Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Wear of coated and uncoated PCBN cutting tool used in turning and milling

This licentiate thesis has the main focus on evaluation of the wear of coated and uncoated polycrystalline cubic boron nitride cutting tool used in cutting operations against hardened steel. And to exam the surface finish and integrity of the work material used. Harder work material, higher cutting speed and cost reductions result in the development of harder and more wear resistance cutting tools. Although PCBN cutting tools have been used in over 30 years, little work have been done on PVD coated PCBN cutting tools. Therefore hard turning and hard milling experiments with PVD coated and uncoated cutting tools have been performed and evaluated. The coatings used in the present study are TiSiN and TiAlN. The wear scar and surface integrity have been examined with help of several different characterization techniques, for example scanning electron microscopy and Auger electron spectroscopy.   The results showed that the PCBN cutting tools used displayed crater wear, flank wear and edge micro chipping. While the influence of the coating on the crater and flank wear was very small and the coating showed a high tendency to spalling. Scratch testing of coated PCBN showed that, the TiAlN coating resulted in major adhesive fractures. This displays the importance of understanding the effect of different types of lapping/grinding processes in the pre-treatment of hard and super hard substrate materials and the amount and type of damage that they can create. For the cutting tools used in turning, patches of a adhered layer, mainly consisting of FexOy were shown at both the crater and flank. And for the cutting tools used in milling a tribofilm consisting of SixOy covered the crater. A combination of tribochemical reactions, adhesive wear and mild abrasive wear is believed to control the flank and crater wear of the PCBN cutting tools. On a microscopic scale the difference phases of the PCBN cutting tool used in turning showed different wear characteristics. The machined surface of the work material showed a smooth surface with a Ra-value in the range of 100-200 nm for the turned surface and 100-150 nm for the milled surface. With increasing crater and flank wear in combination with edge chipping the machined surface becomes rougher and showed a higher Ra-value. For the cutting tools used in milling the tendency to micro edge chipping was significant higher when milling the tools steels showing a higher hard phase content and a lower heat conductivity resulting in higher mechanical and thermal stresses at the cutting edge.

Prodrugs for the treatment of neglected diseases

Recently, World Health Organization ( WHO) and Medicins San Frontieres (MSF) proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as cancer, cardiovascular and mental (CNS) diseases represent the targets of the majority of the R&D efforts of pharmaceutical companies. Neglected diseases affect millions of people in the world yet existing drug therapy is limited and often inappropriate. Furthermore, extremely neglected diseases affect people living under miserable conditions who barely have access to the bare necessities for survival. Most of these diseases are excluded from the goals of the R&D programs in the pharmaceutical industry and therefore fall outside the pharmaceutical market. About 14 million people, mainly in developing countries, die each year from infectious diseases. From 1975 to 1999, 1393 new drugs were approved yet only 1% were for the treatment of neglected diseases [ 3]. These numbers have not changed until now, so in those countries there is an urgent need for the design and synthesis of new drugs and in this area the prodrug approach is a very interesting field. It provides, among other effects, activity improvements and toxicity decreases for current and new drugs, improving market availability. It is worth noting that it is essential in drug design to save time and money, and prodrug approaches can be considered of high interest in this respect. The present review covers 20 years of research on the design of prodrugs for the treatment of neglected and extremely neglected diseases such as Chagas' disease ( American trypanosomiasis), sleeping sickness ( African trypanosomiasis), malaria, sickle cell disease, tuberculosis, leishmaniasis and schistosomiasis.

Treatment of Endometriosis with Local Acetylsalicylic Acid Injection: Experimental Study in Rabbits

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Clinical evaluation of the bicoronal flap in the treatment of facial fractures. Retrospective study of 132 patients

The aim of the present study was to evaluate the postoperative complications of bicoronal flaps used to treat facial fractures. One hundred and thirty two patients that received bicoronal flaps for the treatment of upper and middle third facial fractures were called for clinical and radiographic examination. Minimum follow-up was 1 year and all patients had charts with adequate information about their perioperative care pertinent to the study. Results showed as complications hypoesthesia (17%), partial unilateral frontal motor deficit (11%), infection (3%), hypertrophic scars (3%), varying degrees of alopecia (18%), seroma or hematoma in the immediate postoperative period (5%). The flap provided wide surgical access to the upper and middle facial thirds with very few serious complications, most frequently allowing good aesthetic results. (C) 2011 European Association for Cranio-Maxillo-Facial Surgery.

