Derechos aduaneros vigentes en los países centroamericanos sobre las principales materias primas y productos terminados de ácidos alquilaril sulfónicos, alquilaril sulfonatos y otras sales de ácidos de alquilaril sulfónicos y lustradores-limpiadores para zapatos

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Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids

A malária ainda é um dos mais sérios problemas de saúde pública e a principal causa de mortalidade e morbidade nas regiões endêmicas. O Brasil está entre os 30 países com maior incidência de malária e a maior parte dos casos ocorre na Amazônia Legal. Novos agentes terapêuticos são necessários para o tratamento da malária. Muitas espécies vegetais são utilizadas na medicina tradicional de vários países endêmicos mas é relativamente reduzido o número daquelas que já foram investigadas quanto à sua atividade antimalárica. Menor ainda é o número de espécies das quais foram isoladas substâncias ativas e tiveram sua toxidade determinada. Esta área de pesquisa é, portanto, de alta relevância. Um projeto de descoberta de produtos naturais antimaláricos a partir de plantas de uso tradicional deve incluir ensaios in vitro e in vivo bem como o isolamento biomonitorado de substâncias ativas. Os produtos finais serão substâncias naturais antimaláricas, potenciais fármacos ou protótipos para o desenvolvimento de novos fármacos, e/ou extratos padronizados, com atividade antimalárica, os quais são necessários para estudos pré-clínicos e clínicos quando o objetivo é o desenvolvimento de fitoterápicos (fitomedicamentos) eficazes e seguros. A presente revisão discute estas duas abordagens, apresenta resumidamente as metodologias de bioensaios para avaliação de atividade antimalárica e focaliza a atividade de alcalóides pertencentes a diferentes classes estruturais bem como sua importância como fármacos ou protótipos e como marcadores químicos de fitoterápicos.

Erosion of an active fault scarp leads to drainage capture in the Amazon region, Brazil

Far from the continental margin, drainage basins in Central Amazonia should be in topographic steady state; but they are not. Abandoned remnant fluvial valleys up to hundreds of square kilometers in size are observed throughout Amazonia, and are evidence of significant landscape reorganization. While major Late Miocene drainage shifts occurred due to initiation of the transcontinental Amazon River, local landscape change has remained active until today. Driven either by dynamic topography, tectonism, and/or climatic fluctuations, drainage captures in Amazonia provide a natural experiment for assessing the geomorphic response of low-slope basins to sudden, capture related base-level falls. This paper evaluates the timing of geomorphic change by examining a drainage capture event across the Baependi fault scarp involving the Cuieiras and TarumA-Mirim River basins northwest of the city of Manaus in Brazil. A system of capture-related knickpoints was generated by base-level fall following drainage capture; through numerical modeling of their initiation and propagation, the capture event is inferred to have occurred between the middle and late Pleistocene, consistent with other studies of landscape change in surrounding areas. In low-slope settings like the Amazon River basin, base-level fall can increase erosion rates by more than an order of magnitude, and moderate to large river basins can respond to episodes of base-level fall over timescales of tens to hundreds of thousands of years. Copyright (c) 2013 John Wiley & Sons, Ltd.

Recombinant disintegrin targets alpha(v) beta(3) integrin and leads to mediator production

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

Low abundance of long-tongued pollinators leads to pollen limitation in four specialized hawkmoth-pollinated plants in the Atlantic Rain forest, Brazil

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

Planejamento estratégico e operacional na pequena empresa: impactos da formalização no desempenho e diferenças setoriais

This article analyzes the results of three different field research, carried out simultaneously in small technology-based sectors, metal-mechanical industry and hotel in the city of São Carlos - SP, with goals, concepts and methods of similar research. The studies were classified as quantitative and descriptive and conducted through a survey of opinion with the main leader of the company. It were considered valid for analyses, the responses of 57 leaders, it were 33 technology-based sector, 13 of the metal-mechanic industry and 11 in the hospitality sector. The main results: the formalization of planning has not led to better performance, considering the indicator growth in sales in the three sectors studied and that the degree of formalization of the planning of the companies in the technologybased sector was higher, while the hospitality sector had a percentage smaller. The dynamic aspect of technology-based sector and stability in the hotel sector in the region studied, leads to assume that the turbulence of the environment is a predominant factor, contradicting the proposal of some authors, in which the formal planning is inappropriate for small companies that operate in environments that change quickly.

