The effect of methamphetamine on an animal model of erectile function.

In the US methamphetamine is considered a first-line treatment for attention-deficit hyperactivity disorder. It is also a common drug of abuse. Reports in patients and abusers suggest its use results in impotence. The efficacy of phosphodiesterase-5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies, we determined if the rat is a suitable animal model for the physiological effects of methamphetamine on erectile function, and if a PDE5i (tadalafil) has an effect on erectile function following methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague-Dawley rats, before and after administration of 10 mg/kg methamphetamine i.p. Chronically treated animals received escalating doses of methamphetamine [2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)] i.p. daily for 3 weeks and erectile function compared with untreated controls. The effect of co-administration of tadalafil was also investigated in rats acutely and chronically treated with methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies, we observed a significant increase in the rates of spontaneous erections after methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6 mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function. Tadalafil treatment reversed this effect. In chronically treated animals, the ICP/BP ratio following 4 and 6 mA stimulation decreased by approximately 50% compared with untreated animals and erectile dysfunction (ED) was also reversed by tadalafil. Overall, our data suggest that the rat is a suitable animal model to study the physiological effect of methamphetamine on erectile function. Our work also provides a rationale for treating patients that report ED associated with therapeutics-containing methamphetamine or amphetamine with PDE5i.

Antibody-guided alpha radiation effectively damages fungal biofilms.

The use of indwelling medical devices--pacemakers, prosthetic joints, catheters--is rapidly growing and is often complicated by infections with biofilm-forming microbes that are resistant to antimicrobial agents and host defense mechanisms. We investigated for the first time the use of microbe-specific monoclonal antibodies (MAbs) as delivery vehicles for targeting biofilms with cytocidal radiation. MAb 18B7 (immunoglobulin G1 [IgG1]), which binds to capsular polysaccharides of the human pathogenic fungus Cryptococcus neoformans, penetrated cryptococcal biofilms, as shown by confocal microscopy. When the alpha radiation-emitter 213-Bismuth ((213)Bi) was attached to MAb 18B7 and the radiolabeled MAb was added to C. neoformans biofilms, there was a 50% reduction in biofilm metabolic activity. In contrast, when the IgM MAb 13F1 labeled with (213)Bi was used there was no penetration of the fungal biofilm and no damage. Unlabeled 18B7, (213)Bi-labeled nonspecific MAbs, and gamma and beta types of radiation did not have an effect on biofilms. The lack of efficacy of gamma and beta radiation probably reflects the radioprotective properties of polysaccharide biofilm matrix. Our results indicate that C. neoformans biofilms are susceptible to treatment with antibody-targeted alpha radiation, suggesting a novel option for the prevention or treatment of microbial biofilms on indwelling medical devices.

Cryptococcus neoformans var. neoformans (serotype D) strains are more susceptible to heat than C. neoformans var. grubii (serotype A) strains.

Cryptococcus neoformans var. neoformans (serotype D) and C. neoformans var. grubii (serotype A) differ in geographic prevalence and dermatotropism, with C. neoformans var. neoformans strains being more prevalent among isolates from temperate countries as well as from skin infections. Analysis of 19 strains from each serotype revealed wide variation in thermal susceptibility, with C. neoformans var. neoformans strains being more susceptible, on average, to heat killing. The results suggest a consistent explanation for the geographic differences between serotype A and D strains and for the dermatotropism of serotype D strains.

[Determination by ultrasound of chorionicity in twin pregnancy]. / Determinación de corionicidad por ultrasonido en embarazo gemelar.

Twins, specially those of monochorionic and monoamniotic pregnancies, are exposed to many perinatal risks and complications. The objective of this study was to evaluate the usefulness of ultrasonographic determination of the chorionicity of human placental by counting the number of layers in amniotic membranes. Thirty-eight patients with twin pregnancies were studied prospectively. The ultrasonographic evaluation of membranes layers was made only once, between the weeks and 16 and 30 of pregnancy. When two layers were identified, the placentation was determined as monochorionic, and when four layers were seen, the diagnosis of bichorionic placentation was made. The type of chorionicity was confirmed by histologic study of the placenta. With ultrasound, the chorionicity was correctly determined in 36 out of 38 cases, for a total predictive value of 94.6%. The capacity for diagnosing bichorionic (4 layers) placentation was 100% (22/22) and 87.6% (14/16) for monochorionic (2 layers) placentation. The ultrasonographic evaluation of the amniotic membranes number is an efficient method to recognize the chorionicity of placenta and constitutes an useful and simple method giving important information in perinatal prognosis.

