CARACTERIZACIÓN GEOMORFOLÓGICA, AMENAZAS NATURALES Y RESTRICCIONES DE USO DE LA TIERRA EN ESPARZA, COSTA RICA: UN ENFOQUE DE ORDENAMIENTO TERRITORIAL PARA EL PLAN REGULADOR DEL CANTÓN

Resumen: Este artículo constituye parte del diagnóstico físico-ambiental que se redactó como uno de  los componentes del Plan Regulador de Esparza.   Mediante el acopio de informes  técnicos, mapas  temáticos,  fotos  aéreas  y  trabajo de  campo,  se  caracteriza,geológica  y  geomorfológicamente  el  sector.    En  este  último  apartado  se  identifican veintiséis geoformas   que   son objeto de un cuidadoso análisis para identificar no solo los  tipos de amenazas naturales que hacen vulnerable cada uno de esos territorios, sino que se formulan restricciones de uso y propuestas de uso apropiado.  Abstract: This article  is a part of a physic environmental diagnosis that was composed as  a  section  of  Esparza  Urban  Planning.  In  order  to  characterize  geological  and geomorphological aspects,  it  was  necessary  to  use  technical  reports, thematic  maps, aerial photographs and  fieldwork. As a part of a geomorphologic  research we  identify twenty six landforms. Each one of them has not only a technical name but also a kind of natural  hazard.  At  the  same  time  we  analyze  their  vulnerability  and  propose  use restrictions and made recommendations  about their suitability. 

PLAN REGULADOR DE LA CIUDAD DE HEREDIA

Trata este documento sobre el desarrollo que ha tenido Costa Rica a diferencia de otros países de America Latina con respecto a la ocupacion de territorio y la solucion con lo plan regulador.

Design and synthesis of E3 ligase RNF5 inhibitors as innovative strategy to trigger mutant CFTR rescue in Cystic Fibrosis

In Cystic Fibrosis (CF) the deletion of phenylalanine 508 (F508del) in the CFTR anion channel is associated to misfolding and defective gating of the mutant protein. Among the known proteins involved in CFTR processing, one of the most promising drug target is the ubiquitin ligase RNF5, which normally promotes F508del-CFTR degradation. In this context, a small molecule RNF5 inhibitor is expected to chemically mimic a condition of RNF5 silencing, thus preventing mutant CFTR degradation and causing its stabilization and plasma membrane trafficking. Hence, by exploiting a virtual screening (VS) campaign, the hit compound inh-2 was discovered as the first-in-class inhibitor of RNF5. Evaluation of inh-2 efficacy on CFTR rescue showed that it efficiently decreases ubiquitination of mutant CFTR and increases chloride current in human primary bronchial epithelia. Based on the promising biological results obtained with inh-2, this thesis reports the structure-based design of potential RNF5 inhibitors having improved potency and efficacy. The optimization of general synthetic strategies gave access to a library of analogues of the 1,2,4-thiadiazol-5-ylidene inh-2 for SAR investigation. The new analogues were tested for their corrector activity in CFBE41o- cells by using the microfluorimetric HS-YFP assay as a primary screen. Then, the effect of putative RNF5 inhibitors on proliferation, apoptosis and the formation of autophagic vacuoles was evaluated. Some of the new analogs significantly increased the basal level of autophagy, reproducing RNF5 silencing effect in cell. Among them, one compound also displayed a greater rescue of the F508del-CFTR trafficking defect than inh-2. Our preliminary results suggest that the 1,2,4-thiadiazolylidene could be a suitable scaffold for the discovery of potential RNF5 inhibitors able to rescue mutant CFTRs. Biological tests are still ongoing to acquire in-depth knowledge about the mechanism of action and therapeutic relevance of this unprecedented pharmacological strategy.

Longitudinal Micro CT-driven biomarkers as a tool to evaluate lung fibrosis progression and antifibrotic efficacy in a refined Bleomycin mouse model

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with no curative pharmacological treatment. Animal models play an essential role in revealing molecular mechanisms involved in the pathogenesis of the disease. Bleomycin (BLM)-induced lung fibrosis is the most widely used and characterized model for anti-fibrotic drugs screening. However, several issues have been reported, such as the identification of an optimal BLM dose and administration scheme as well as gender-specificity. Moreover, the balance between disease resolution, an appropriate time window for therapeutic intervention and animal welfare remains critical aspects yet to be fully elucidated. In this thesis, Micro CT imaging has been used as a tool to identify the ideal BLM dose regimen to induce sustained lung fibrosis in mice as well as to assess the anti-fibrotic effect of Nintedanib (NINT) treatment upon this BLM administration regimen. In order to select the optimal BLM dose scheme, C57bl/6 male mice were treated with BLM via oropharyngeal aspiration (OA), following either double or triple BLM administration. The triple BLM administration resulted in the most promising scheme, able to balance disease resolution, appropriate time-window for therapeutic intervention and animal welfare. The fibrosis progression was longitudinally assessed by micro-CT every 7 days for 5 weeks after BLM administration and 5 animals were sacrificed at each timepoint for the BALF and histological evaluation. The antifibrotic effect of NINT was assessed following different treatment regimens in this model. Herein, we have developed an optimized mouse model of pulmonary fibrosis, enabling three weeks of the therapeutic window to screen putative anti-fibrotic drugs. micro-CT scanning, allowed us to monitor the progression of lung fibrosis and the therapeutical response longitudinally in the same subject, drastically reducing the number of animals involved in the experiment.

