The examination of the nephroprotective effect of montelukast sodium and N-acetylcysteine in renal ischemia with dimercaptosuccinic acid imaging in a placebo-controlled rat model

Abstract Purpose To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia. Methods Twenty-seven rats were randomly divided into 3 study groups, which received NAC, montelukast and placebo, and 3 rats were included in the sham-treated control group. Medications were given 3 days before the procedure. DMSA renal scintigraphy was performed before and after surgery. The right renal pedicle was occluded for 45 min to induce ischemia and then subjected to reperfusion for 6 h (I/R groups). Results On pathological examination, the mean pathological scores of the montelukast and NAC groups were significantly lower than those of the placebo group. (p <0.05). In biochemical examination, significant differences were found in all parameter levels between the placebo group and the montelukast and NAC groups. (p <0.05) When postoperative DMSA renal scintigraphy measurements and renal function levels were compared, significant differences were found between the montelukast and NAC groups and the placebo and sham groups. Conclusion The administration of NAC and montelukast sodium was seen to have a nephroprotective effect against the development of renal damage associated with warm renal ischemia.

The NK1 receptor antagonist NKP608 inhibits proliferation of human colorectal cancer cells via Wnt signaling pathway

BACKGROUND: Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism. METHODS: The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot. RESULTS: In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, ß-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3. CONCLUSIONS: Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/ß-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.

Antioxidant effect of quinoline derivatives containing or not selenium: Relationship with antinociceptive action quinolines are antioxidant and antinociceptive

ABSTRACT The present study investigated the antioxidant effect of a new class of quinoline derivatives (a-d) on assays in vitro. Lipid peroxidation, thiol peroxidase-like and free radical scavenging activities were determined to evaluate antioxidant activity of compounds. Thiol oxidase-like and δ-aminolevulinate dehydratase activities were performed as a toxicological parameter. A second objective of this study was to evaluate the in vivo antinociceptive effect of the compound with better antioxidant effect and without toxic effects in a model of nociception induced by formalin in mice. In liver, at 100 µM, compound a reduced the lipid peroxidation to the control levels, while compounds c and d partially reduced it. In brain, only compound d partially reduced the lipid peroxidation at 50 and 100 µM. Compound b did not have an effect on the lipid peroxidation. Thiol peroxidase-like and free radical scavenging activities are not involved in the antioxidant mechanisms of these compounds. Compounds did not present thiol oxidase-like activity and effect on the δ-aminolevulinate dehydratase. In vivo experiments showed that compound a caused an inhibition of licking time in the first and second phases, and edema formation induced by formalin. In conclusion, quinoline derivative without selenium presented better in vitro antioxidant effect and in vivo antinociceptive activity.

The beneficial effects of Montelukast against 2 3 7 8 tetrachlorodibenzo dioxin toxicity in female reproductive system in rats

ABSTRACT PURPOSE: To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis. METHODS: Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed. RESULTS: The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment. CONCLUSION: The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.

Montelukast reduces seizures in pentylenetetrazol-kindled mice

Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.

Dual-Blocking of PI3K and mTOR Improves Chemotherapeutic Effects on SW620 Human Colorectal Cancer Stem Cells by Inducing Differentiation

Cancer stem cells (CSCs) have tumor initiation, self-renewal, metastasis and chemo-resistance properties in various tumors including colorectal cancer. Targeting of CSCs may be essential to prevent relapse of tumors after chemotherapy. Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signals are central regulators of cell growth, proliferation, differentiation, and apoptosis. These pathways are related to colorectal tumorigenesis. This study focused on PI3K and mTOR pathways by inhibition which initiate differentiation of SW620 derived CSCs and investigated its effect on tumor progression. By using rapamycin, LY294002, and NVP-BEZ235, respectively, PI3K and mTOR signals were blocked independently or dually in colorectal CSCs. Colorectal CSCs gained their differentiation property and lost their stemness properties most significantly in dual-blocked CSCs. After treated with anti-cancer drug (paclitaxel) on the differentiated CSCs cell viability, self-renewal ability and differentiation status were analyzed. As a result dual-blocking group has most enhanced sensitivity for anti-cancer drug. Xenograft tumorigenesis assay by using immunodeficiency mice also shows that dual-inhibited group more effectively increased drug sensitivity and suppressed tumor growth compared to single-inhibited groups. Therefore it could have potent anti-cancer effects that dual-blocking of PI3K and mTOR induces differentiation and improves chemotherapeutic effects on SW620 human colorectal CSCs.

