Effects of Pentoxyfilline and Heparin on Reperfusion Injury Island Skin Flaps in Rats Exposed to Tobacco

Background. Ischemia-reperfusion injury is believed to be a major cause of transferred skin flap failure. Cigarette smoking is known to be associated with endogenous antioxidant depletion, hypercoagulability, and cutaneous vasoconstriction. This investigation was carried out to study possible effects of pentoxyfilline or heparin on rat skin reperfusion injury under tobacco exposure. Materials and Methods. Thirty-six rats were randomized into two major groups: 18 were exposed to cigarette smoke during a 4 wk period prior to surgery; the remaining 18 underwent a sham smoking procedure. Each group was further divided into three equal subgroups: heparin, pentoxyfilline, and saline solution. One identical skin flap was raised in each animal. The vasculature of the flap was clamped for 3 h and reperfused for 5 min. A venous blood sample was obtained from the flap after reperfusion for serum malondialdehyde (MDA) and myeloperoxidase (MPO) analysis. Flap survival was assessed 7 d after the procedure. Results. The lipid peroxidation levels and flap necrosis were significantly higher in the cigarette-smoking group skin flaps. There was also a decrease of MPO activity in this group compared with the nonsmoking group. Heparin-treated rats had significantly lower MDA levels and showed the most viable percent area among smoking rats. Conclusions. These data suggest that heparin had a significant beneficial effect both on flap survival and on the lipid peroxidation reduction after smoke exposure in the rat axial-pattern skin flap subjected to ischemia and reperfusion injury. Pharmacologic therapy may represent an alternative way to counteract tobacco effects in flap surgery in emergency situations. (C) 2010 Elsevier Inc. All rights reserved.

Influence of Quinidine, Cimetidine, and Ketoconazole on the Enantioselective Pharmacokinetics and Metabolism of Metoprolol in Rats

Metoprolol is a beta-blocker and its racemic mixture is used for the treatment of hypertension. In the present study we investigated the influence of CYP2D and CYP3A on the stereoselective metabolism of metoprolol in rats. Male Wistar rats (n = 6 per group) received racemic metoprolol (15 mg/kg) orally, with or without pretreatment with the CYP inhibitor ketoconazole (50 mg/kg), cimetidine (150 mg/kg), or quinidine (80 mg/kg). Blood samples were collected up to 48 h after metoprolol administration. The plasma concentrations of the stereoisomers of metoprolol, O-demethylmetoprolol (ODM), alpha-hydroxymetoprolol (OHM) (Chiralpak(R) AD column), and metoprolol acidic metabolite (AODM) (Chiralcel(R) OD-R column) were determined by HPLC using fluorescence detection (lambda(exc) = 229 nm; lambda(em) = 298 nm). CYP3A inhibition by ketoconazole reduced the plasma concentrations of ODM and AODM and favored the formation of OHM. CYP2D and CYP3A inhibition by cimetidine reduced the plasma concentrations of OHM and AODM and favored the formation of ODM. The inhibition of CYP2D by quinidine reduced the plasma concentrations of OHM and favored the formation of ODM. In conclusion, the results suggest that CYP3A is involved in the formation of ODM and CYP2D is involved in the formation of AODM. Chirality 21:886-893, 2009. (C) 2009 Wiley-Liss, Inc.

EFFECT OF THE TEMPERATURE AND pH ON METHANOL RELEASE IN COFFEE BREW SWEETENED WITH ASPARTAME

Methanol is an alcohol which is metabolized to folmaldehyde in humans. It is a very toxic substance, responsible for blindness in cases of methanol intoxication. This study shows the production of methanol when aspartame is used to sweeten coffee brew. The temperature versus pH binomium was also tested. When assayed at 90 degrees C coffee brew+aspartame and aspartame solution showed an increase in methanol release of 17.8 and 19.3%, respectively, as compared with coffee brew. At 180 degrees C, the increase was 32.5 and 26.3%, respectively. Our data revealed a protective effect of the pH of coffee on the degradation of aspartame and formation of methanol; an important fact, mainly for specific populations that use aspartame, like diabetics.