Pyrimidine-5'-nucleotidase Campinas, A New Mutation (p.r56g) In The Nt5c3 Gene Associated With Pyrimidine-5'-nucleotidase Type I Deficiency And Influence Of Gilbert's Syndrome On Clinical Expression.

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.

Volumetric Capnography For The Evaluation Of Chronic Airways Diseases.

Obstructive lung diseases of different etiologies present with progressive peripheral airway involvement. The peripheral airways, known as the silent lung zone, are not adequately evaluated with conventional function tests. The principle of gas washout has been used to detect pulmonary ventilation inhomogeneity and to estimate the location of the underlying disease process. Volumetric capnography (VC) analyzes the pattern of CO2 elimination as a function of expired volume. To measure normalized phase 3 slopes with VC in patients with non-cystic fibrosis bronchiectasis (NCB) and in bronchitic patients with chronic obstructive pulmonary disease (COPD) in order to compare the slopes obtained for the groups. NCB and severe COPD were enrolled sequentially from an outpatient clinic (Hospital of the State University of Campinas). A control group was established for the NCB group, paired by sex and age. All subjects performed spirometry, VC, and the 6-Minute Walk Test (6MWT). Two comparisons were made: NCB group versus its control group, and NCB group versus COPD group. The project was approved by the ethical committee of the institution. Statistical tests used were Wilcoxon or Student's t-test; P<0.05 was considered to be a statistically significant difference. Concerning the NCB group (N=20) versus the control group (N=20), significant differences were found in body mass index and in several functional variables (spirometric, VC, 6MWT) with worse results observed in the NCB group. In the comparison between the COPD group (N=20) versus the NCB group, although patients with COPD had worse spirometric and 6MWT values, the capnographic variables mean phase 2 slope (Slp2), mean phase 3 slope normalized by the mean expiratory volume, or mean phase 3 slope normalized by the end-tidal CO2 concentration were similar. These findings may indicate that the gas elimination curves are not sensitive enough to monitor the severity of structural abnormalities. The role of normalized phase 3 slope may be worth exploring as a more sensitive index of small airway disease, even though it may not be equally sensitive in discriminating the severity of the alterations.

Myocardial Extracellular Volume Expansion And The Risk Of Recurrent Atrial Fibrillation After Pulmonary Vein Isolation.

This study tested whether myocardial extracellular volume (ECV) is increased in patients with hypertension and atrial fibrillation (AF) undergoing pulmonary vein isolation and whether there is an association between ECV and post-procedural recurrence of AF. Hypertension is associated with myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are limited. T1 measurements pre-contrast and post-contrast in a cardiac magnetic resonance (CMR) study provide a method for quantification of ECV. Consecutive patients with hypertension and recurrent AF referred for pulmonary vein isolation underwent a contrast CMR study with measurement of ECV and were followed up prospectively for a median of 18 months. The endpoint of interest was late recurrence of AF. Patients had elevated left ventricular (LV) volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34 ± 0.03; healthy control patients, 0.29 ± 0.03; p < 0.001). There were positive associations between ECV and left atrial volume (r = 0.46, p < 0.01) and LV mass and a negative association between ECV and diastolic function (early mitral annular relaxation [E'], r = -0.55, p < 0.001). In the best overall multivariable model, ECV was the strongest predictor of the primary outcome of recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p < 0.0001) and the secondary composite outcome of recurrent AF, heart failure admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51; p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of recurrent AF. In patients with AF and hypertension, expansion of ECV is associated with diastolic function and left atrial remodeling and is a strong independent predictor of recurrent AF post-pulmonary vein isolation.

Synchronous Oral Paracoccidioidomycosis And Pulmonary Tuberculosis In An Immunocompetent Patient.