Neuropsychomotor developmental delay: conceptual map, term definitions, uses and limitations / Atraso do desenvolvimento neuropsicomotor: mapa conceitual, definições, usos e limitações do termo

OBJECTIVE: To retrieve the origin of the term neuropsychomotor developmental delay" (NPMD), its conceptual evolution over time, and to build a conceptual map based on literature review. DATA SOURCE: A literature search was performed in the SciELO Brazil, Web of Science, Science Direct, OneFile (GALE), Pubmed (Medline), Whiley Online, and Springer databases, from January of 1940 to January of 2013, using the following keywords: NPMD delay, NPMD retardation, developmental delay, and global developmental delay. A total of 71 articles were selected, which were used to build the conceptual map of the term. DATA SYNTHESIS: Of the 71 references, 55 were international and 16 national. The terms developmental delay and global developmental delay were the most frequently used in the international literature and, in Brazil, delayed NPMD was the most often used. The term developmental delay emerged in the mid 1940s, gaining momentum in the 1990s. In Brazil, the term delayed NPMD started to be used in the 1980s, and has been frequently cited and published in the literature. Delayed development was a characteristic of 13 morbidities described in 23 references. Regarding the type of use, 19 references were found, with seven forms of use. Among the references, 34 had definitions of the term, and 16 different concepts were identified. CONCLUSIONS: Developmental delay is addressed in the international and national literature under different names, various applications, and heterogeneous concepts. Internationally, ways to improve communication between professionals have been indicated, with standardized definition of the term and use in very specific situations up to the fifth year of life, which was not found in Brazilian publications. .

OBJETIVO: Resgatar a origem do termo atraso do desenvolvimento neuropsicomotor (DNPM), sua evolução conceitual ao longo do tempo e construir mapa conceitual do termo com base em busca bibliográfica. FONTES DE DADOS: Foi realizada busca nas bases de dados eletrônicas do Portal da Capes, que incluem Scielo Brazil, Web of Science, Science Direct, OneFile (GALE), Pubmed (Medline), Whiley Online e Springer, referente a Janeiro/1940-Janeiro/2013. Palavras-chave: atraso e retardo do DNPM, developmental delay e global developmental delay. Foram selecionados 71 artigos e construído o mapa conceitual do termo. SÍNTESE DE DADOS: Das 71 referências, 55 eram internacionais e 16 nacionais. Os termos mais encontrados foram global developmental delay e developmental delay na literatura internacional e retardo e atraso do DNPM no Brasil. Internacionalmente, o termo surgiu em meados da década de 40 ganhando força nos anos 90. No Brasil, o termo começou a ser usado na década de 80 e vem sendo frequentemente citado na literatura. O atraso é citado em 23 trabalhos como característica presente em 13 tipos de condições clínicas. Com relação ao uso, foram encontrados 19 estudos, com sete situações de uso. Dentre os artigos revisados, 34 deles apresentaram definições, sendo identificados 16 conceitos diferentes. CONCLUSÕES: O atraso do desenvolvimento é abordado na literatura internacional e nacional sob diversos nomes, diferentes aplicações e conceitos heterogêneos. Internacionalmente, apontam-se caminhos para melhorar a comunicação entre profissionais, com definição padronizada do termo e uso em situações específicas até o quinto ano de vida, o que não foi encontrado nas publicações nacionais. .

Effects of Interleukin-13 and Montelukast on the Expression of Zonula Occludens-1 in Human Podocytes

PURPOSE: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 restoration in cultured human podocytes. MATERIALS AND METHODS: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and then examined for distribution using confocal microscopy and for ZO-1 protein levels using Western blotting. RESULTS: ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 h (both p<0.01; n=3), which were significantly reversed by a high dose (0.5 microM) montelukast treatment (p<0.01; n=3). CONCLUSION: Our results suggest that IL-13 alters the expression of ZO-1, and such alterations in the content and distribution of ZO-1 may be relevant in the pathogenesis of proteinuria in the MCNS model.

Effects of Interleukin-13 and Montelukast on the Expression of Zonula Occludens-1 in Human Podocytes

PURPOSE: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 restoration in cultured human podocytes. MATERIALS AND METHODS: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and then examined for distribution using confocal microscopy and for ZO-1 protein levels using Western blotting. RESULTS: ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 h (both p<0.01; n=3), which were significantly reversed by a high dose (0.5 microM) montelukast treatment (p<0.01; n=3). CONCLUSION: Our results suggest that IL-13 alters the expression of ZO-1, and such alterations in the content and distribution of ZO-1 may be relevant in the pathogenesis of proteinuria in the MCNS model.

Compuestos sintéticos del tipo de estirilquinolinas con actividades leishmanicida y citotóxica / Styrylquinolines-type synthetic compounds with leishmanicidal and cytotoxic activities

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Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits / O Efeito da Pitavastatina na Reatividade Vascular em Coelhos Hipercolesterolêmicos

Background: 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. Objective: 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. Methods: 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%. Results: 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. Conclusion: Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits. .

