The metabolic fate of an oral 14C-alanine load in the obese Zucker rat.

Following an oral 14C-alanine load, obese Zucker rats showed the same rate of intestinal amino acid absorption as their lean counterparts. Alanine absorption was unchanged by a 24 h starvation period. The whole-body oxidation of the absorbed tracer was lower in the fa/fa rats and was significantly decreased in both lean and obese groups when the animals were submitted to starvation. The incorporation of the 14C-tracer into 14C-lipid was significantly higher in the carcass, skeletal muscle, white adipose tissue and liver of the obese animals, while that of brown adipose tissue was decreased as compared to that of the lean rats. Starvation induced no variation in 14C-lipid incorporation in the lean (+/?) animals while it sharply decreased this parameter in the obese. The incorporation of the tracer into 14C-glycogen and 14C-protein was also increased in the liver of the obese rats while no changes in incorporation into these fractions were observed in skeletal muscle. It is concluded that dietary amino acids significantly contribute to the hyperlipogenesis found in the liver and adipose tissue of the fa/fa rats.     

Cancer cachexia results in an increase in TNF-alpha receptor gene expression in both skeletal muscle and adipose tissue

The mRNA content of both TNF-alpha and its receptors (TNFR1 and TNFR2) in skeletal muscle and adipose tissue from cachectic rats has been assessed. The implantation of the Yoshida AH-130 ascites hepatoma resulted in substantial decrease in skeletal muscle TNF-alpha expression as early as at day 2 following tumour implantation. However, the mRNA content for the two receptors followed a different pattern, being significantly increased at day 7. In adipose tissue the expression of the TNF-alpha gene was significantly increased at all the time points studied, whereas TNF-alpha receptors expression followed a similar pattern to that observed in skeletal muscle. Western blot analysis indicated that the TNFR1 protein followed an identical pattern to that observed in the mRNA content both in muscle and adipose tissue. It is concluded that, during experimental cancer cachexia, the contribution of muscle-produced TNF-alpha is decreased; however, significant changes were observed in relation with TNF-alpha receptors at the skeletal muscle level that could possibly be related to the muscle wasting process associated with tumour growth.     

Plasma from pregnant rats has anti-tumoural activity

Plasma from 12-day pregnant rats showed a marked anti-tumoural activity when added to short-term cultures of rat Yoshida AH-130 cells. Indeed, 24 h after the addition of 10% pregnant rat plasma resulted in a 34% decrease in cell number as compared with cells without any serum additions or those that were added with virgin plasma. The decrease in cell number was associated with the presence of a marked aneuploid peak, as indicated by flow cytometry analysis, which suggests that pregnant plasma induces apoptosis in this particular tumour cell line. Interestingly, addition of human chorionic gonatrophin to the cell cultures did not exert any effects either on cell content of cell cycle distribution, therefore suggesting that the presence of high concentrations of this hormone in pregnant plasma is unlikely to be the cause of the increased cell death.     

Non-palpable testicle: joint review of pediatric endo-surgical group and its management by laparoscopy

We present the joint serie of 5 Pediatric Centers with 256 patients diagnosed of cryptorchidism with nonpalpable testis treated by laparoscopy. We have found that Ultrasound examination is not very useful. This entity affects more to the left side 60%. In near half of the cases 46% we have not found any testicle and in 54% it was carried out an orquidopexy by different methods. In 27% we made an orquidopexy by Fowler-Stephens technique with 86% of good results. We think that laparoscopy is the best way of diagnosis and treatment of this patients.     

Leptin and tumor growth in rats.

We have examined the role of leptin in tumor-induced anorexia in 2 different tumor models. In rats bearing the Yoshida AH-130 ascites hepatoma, the reduction in food intake becomes important from day 6 after tumor inoculation. Interestingly, at day 4, when the animals do not show any anorectic behavior, circulating leptin levels were already reduced. Indeed, in all the tumor-bearing groups studied the levels of leptin were lower than in control animals. Moreover, the changes in the circulating levels paralleled changes in adipose tissue leptin mRNA expression, even at early stages following tumor inoculation when neither food intake nor fat stores were modified by the presence of a tumor. Interestingly, 7-day pair-fed controls showed changes similar to those present in tumor-bearing rats. These results agree with previous observations relating fasting to decreased leptin expression. Similar results were observed in another tumor model, the mouse Lewis lung carcinoma; i.e., at day 8 after tumor inoculation (when the animals did not show anorexia) both the circulating levels and the adipose leptin mRNA expression were also reduced. Our results suggest that experimental cancer-induced anorexia is not related to leptin changes.     

