Effect Of Pitavastatin On Vascular Reactivity In Hypercholesterolemic Rabbits.

Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

Impact Of Pregabalin Treatment On Synaptic Plasticity And Glial Reactivity During The Course Of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that affects young adults. It is characterized by generating a chronic demyelinating autoimmune inflammation in the central nervous system. An experimental model for studying MS is the experimental autoimmune encephalomyelitis (EAE), induced by immunization with antigenic proteins from myelin. The present study investigated the evolution of EAE in pregabalin treated animals up to the remission phase. The results demonstrated a delay in the onset of the disease with statistical differences at the 10th and the 16th day after immunization. Additionally, the walking track test (CatWalk) was used to evaluate different parameters related to motor function. Although no difference between groups was obtained for the foot print pressure, the regularity index was improved post treatment, indicating a better motor coordination. The immunohistochemical analysis of putative synapse preservation and glial reactivity revealed that pregabalin treatment improved the overall morphology of the spinal cord. A preservation of circuits was depicted and the glial reaction was downregulated during the course of the disease. qRT-PCR data did not show immunomodulatory effects of pregabalin, indicating that the positive effects were restricted to the CNS environment. Overall, the present data indicate that pregabalin is efficient for reducing the seriousness of EAE, delaying its course as well as reducing synaptic loss and astroglial reaction.

Mesenchymal Stem Cells Engrafted In A Fibrin Scaffold Stimulate Schwann Cell Reactivity And Axonal Regeneration Following Sciatic Nerve Tubulization.

The present study investigated the effectiveness of mesenchymal stem cells (MSCs) associated with a fibrin scaffold (FS) for the peripheral regenerative process after nerve tubulization. Adult female Lewis rats received a unilateral sciatic nerve transection followed by repair with a polycaprolactone (PCL)-based tubular prosthesis. Sixty days after injury, the regenerated nerves were studied by immunohistochemistry. Anti-p75NTR immunostaining was used to investigate the reactivity of the MSCs. Basal labeling, which was upregulated during the regenerative process, was detected in uninjured nerves and was significantly greater in the MSC-treated group. The presence of GFP-positive MSCs was detected in the nerves, indicating the long term survival of such cells. Moreover, there was co-localization between MSCs and BNDF immunoreactivity, showing a possible mechanism by which MSCs improve the reactivity of SCs. Myelinated axon counting and morphometric analyses showed that MSC engrafting led to a higher degree of fiber compaction combined with a trend of increased myelin sheath thickness, when compared with other groups. The functional result of MSC engrafting was that the animals showed higher motor function recovery at the seventh and eighth week after lesion. The findings herein show that MSC+FS therapy improves the nerve regeneration process by positively modulating the reactivity of SCs.

Antiangiogenic And Finasteride Therapies: Responses Of The Prostate Microenvironment In Elderly Mice.

The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice. 90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20mg/kg); SU5416 group: SU5416 (6 mg/kg); TNP-470 group: TNP-470 (15 mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21 days, prostate ventral lobes were collected for morphological, immunohistochemical and Western blotting analyses. The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and endostatin reactivities, and an increase for ER-α, ER-β and VEGF, were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels. The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.

The Soluble Guanylyl Cyclase Activator Bay 60-2770 Potently Relaxes The Pulmonary Artery On Congenital Diaphragmatic Hernia Rabbit Model.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage, and a significant cause of morbidity and mortality. In this study, we have used a rabbit model of CDH to evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary artery. CDH was performed in New Zealand rabbit fetuses (n = 10 per group) and compared to controls. Measurements of body, total and left lung weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with phenylephrine (10 μM), after which cumulative concentration-response curves to glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770 (sGC activator) were obtained as well as the levels of NO (NO3/NO2). LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the potency (pEC50) for GTN was markedly lower in CDH (8.25 ± 0.02 versus 9.27 ± 0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in CDH (11.7 ± 0.03 versus 10.5 ± 0.06; p < 0.01). The NO2/NO3 levels were 62 % higher in CDH (p < 0.05). BAY 60-2770 exhibits a greater potency to relax the pulmonary artery in CDH, indicating a potential use for pulmonary hypertension in this disease.