Induction of the split sting trait in Africanized Apis mellifera (Hymenoptera : Apidae) by cold treatment of pupae

Split sting is the name given to a nonfunctional honey bee sting characterized by lancets not attached to the stylet. It has appeared in a mutant line in Brazil, and has provoked interest as a possible means to reduce honey bee colony defensiveness. We induced this alteration in Africanized Apis mellifera L. workers and queens by maintaining pupae at 20 degrees C. In particular, we determined the pupal phase most susceptible to alterations in the sting caused by cold treatment, and we investigated whether this treatment also affected survival to the adult phase and wing morphology. The highest frequency of split sting was detected in workers treated at the pink-eyed pupal phase. The lowest frequency was observed in the bees treated at the oldest worker pupal phase studied (brown-eyed pupae with lightly pigmented cuticle). Both queen pupal phases tested (white and pink-eyed pupae) were equally sensitive and produced high percentages of adults with split sting. However, the 20 degrees C treatment of workers and queens, at the different pupal phases, resulted in high frequencies of adults with deformed wings. Also, fewer workers and queens treated at the earlier pupal stages reached adult emergence. There was also an arrest in developmental time, corresponding to the period of cold treatment.

Effects of histone hyperacetylation on the preimplantation development of male and female bovine embryos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chemical and biochemical characterization of guava and araçá fruits from different regions of Brazil

Guava and araçá, species of the Psidium genus, are important options for Brazilian agribusiness, especially the former species, due to their fruit characteristics, such as appearance, taste and richness in minerals and phenolic compounds. These fruits can be consumed in natura or in several processed forms. The active germplasm bank is an important tool for genetic resource characterization and plant breeding studies. Sixty guava and ten araçá accessions of the Psidium active germplasm, sampled in 44 different Brazilian regions and grown at Embrapa Semiarid, were chemically and biochemically characterized in order to support breeding programs. The accessions were grown in a randomized block design, with two replications and three plants/plot. The sugar, proteins, soluble solids, titratable acidity, calcium, magnesium, iron and phosphorus contents were determined. Large variations were observed in the analyzed compounds, which could be attributed to the diversity of genotypes and also to the environmental conditions, which affect the plant metabolism. The high variability observed in most parameters of the accessions is an important factor for the improvement of these species. Most guava accessions showed higher titratable acidity and soluble solids than those found in commercial cultivars and, in araçá, these levels were even higher, which makes them promising for commercial exploitation. Moreover, fruits of the guava and araçá accessions present good sources of sugars and minerals. Special attention should be given to some guava and araçá accessions from Maranhão and Pernambuco States, respectively, which showed high levels for titratable acidity, soluble solids, SS/TA ratio, total soluble sugars, calcium, magnesium and iron, should be targets of breeding programs for new Psidium cultivars. © ISHS.

Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328) or two doses of placebo (n = 325) at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI) 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6%) against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.

Forced orthodontic eruption for augmentation of soft and hard tissue prior to implant placement

Forced orthodontic eruption (FOE) is a non-surgical treatment option that allows modifying the osseous and gingival topography. The aim of this article is to present a clinical case of a FOE, which resulted in an improvement of the amount of available bone and soft-tissues for implant site development. Patient was referred for treatment of mobility and unesthetic appearance of their maxillary incisors. Clinical and radiographic examination revealed inflamed gingival tissue, horizontal and vertical tooth mobility and interproximal angular bone defects. It was chosen a multidisciplinary treatment approach using FOE, tooth extraction, and immediate implant placement to achieve better esthetic results. The use of FOE, in periodontally compromised teeth, promoted the formation of a new bone and soft-tissue in a coronal direction, without additional surgical procedures, enabling an esthetic, and functional implant-supported restoration.

Pyridinic analog of the natural product (-)-spectaline as potential adjuvant for the treatment of central nervous system disorders

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Different addictive drug exposure induces selective alterations of the Endogenous Opioid System : modulation of transcription and epigenetic mechanisms

