Solubility and phase separation of benzocaine and salicylic acid in 1,4-dioxane-water mixtures at several temperatures

The solubilities of benzocaine and salicylic acid were determined in water-dioxane mixtures at several temperatures (5-40 degrees C for benzocaine and 10-40 degrees C for salicylic acid). The solubility curves as a function of dioxane ratio showed a maximum at 90% dioxane at all temperatures. Above 25 degrees C, the homogeneous mixture splits into two liquid immiscible phases. For benzocaine, the initial dioxane concentration range at which phase separation takes place increased with temperature (50-60% at 25 degrees C, 50-70% at 30-35 degrees C and 40-70% at 40 degrees C). For salicylic acid, the dioxane concentration required for phase separation (40-60% dioxane) did not change with temperature. Phase separation was not related to solid phase changes (polymorphism or solvates). The phase composition and drug extraction at the drug-rich phase were determined. The apparent enthalpies of the solution process were a nonlinear function of the dioxane ratio for both drugs. The apparent enthalpy of solution of benzocaine was larger than that expected at the upper limit of phase separation (70% dioxane), whereas for salicylic acid the apparent enthalpy of solution decreased abruptly at the region corresponding to phase separation (40-70% dioxane). Both drugs showed a nonlinear pattern of enthalpy-entropy compensation.     

Habitats, dispersion and invasion of sylvatic Triatoma dimidiata (Hemiptera: Reduviidae: Triatominae) in Petén, Guatemala

Dispersion and invasion capacity of sylvatic populations of Triatoma dimidiata (Latreille) were investigated during 14 mo by means of experimental chicken coops installed in a nature reserve within the Maya Biosphere, Petén, Guatemala. In addition, palm trees, underground archeological holes (chultunes) and piles of limestones within the forest were inspected as potential sylvatic habitats of T. dimidiata. From the three types of sylvatic habitats we inspected, all served as shelter and breeding sites for T dimidiata. The natural infection of these bugs (n = 72) with Trypanosoma cruzi (Chagas) was high (25%) and represent a risk for humans who colonize the forest. T. dimidiata quickly invaded the experimental chicken coops installed in the primary forest, albeit at very low densities. However, only one adult bug was encountered in the chicken coops installed in a secondary forest. Dispersal of adult T. dimidiata was most apparent at the end of the dry season. Overall, our results indicate a potential risk for invasion by sylvatic T. dimidiata of domestic environments in this area, with a risk of T. cruzi transmission to humans. We suggest that a system of community-based surveillance should be developed to detect new infestations and organize prompt treatment of any new cases of acute Chagas disease that may result.     

Study of the activity of glutathione-peroxidase,glutathione-transferase,and glutathione-reductase in renal transplants

The aim of this work was to study the temporare variation of oxidative stress in the plasma and erythrocytes (CR) of renal transplant patients We determined total glutathione (GST), as well as oxidized (GSSG) and reduced (GSH) fractions and the activity of glutathione peroxidase (G-px), glutathione reductase (G-red) and glutathione transferase (GSt). Determinations were performed 48 hours before transplant as well as 1 and 2 weeks after the renal transplant. The results showed a high "oxidative stress" rate, resulting from the equilibrium between the production of free radicals and the activity of antioxidants, the former being higher proportionally. Immediately after the transplant, there was an increase in oxidative stress, which resulted in an increased G-red, a marked decrease in plasma and in erythrocyte G-px (CR9 and an abrupt drop both in GST levels in plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). Thereafter there was a significant improvement in the activity of antioxidant enzymes, but without normalization; the total glutathione levels and the activity of various enzymes approached the average values of the control group.     

Isolation, characterization, and evaluation of metallothionein in renal transplant patients

The plasma metallothionein concentration was studied in renal transplant patients. These patients are submitted to an attack of free radicals catalyzed by metals such as copper, zinc, cadmium, and others. The function of metallothionein is to bind toxic metals inhibiting the attack of free radicals and oxidative stress that patients receiving renal transplants are submitted to. This is the reason for studying this protein in this work. The metalloprotein was separated from the plasma by thermoprecipitation and molecular exclusion chromatography with Sephadex G-75 followed by anionic-ionic exchange chromatographic purification with a CINa gradient. Identification was done by SDS electrophoresis in acrylamide gel with markers and commercial protein. Finally, determinations were made by atomic absorption, silver saturation method. In this work, determinations were made in the plasma of 11 patients before and 48 h and 1 and 2 weeks after renal transplantation. The same study was carried out in parallel in a control group of 11 blood donors. The results obtained show the existence in the plasma of metallothionein, with lower concentrations in patients than in controls (19 +/- 1.2 mg vs. 12 +/- 1.2 mg). The levels were lowest in the patient group analyzed 48 h after having received the transplant (6.34 mg) and had recovered slightly one and two weeks later.     

Benign retroperitoneal schwannoma in patient with antecedents of Willm's tumor in the infancy

We report a case of benign retroperitoneal schwannoma diagnosed casual in a 23 years old woman treated of a Wilm's tumour twenty years ago. A review of the on this unusual tumour is included.     