Influence of quinidine, fluvoxamine, and ketoconazole on the enantioselective pharmacokinetics of citalopram in rats

Citalopram (CITA) is available as a racemic mixture or as (+)-(S)-CITA. In humans, CITA is metabolized to demethylcitalopram (DCITA) by CYP2C19, CYP2D6, and CYP3A and to didemethylcitalopram by CYP2D6. There are no data regarding the enzymes involved in CITA and DCITA metabolism in rats. The present study investigated the influence of CYP inhibitors on the enantioselective metabolism of CITA in rats. Male Wistar rats (n = 6) received a single dose of 20 mg.kg(-1) CITA after pretreatment with 80 mg.kg(-1) quinidine, 10 mg.kg(-1) fluvoxamine, 50 mg.kg(-1) ketoconazole, or vehicle (control). Blood samples were collected up to 20 h after CITA administration. The CITA and DCITA enantiomers were analyzed by LC-MS/MS using a Chiralcel OD-R column. The kinetic disposition of CITA was enantioselective in rats (AUC(S/R) ratio = 0.4). Coadministration with quinidine resulted in non-enantioselective inhibition of the metabolism of CITA. Coadministration with fluvoxamine or ketoconazole, however, inhibited only the metabolism of (+)-(S)-CITA, but not of (-)-(R)-CITA when the racemic drug was administered to rats.

Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease

Objectives Alterations in the enzymes involved in homocysteine (Hcy) metabolism or vitamin deficiency could play a role in coronary artery disease (CAD) development. This study investigated the influence of MTHFR and MTR gene polymorphisms, plasma folate and MMA on Hcy concentrations and CAD development. MMA and folate concentrations were also investigated according to the polymorphisms. Methods Two hundred and eighty-three unrelated Caucasian individuals undergoing coronary angiography (175 with CAD and 108 non-CAD) were assessed in a case-control study. Plasma Hcy and MMA were measured by liquid chromatography/tandem mass spectrometry. Plasma folate was measured by competitive immunoassay. Dietary intake was evaluated using a nutritional questionnaire. Polymorphisms MTHFR and MTR were investigated by polymerase chain reaction (PCR) followed by enzyme digestion or allele-specific PCR. Results Hcy mean concentrations were higher in CAD patients compared to controls, but below statistical significance (P = 0.246). Increased MMA mean concentrations were frequently observed in the CAD group (P = 0.048). Individuals with MMA concentrations > 0.5 mu mol/l (vitamin B(12) deficiency) were found only in the CAD group (P = 0.004). A positive correlation between MMA and Hcy mean concentrations was observed in both groups, CAD (P = 0.001) and non-CAD (P = 0.020). MMA mean concentrations were significantly higher in patients with hyperhomocysteinemia in both groups, CAD and non-CAD (P = 0.0063 and P = 0.013, respectively). Folate mean concentration was significantly lower in carriers of the wild-type MTHFR 1298AA genotype (P = 0.010). Conclusion Our results suggest a correlation between the MTHFR A1298C polymorphism and plasma folate concentration. Vitamin B(12) deficiency, reflected by increased MMA concentration, is an important risk factor for the development both of hyperhomocysteinemia and CAD.

Opposite Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology

Delta-9-tetrahydrocannabinol (Delta-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Delta-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Delta-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Delta-9-tetrahydrocannabinol. Delta-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD`s ability to block the psychotogenic effects of Delta-9-THC. Neuropsychopharmacology (2010) 35, 764-774; doi:10.1038/npp.2009.184; published online 18 November 2009

Distinct Effects of Delta 9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

Context: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. Objective: To investigate the effects of 2 main psycho-active constituents of Cannabis sativa (Delta 9-tetrahydrocannabinol [Delta 9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. Design: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta 9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. Participants: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. Main Outcome Measures: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. Results: Delta 9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta 9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta 9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. Conclusions: Delta 9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta 9-THC may be related to effects in other brain regions.

Influence of pregnancy and smoking on brachial artery flow-mediated dilation values and time until maximum response

To evaluate the effect of pregnancy and smoking on endothelial function using brachial artery flow-mediated dilation (FMD) and to determine the time necessary until the occurrence of maximum brachial artery dilation after stimulus. This study was an observational study evaluating 133 women, who were grouped as follows: non-smoking pregnant women (N = 47), smoking pregnant women (N = 33), non-smoking women (N = 34), and smoking pregnant women (N = 19). The diameter of the brachial artery was measured at baseline and at 30, 60, 90 and 120 s after stimulus. The relative change of brachial artery was determined for each of these four moments. FMD measured at 60 s after stimulus was compared between the groups. The maximum FMD was observed at 60 s after cuff release in all groups. FMD was greater among non-smoking pregnant women compared to smoking pregnant women (11.50 +/- A 5.77 vs. 8.74 +/- A 4.83; p = 0.03) and also between non-smoking non-pregnant women compared to smoking non-pregnant women (10.52 +/- A 4.76 vs. 7.21 +/- A 5.57; p = 0.03). Maximum FMD was observed approximately 60 s after stimulus in all groups regardless of smoking and pregnancy status. The smoking habit seems to lead to endothelial dysfunction both in pregnant and non-pregnant women, as demonstrated by the lower FMD in smokers.

