Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene

Toluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal-Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng.h.mL(-1); p <= 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng.h.mL(-1); p <= 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.

Influence of N-Hexane Inhalation on the Enantioselective Pharmacokinetics and Metabolism of Verapamil in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

Anatomy of the frontal gland and ultramorphology of the frontal tube in the soldier caste of species of Nasutitermitinae (Isoptera, Termitidae)

is a predominant characteristic, conditioned by the presence of castes with different morphology, ontogeny, and development. The soldier caste is unique among social insects and it is responsible for colony defense. Soldiers belonging to the Nasutitermitinae subfamily are very peculiar, since they may be polymorphic and present a nasus in addition to either developed or vestigial mandibles. The defensive secretions of soldiers of the neotropical Nasutitermitinae have been the aim of several chemical studies, but few data exist concerning the anatomy and histology of the exocrine glands. This article presents a comparative study on the anatomy of the frontal gland of soldiers of several Nasutitermitinae species: Syntermes dirus (Burmeister), Syntermes nanus (Constantino), Constrictotermes cyphergaster (Silvestri), Nasutitermes corniger (Motschulsky) and Velocitermes heteropterus (Silvestri), with emphasis on the ultramorphology and ultrastructure of the frontal tube.

Growth and metabolism of pacu (Piaractus mesopotamicus Holmberg 1887) juveniles fed diets containing different protein, lipid and carbohydrate levels

To verify the potential of lipids and carbohydrates to spare dietary protein and to understand the intermediary metabolism of interaction of these nutrients in pacu juveniles, an experiment was carried out to evaluate pacu physiological and performance parameters. The experimental design was completely randomized with 12 treatments in a 2 x 2 x 3 factorial arrangement, consisting of diets containing two digestible protein levels (200 and 230 g kg(-1) PD), two lipid levels (40 and 80 g kg(-1)) and three carbohydrate levels (410, 460 and 500 g kg(-1)). Fish-fed 230 g kg(-1) digestable protein (DP) showed increased glycaemia, decreased hepatic glycogen, as well as a smaller intake index and better feed conversion ratio. The higher dietary lipid level (80 g kg(-1)) reduced protein intake and serum protein concentration, increased liver and body fat content, but did not affect growth. At a lipid level of 80 g kg(-1), the increase in dietary carbohydrate levels promoted greater weight gain (WG), crude protein intake (CPI) and better feed conversion ratio (FCR). For fish fed diets containing 40 g kg(-1) lipid, the best energy-productive values (EPV) were obtained at 460 g kg(-1) carbohydrate. Increased levels of the main nutrients in the diets reduced the levels of serum triglycerides, while the increase in energy concentration increased the hepatosomatic (HSI) and glycaemia index values. Pacu used lipids as effectively as carbohydrates in the maximization of protein usage, as long as dietary protein was at a level of 230 g kg(-1) DP. The physiological parameters indicated that the best balance between the DP, dietary lipid and carbohydrate levels within the ranged this trial was obtained at 230, 40 and 460 g kg(-1), respectively, without lower growth.

AGONISTIC PROFILE AND METABOLISM IN ALEVINS OF THE NILE TILAPIA

Metabolic differences derived from social stress usually show data with high variance that may hinder the finding of important differences. Since such high variance may be caused by agonistic variability occurring during social interactions, this work tested whether metabolism is associated with agonistic profile in the cichlid fish Nile tilapia, Oreochromis niloticus (L.). Metabolism was inferred from oxygen consumption, resistance to progressive hypoxia and ventilatory rate. Fifteen pairs of alevins were used for each metabolic and behavioral series. An ethogram based on 8 types of agonistic interactions was employed. Agonistic profiles were determined and associated with the physiological parameters later on. The test of canonical correlation showed significant association between some agonistic profiles and metabolism. Ventral nipping and lateral fight appeared as the two most important in promoting association with metabolism.

Arteriovenous fistula between the right internal mammary artery and the subclavian vein: percutaneous closure with detachable ballooncatheter embolization

A case of iatrogenic fistula from the right internal mammary artery to the subclavian vein following subclavian vein catheterization is reported. The patient had undergone percutaneous Intracath catheterization of the subclavian vein to treat hypovolemic shock during the surgical treatment of ectopic pregnancy. She had remained symptom-free for 7 years and then started to complain of effort dyspnea. The patient was found to have a thrill and a bruit at the subclavian region, and arteriography demonstrated a fistula between the right internal mammary artery and the subclavian vein. The fistula was successfully closed by embolization with a percutaneous detachable balloon catheter. © 1993.