Basilar Invagination: Surgical Results.

Basilar invagination (BI) is a congenital craniocervical junction (CCJ) anomaly represented by a prolapsed spine into the skull-base that can result in severe neurological impairment. In this paper, we retrospective evaluate the surgical treatment of 26 patients surgically treated for symptomatic BI. BI was classified according to instability and neural abnormalities findings. Clinical outcome was evaluated using the Nürick grade system. A total of 26 patients were included in this paper. Their age ranged from 15 to 67 years old (mean 38). Of which, 10 patients were male (38%) and 16 (62%) were female. All patients had some degree of tonsillar herniation, with 25 patients treated with foramen magnum decompression. Nine patients required a craniocervical fixation. Six patients had undergone prior surgery and required a new surgical procedure for progression of neurological symptoms associated with new compression or instability. Most of patients with neurological symptoms secondary to brainstem compression had some improvement during the follow-up. There was mortality in this series, 1 month after surgery, associated with a late removal of the tracheal cannula. Management of BI requires can provide improvements in neurological outcomes, but requires analysis of the neural and bony anatomy of the CCJ, as well as occult instability. The complexity and heterogeneous presentation requires attention to occult instability on examination and attention to airway problems secondary to concomitant facial malformations.

Effect Of Particles Of Ashes Produced From Sugarcane Burning On The Respiratory System Of Rats.

The practice of burning sugarcane obtained by non-mechanized harvesting exposes workers and the people of neighboring towns to high concentrations of particulate matter (PM) that is harmful to health, and may trigger a series of cardiorespiratory diseases. The aim of this study was to analyze the chemical composition of the micro-particles coming from sugarcane burning residues and to verify the effects of this micro-particulate matter on lung and tracheal tissues. Micro-particulate matter (PM10) was obtained by dissolving filter paper containing burnt residues in NaCl solution. This material was instilled into the Wistar rats' nostrils. Histological analyses (hematoxylin and eosin - HE) of cardiac, lung and tracheal tissues were performed. Inflammatory mediators were measured in lung tissues by using ELISA. The chemical composition of the particulate material revealed a large quantity of the phthalic acid ester, high concentrations of phenolic compounds, anthracene and polycyclic aromatic hydrocarbons (PAH). Histological analysis showed a reduction in subjacent conjunctive tissue in the trachea, lung inflammation with inflammatory infiltrate formation and reduction of alveolar spaces and a significant increase (p<0.05) in the release of IL-1α, IL-1β, IL-6, and INF-γ in the group treated with PM10 when compared to the control group. We concluded that the burning sugarcane residues release many particles, which have toxic chemical compounds. The micro-particulate matter can induce alterations in the respiratory system.

Effectiveness Of The Endotracheal Tube Cuff On The Trachea: Physical And Mechanical Aspects.

The inflation pressure of the endotracheal tube cuff can cause ischemia of the tracheal mucosa at high pressures; thus, it can cause important tracheal morbidity and tracheal microaspiration of the oropharyngeal secretion, or it can even cause pneumonia associated with mechanical ventilation if the pressure of the cuff is insufficient. In order to investigate the effectiveness of the RUSCH® 7.5 mm endotracheal tube cuff, this study was designed to investigate the physical and mechanical aspects of the cuff in contact with the trachea. For this end, we developed an in vitro experimental model to assess the flow of dye (methylene blue) by the inflated cuff on the wall of the artificial material. We also designed an in vivo study with 12 Large White pigs under endotracheal intubation. We instilled the same dye in the oral cavity of the animals, and we analyzed the presence or not of leakage in the trachea after the region of the cuff after their deaths (animal sacrifice). All cuffs were inflated at the pressure of 30 cmH2O. We observed the passage of fluids through the cuff in all in vitro and in vivo experimental models. We conclude that, as well as several other cuff models in the literature, the RUSCH® 7.5 mm tube cuffs are also not able to completely seal the trachea and thus prevent aspiration of oropharyngeal secretions. Other prevention measures should be taken.