Drug addiction manifests clinically as compulsive drug seeking, and cravings that can persist and recur even after extended periods of abstinence. The fundamental principle that unites addictive drugs is that each one enhances synaptic DA by means that dissociate it from normal behavioral control, so that they act to reinforce their own acquisition. Our attention has focused on the study of phenomena associated with the consumption of alcohol and heroin. Alcohol has long been considered an unspecific pharmacological agent, recent molecular pharmacology studies have shown that acts on different primary targets. Through gene expression studies conducted recently it has been shown that the classical opioid receptors are differently involved in the consumption of ethanol and, furthermore, the system nociceptin / NOP, included in the family of endogenous opioid system, and both appear able to play a key role in the initiation of alcohol use in rodents. What emerges is that manipulation of the opioid system, nociceptin, may be useful in the treatment of addictions and there are several evidences that support the use of this strategy. The linkage between gene expression alterations and epigenetic modulation in PDYN and PNOC promoters following alcohol treatment confirm the possible chromatin remodeling mechanism already proposed for alcoholism. In the second part of present study, we also investigated alterations in signaling molecules directly associated with MAPK pathway in a unique collection of postmortem brains from heroin abusers. The interest was focused on understanding the effects that prolonged exposure of heroin can cause in an individual, over the entire MAPK cascade and consequently on the transcription factor ELK1, which is regulated by this pathway. We have shown that the activation of ERK1/2 resulting in Elk-1 phosphorylation in striatal neurons supporting the hypothesis that prolonged exposure to substance abuse causes a dysregulation of MAPK pathway.

Synthesis of carbolines and analogues via rhodhium-catalyzed [2+2+2] cycloaddition with alkynyl-ynamides : application to the total synthesis of alkaloids

The main research theme of this dissertation is the synthesis of g- and b-carbolines using a metal-catalyzed [2+2+2] cycloaddition strategy of tethered alkynyl-ynamides (diynes) with nitriles. g- and b-carbolines form the core of a large group of natural product and represent important targets for organic chemists. Many of these carbolines showed pharmacological effects ranging from anti-tumor to anxiolytic and anti-HIV activity. A model study with N-Ethynyl-N-tosyl-2-(2-phenylethynyl)aniline and methyl cyanoformate showed that rhodium-based catalysts promote efficiently the reaction. A further optimization showed that the regioselectivity of the reaction can be tuned by the choice of the solvent or by the catalytic system. Application to a larger scope of diynes showed that the regioselectivity strongly depends on the type of substitution of the alkynyl moieties, giving regioselectivities in the range g:b = 1/0 to g:b = 0/1. This [2+2+2] cycloaddition approach for the synthesis of the g- and b-carboline cores was successfully applied to the first total synthesis of Isoperlolyrine and the total synthesis of Perlolyrine. Extension of this strategy to heterocumulenes as cycloaddition partners allowed the synthesis of a g-carbolinone, a thiopyrano[3,4-b]indol-3-imine and thiopyranothiones.

Excellent outcome after surgical treatment of massive pulmonary embolism in critically ill patients

OBJECTIVE: Treatment of central and paracentral pulmonary embolism in patients with hemodynamic compromise remains a subject of debate, and no consensus exists regarding the best method: thrombolytic agents, catheter-based thrombus aspiration or fragmentation, or surgical embolectomy. We reviewed our experience with emergency surgical pulmonary embolectomy. METHODS: Between January of 2000 and March of 2007, 25 patients (17 male, mean age 60 years) underwent emergency open embolectomy for central and paracentral pulmonary embolism. Eighteen patients presented in cardiogenic shock, 8 of whom had cardiac arrest and required cardiopulmonary resuscitation. All patients underwent operation with mild hypothermic cardiopulmonary bypass. Concomitant procedures were performed in 8 patients (3 coronary artery bypass grafts, 2 patent foramen ovale closures, 4 ligations of the left atrial appendage, 3 removals of a right atrial thrombus). Follow-up is 96% complete with a median of 2 years (range, 2 months to 6 years). RESULTS: All patients survived the procedure, but 2 patients died in the hospital on postoperative days 1 (intracerebral bleeding) and 11 (multiorgan failure), accounting for a 30-day mortality of 8% (95% confidence interval: 0.98-0.26). Four patients died later because of their underlying disease. Pre- and postoperative echocardiographic pressure measurements demonstrated the reduction of the pulmonary hypertension to half of the systemic pressure values or less. CONCLUSION: Surgical pulmonary embolectomy is an excellent option for patients with major pulmonary embolism and can be performed with minimal mortality and morbidity. Even patients who present with cardiac arrest and require preoperative cardiopulmonary resuscitation show satisfying results. Immediate surgical desobstruction favorably influences the pulmonary pressure and the recovery of right ventricular function, and remains the treatment of choice for patients with massive central and paracentral embolism with hemodynamic and respiratory compromise.