Simultaneous Determination of Refractive Index and Thickness of Submicron Optical Polymer Films from Transmission Spectra.

High-transparency polymers, called optical polymers (OPs), are used in many thin-film devices, for which the knowledge of film thickness (h) and refractive index (n) is generally required. Spectrophotometry is a cost-effective, simple and fast non-destructive method often used to determine these parameters simultaneously, but its application is limited to films where h > 500 nm. Here, a simple spectrophotometric method is reported to obtain simultaneously the n and h of a sub-micron OP film (down to values of a few tenths of a nm) from its transmission spectrum. The method is valid for any OP where the n dispersion curve follows a two-coefficient Cauchy function and complies with a certain equation involving n at two different wavelengths. Remarkably, such an equation is determined through the analysis of n data for a wide set of commercial OPs, and its general validity is demonstrated. Films of various OPs (pristine or doped with fluorescent compounds), typically used in applications such as thin-film organic lasers, are prepared, and n and h are simultaneously determined with the proposed procedure. The success of the method is confirmed with variable-angle spectroscopic ellipsometry.

Efficacy of PPI, levofloxacin and amoxicillin in the eradication of Helicobacter pylori compared to conventional triple therapy at a Venezuelan hospital.

BACKGROUND AND STUDY AIMS: Helicobacter pylori is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. In the past two decades, the recommended treatment for its eradication as a first-line regimen is the standard triple therapy consisting of a proton pump inhibitor (PPI), amoxicillin and clarithromycin or metronidazole. However, the effectiveness of this traditional regime, which initially was 90%, progressively declined in many parts of the world and is currently 57-73%. The aim of this study was to evaluate whether the eradication rate with triple therapy with levofloxacin is superior as first-line therapy to that with treatment using clarithromycin in the population that attended as outpatients at the Hospital of Lídice. PATIENTS AND METHODS: We designed a prospective study, with two groups of patients presenting dyspeptic symptoms, from October 2010 to October 2011, who underwent upper gastrointestinal endoscopy and whose biopsies were positive for infection with H. pylori. At the end, 81 patients were included in the order of biopsy result arrival to fill the quota of each group. The first group with 42 patients underwent triple therapy with clarithromycin and the second group with 39 patients underwent therapy with levofloxacin, amoxicillin and a PPI. The patients' age ranged between 23 and 76years, the average being 49.5. The predominant sex was female, at 72.84%. Both treatments lasted for 10days and the patients were clinically re-evaluated 15days after their conclusion and programmed for a second endoscopy to verify H. pylori eradication. RESULTS: Among the 42 patients in the control group, there were 14 eradication failures with 33.33% resistance to clarithromycin. Among the 39 patients in the experimental group, two eradication failures with 5.13% resistance to levofloxacin were observed. The χ(2) value was 6.96. CONCLUSIONS: Treatment with levofloxacin was more effective than conventional triple therapy. Triple therapy with levofloxacin can be implemented in populations where resistance to clarithromycin has been observed.

The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis.

BACKGROUND: ECBio has developed proprietary technology to consistently isolate, expand and cryopreserve a well-characterized population of stromal cells from human umbilical cord tissue (UCX® cells). The technology has recently been optimized in order to become compliant with Advanced Medicine Therapeutic Products. In this work we report the immunosuppressive capacity of UCX® cells for treating induced autoimmune inflammatory arthritis. METHODS: UCX® cells were isolated using a proprietary method (PCT/IB2008/054067) that yields a well-defined number of cells using a precise proportion between tissue digestion enzyme activity units, tissue mass, digestion solution volume and void volume. The procedure includes three recovery steps to avoid non-conformities related to cell recovery. UCX® surface markers were characterized by flow cytometry and UCX® capacity to expand in vitro and to differentiate into adipocyte, chondrocyte and osteoblast-like cells was evaluated. Mixed Lymphocyte Reaction (MLR) assays were performed to evaluate the effect of UCX® cells on T-cell activation and Treg conversion assays were also performed in vitro. Furthermore, UCX® cells were administered in vivo in both a rat acute carrageenan-induced arthritis model and rat chronic adjuvant induced arthritis model for arthritic inflammation. UCX® anti-inflammatory activity was then monitored over time. RESULTS: UCX® cells stained positive for CD44, CD73, CD90 and CD105; and negative for CD14, CD19 CD31, CD34, CD45 and HLA-DR; and were capable to differentiate into adipocyte, chondrocyte and osteoblast-like cells. UCX® cells were shown to repress T-cell activation and promote the expansion of Tregs better than bone marrow mesenchymal stem cells (BM-MSCs). Accordingly, xenogeneic UCX® administration in an acute carrageenan-induced arthritis model showed that human UCX® cells can reduce paw edema in vivo more efficiently than BM-MSCs. Finally, in a chronic adjuvant induced arthritis model, animals treated with intra-articular (i.a.) and intra-peritoneal (i.p.) infusions of UCX® cells showed faster remission of local and systemic arthritic manifestations. CONCLUSION: The results suggest that UCX® cells may be an effective and promising new approach for treating both local and systemic manifestations of inflammatory arthritis.

