High-pressure phase diagram of the drug mitotane in compressed and/or supercritical CO(2)

This work provides experimental phase diagram of mitotane, a drug used in the chemotherapy treatment of adrenocortical carcinoma, in compressed and/or supercritical CO(2). The synthetic-static method in a high-pressure variable-volume view cell coupled with a transmitted-light intensity probe was used to measure the solid-fluid (SF) equilibrium data. The phase equilibrium experiments were determined in temperature ranging from (298.2 to 333.1) K and pressure up to 22 MPa. Peng-Robinson equation of state (PR-EoS) with classical mixing rule was used to correlate the experimental data. Excellent agreement was found between experimental and calculated values. (C) 2009 Elsevier Ltd. All rights reserved.

Effects of Erosive, Cariogenic or Combined Erosive/Cariogenic Challenges on Human Enamel An in situ/ex vivo Study

Individuals with cariogenic diet can also consume erosive beverages. Thus, it seems necessary to investigate a possible caries/erosion interaction. To test in situ/ex vivo a combination of these challenges, 11 subjects wore intraoral appliances containing four enamel blocks randomly assigned. In the first 2-week phase, the appliances were immersed in a cola drink 3 times/day. Two blocks were free of plaque (erosion only: EO) and two blocks were covered with plaque (erosion + plaque: EP). In the second 2-week phase, four new blocks were all covered with plaque and subjected to a sucrose solution 8 times/day. Among the four new blocks, two were also subjected to the cola drink 3 times/day (erosion + caries: EC) while the other two were not (caries only: CO). Thus, in EO, the specimens were fixed at the intraoral appliance level. In EP, EC and CO they were fixed 1.0 mm under the appliance level and covered with plastic meshes for dental plaque accumulation. Changes in wear and hardness were measured. Data were tested using ANOVA and Tukey`s test (p < 0.05). Mean values of wear (mu m) and change in hardness (kp/mm(2)) were: EO 4.82/310; EP 0.14/48; EC 0.34/245; CO 0.42/309. With respect to surface softening, EP and EC differed significantly from each other and from EO and CO, which did not differ significantly. EO presented significantly higher wear than the other groups. The data suggest that the presence of dental plaque can decrease the acid attack of an erosive drink and the association of erosive and cariogenic challenges showed less enamel alterations when compared to erosive or cariogenic challenges only. Copyright (C) 2008 S. Karger AG, Basel

Effects of Orthopedic Rapid Maxillary Expansion on Internal Nasal Dimensions in Children With Cleft Lip and Palate Assessed by Acoustic Rhinometry

The objective of the current study was to characterize the internal nasal dimensions of children with repaired cleft lip and palate and transverse maxillary deficiency, using acoustic rhinometry and analyze the changes caused by rapid maxillary expansion (RME). A convenience sampling of 19 cleft lip and palate individuals, aged 14 to 18 years, of both sexes, previously submitted to primary surgeries and referred for RME were analyzed prospectively at the Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo, Bauru, Sao Paulo, Brazil. All patients underwent acoustic rhinometry before installation of the expansor and at 30 and 180 days after the active expansion phase. Nasal cross-sectional areas and volumes corresponding to the nasal valve (CSA(1) and V(1)) and the turbinates (CSA(2), CSA(3), and V(2)) regions were determined before and after nasal decongestion. Rapid maxillary expansion led to a statistically significant increase (P < 0.05) in mean CSA(1), CSA(2), V(1), and V(2) (without nasal decongestion) and in CSA(1) and V(1) (with decongestion) in the group as a whole. Individual data analysis showed that 58% of the patients responded positively to RME, with an average increase in CSA(1) of 26% (with decongestion), whereas 37% of the patients had no significant change. Only 1 patient (5%) showed a decrease. The findings contribute toward the characterization of nasal deformities determined by the cleft and demonstrate the positive effect RME had on nasal morphophysiology in a significant number of the patients who underwent this procedure.

Central NOS inhibition differentially affects vasopressin gene expression in hypothalamic nuclei in septic rats

Our aim was to investigate the effect of central NOS inhibition on hypothalamic arginine vasopressin (AVP) gene expression, hormone release and on the cardiovascular response during experimental sepsis. Male Wistar rats were intracerebroventricularly injected with the non-selective NO synthase (NOS) inhibitor (L-NAME) or aminoguanidine, a selective inhibitor of the inducible isoform (iNOS). After 30 min. sepsis was induced by cecal ligation and puncture (CLP) causing an increase in heart rate (HR), as well as a reduction in median arterial pressure (MAP) and AVP expression ratio (AVP(R)), mainly in the supraoptic nucleus. AVP plasma levels (AVP(P)) increased in the early but not in the late phase of sepsis. L-NAME pretreatment increased MAP but did not change HR. It also resulted in an increase in AVP(P) at all time points, except 24 h, when it returned to basal levels. AVP(R), however remained reduced in both nuclei. Aminoguanidine pretreatment resulted in increased MAP in the early phase and higher AVP(R) in the supraoptic, but not in the paraventricular nucleus, while AVP(P) remained elevated at all time points. We suggest that increased central NO production, mainly inducible NOS-derived, reduces AVP gene expression differentially in supraoptic and paraventricular nuclei, and that this may contribute to low AVP plasma levels and hypotension in the late phase of sepsis. (c) 2010 Elsevier B.V. All rights reserved.

Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson`s Disease

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson`s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD, indicating that the i.n. administration of MPTP represents a valuable mouse model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Neonatal endotoxin exposure changes neuroendocrine, cardiovascular function and mortality during polymicrobial sepsis in adult rats

Our aim was to investigate whether neonatal LPS challenge may improve hormonal, cardiovascular response and mortality, this being a beneficial adaptation when adult rats are submitted to polymicrobial sepsis by cecal ligation and puncture (CLP). Fourteen days after birth, pups received an intraperitoneal injection of lipopolysaccharide (LPS; 100 mu g/kg) or saline. After 8-12 weeks, they were submitted to CLP, decapitated 4,6 or 24 h after surgery and blood was collected for vasopressin (AVP), corticosterone and nitrate measurement, while AVP contents were measured in neurohypophysis, supra-optic (SON) and paraventricular (PVN) nuclei. Moreover, rats had their mean arterial pressure (MAP) and heart rate (HR) evaluated, and mortality and bacteremia were determined at 24 h. Septic animals with neonatal LPS exposure had higher plasma AVP and corticosterone levels, and higher c-Fos expression in SON and PVN at 24 h after surgery when compared to saline treated rats. The LPS pretreated group showed increased AVP content in SON and PVN at 6 h, while we did not observe any change in neurohypophyseal AVP content. The nitrate levels were significantly reduced in plasma at 6 and 24 h after surgery, and in both hypothalamic nuclei only at 6 h. Septic animals with neonatal LPS exposure showed increase in MAP during the initial phase of sepsis, but HR was not different from the neonatal saline group. Furthermore, neonatally LPS exposed rats showed a significant decrease in mortality rate as well as in bacteremia. These data suggest that neonatal LPS challenge is able to promote beneficial effects on neuroendocrine and cardiovascular responses to polymicrobial sepsis in adulthood. (C) 2011 Elsevier B.V. All rights reserved.

Muscarinic acetylcholine neurotransmission enhances the late-phase of long-term potentiation in the hippocampal-prefrontal cortex pathway of rats in vivo: A possible involvement of monoaminergic systems

The prefrontal cortex is continuously required for working memory processing during wakefulness, but is particularly hypoactivated during sleep and in psychiatric disorders such as schizophrenia. Ammon`s horn CA1 hippocampus subfield (CA1) afferents provide a functional modulatory path that is subjected to synaptic plasticity and a prominent monoaminergic influence. However, little is known about the muscarinic cholinergic effects on prefrontal synapses. Here, we investigated the effects of the muscarinic agonist, pilocarpine (PILO), on the induction and maintenance of CA1-medial prefrontal cortex (mPFC) long-term potentiation (LTP) as well as on brain monoamine levels. Field evoked responses were recorded in urethane-anesthetized rats during baseline (50 min) and after LTP (130 min), and compared with controls. LTP was induced 20 min after PILO administration (15 mg/kg, i.p.) or vehicle (NaCl 0.15 M, i.p.). In a separate group of animals, the hippocampus and mPFC were microdissected 20 min after PILO injection and used to quantify monoamine levels. Our results show that PILO potentiates the late-phase of mPFC UP without affecting either post-tetanic potentiation or early LTP (20 min). This effect was correlated with a significant decrease in relative delta (1-4 Hz) power and an increase in sigma (10-15 Hz) and gamma (2540 Hz) powers in CA1. Monoamine levels were specifically altered in the mPFC. We observed a decrease in dopamine, 5-HT, 5-hydroxyindolacetic acid and noradrenaline levels, with no changes in 3,4-hydroxyphenylacetic acid levels. Our data, therefore, suggest that muscarinic activation exerts a boosting effect on mPFC synaptic plasticity and possibly on mPFC-dependent memories, associated to monoaminergic changes. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Low Intensity Laser Therapy in Temporomandibular Disorder: a Phase II Double-Blind Study

The purpose of this study was to evaluate the analgesic effect of Low Intensity Laser Therapy (LILT) and its influence on masticatory efficiency in patients with temporomandibular dysfunction (TMD). This study was performed using a random, placebo-controlled, and double-blind research design. Fourteen patients were selected and divided into two groups (active and placebo). Infrared laser (780 nm, 70 mw, 60s, 105J/cm(2)) was applied precisely and continuously into five points of the temporomandibular joint (TMJ) area: lateral point (LP), superior point (SP), anterior point (AP), posterior point (PP), and posterior-inferior point (PIP) of the condylar position. This was performed twice per week, for a total of eight sessions, To ensure a double-blind study, two identical probes supplied by the manufacturer were used: one for the active laser and one for the inactive placebo laser. They were marked with different letters (A and B) by a clinician who did not perform the applications. A Visual Analogue Scale (VAS) and a colorimetric capsule method were employed. Data were obtained three times: before treatment (Ev1), shortly after the eighth session (Ev2), and 30 days after the first application (Ev3). Statistical tests revealed significant differences at one percent (1%) likelihood, which implies that superiority of the active group offered considerable TMJ pain improvement. Both groups presented similar masticatory behavior, and no statistical differences were found. With regard to the evaluation session, Ev2 presented the lowest symptoms and highest masticatory efficiency throughout therapy. Therefore, low intensity laser application is effective in reducing TMD symptoms, and has influence over masticatory efficiency [Ev2 (0.2423) and Ev3 (0.2043), observed in the interaction Evaluations x Probes for effective dosage].