroreverted had experienced 1 or more episodes, and none had had 6 or more. HIV-infected children with normal T4 lymphocyte counts had a mean of 1.18 episodes of AOM in the first year of life compared with 2.35 episodes in HIV-infected children with decreased counts (P = 0.023). HIV-infected children with low counts had a nearly 3-fold increased risk of recurrent AOM (47% vs. 18%).     

Muscle metabolism during sprint exercise in man: influence of sprint training.

In order to examine the influence of sprint training on metabolism and exercise performance during sprint exercise, 16 recreationally-active, untrained, men (VO2peak= 3.8+/-0.1 l.min(-1)) were randomly assigned to either a training (n= 8) or control group (n= 8). Each subject performed a 30-sec cycle sprint and a test to measure VO2peak before and after eight weeks of sprint training. The training group completed a series of sprints three times per week which progressed from three 30-sec cycle sprints in weeks 1 and 2, to six 30-sec sprints in weeks 7 and 8. Three mins of passive recovery separated each sprint throughout the training period. Muscle samples were obtained at rest and immediately following the pre- and post-training sprints and analysed for high energy phosphagens, glycogen and lactate; the activities of both phosphofructokinase (PFK) and citrate synthase (CS) were also measured and muscle fibre types were quantified. Training resulted in a 7.1% increase in mean power output (p<0.05), an 8% increase in VO2peak (p< 0.001), a 42% increase (p< 0.01) in CS activity and a 17% increase (p< 0.05) in resting intramuscular glycogen content. In contrast, neither PFK activity nor fibre type distribution changed with training. An increase (p< 0.05) in mean power output and attenuated (p< 0.01) ATP degradation were observed during sprint exercise following training. Glycogen degradation during sprint exercise was unaffected by sprint training. These data demonstrate that sprint training may have enhanced muscle oxidative but not glycolytic capacity.     

Comparison of glomerular and mesangial prostaglandin synthesis and glomerular contraction in two rat models of diabetes mellitus

Enhanced prostaglandin production is postulated to contribute to altered vascular reactivity and glomerular hyperfiltration in early insulin-deficient diabetes mellitus. Rats with streptozocin-induced diabetes (STZ-D) show glomerular hyperfiltration and develop renal disease. BB rats with genetic diabetes (BB-D) also hyperfilter but have only minor renal lesions. We therefore compared glomerular and mesangial prostaglandin E2 (PGE2) production and glomerular contractility in response to pressors as a reflection of in vitro vascular reactivity in these models. Glomeruli isolated from rats with 3 wk of STZ-D produced significantly more PGE2 under basal and ionophore A23187-stimulated conditions than those from control rats. Glomeruli from BB-D rats under basal and stimulated conditions, however, generated amounts of PGE2 that were comparable to either those of nondiabetic littermates or of normal Wistar rats. Mesangial cells cultured from glomeruli of STZ-D, BB-D, and control rats all had identical prostaglandin profiles judged by conversion of [14 C]arachidonic acid. They also produced comparable amounts of PGE2 under basal conditions and after stimulation with angiotensin II or A23187, as determined by radioimmunoassay. Planar surface area of glomeruli isolated from control rats showed a dose-dependent decrease in response to angiotensin II (10(-11)-10(-9) M). This response to angiotensin II was at least as great in glomeruli from STZ-D rats. Contraction of glomeruli from control and STZ-D rats was also comparable after vasopressin or norepinephrine. Similarly, glomeruli from BB-D and BB control rats contracted in a comparable fashion to angiotensin II and norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)