Evaluation of the growth-inhibitory effect of trifluralin analogues on in vitro cultured Babesia bovis parasites.

Bovine babesiosis, caused by Babesia bovis, is a global tick borne hemoprotozoan parasite disease characterized by fever, anemia, weight losses and ultimately death. Several babesicidal drugs that have been in use in cattle for years have proven to be only partially effective and the development of alternative chemotherapeutics that are highly specific and have low toxicity against babesiosis is needed. Trifluralin derivatives specifically bind alpha-tubulin in plants and protozoa parasites causing growth inhibition. A set of 12 trifluralin analogues (TFLA) has previously been shown to be inhibitory for the growth of Leishmania species. The conservation of several key amino acids involved in the trifluralin binding site of alpha-tubulin among Leishmania sp. and B. bovis provides rationale for testing these compounds also as babesiacides. The previously tested Leishmania inhibitory, TFLA 1-12 minus TFLA 5, in addition to three novel TFLA (termed TFLA 13-15), were tested against in vitro cultured B. bovis parasites. While all of the TFLA tested in the study showed inhibition of B. bovis growth in vitro TFLA 7, TFLA 10 and TFLA 13, were the most effective inhibitors with estimated IC50 (µM) at 72 h of 8.5 ± 0.3; 9.2 ± 0.2; 8.9 ± 0.7, respectively for the biologically attenuated cloned B. bovis Mo7 strain, and 13.6 ± 1.5; 18.7 ± 1.6; 10.6 ± 1.9, respectively for the virulent B. bovis T3Bo strain. The differences found between the two strains were not statistically significant. Importantly, these drugs displayed low levels of toxicity for the host erythrocytes and bovine renal arterial endothelial cells at the doses tested. The demonstrated ability of trifluralin analogues to inhibit in vitro growth of B. bovis parasites combined with their low toxicity for host cells suggests that these compounds may be further developed as novel alternatives for the treatment of bovine babesiosis.

Targeted and intracellular triggered delivery of therapeutics to cancer cells and the tumor microenvironment: impact on the treatment of breast cancer.

Limiting tumor invasion to the surrounding healthy tissues has proven to be clinically relevant for anticancer treatment options. We have demonstrated that, within a solid tumor, it is possible to achieve such a goal with the same nanoparticle by intracellular and triggered targeted drug delivery to more than one cell population. We have identified the nucleolin receptor in endothelial and cancer cells in tissue samples from breast cancer patients, which enabled the design of a F3-peptide-targeted sterically stabilized pH-sensitive liposome. The clinical potential of such strategy was demonstrated by the successful specific cellular association by breast cancer cells harvested from tumors of patients submitted to mastectomy. In vitro, the nanoparticle targeted the nucleolin receptor on a cell and ligand-specific manner and improved cytotoxicity of doxorubicin (used as a model drug) towards breast cancer and endothelial cells by 177- and 162-fold, respectively, relative to the commercially available non-targeted non-pH-sensitive liposomes. Moreover, active accumulation of F3-targeted pH-sensitive liposomes into human orthotopic tumors, implanted in the mammary fat pad of nude mice, was registered for a time point as short as 4 h, reaching 48% of the injected dose/g of tissue. Twenty-four hours post-injection the accumulation of the dual-targeted pH-sensitive nanoparticle in the tumor tissue was 33-fold higher than the non-targeted non-pH-sensitive counterpart. In mice treated with the developed targeted nanoparticle significant decrease of the tumor viable rim area and microvascular density, as well as limited invasion to surrounding healthy tissues were observed (as opposed to other tested controls), which may increase the probability of tumors falling in the category of "negative margins" with reduced risk of relapse.