Tumour growth and nitrogen metabolism in the host (Review)

Tumour growth is frequently associated with massive loss of body weight and negative nitrogen balance leading to cachexia, one of the worst features of malignancy accounting for nearly two thirds of cancer deaths. At the metabolic level, cachexia is associated with depletion of body lipid stores as well as loss of skeletal muscle protein, which is manifested as an excessive nitrogen loss. The present study reviews the modulations of nitrogen metabolism in tumour-bearing conditions. In addition, the role of different mediators (such as cytokines) in the development of protein wasting is discussed. Particular emphasis has been given to tumour necrosis factor-alpha (TNF-alpha) which seems to have a key role in mediating changes related to nitrogen metabolism in the tumour-bearing host.     

Divided or kissing nevus of the penis: A new case with dermoscopic findings

We report on a child with a divided or kissing nevus of the penis with benign symmetric globular pattern on dermoscopic examination that evolved into a globular‐reticular pattern after 1 year of follow‐up. Divided nevus of the penis is exceedingly rare, with only four cases with dermoscopic findings reported to date. Dermoscopy seems to be useful when deciding on the most appropriate management of these cases.     

Influence of food on the oral bioavailability of rupatadine tablets in healthy volunteers: a single-dose, randomized, open-label, two-way crossover study

BACKGROUND: Rupatadine is an oral active antihistamine for the management of diseases with allergic inflammatory conditions, such as perennial and seasonal rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for the treatment of allergic rhinitis and chronic urticaria in adults and adolescents in several European countries. OBJECTIVE: The purpose of this study was to describe the effect of the concomitant intake of food on the pharmacokinetic profile and bioavailability of a single dose of rupatadine. METHODS: This was a single-dose, randomized, open-label, 2-way crossover study in which healthy male and female volunteers received a single, 20-mg oral dose of rupatadine under fed and fasting conditions. Blood samples were collected and plasma concentrations of rupatadine and its active metabolites desloratadine and 3-hydroxydesloratadine were determined by liquid chromatography tandem mass spectrometry. Tolerability was based on the recording of adverse events (AEs), physical examinations, electrocardiograms, and laboratory tolerability tests immediately before each treatment period and at the final visit of the study. RESULTS: Twenty-four volunteers (12 males; mean [SD] age, 25.4 [5.3] years [range, 18-34 years]; mean [SD] weight, 71.2 [4.3] kg [range, 64-77 kg]; 12 females; mean [SD] age, 26.8 [6.5] years [range, 18-38 years]; mean [SD] weight, 58.4 [6.8] kg, [range 50-69 kg]) were enrolled and randomized with equal distribution of sex. A significant increase in AUC from drug administration to the final quantifiable sample (AUC(0-t)) and AUC from drug administration to infinity (AUC(0-infinity)) values of rupatadine was seen under fed conditions without affecting C(max). The ratios (90% CI) of the mean log-transformed AUC(0-t) and AUC(0-infinity) for rupatadine revealed a significant increase in AUC(0-t) (ratio 131%; 90% CI, 111%-154%) and AUC(0-infinity) (ratio 133%; 90% CI, 113%-156%), whereas C(max) remained unaltered (ratio 97%; 90% CI, 80%-116%). Plasma concentration-time profiles of desloratadine and 3-hydroxydesloratadine were similar with and without food, and no differences were seen for AUC(0-t), AUC(0-infinity), or C(max). Seven (28%) subjects reported > or =1 AE. All AEs were mild, resolved spontaneously, and did not affect the outcome of the study. CONCLUSIONS: The results of this study indicate that concomitant intake of food with a single 20-mg oral dose of rupatadine exhibits a significant increase in rupatadine bioavailability. Despite the absence of bioequivalence, the drug was well tolerated under fed and fasting conditions, and no major changes in severity and/or prevalence of AEs were reported.