Influence of melatonin therapy and orchiectomy on T cell subsets in male Wistar rats infected with Trypanosoma cruzi

Gonadal steroids exert an important influence on the host immune response during infection. Changes resulting from the absence or replacement of gonadal hormones may represent a distinct evolution of a particular parasite. Taking into account the greater susceptibility of males to parasites, the magnitude of the immune response seems to depend on the interaction of many hormones that will act synergistically with other immune cells. The aims of this research were to evaluate the effects of the luck of male sex hormones due to orchiectomy, and the influence of oral administration of melatonin on the immune response of male Wistar rats infected with the Y strain of Trypanosoma cruzi. The percentage of CD3(+) CD4(+) and CD3(+) CD8(+) lymphocyte T cell subsets were evaluated using flow cytometry and the measurement of IL-2 and IL-12. For all parameters examined, a synergistic action of melatonin and orchiectomy on the host`s immune response was observed, promoting an effective response against the parasite during the acute phase of infection. These results offer insight into other possibilities for possibly controlling T. cruzi proliferation through melatonin therapy and also the stimulatory effects on host`s immune response triggered by the absence of male gonadal steroids during the acute phase of infection.

Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients

Purpose This study investigated the influence of gestational diabetes mellitus on the kinetic disposition and stereoselective metabolism of labetalol administered intravenously or orally. Methods Thirty hypertensive women during the last trimester of pregnancy were divided into four groups: non-diabetic and diabetic women treated with intravenous or oral labetalol. Results The pharmacokinetics of labetalol was not stereoselective in diabetic or non-diabetic pregnant women receiving the drug intravenously. However, oral administration of labetalol resulted in lower values of the area under the plasma concentration versus time curve (AUC) for the beta-blocker (RR) than for the other enantiomers in both diabetic and non-diabetic women. Gestational diabetes mellitus caused changes in the kinetic disposition of the labetalol stereoisomers when administered orally. The AUC values for the less potent adrenoceptor antagonist (SS) and for the alpha-blocking (SR) isomers were higher in diabetic than in non-diabetic pregnant women. Conclusions The approximately 100% higher AUC values obtained for the (SR) isomer in diabetic pregnant women treated with oral labetalol may be of clinical relevance in terms of the alpha-blocking activity of this isomer.

Influence of Plasma Protein Binding on Pharmacodynamics: Estimation of In Vivo Receptor Affinities of beta Blockers Using a New Mechanism-Based PK-PD Modelling Approach

The objective of this investigation was to examine in a systematic manner the influence of plasma protein binding on in vivo pharmacodynamics. Comparative pharmacokinetic-pharmacodynamic studies with four beta blockers were performed in conscious rats, using heart rate under isoprenaline-induced tachycardia as a pharmacodynamic endpoint. A recently proposed mechanism-based agonist-antagonist interaction model was used to obtain in vivo estimates of receptor affinities (K(B),(vivo)). These values were compared with in vitro affinities (K(B),(vitro)) on the basis of both total and free drug concentrations. For the total drug concentrations, the K(B),(vivo) estimates were 26, 13, 6.5 and 0.89 nM for S(-)-atenolol, S(-)-propranolol, S(-)-metoprolol and timolol. The K(B),(vivo) estimates on the basis of the free concentrations were 25, 2.0, 5.2 and 0.56 nM, respectively. The K(B),(vivo)-K(B),(vitro) correlation for total drug concentrations clearly deviated from the line of identity, especially for the most highly bound drug S(-)-propranolol (ratio K(B),(vivo)/K(B),(vitro) similar to 6.8). For the free drug, the correlation approximated the line of identity. Using this model, for beta-blockers the free plasma concentration appears to be the best predictor of in vivo pharmacodynamics. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3816-3828, 2009

Influence of insulin treatment on the lacrimal gland and ocular surface of diabetic rats

Previous studies have observed changes in the lacrimal gland and ocular surface related to diabetes mellitus and related it to insulin resistance or insufficiency and oxidative damage. The aim of this study was to evaluate whether insulin treatment inhibits those changes. Diabetes was induced in male Wistar rats with a single intravenous injection of streptozotocin and a subgroup was treated with insulin. After 5 and 10 weeks, the three groups (n = 5-10/group/experimental procedure) were compared for biochemical, functional, and histological parameters. After 5 weeks, changes in morphology and increased numbers of lipofucsin-like inclusions were observed in lacrimal glands of diabetic but not insulin-treated rats. After 5 weeks, malonaldehyde and total peroxidase activity were significantly higher in diabetic rats, but similar to control in insulin-treated diabetic rats (P = 0.03, P = 0.02, respectively). Our data indicate that diabetes induces histological alterations in lacrimal gland and suggests that hyperglycemia-related oxidative stress may participate in diabetic dry eye syndrome. Prevention by insulin replacement suggests direct hormone action and/or benefit by early sub optimal metabolic control.