Synthesis, stability, biochemical and pharmacokinetic properties of a new potent and selective 4-oxo-ß-lactam inhibitor of human leukocyte elastase.

The 4-oxo-ß-lactams (azetidine-2,4-diones) are potent acylating agents of the human leukocyte elastase (HLE), a neutrophil serine protease that plays a key role in several inflammatory diseases. A novel 4-oxo-ß-lactam containing a N-(4-(phenylsulphonylmethyl)phenyl) group, 3, was designed as a potential mechanism-based inhibitor capable of undergoing elimination of phenylsulphinate upon Ser-195 acylation. Compound 3 was found to be a potent slow-tight binding inhibitor of HLE, presenting a remarkable second-order rate constant of 1.46 x 106 M⁻¹s⁻¹ and displaying selectivity over the proteinase 3 and cathepsin G. However, liberation of phenylsulphinate was not observed in the hydrolysis of 3 in both pH 7.4 phosphate buffer and human plasma. The C(max) values of 1207 µg/total blood, 179 µg/g spleen and 106 µg/g lung were determined by HPLC, following a single 30 mg/kg dose of 3 given intraperitoneally to NMRI mice, suggesting that the inhibitor distributes well into tissues. Although being a powerful selective inhibitor of HLE, 4-oxo-ß-lactam 3 has a limited stability, being susceptible to off-target reactions (plasma and liver enzymes).

ación del child-pugh y sodio sérico en pacientes con diagnóstico de cirrosis hepática en el servicio de gastroenterología Dr. Alí Rivas. Hospital Jesús Yerena, Lídice: Años 2002-2006

La clasificación de Child-Pugh mide la severidad de la enfermedad hepática crónica en pacientes con cirrosis hepática. El nivel de sodio (Na) sérico en estos pacientes disminuye a medida que progresa la enfermedad hepática. Objetivo: determinar la relación de la severidad de la enfermedad hepática crónica medida con la escala de Child-Pugh, con el nivel de sodio sérico. Metodología: se realizó un estudio retrospectivo descriptivo, analizando las historias clínicas de los pacientes evaluados en las consultas externas y hospitalizados en el servicio de Gastroenterología del Hospital "Jesús Yerena" de Lídice entre los años 2002 y 2006. Se calculó el puntaje de Child-Pugh a cada paciente, y luego se relacionó con los valores séricos de Na. Resultados: se hallaron 12 pacientes (24,49%) en la categoría Child- Pugh A, 21 (42,86%) clase B, y 16 (32,65%) clase C. Se encontró una relación inversa en cuanto al nivel sérico de Na y el puntaje de Child-Pugh. Conclusión: La severidad de la enfermedad hepática crónica, medida por la escala Child-Pugh, es inversamente proporcional con en nivel de Na sérico de estos paciente.

The Child-Pugh classification assesses the severity of chronic hepatic disease in patients with hepatic cirrhosis. Serum sodium level in these patients decreases along with the severity of the hepatic disease. Objective: to determine the relationship between the severity of chronic hepatic disease, measured with the Child-Pugh scale, and serum sodium levels. Methods: we made a retrospective descriptive study, analyzing the clinical history of outpatients and hospitalized patients of the Gastroenterology Service of "Jesús Yerena Hospital of Lidice" between 2002 and 2006. We calculated the Child-Pugh scale of each patient, and then correlated it to serum sodium levels. Results: we found 12 patients (24, 49%) in the Child- Pugh A category, 21 (42, 86%) in the class B category, and 16 (32, 65%) in the class C category. They all had an inverse relationship with serum sodium levels. Conclusion: the severity of chronic hepatic disease, measured in the Child-Pugh scale, is inversely proportional to the serum sodium level in these patients.