Enhanced Endothelium-dependent Relaxation Of Rat Pulmonary Artery Following β-adrenergic Overstimulation: Involvement Of The No/cgmp/vasp Pathway.

The aim of this study was to investigate whether β-adrenoceptor (β-AR) overstimulation induced by in vivo treatment with isoproterenol (ISO) alters vascular reactivity and nitric oxide (NO) production and signaling in pulmonary arteries. Vehicle or ISO (0.3mgkg(-1)day(-1)) was administered daily to male Wistar rats. After 7days, the jugular vein was cannulated to assess right ventricular (RV) systolic pressure (SP) and end diastolic pressure (EDP). The extralobar pulmonary arteries were isolated to evaluate the relaxation responses, protein expression (Western blot), NO production (diaminofluorescein-2 fluorescence), and cyclic guanosine 3',5'-monophosphate (cGMP) levels (enzyme immunoassay kit). ISO treatment induced RV hypertrophy; however, no differences in RV-SP and EDP were observed. The pulmonary arteries from the ISO-treated group showed enhanced relaxation to acetylcholine that was abolished by the NO synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (l-NAME); whereas relaxation elicited by sodium nitroprusside, ISO, metaproterenol, mirabegron, or KCl was not affected by ISO treatment. ISO-treated rats displayed enhanced endothelial NOS (eNOS) and vasodilator-stimulated phosphoprotein (VASP) expression in the pulmonary arteries, while phosphodiesterase-5 protein expression decreased. ISO treatment increased NO and cGMP levels and did not induce eNOS uncoupling. The present data indicate that β-AR overactivation enhances the endothelium-dependent relaxation of pulmonary arteries. This effect was linked to an increase in eNOS-derived NO production, cGMP formation and VASP content and to a decrease in phosphodiesterase-5 expression. Therefore, elevated NO bioactivity through cGMP/VASP signaling could represent a protective mechanism of β-AR overactivation on pulmonary circulation.

Hemodynamic Changes With Two Lipid Emulsions For Treatment Of Bupivacaine Toxicity In Swines.

To compare the hemodynamic changes following two different lipid emulsion therapies after bupivacaine intoxication in swines. Large White pigs were anesthetized with thiopental, tracheal intubation performed and mechanical ventilation instituted. Hemodynamic variables were recorded with invasive pressure monitoring and pulmonary artery catheterization (Swan-Ganz catheter). After a 30-minute resting period, 5 mg.kg-1 of bupivacaine by intravenous injection was administered and new hemodynamic measures were performed 1 minute later; the animals were than randomly divided into three groups and received 4 ml.kg-1 of one of the two different lipid emulsion with standard long-chaim triglyceride, or mixture of long and medium-chain triglyceride, or saline solution. Hemodynamic changes were then re-evaluated at 5, 10, 15, 20 and 30 minutes. Bupivacaine intoxication caused fall in arterial blood pressure, cardiac index, ventricular systolic work index mainly and no important changes in vascular resistances. Both emulsion improved arterial blood pressure mainly increasing vascular resistance since the cardiac index had no significant improvement. On the systemic circulation the hemodynamic results were similar with both lipid emulsions. Both lipid emulsions were efficient and similar options to reverse hypotension in cases of bupivacaine toxicity.

Phylogenetic And Phylogeographic Mapping Of The Avian Coronavirus Spike Protein-encoding Gene In Wild And Synanthropic Birds.

The evolution and population dynamics of avian coronaviruses (AvCoVs) remain underexplored. In the present study, in-depth phylogenetic and Bayesian phylogeographic studies were conducted to investigate the evolutionary dynamics of AvCoVs detected in wild and synanthropic birds. A total of 500 samples, including tracheal and cloacal swabs collected from 312 wild birds belonging to 42 species, were analysed using molecular assays. A total of 65 samples (13%) from 22 bird species were positive for AvCoV. Molecular evolution analyses revealed that the sequences from samples collected in Brazil did not cluster with any of the AvCoV S1 gene sequences deposited in the GenBank database. Bayesian framework analysis estimated an AvCoV strain from Sweden (1999) as the most recent common ancestor of the AvCoVs detected in this study. Furthermore, the analysis inferred an increase in the AvCoV dynamic demographic population in different wild and synanthropic bird species, suggesting that birds may be potential new hosts responsible for spreading this virus.