Cytotoxic and mutagenic evaluation of extracts from plant species of the Miconia genus and their influence on doxorubicin-induced mutagenicity: An in vitro analysis

The Miconia genus, a plant widely used for medicine, occurs in tropical America and its extracts and isolated compounds have demonstrated antibiotic, antitumoral, analgesic and antimalarial activities. However, no study concerning its genotoxicity has been conducted and it is necessary to determine its potential mutagenic effects to develop products and chemicals from these extracts. This study assessed the cytotoxicity, mutagenicity and the protective effects of methanolic extracts from Miconia species on Chinese hamster lung fibroblast cell cultures (V79). The cytotoxicity was evaluated using a clonogenic assay. Cultures exposed to the extract of Miconia albicans up to a concentration of 30 mu g/mL, M. cabucu up to 40 mu g/mL, M. albicans up to 40 mu g/mL and M. stenostachya up to 60 mu g/mL exhibited a cytotoxic effect on the cells. The clonogenic assay used three non-cytotoxic concentrations (5, 10 and 20 mu g/mL) to evaluate mutagenicity and antimutagenicity of the extracts. Cultures were treated with these three extract concentrations (mutagenicity test) or the extract associated with doxorubicin (DXR) (antimutagenicity test) in three protocols (pre-, simultaneous and post-treatments). Distilled water and DXR were used as negative and positive controls, respectively. In the micronucleus (MN) test, a significant reduction was observed in MN frequency in cultures treated with DXR and extracts compared to those receiving only DXR; a significant reduction was also observed for the presence of mutagenicity in all treatments. This study confirmed the safe use of Miconia extracts at the concentrations tested and reinforced the therapeutic properties previously described for Miconia species by showing their protective effects on doxorubicin-induced mutagenicity. (C) 2010 Elsevier GmbH. All rights reserved.

Analysis of Liquid Crystalline Nanoparticles by Small Angle X-Ray Diffraction: Evaluation of Drug and Pharmaceutical Additives Influence on the Internal Structure

The goal of this work was to study the liquid crystalline structure of a nanodispersion delivery system intended to be used in photodynamic therapy after loading with photosensitizers (PSs) and additives such as preservatives and thickening polymers. Polarized light microscopy and light scattering were performed on a standard nanodispersion in order to determine the anisotropy of the liquid crystalline structure and the mean diameter of the nanoparticles, respectively. Small angle X-ray diffraction (SAXRD) was used to verify the influence of drug loading and additives on the liquid crystalline structure of the nanodispersions. The samples, before and after the addition of PSs and additives, were stable over 90 days, as verified by dynamic light scattering. SAXRD revealed that despite the alteration observed in some of the samples analyzed in the presence of photosensitizing drugs and additives, the hexagonal phase still remained in the crystalline phase. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2849-2857, 2011

Cytoplasmic incompatibility in Drosophila populations: influence of assortative mating on symbiont distribution

Cytoplasmic incompatibility is known to occur between strains of both Drosophila simulans and D. melanogaster. Incompatibility is associated with the infection of Drosophila with microorganismal endosymbionts. This paper reports survey work conducted on strains of D. simulans and D. melanogaster from diverse geographical locations finding that infected populations are relatively rare and scattered in their distribution. The distribution of infected populations of D. simulans appears to be at odds with deterministic models predicting the rapid spread of the infection through uninfected populations. Examination of isofemale lines from four localities in California where populations appear to be polymorphic for the infection failed to find evidence for consistent assortative mating preferences between infected and uninfected populations that may explain the basis for the observed polymorphism.

Media influence to suicide: The search for solutions

This review explores the influence to suicide in print and electronic media, and considers both real and fictional deaths. The conclusion appears inescapable that reports about celebrities which are multi-modal, repeated, explicit, front page, glorify the suicide, and describe the method lead to an increase in deaths from suicide, particularly in the region in which reports are published. The paper argues that even if there was multi-national agreement to international guidelines, media will continue to report suicide when it is considered to be a matter of public interest. What appears crucial is a collaborative approach between professionals and the media to promote a negative attitude toward suicide without increasing stigma toward those with mental health problems.

The influence of joint position on the dynamics of perception-action coupling

Six right-handed subjects performed rhythmic flexion and extension movements of the index finger in time with an auditory metronome. On each block of trials, the wrist of the response hand was placed in a extended, neutral or flexed position. In the flex-on-the-beat condition, subjects were instructed to coordinate maximum excursion in the direction of finger flexion with each beat of the metronome. In the extend-on-the-beat condition, subjects were instructed to coordinate maximum excursion in the direction of finger extension with each beat of the metronome. The frequency of the metronome was increased from 2.00 Hz to 3.75 Hz in 8 steps (8 s epochs) of 0.25 Hz. During trials prepared in the extend-on-the-beat pattern, all subjects exhibited transitions to either a flex-on-the-beat pattern or to phase wandering as the frequency of pacing was increased. The time at which these transitions occurred was reliably influenced by the position of the wrist. Four subjects exhibited qualitative departures from the flex-on-the-beat pattern at pacing frequencies that were greater than those at which the extend-on-the-beat pattern could be maintained. The lime at which these departures occurred was not influenced by the position of the wrist. These results are discussed with reference to the constraints imposed on the coordination dynamics by the intrinsic properties of the neuromuscular-skeletal system.

Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pairfed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs, that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity. (C) 1999 Elsevier Science B.V. All rights reserved.

Influence of microstructure on the corrosion of diecast AZ91D

The corrosion of die cast AZ91D was studied and related to its microstructure. For comparison and to more fully understand the behaviour of die cast AZ91D, corrosion studies and microstructural examinations were also carried out using slowly solidified high purity AZ91, Mg-2%Al, Mg-9%Al, low purity magnesium and high purity magnesium. Corrosion was studied in 1N NaCl at pH 11 by (1) observing the corrosion morphology, (2) measuring electrochemical polarisation curves and (3) simultaneously measuring both the hydrogen evolution rate and the magnesium dissolution rate. The skin of die cast AZ91D showed better corrosion resistance than the interior. This is attributed to a combination of(1) a higher volume fraction of the beta phase, (2) a more continuous beta phase distribution around finer alpha grains, and (3) lower porosity in the skin layer than in the interior of the die casting. This study showed that the casting method can influence the corrosion performance by its influence on the alloy microstructure. (C) 1999 Elsevier Science Ltd. All rights reserved.

The influence of Lys68 in decapeptide agonists of C5a on C5a receptor binding, activation and selectivity

The potent, conformationally biased C5a agonist peptide YSFKPMPLaR (C5a(65-74), Y65, F67, P69, P71, D-Ala73) was used as a template to gain insight into the nature and importance of lysine at position 68 in the peptide-receptor interaction. A panel of YSFKPMPLaR analogs with systematic substitutions for Lys68 was evaluated for C5a receptor (C5aR) binding affinity and activation in two well-characterized assay systems: human polymorphonuclear leukocytes (PMNs) and human fetal artery. In addition, we determined the activity of these new analogs in transfected rat basophilic leukemia (RBL) cells in which the Glu at position 199 of the C5aR (wtGlu199) was replaced by a Gin (C5aR-Gln199) or a Lys (C5aR-Lys199). Our results indicated that Lys68 in YSFKPMPLaR plays an important role in binding the C5aR expressed on PMNs and RBL cells. Furthermore, the data indicated that Lys68 interacted with Glu199 of the C5aR in PMNs and RBL cells. In human fetal artery, however, Lys68 substitutions had little or no effect on activity, which suggested that the receptor conformation may be different in this tissue. Thus, the interaction between Lys68 of the decapeptide agonist and Glu199 of the C5aR may be cell type-specific and may form the molecular basis for tissue-specific responses to C5a agonists.

Influence of field-based nutrient enrichment on the photobiology of the giant clam Tridacna maxima

Nutrients were added to 12 microatolls in One Tree Island lagoon every low tide for 13 mo to an initial concentration of 10 mu M (ammonium, N) and 2 mu M (phosphate, P). These concentrations remained above background for 2 to 3 h after addition. The addition of ammonium (N and NI-P but not P alone) significantly increased P, (gross photosynthesis) P,, (net photosynthesis) and R (respiration) per unit wet-tissue weight and cc (photosynthetic efficiency) in Tridacna maxima after 3 mo nutrient enrichment. These responses to small and transient changes in ammonium concentrations suggest that symbiotic clams are not nutrient-replete, and that even subtle changes in nutrients can have a measurable effect on photosynthesis. The same clams did not show significant differences in photosynthetic parameters 6 mo after the beginning of nutrient enrichment, suggesting that their previous responses had either been seasonal or that symbiotic clams such as T. maxima are able to adjust their photophysiology following external changes in nutrient concentrations.

The crack tip strain field of AISI 4340 - Part III - Hydrogen influence

This paper studied the influence of hydrogen and water vapour environments on the plastic behaviour in the vicinity of the crack tip for AISI 4340. Hydrogen and water vapour (at a pressure of 15 Torr) significantly increased the crack tip opening displacement. The crack tip strain distribution in 15 Torr hydrogen was significantly different to that measured in vacuum. In the presence of sufficient hydrogen, the plastic zone was larger, was elongated in the direction of crack propagation and moreover there was significant creep. These observations support the hydrogen enhanced localised plasticity model for hydrogen embrittlement in this steel. The strain distribution in the presence of water vapour also suggests that SCC in AISI 4340 occurs via the hydrogen enhanced localised plasticity mechanism. (C) 1999 Kluwer Academic Publishers.