Electrical dimension of the nuclear envelope

Eukaryotic chromosomes are confined to the nucleus, which is separated from the rest of the cell by two concentric membranes known as the nuclear envelope (NE). The NE is punctuated by holes known as nuclear pore complexes (NPCs), which provide the main pathway for transport of cellular material across the nuclear-cytoplasmic boundary. The single NPC is a complicated octameric structure containing more than 100 proteins called nucleoporins. NPCs function as transport machineries for inorganic ions and macromolecules. The most prominent feature of an individual NPC is a large central channel, ~7 nm in width and 50 nm in length. NPCs exhibit high morphological and functional plasticity, adjusting shape to function. Macromolecules ranging from 1 to >100 kDa travel through the central channel into (and out of) the nucleoplasm. Inorganic ions have additional pathways for communication between cytosol and nucleus. NE can turn from a simple sieve that separates two compartments by a given pore size to a smart barrier that adjusts its permeabiltiy to the metabolic demands of the cell. Early microelectrode work characterizes the NE as a membrane barrier of highly variable permeability, indicating that NPCs are under regulatory control. Electrical voltage across the NE is explained as the result of electrical charge separation due to selective barrier permeability and unequal distribution of charged macromolecules across the NE. Patch-clamp work discovers NE ion channel activity associated with NPC function. From comparison of early microelectrode work with patch-clamp data and late results obtained by the nuclear hourglass technique, it is concluded that NPCs are well-controlled supramolecular structures that mediate transport of macromolecules and small ions by separate physical pathways, the large central channel and the small peripheral channels, respectively. Electrical properties of the two pathways are still unclear but could have great impact on the understanding of signal transfer across NE and gene expression.     

NK2 tachykinin receptors mediate contraction of the pig intravesical ureter: tachykinin-induced enhancement of non-adrenergic non-cholinergic excitatory neurotransmission

The current study was designed to characterize the functionally active tachykinin receptors involved in tachykinin-elicited contractions in the pig intravesical ureter, and to investigate the possible modulation exerted by the natural tachykinins substance P (SP) and neurokinin A (NKA) on the non-adrenergic non-cholinergic (NANC) excitatory ureteral neurotransmission. In pig intravesical ureteral strips pretreated with phosphoramidon (10(-5) mol/L) to block the endopeptidase activities, isometric force recordings showed that SP, NKA, and the NK2 receptor selective agonist [beta-Ala(8)]-NKA (4-10), all three induced contractions, with the following potency order: NKA > [beta-Ala(8) ]-NKA (4-10) > SP. [Sar(9), Met(O(2))(11)]-SP and senktide, selective agonists of the NK1 and NK3 receptors, respectively, failed to modify the ureteral tone. Urothelium removal and incubation with tetrodotoxin (10(-6) mol/L), phentolamine (10(-7) mol/L), propranolol (3 x 10(-6) mol/L), atropine (10(-7) mol/L) and indomethacin (3 x 10(-6) mol/L), did not alter the contraction induced by a submaximal (10(-7) mol/L) dose of [beta-Ala(8)]-NKA (4-10). MEN 10,376 (10(-8)-10(-7) mol/L), a NK2 receptor antagonist, reduced the contraction to 3 x 10(-8) mol/L NKA. GR 82334 (10(-6) -10(-5) mol/L) and SR 142801 (10(-8)-10(-7) mol/L), selective antagonists of the NK1 and NK3 receptors, respectively, did not modify that contraction. In pig intravesical ureteral strips in NANC conditions, SP and NKA induced a potentiation of the contractions to electrical field stimulation (EFS) and to exogenous ATP. The results suggest that the tachykinins evoke a direct contraction of pig intravesical ureteral strips through NK2 receptors located in the smooth muscle. SP and NKA exert an enhancement of the NANC excitatory neurotransmission of the pig intravesical ureter.     

Cryoglobulinemia following liver transplantation for cirrhosis secondary to hepatitis C virus infection

Hepatitis C virus (HCV) infection has been linked with some extrahepatic immunologic abnormalities. Cryoglobulinemia is one of the most frequently reported. Nevertheless, there are only a few reports of cryoglobulinemia in the setting of liver transplantation. More studies are needed to clarify the frequency of post-OLT cryoglobulinemia in patients with HCV-related cirrhosis and its impact on OLT outcome. A case of a patient who underwent liver transplantation because of HCV end-stage liver disease and in whom cryoglobulinemia appeared 3 years after transplantation is reported. Treatment with cyclophosphamide and steroids was attempted but patient died of septicemia 3 years after liver transplantation.     

Predicting the solubility of sulfamethoxypyridazine in individual solvents. I: Calculating partial solubility parameters

Sulfamethoxypyridazine, a representative model of a drug molecule, is used to test the extended Hansen method for estimating partial solubility parameters of solid compounds. Solubilities are determined in polar and nonpolar solvents. The method provides reasonable partial parameters for the sulfonamide, and it may be useful in obtaining partial parameters for other drug molecules. A four-parameter extended Hansen approach involving proton donor and acceptor parameters is used in fitting the data to a theoretical model. A term, Wh, is introduced as an empirical measure of solute-solvent interactions due to hydrogen bonding. The use of the empirical term Wh allows the researcher to fit experimental solubilities and thus design regression models and equations which provide a reasonable prediction of solubilities of a polar drug in a number of very different solvents. A Flory-Huggins size correction term improves the prediction of sulfamethoxypyridazine solubilities in these irregular solutions.