Paracoccidioidomycosis (PCM) and tuberculosis (TB) are chronic granulomatous infectious diseases, in which the main form of contraction is through inhalation of the microorganism-Paracoccidioides brasiliensis and Mycobacterium tuberculosis. Oral involvement of PCM is observed in up to 70 % of the cases and usually presents clinically as ulcerations with granular surface showing tiny hemorrhagic areas. Oral presentation of TB is rare with prevalence smaller than 0.5 % of all cases. Clinical presentation of oral TB mainly consists of single ulcers with irregular limits and necrotic base. A 70-year-old immunocompetent man presented simultaneously oral PCM and pulmonary TB. Medical history revealed a previous diagnosis of pulmonary TB; however, even under treatment for TB, the patient remained with oral lesions and intense pulmonary fibrosis. The physician requested P. brasiliensis serological analysis, which resulted positive. Although the combination of PCM and TB has been reported in the literature, it is still considered an uncommon condition and their diagnosis may represent a challenge to healthcare professionals because of the similarity between their clinical and radiological presentations.

The Effects Of Cyclosporin A And Heteropterys Tomentosa On The Rat Liver.

Cyclosporin A (CsA) is a widely employed immunosuppressive drug that is associated with several side effects, among then hepatotoxicity. Heteropterys tomentosa is a Brazilian plant efficient in reducing damage caused by CsA on the rat testis and prostate. The aim of this study was to evaluate the effect of CsA and H. tomentosa (administered isolated or simultaneously) on the liver of Wistar rats. The animals were treated daily with water (control), CsA (15mg/kg/day), H. tomentosa infusion or CsA+H. tomentosa, for 21 or 56 days. The treatments did not alter liver morphology or cause fibrosis. H. tomentosa administered for 21 days increased the number of hepatocyte nuclei and Kupffer cell volumetric proportion. After 56 days of treatment, H. tomentosa administration did not alter the parameters analyzed. Biochemical plasma dosages and liver stereology showed impairment caused by CsA-treatment after 21 days; these results were not observed after 56 days of treatment. The simultaneous treatment with CsA and H. tomentosa for 21 or 56 days did not alleviate nor accentuate CsA hepatic effects. The present study showed that the 21 days treatment with CsA caused more alteration to the liver than the 56 days treatment; this could be related to hepatic recovery after the long term treatment.

Hormônio de crescimento em crianças e adolescentes com fibrose cística

The recombinant human growth hormone (rhGH) can improve weight gain, physical growth, clinical and lung in cystic fibrosis (CF). However, the routine use, although promising, is not established in the literature. The objective of this study was to assess the benefits of rhGH in children and adolescents with CF. We conducted a systematic review in the database PubMed, Lilacs, SciELO and Cochrane, in the period 2000-2010, using the keywords: cystic fibrosis, growth hormone, children and adolescents. We found 77 articles and included 11 randomized controlled trials, with 290 children and adolescents with CF. The short-term use (1-24 months) of rhGH improved the height, weight, growth rate, bone mineral content and components of pulmonary function. Adverse effects, like diabetes, were not observed in the studies. The short-term use of rhGH improved growth and body composition in patients with CF.

Fibrose congênita de reto inferior atípica com hipotonia muscular generalizada: relato de um caso

A case report of an atipical inferior rectus congenital fibrosis associated with a generalized muscular hypotonia is presented. It shows mild hipotropia with a normal visual acuity and binocularity in infraversion position contrasting with the severe hipotropia and ambliopy found. The surgical procedure took these facts into consideration, so we performed a small retrocess of the muscle with the objective to correct the head position without changes in the reading position. The postoperative results were satisfactory.

Politetrafluoroetileno e esclera humana no tratamento cirúrgico de perfuração escleral em coelhos

Purpose: An experimental study to evaluate the behavior of polytetrafluoroethylene (Gore-Tex®) compared with human sclera, in scleral perforations induced in rabbits eyes was performed. Methods: Twenty-two eyes of rabbits were submitted to scleral perforation followed by Gore-Tex® graft in the left eye and human sclera graft in the right eye respectively. During one month the postoperative evolution was analyzed every day: intensity of hyperemia, presence of infection, secretion, rejection and tonicity of the eyes. Results: No cases of secretion, infection or rejection were observed. The histological sections showed fibrosis in the eyes with Gore-Tex®, good adhesion and epithelization. Conclusion: The Gore-Tex® showed to be a plausible material to be used as graft in scleral defects with some advantages such as easy obtention, good handling and durability.