Hypobromous Acid, A Powerful Endogenous Electrophile: Experimental And Theoretical Studies.

Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the bromide anion (Br(-)). The blood plasma level of Br(-) is more than 1,000-fold lower than that of chloride anion (Cl(-)). Consequently, the endogenous production of HOBr is also lower compared to hypochlorous acid (HOCl). Nevertheless, there is much evidence of the deleterious effects of HOBr. From these data, we hypothesized that the reactivity of HOBr could be better associated with its electrophilic strength. Our hypothesis was confirmed, since HOBr was significantly more reactive than HOCl when the oxidability of the studied compounds was not relevant. For instance: anisole (HOBr, k2=2.3×10(2)M(-1)s(-1), HOCl non-reactive); dansylglycine (HOBr, k2=7.3×10(6)M(-1)s(-1), HOCl, 5.2×10(2)M(-1)s(-1)); salicylic acid (HOBr, k2=4.0×10(4)M(-1)s(-1), non-reactive); 3-hydroxybenzoic acid (HOBr, k2=5.9×10(4)M(-1)s(-1), HOCl, k2=1.1×10(1)M(-1)s(-1)); uridine (HOBr, k2=1.3×10(3)M(-1)s(-1), HOCl non-reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the products of the reactions between HOBr and anisole or uridine, respectively, i.e. typical products of electrophilic substitutions. Together, these results show that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This chemical property was theoretically confirmed by measuring the positive Mulliken and ChelpG charges upon bromine and chlorine. In conclusion, the high electrophilicity of HOBr could be behind its well-established deleterious effects. We propose that HOBr is the most powerful endogenous electrophile.

Edema pulmonar neurogênico: relato de dois casos

Neurogenic pulmonary edema is a rare and serious complication in patients with head injury. It also may develop after a variety of cerebral insults such as subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six patients with severe head injury and four patients with cerebrovascular insults treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were evaluated. In this period there were two patients with neurogenic pulmonary edema, one with head injury and other with intracerebral hemorrhage. Diagnosis was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of pulmonary complacence and diffuse pulmonary infiltrations, without previous history of tracheal aspiration or any other risk factor for developement of adult respiratory distress syndrom. In the first case, with severe head trauma, neurogenic pulmonary edema was diagnosed at admission one hour after trauma, associated with severe systemic inflammatory reaction, and good outcome in three days. The second case, with hemorragic vascular insult, developed neurogenic pulmonary edema the fourth day after drenage of intracerebral hematom and died.

Síntese de complexo ferro(II)-nitrogênio: abordagem dos conceitos de reatividade e retro-doação para alunos de graduação em química

There has been a considerable interest in coordination complexes of molecular nitrogen (N2), partly due to a possible relationship between such complexes and the nitrogen activation process in nature. The present paper describes the synthesis and infrared spectroscopic characterization of an iron-nitrogen derivative with ethylenediamine-N,N,N',N'-tetraacetate (edta) as an experiment for an undergraduate course. The topics covered here include synthesis, reactivity and spectroscopy.

A relevante potencialidade dos centros básicos nitrogenados disponíveis em polímeros inorgânicos e biopolímeros na remoção catiônica

This review reports the application of inorganic and organic polymeric materials for cation removal by using nitrogenated basic centers. The data demonstrate the importance of the desired groups when free or immobilized on natural or synthesized inorganic polymers through silanol groups. Thus, the most studied silica gel is followed by natural crysotile and talc polymers, and the synthesized mesopore silicas, talc-like, silicic acids, phosphates and phyllosilicates. The organic natural biopolymeric chitin and cellulose were chemically modified to improve the availability of the amine groups or the reactivity with desirable molecules to enlarge the content of basic centers. The cation removal takes place at the solid/liquid interface and some interactive effects have their thermodynamic data determined.