Co-existing squamous cell carcinoma and hemangioma on the ocular surface of a cat

A 14-year-old spayed female domestic short-haired cat was presented for evaluation of a mass in the right eye. Ophthalmic examination revealed a blind right eye and presence of two distinct masses: a pink and a red-to-brown mass, the latter occupying most of the cornea and part of the conjunctiva. Exenteration was performed under general anesthesia, and the ocular tissues were processed routinely for histopathology. Upon microscopic examination, a malignant epithelial neoplasm and a benign vascular neoplasm were present in the cornea. The conjunctiva and the third eyelid were also affected. Upon immunohistochemistry, the epithelial tumor was positive for cytokeratin and negative for vimentin and the endothelial tumor was negative for cytokeratin and positive for vimentin. A diagnosis of squamous cell carcinoma (SCC) and hemangioma was made. The SCC was affecting the cornea, bulbar conjunctiva (lateral and inferior) and the base of the third eyelid, whereas the hemangioma was affecting the cornea and medial limbus. To the authors` knowledge, this is the first report of concomitant SCC and hemangioma affecting the ocular surface in a cat.

Effect of beta-lactoglobulin polymorphism and seasonality on bovine milk composition

The objective was to evaluate the effect of beta-lactoglobulin (beta-lg) polymorphism and seasonality on milk composition (fat, lactose, total solids, milk urea nitrogen, total protein, true protein, casein and somatic cell counts) of Holstein and Girolando cows. Milk and blood samples from 278 Holsteins cows and 156 Girolando cows were taken during two dry seasons and two rainy seasons, for milk composition analysis and to determine beta-lg genotypes, respectively. BB genotype was the most frequent for both breeds, followed by AA genotype for Holstein (BB>AA>AB) and by AB for Girolando cows (BB>AB>AA). No differences were found in milk compositional characteristics among genetic variants of beta-lg (AA, AB and BB) either between Holstein or Girolando cows. No association between milk composition and beta-lg genetic polymorphism was observed. During the dry season, independently of the breed considered, higher contents of lactose, true protein, casein and casein :true protein ratio were found.

Influence of Photoperiod and Temperature on the Larval Behavioral Diapause of Amblyomma cajennense (Acari: Ixodidae)

Larval behavioral diapause was shown to be the major factor controlling the 1-yr generation pattern of Amblyomma cajennense (F.) (Acari: Ixodidae) in Brazil. During fieldwork, this behavior was shown to coincide with long daylength (>12 h) and high mean ground temperature (approximate to 25 degrees C), which prevail during spring-summer in Brazil. The current study evaluated biological parameters of engorged females, their eggs, and the resultant larvae inside plastic pots planted with the grass Brachiaria decumbens Stapf. held in incubators set with different combinations of temperature and photoperiod. Both the long daylength (photoperiod 14:10 [L:D]h) and high temperature (25 degrees C) during larval hatching induced larval behavioral diapause, characterized by the confinement of hatched larvae on the ground below the vegetation for many weeks. When long daylength was present during hatching, but temperature was low (15 degrees C), larvae did not enter diapause. Similarly, when short daylength (10:14 or 12:12) was present during larval hatching, larvae did not enter diapause regardless whether temperature was high (25 degrees C). Termination of diapause was induced by shifting photoperiod from 14:10 to 12:12 or the temperature from 25 to 15 degrees C. When applied to field conditions, the present results indicate that both high ground mean temperature (approximate to 25 degrees C) and long daylength (>12 h) during spring-summer (October-March) are responsible for the induction and maintenance of A. cajennense larval behavioral diapause in the field. Furthermore, both the low ground mean temperature (-20 degrees C) and the short daylength (<12h) during autumn (April-May) are responsible for termination of larval behavioral diapause in the field.

Comparative Analysis between Chamomilla recutita and Corticosteroids on Wound Healing. An In Vitro and In Vivo Study

The comparison of chamomile and corticosteroids for treating ulcers was done in vitro and in vivo. The experimental groups were: control; chamomile recutita; triamcinolone acetonide and clobetasol propionate. For the in vitro study the cell viability of fibroblasts cultured for 24 h in media conditioned by the substances was obtained by the MITT reduction analysis. For the in vivo study, 125 male rats were submitted to experimental ulcers treated or not (control) by the substances tested. At 1, 3, 5, 7 and 14 days later 5 animals of each group were sacrificed. The lesions were analyzed by means of clinical observation and histological wound-healing grading. Data were compared by ANOVA (p <= 0.05). All experimental groups presented positive cell viability in 24 h. The cultures treated with chamomile presented the smallest cell viability. All animals of the chamomile group exhibited complete wound healing 9 days before the other groups. Complete repaired lesions were observed after 5 days of treatment only in the chamomile group. Animals treated with chamomile presented significantly faster wound healing in comparison to those treated with corticosteroids. Based on the conditions of this study, we concluded that chamomile in comparison to corticosteroids promotes faster wound healing process. Copyright (C) 2008 John Wiley & Sons, Ltd.