Persistence and metabolism of fenthion in orange fruit

The persistence and metabolism of fenthion in orange fruit were studied in field conditions. The fenthion was transformed to fenthion sulfoxide and fenthion sulfone. Sunlight photodegradation experiments showed that this transformation is due to the action of sunlight. Residues were found only in the fruit peel. Fenthion showed a rapid degradation rate with a half-life of ca. 6 days. Fenthion sulfoxide was degraded more slowly with a half-life of ca. 14 days and represented the major residue. Fenthion sulfone was present in low quantities.

Persistence and Metabolism of Folpet in Grapes and Wine

The fate of folpet from the treatment on vine to the production of wine was studied. Sunlight degraded folpet to unknown products. Phthalimide was a minor metabolite formed on grapes from folpet. Folpet degraded in must, giving 80% phthalimide; the results obtained with model solutions showed that in must folpet can also give small amounts of phthalic acid. During wine-making folpet degraded completely, and at the end of fermentation phthalimide was only present in wine. This compound was stable in wine after several months. The presence of folpet in grapes inhibited the alcoholic fermentation of Saccharomyces cerevisiae and Kloeckera apiculata completely. Phthalimide, on the contrary, had no negative effect on the fermentative action of the two yeasts. GC and HPLC methods were developed to determine folpet and its metabolites.

Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor

The pineal gland, the gland that translates darkness into an endocrine signal by releasing melatonin at night, is now considered a key player in the mounting of an innate immune response. Tumor necrosis factor (TNF), the first pro-inflammatory cytokine to be released by an inflammatory response, suppresses the translation of the key enzyme of melatonin synthesis (arylalkylamine-N-acetyltransferase, Aanat). Here, we show that TNF receptors of the subtype 1 (TNF-R1) are expressed by astrocytes, microglia, and pinealocytes. We also show that the TNF signaling reduces the level of inhibitory nuclear factor kappa B protein subtype A (NFKBIA), leading to the nuclear translocation of two NFKB dimers, p50/p50, and p50/RelA. The lack of a transactivating domain in the p50/p50 dimer suggests that this dimer is responsible for the repression of Aanat transcription. Meanwhile, p50/RelA promotes the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide, which inhibits adrenergically induced melatonin production. Together, these data provide a mechanistic basis for considering pinealocytes a target ofTNF and reinforce the idea that the suppression of pineal melatonin is one of the mechanisms involved in mounting an innate immune response. © 2011 Carvalho-Sousa, da Silveira Cruz-Machado, Tamura, Fernandes, Pinato, Muxel, Cecon and Markus.

Salmonella enterica serovar typhimurium colonizing the lumen of the chicken intestine grows slowly and upregulates a unique set of virulence and metabolism genes

The pattern of global gene expression in Salmonella enterica serovar Typhimurium bacteria harvested from the chicken intestinal lumen (cecum) was compared with that of a late-log-phase LB broth culture using a whole-genome microarray. Levels of transcription, translation, and cell division in vivo were lower than those in vitro. S. Typhimurium appeared to be using carbon sources, such as propionate, 1,2-propanediol, and ethanolamine, in addition to melibiose and ascorbate, the latter possibly transformed to D-xylulose. Amino acid starvation appeared to be a factor during colonization. Bacteria in the lumen were non- or weakly motile and nonchemotactic but showed upregulation of a number of fimbrial and Salmonella pathogenicity island 3 (SPI-3) and 5 genes, suggesting a close physical association with the host during colonization. S. Typhimurium bacteria harvested from the cecal mucosa showed an expression profile similar to that of bacteria from the intestinal lumen, except that levels of transcription, translation, and cell division were higher and glucose may also have been used as a carbon source. © 2011, American Society for Microbiology.

Effects of hydric deficiency on gas exchange parameters and metabolism of Eucalyptus grandis clones

The metabolic effects caused by hydric deficiency (HD) on Eucalyptus grandis clones were assessed by an experiment where plants were cultivated in four blocks. The first was the control block, normally irrigated, whereas the other three blocks were submitted to cycles of hydric deficiency. Analysis of photosynthetic efficiency, enzymatic activity of antioxidant response system, level of pigments and L-proline concentration were performed to evaluate the HD effects. Results showed that HD altered some parameters related to photosynthetic activity, pigments accumulation, proline and enzymatic activity. Clone 433 of E. grandis presented higher response ability to HD.