Sevoflurane induces DNA damage whereas isoflurane leads to higher antioxidative status in anesthetized rats

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

The oxidation of p-phenylenediamine, an ingredient used for permanent hair dyeing purposes, leads to the formation of hydroxyl radicals: oxidative stress and DNA damage in human immortalized keratinocytes

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

SELLING BIRD CONTROL

The remarks that I have prepared deal with direct contacts selling pest and bird control programs. I am going to limit my remarks to what I feel are the more important aspects of selling Bird Control. I think it is safe to say that one of the most difficult aspects of selling for most sales personnel is prospecting, that is, finding accounts to call on. Our sales personnel have to more or less come up with their own leads. They have to find out who to contact once they get there. I have found that the best prospect most of us have for selling Bird Control accounts are our present pest control accounts. Generally speaking, we try to main¬tain contact with our applicators in the field, who are in these accounts every day, asking them if there are any of their accounts that are having bird control problems. Another method of finding potential accounts, is driving around looking. It is more difficult to drive around and look for rat and/or roach problems, but generally speaking if a building or some type of business has a bird problem, it is fairly easy to locate. Another thing we can do is call on specific accounts. There are generally cer¬tain accounts that just by the manufacturing process do attract birds, for example: food plants, mills, beet plants, grain elevators, food processors, and so on. Other type operations which lend themselves to bird problems are industrial plants because of the super-structure (physical plant) that they have. Sub-stations and power plants are very attractive to birds. Some other situations that should be checked for bird problems are lumber yards and contractors' storage buildings. After deciding on a contact we get into what I call my basic four. There are four basic things that I try to impress upon our personnel to keep in mind when they go in to make a contact. The first one is the interview or actually making the contact so that you get an opportunity to have the interview, either calling for an appointment or making a "cold" call. The second one is closing for the survey. The third one is making the survey and preparing a proposal. The fourth and last one is the proposal presentation and closing of the sale. An additional item which would make a basic five is after you make the sale don't forget to follow up on the sale.

Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease

Recent studies have identified the genetic underpinnings of a growing number of diseases through targeted exome sequencing. However, this strategy ignores the large component of the genome that does not code for proteins, but is nonetheless biologically functional. To address the possible involvement of regulatory variation in congenital heart diseases (CHDs), we searched for regulatory mutations impacting the activity of TBX5, a dosage-dependent transcription factor with well-defined roles in the heart and limb development that has been associated with the HoltOram syndrome (hearthand syndrome), a condition that affects 1/100 000 newborns. Using a combination of genomics, bioinformatics and mouse genetic engineering, we scanned approximate to 700 kb of the TBX5 locus in search of cis-regulatory elements. We uncovered three enhancers that collectively recapitulate the endogenous expression pattern of TBX5 in the developing heart. We re-sequenced these enhancer elements in a cohort of non-syndromic patients with isolated atrial and/or ventricular septal defects, the predominant cardiac defects of the HoltOram syndrome, and identified a patient with a homozygous mutation in an enhancer approximate to 90 kb downstream of TBX5. Notably, we demonstrate that this single-base-pair mutation abrogates the ability of the enhancer to drive expression within the heart in vivo using both mouse and zebrafish transgenic models. Given the population-wide frequency of this variant, we estimate that 1/100 000 individuals would be homozygous for this variant, highlighting that a significant number of CHD associated with TBX5 dysfunction might arise from non-coding mutations in TBX5 heart enhancers, effectively decoupling the heart and hand phenotypes of the HoltOram syndrome.

Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats

Background: Given the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity. Methods: Male rats were treated neonatally with monosodium glutamate (MSG) at doses of 4 mg/kg subcutaneously, or with saline solution (control group), on postnatal days 2, 4, 6, 8 and 10. On day 120, obesity was confirmed by the Lee index in all MSG-treated rats. After this, all animals from the two experimental groups were anesthetized and killed to evaluate body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology. Results: Significant reductions in absolute and relative weights of testis, epididymis, prostate and seminal vesicle were noted in MSG-treated animals. In these same animals plasma testosterone and follicle-stimulating hormone (FSH) concentrations were decreased, as well as sperm counts in the testis and epididymis and seminiferous epithelium height and tubular diameter. The sperm transit time was accelerated in obese rats. However, the number of Sertoli cells per seminiferous tubule and stereological findings on the epididymis were not markedly changed by obesity. Conclusions: Neonatal MSG-administered model of obesity lowers sperm production and leads to a reduction in sperm storage in the epididymis of adult male rats. The acceleration of sperm transit time can have implications for the sperm quality of these rats.