The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model.

There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E2) serum concentrations during the estrous cycle. The results indicate that ULO effects on E2 concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation. Perforation of the left peritoneum resulted in lower E2 serum concentrations in the three stages of the estrous cycle. At proestrus, unilateral or bilateral perforation of the peritoneum resulted in lower E2 serum concentrations.ULO of the right ovary (left ovary in situ) resulted in significantly higher E2 concentrations than animals with ULO of the left ovary (right ovary in situ). ATR treatment to ULO rats on D1 resulted in a significant drop of E2 serum concentrations. ULO rats treated with ATR on D2 or P, resulted in an asymmetrical E2 secretion response; when the right ovary remained in situ an increase in E2 was observed, and a decrease when the left ovary remained in situ. The results obtained in the present study suggest that each ovary's ability to compensate the secretion of E2 from the missing ovary is different and varies during the estrous cycle. The results also suggest that the cholinergic system participates in regulating ovarian E2 secretion. Such participation varies according to the ovary remaining in situ and the stage of the estrous cycle of the animal. The results agree with previously stated hypothesis of a neural pathway arising from the peritoneum that participates in regulating E2 secretion, and also supports the idea of cross-talk between the ovaries, via a neural communication, that modulates E2 secretion.

c-fos and estrogen receptor gene expression pattern in the rat uterine epithelium during the estrous cycle.

Different studies in ovariectomized estrogen treated animals support the idea that c-fos plays a role in the proliferation of uterine epithelial cells. However, these studies invite us to reassess the role played by c-fos in epithelial cell types of the endometrium during the estrous cycle. The present study was undertaken to determine the c-fos and estrogen receptor (ER) gene expression pattern in the rat uterine epithelium during the estrous cycle in which natural and cyclic changes of steroid hormones occur, and correlate these changes with the proliferation status of this cellular types. Proliferation was assessed during the estrous cycle using bromodeoxyuridine incorporation to DNA. ERalpha and beta proteins were assessed by immunohistochemistry. The regulation of c-fos gene expression in the uterus of intact animals during the estrous cycle was evaluated using both in situ hybridization and immunohistochemistry. Estradiol (E(2)) and progesterone (P(4)) plasma levels were assessed by radioimmunoassay. The results indicated that luminal (LE) and glandular epithelia (GE) presented maximal proliferation during the metestrus (M) and the diestrus (D) days. However, during the proestrus (P) day only LE presented proliferation, and during the estrus (E) day only the stromal cells proliferated. A marked immunostaining for ERalpha was detected in both LE and GE cells during the early phases of the cycle but diminished on the P and the E day. In contrast, ERbeta was undetectable in both epithelia during all stages of the cycle. The highest c-fos mRNA level was detected in both epithelia on the M day, followed by a significant reduction during the other days of the cycle. The highest protein content was observed on the M and D days, and the minimal value was detected on the E day. The c-Fos protein level in LE was increased during M and D days, presenting a high correlation with the cellular proliferation pattern of this cell type. In conclusion, the overall results indicate that c-Fos protein presented a good correlation with uterine epithelial cell proliferation of LE. In the case of GE, the same tendency was observed, although no significant correlation was found. Both in LE and GE, c-fos mRNA did not strictly correlate with its protein levels. c-fos seems to have a postranscriptional regulation in uterine epithelial cells during the rat's estrous cycle.

Tratamento de cáries incipientes: estudo experiemental sobre remineralização de "manchas brancas" / Treatment of incipient caries: experimental study of remineralisation of white spot lesions

Neste trabalho testamos clinicamente 6 tratamentos para remineralização de cáries incipientes em crianças de 7 a 15 anos e de ambos os sexos. Também estabelecemos alguns critérios básicos para o diagnóstico e a avaliação clínica das lesões. Os resultados estatísticos comprovaram a eficácia dos tratamentos com 8 semanas de aplicação