Effect of Test Environment and Microstructure on the Flexural Strength of Dental Porcelains

Purpose: The objective of this study was to verify the influence of test environment on the flexural strength of dental porcelains with distinct microstructures. Material and Methods: Disk-shaped specimens from three dental porcelains with distinct leucite content (VM: zero; CE: 12; NS: 22 vol%) were manufactured and tested for biaxial flexural strength in air and immersed in artificial saliva. The results were analyzed by means of two-way ANOVA and Tukey`s test (alpha = 0.05). Results: The flexural strength (MPa) obtained for ambient air and artificial saliva environments, respectively, were: 110.0 +/- 16.0 and 81.5 +/- 10.8 for VM; 51.9 +/- 4.0 and 42.0 +/- 4.7 for CE; 72.0 +/- 11.5 and 63.6 +/- 5.8 for NS. A numerical decrease in the mean flexural strength was observed for all groups when specimens were tested under artificial saliva; however, the difference was only statistically significant for VM. Conclusions: The results indicate that the effect of water immersion on the flexural strength of dental porcelains varies according to their leucite content, as only the material without leucite in its microstructure (VM) showed significant strength degradation when tested under water.

Effect of the Combination of Sodium Hypochlorite and Chlorhexidine on Dentinal Permeability and Scanning Electron Microscopy Precipitate Observation

Introduction: This study compared the combined use of sodium hypochlorite (NaOCl) and chlorhexidine (CXH) with citric acid and CXH on dentinal permeability and precipitate formation. Methods: Thirty-four upper anterior teeth were prepared by rotary instrumentation and NaOCl. The root canal surfaces were conditioned for smear layer removal using 15% citric acid solution under ultrasonic activation and a final wash with distilled water. All teeth were dried, and 30 specimens were randomly divided into three equal groups as follows: positive control group (PC), no irrigation; 15% citric acid + 2% CHX group (CA + CHX); and 1% NaOCl + 2% CHX group (NaOCl + CHX). All roots were immersed in a 0.2% Rhodamine B solution for 24 hours. One-millimeter-thick slices from the cementum-enamel junction were scanned at 400 dpi and analyzed using the software ImageLab (LIDO-USP, Sao Paulo, Brazil) for the assessment of leakage in percentage. For scanning electron microscopy analysis, four teeth, irrigated for NaOCl + CHX samples, were split in half, and each third was evaluated at 1,000x and 5,000x (at the precipitate). Results: Using the analysis of variance test followed by the Bonferroni comparison method, no statistical differences between groups were found when analyzed at the cervical and medium thirds. At the apical third, differences between the PC and NaOCl + CHX (p<0.05) and CA + CHX and NaOCl + CHX could be seen (p < 0.05). Conclusion: The combination of 1% NaOCl and 2% CHX solutions results in the formation of a flocculate precipitate that acts as a chemical smear layer reducing the dentinal permeability in the apical third. (J Endod 2010;36:847-850)

Comparison of the effects of pilocarpine and cevimeline on salivary flow

Objective: The aim of the present study was to compare the effect of low-dose pilocarpine and cevimeline as stimulants for salivary flow in healthy subjects. Methods: In this cross-over clinical trial with a 1-week washout period, 40 male volunteers were submitted to an oral dose of pilocarpine 1% (Salagen (TM)) -60 mu g kg(-1) body-weight (Group 1) or Cevimeline (Evoxac (TM)) -30 mg (Group 2). Saliva samples were collected and the salivary flow rate was measured (ml min(-1)) at baseline and 20, 40, 60, 80, 140 and 200 min after administration of drugs. In addition, salivary secretion was also measured under mechanical stimulation to observe salivary gland function. Results: The data were analyzed by Friedman and Wilcoxon signed-rank tests (significance level = 5%). Pilocarpine and cevimeline significantly increased salivary flow 140 min after intake. There was a significant higher secretion with cevimeline 140 and 200 min after administration. There were no differences seen among subjects in the salivary glands function by mechanical stimulation. Conclusion: Both drugs showed efficacy in increasing the salivary flow in healthy volunteers, but cevimeline was more effective than pilocarpine.