Energy balance in endurance-trained female cyclists and untrained controls.

Reports of low energy intakes in trained female athletes imply they have an increased energetic efficiency. To address this question, we determined how energy balance was achieved in endurance-trained females cyclists and lean controls (n = 5 in each group). Daily energy expenditure was measured by using standardized physical activity protocols in a whole room calorimeter on two separate occasions: a cycling day and a noncycling day. Energy intake for weight maintenance was determined by a period of controlled feeding 5 days before and the day of each energy expenditure measurement. Energy balance was achieved in the cyclists on the cycling day while they consumed 2,900-3,000 kcal (their usual condition) and in controls on the noncycling day while they consumed 2,100-2,200 kcal (their usual condition). Total daily energy expenditure was not significantly different between the cyclists and controls on the noncycling day with both groups performing similar levels of activity. On the cycling day, daily energy expenditure was significantly greater in the cyclists vs. controls (P < 0.03) as a result of their greater amount of cycling activity. Components of daily energy expenditure, i.e., resting metabolic rate and thermic effect of food and activity (noncycling), were not significantly different between groups. Overall, we found no significant increase in the energetic efficiency of endurance-trained female cyclists compared with controls.

Substrate utilization during treadmill running in prepubertal girls and women.

Ten prepubertal girls (9.1 yr) and 10 women (24.4 yr) were studied during 30-min runs at the same relative (70% VO2max) (RI) and absolute (7.2 km.h-1) (AI) intensities. Oxygen consumption and respiratory exchange ratio (RER) were monitored continuously during the exercise test. Venous blood samples were obtained before and immediately after exercise and were analyzed for glucose, lactate, FFA, and glycerol. During exercise at the same RI, RER was significantly (P less than 0.05) lower in the girls compared with the women. In addition, RER decreased significantly during exercise in the girls while the change did not reach significance in the women. Lactate concentration increased significantly during the exercise tests, this increase being greater in the women than in the girls during exercise at the same RI, but greater in the girls than in the women during exercise at the same AI. FFA and glycerol concentrations were significantly higher after the exercise tests in both groups. Glucose concentration did not change significantly during the tests in either group. Prepubertal girls rely more on fat utilization and less on carbohydrate metabolism than women during exercise of moderately heavy intensity.

Rosoxacin (Win 35,213) in the treatment of uncomplicated acute gonococcal infection.

The results of this open multicenter trial with 100 patients of both sexes show that a single 300-mg dose of rosoxacin (Win 35,213) was effective in achieving a 94% cure rate, both clinical and bacteriological, on the seventh day after treatment in patients with uncomplicated acute gonococcal infection. The cure rate in men was 94% (86/92) and in women 100% (8/8). All isolates of Neisseria gonorrhoeae were susceptible to rosoxacin, as determined by 5-micrograms sensitivity disks. Adverse effects were seen in 14 patients--13 men and one woman. Twelve patients reported dizziness, one drowsiness, and one visual changes. It is concluded that rosoxacin can be of great usefulness in the epidemiological control of acute gonococcal infection, because of the lack of in vitro resistance to it, its minimal adverse effects, the low dose requirements, and the effectiveness of a single dose. The drug does not appear to have any treponemicidal action.

pH homeostasis during cardiopulmonary resuscitation in critically ill patients.

We investigated the effect of repeated administration of sodium bicarbonate on acid-base balance and serum chemistry in a group of patients who developed cardiac arrest. A mixed acidosis persisted throughout the duration of resuscitation in the majority of patients in spite of the large ventilatory volume and multiple doses of bicarbonate they received. However, the repeated administration of bicarbonate prevented a severe fall in serum pH. Our study demonstrated the beneficial role of bicarbonate in the treatment of metabolic acidosis associated with cardiac arrest of prolonged duration. Analysis of our data strongly indicated that the primary factors which determine the serum pH during cardiopulmonary resuscitation are the duration of circulatory arrest, adequacy of ventilation and circulation, pH immediately before arrest, and quantity of bicarbonate administered and its volume of distribution in the various fluid and tissue compartments.