Unilateral ablation of follicles >= 4 mm leads to compensatory follicle response from the contralateral ovary in heifers

In each of two experiments, heifers were assigned to a control group and a unilaterally ablated (UA) group (n = 6/group). In the UA group, follicles >= 4 mm in the left ovary were ablated by transvaginal ultrasound-guided technique at Hour 0 (8:00 AM) on the day of ovulation. Follicles in the CL-bearing right ovary remained intact. In Experiment 1, ablations continued until the next ovulation, and new follicles emerged in the right ovary in 9 of 14 (64%) waves. The number of follicles/wave (combined, 6.4 +/- 0.4) did not differ between groups. In Experiment 2, follicles were counted at Hours 0, 4, 8, 12, and 24; the resistance index (RI) for blood flow in the ovarian pedicle was determined at Hours 0 and 12; and blood samples were collected every hour from Hours 0 to 12 and Hour 24. An increase (P < 0.05) in the number of follicles in the follicle-intact ovary began at Hour 4 with complete compensation by Hour 24. Concentrations of FSH did not change between Hours 0 and 24 in the UA group but decreased (P < 0.05) in the controls by Hour 7. At Hour 12, RI to the right ovary approached being lower (P < 0.06) in the UA group than in the control group. Results indicated that unilateral ablation of follicles >= 4 mm led to compensatory follicle response in the follicle-intact ovary, and initially circulatory FSH concentrations were maintained and blood flow to the follicle-intact ovary increased. (c) 2012 Elsevier Inc. All rights reserved.

IL-12p40 Deficiency Leads to Uncontrolled Trypanosoma cruzi Dissemination in the Spinal Cord Resulting in Neuronal Death and Motor Dysfunction

Chagas' disease is a protozoosis caused by Trypanosoma cruzi that frequently shows severe chronic clinical complications of the heart or digestive system. Neurological disorders due to T. cruzi infection are also described in children and immunosuppressed hosts. We have previously reported that IL-12p40 knockout (KO) mice infected with the T. cruzi strain Sylvio X10/4 develop spinal cord neurodegenerative disease. Here, we further characterized neuropathology, parasite burden and inflammatory component associated to the fatal neurological disorder occurring in this mouse model. Forelimb paralysis in infected IL-12p40KO mice was associated with 60% (p<0.05) decrease in spinal cord neuronal density, glutamate accumulation (153%, p<0.05) and strong demyelization in lesion areas, mostly in those showing heavy protein nitrosylation, all denoting a neurotoxic degenerative profile. Quantification of T. cruzi 18S rRNA showed that parasite burden was controlled in the spinal cord of WT mice, decreasing from the fifth week after infection, but progressive parasite dissemination was observed in IL-12p40KO cords concurrent with significant accumulation of the astrocytic marker GFAP (317.0%, p<0.01) and 8-fold increase in macrophages/microglia (p<0.01), 36.3% (p<0.01) of which were infected. Similarly, mRNA levels for CD3, TNF-alpha, IFN-gamma, iNOS, IL-10 and arginase I declined in WT spinal cords about the fourth or fifth week after infection, but kept increasing in IL-12p40KO mice. Interestingly, compared to WT tissue, lower mRNA levels for IFN-gamma were observed in the IL-12p40KO spinal cords up to the fourth week of infection. Together the data suggest that impairments of parasite clearance mechanisms in IL-12p40KO mice elicit prolonged spinal cord inflammation that in turn leads to irreversible neurodegenerative lesions.

Hox Gene Expression Leads to Differential Hind Leg Development between Honeybee Castes

Beyond the physiological and behavioural, differences in appendage morphology between the workers and queens of Apis mellifera are pre-eminent. The hind legs of workers, which are highly specialized pollinators, deserve special attention. The hind tibia of worker has an expanded bristle-free region used for carrying pollen and propolis, the corbicula. In queens this structure is absent. Although the morphological differences are well characterized, the genetic inputs driving the development of this alternative morphology remain unknown. Leg phenotype determination takes place between the fourth and fifth larval instar and herein we show that the morphogenesis is completed at brown-eyed pupa. Using results from the hybridization of whole genome-based oligonucleotide arrays with RNA samples from hind leg imaginal discs of pre-pupal honeybees of both castes we present a list of 200 differentially expressed genes. Notably, there are castes preferentially expressed cuticular protein genes and members of the P450 family. We also provide results of qPCR analyses determining the developmental transcription profiles of eight selected genes, including abdominal-A, distal-less and ultrabithorax (Ubx), whose roles in leg development have been previously demonstrated in other insect models. Ubx expression in workers hind leg is approximately 25 times higher than in queens. Finally, immunohistochemistry assays show that Ubx localization during hind leg development resembles the bristles localization in the tibia/basitarsus of the adult legs in both castes. Our data strongly indicate that the development of the hind legs diphenism characteristic of this corbiculate species is driven by a set of caste-preferentially expressed genes, such as those encoding cuticular protein genes, P450 and Hox proteins, in response to the naturally different diets offered to honeybees during the larval period.