Subcutaneous tissue response of isogenic mice to calcium hydroxide-based pastes with chlorhexidine

This study was evaluated the response of subcutaneous connective tissue of isogenic mice to calcium hydroxide-based pastes with chlorhexidine digluconate (CHX). Seventy isogenic male BALB/c mice aged 6-8 weeks and weighing 15-20 g were randomly assigned to 8 groups. The animals received polyethylene tube implants as follows: Groups I, II, and III (n=10) - Calen® paste mixed with 0.4% CHX (experimental paste; Calen/CHX) for 7, 21, and 63 days, respectively; Groups IV, V, and VI (n=10) - UltraCal™ paste mixed with 2% CHX (experimental paste supplied by Ultradent Products Inc.; Ultracal/CHX) for 7, 21, and 63 days, respectively; and Groups VII and VIII (n=5): empty tube for 7 and 21 days, respectively. At the end of the experimental periods, the implants were removed together with the surrounding tissues (skin and subcutaneous connective tissue). The biopsied tissues were subjected to routine processing for histological analysis. Using a descriptive analysis and a four-point (0-3) scoring system, the following criteria were considered for qualitative and quantitative analysis of the tissue around the implanted materials: collagen fiber formation, tissue thickness and inflammatory infiltrate. A quantitative analysis was performed by measuring the thickness (µm), area (µm²) and perimeter (µm) of the reactionary granulomatous tissue formed at the tube ends. Data were analyzed statistically by the Kruskal-Wallis test and Dunn's post-test (α=0.05). Calen/CHX showed biocompatibility with the subcutaneous and reactionary tissues, with areas of discrete fibrosis and normal conjunctive fibrous tissue, though without statistically significant difference (p>0.05) from the control groups. In Groups I to III, there was a predominance of score 1, while in Groups IV to VI scores 2 and 3 predominated for all analyzed parameters. UltraCal/CHX, on the other hand, induced the formation of an inflammatory infiltrate and abundant exudate, suggesting a persistent residual aggression from the material, even 63 days after implant placement. In conclusion, the Calen paste mixed with 0.4% CHX allowed an adequate tissue response, whereas the UltraCal paste mixed with 2% CHX showed unsatisfactory results.

Oxigenoterapia domiciliar prolongada em crianças e adolescentes: uma análise do uso clínico e de custos de um programa assistencial

OBJETIVOS: Descrever as características clínicas e laboratoriais dos pacientes em oxigenoterapia domiciliar prolongada acompanhados pelo programa de atendimento domiciliar do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, durante um período de 8 anos, e comparar os grupos com e sem hipertensão pulmonar secundária. Estimar o custo do programa utilizando concentradores versus cilindros de oxigênio arcados pela instituição. MÉTODOS: Estudo descritivo retrospectivo e de coorte dos pacientes em oxigenoterapia domiciliar prolongada, em seguimento no período de 2002 a 2009, na Unidade de Pneumologia do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTADOS: Foram estudados 165 pacientes, 53% do sexo masculino, com as medianas: idade de início da oxigenoterapia - 3,6 anos; tempo de oxigenoterapia - 7 anos; e tempo de sobrevida após início da oxigenoterapia - 3,4 anos. Os principais diagnósticos foram: fibrose cística (22%), displasia broncopulmonar (19%) e bronquiolite obliterante (15%). Dos 33 pacientes que realizaram espirometria, 70% apresentavam distúrbio ventilatório obstrutivo grave. O exame ecocardiográfico foi executado em 134 pacientes; 51% deles tinham hipertensão pulmonar secundária. Houve associação estatisticamente significante entre: presença de hipertensão pulmonar e necessidade de maiores fluxos de oxigênio (qui-quadrado, p = 0,011); e presença de hipertensão pulmonar e maior tempo de oxigenoterapia (Logrank, p = 0,0001). Não houve diferença estatisticamente significante entre tempo de sobrevida após início da oxigenoterapia e presença de hipertensão pulmonar. Os custos médios mensais do programa foram: US$ 7.392,93 para os concentradores e US$ 16.630,92 para cilindros. CONCLUSÕES: A oxigenoterapia domiciliar prolongada foi empregada em distintas doenças crônicas, predominantemente em lactentes e pré-escolares. Houve alta frequência de hipertensão pulmonar associada a maiores períodos de uso e fluxos de oxigênio, sem associação à sobrevida. A substituição dos cilindros por concentradores poderá reduzir custos significativamente.

Biologia molecular como ferramenta no esporte de alto rendimento: possibilidades e perspectivas

Várias estratégias têm sido pensadas com o propósito de se utilizar a biologia molecular como ferramenta na pré-seleção e na seleção de talentos esportivos, na manipulação genética visando ao aumento ou à diminuição da produção de determinadas substâncias pelo organismo, na prescrição do treinamento e na recuperação de lesões. Portanto, o objetivo desta revisão é apresentar o DNA como regulador do funcionamento do organismo e de que forma alterações no perfil genético, tanto espontâneas como induzidas artificialmente, podem modular respostas fisiológicas e morfológicas por alterar a expressão de determinadas proteínas. Será dada especial atenção à descrição dos procedimentos utilizados para a manipulação genética, nos baixos riscos associados e nas estratégias que têm sido desenvolvidas com o objetivo de detectá-la. Com base em conhecimentos científicos, coerência e bom senso, diversas visões devem ser expostas e amplamente discutidas para ser definido o que é permitido e o que é proibido nas competições esportivas.