Fundamento: A pitavastatina é a mais nova estatina disponível no Brasil e com prováveis menores efeitos colaterais. Assim, a pitavastatina foi avaliada em coelhos hipercolesterolêmicos em relação à ação na reatividade vascular. Objetivo: Investigar a menor dose de pitavastatina na redução dos lípides plasmáticos, colesterol e peroxidação lipídica tecidual e função endotelial em coelhos hipercolesterolêmicos. Métodos: Trinta coelhos divididos em seis grupos (n=5): G1 - dieta ração padrão; G2 - dieta hipercolesterolêmica por 30 dias; G3 - dieta hipercolesterolêmica e a partir do 16º dia suplementada com pitavastatina (0,1 mg); G4 - dieta hipercolesterolêmica e suplementada com pitavastatina (0.25 mg); G5 - dieta hipercolesterolêmica e suplementada com pitavastatina (0,5 mg); G6 - dieta hipercolesterolêmica e suplementada com pitavastatina (1,0 mg). Após 30 dias foram dosados o colesterol total, HDL, triglicérides, glicose, creatinoquinase, aspartato aminotransferase, alanina aminotransferase e o LDL calculado. Aprofundada a anestesia com tiopental sódico e retirado segmentos de aorta para estudo da função endotelial, colesterol e peroxidação lipídica tecidual. O nível de significância adotado para os testes estatísticos foi 5%. Resultados: Colesterol total e LDL elevados significativamente em relação ao G1. HDL reduzida significativamente em G4, G5 e G6 em relação ao G2. Triglicérides, creatinoquinase, aspartato aminotransferase, alanina aminotransferase, colesterol e peroxidação lipídica tecidual sem diferença estatística entre G3-G6 e G2. Disfunção endotelial revertida significativamente em G5 e G6 em relação ao G2. Conclusão: A pitavastatina, a partir da ...

Inhibition of phospholipase D2 induces autophagy in colorectal cancer cells

Autophagy is a conserved lysosomal self-digestion process used for the breakdown of long-lived proteins and damaged organelles, and it is associated with a number of pathological processes, including cancer. Phospholipase D (PLD) isozymes are dysregulated in various cancers. Recently, we reported that PLD1 is a new regulator of autophagy and is a potential target for cancer therapy. Here, we investigated whether PLD2 is involved in the regulation of autophagy. A PLD2-specific inhibitor and siRNA directed against PLD2 were used to treat HT29 and HCT116 colorectal cancer cells, and both inhibition and genetic knockdown of PLD2 in these cells significantly induced autophagy, as demonstrated by the visualization of light chain 3 (LC3) puncta and autophagic vacuoles as well as by determining the LC3-II protein level. Furthermore, PLD2 inhibition promoted autophagic flux via the canonical Atg5-, Atg7- and AMPK-Ulk1-mediated pathways. Taken together, these results suggest that PLD2 might have a role in autophagy and that its inhibition might provide a new therapeutic basis for targeting autophagy.

Binding chemistry and molecular heterogeneity of neurotensin binding protein(s)/receptor in adult chicken tissues.

The study focuses on the importance of Tyr11 amino acid (AA) and subsequent stereochemistry involved in the binding process of neurotensin (NT) with its receptor (NTR)/binding protein(s) as well as the size heterogeneity. Using the binding of 125I-NT with several chicken tissues, it is identified that one of the crucial factors behind all high affinity (Kd ~10 pM) interactions is due to phenolic-OH (Φ-OH) at the para (p) position of Tyr11 within RRPYIL-CO2H (NT8-13) sequence. Replacing the p-OH only in Tyr11 by substituting with p-Cl, p-F and p-NH2 results in significant change of the binding affinity (Kd); p-OH ≈ p-NH2 (~10 pM), p-Cl (~100 pM), p-F (~120 pM). Interestingly, p-NH2 equals to p-OH displaying the highest affinity. Experiments conducted by binding several of the 125I-azido–NT analogs having azido group attached at different positions within the NT molecule have further confirmed the necessity of RRPYIL sequence for high affinity ligand-receptor interaction. The role of Tryp11 in place of Tyr11 in addition to the results above establishes a significant possibility of H–bonding occurring between p-OH of NT and NTR inside the docking space. Photo labeling of the liver tissue by substituted 125I-Y3-azido-NT analogs shows several specifically labeled bands with considerable range of molecular weight (Mr ~90-30 kDa) variations. These results indicate the existence of molecular heterogeneity concerning the sizes of NTR or else any NT binding proteins in the avian tissues. Further, the study has revealed that besides liver, several other chicken tissues also express similar specific high affinity binding (Kd ~20 pM) with varying capacities (Bmax). The order for Bmax is: liver (1.2 pMol/mg) gall bladder (1.03 pMol/mg) > spleen (0.43 pMol/mg) > brain (0.3 pMol/mg) > colon lung (0.15 pMol/mg). In all cases, the binding was reduced by GTPgS (ED50 ~ 0.05 nM), NEM (ED50 ~ 0.50 mM) and NaCl (ED50 ~30 mM), indicating the existence of NTR identical to the mammalian type-1.

Efficacy and Safety of Montelukast Plus Fexofenadine Fixed Dose Combination in Allergic Rhinitis : Results of Post-Marketing Study In India.

Background:Allergic rhinitis is one of the most common conditions in clinical practice. Motelukast and second generation antihistamine fexofenadine are routinely used in the management of allergic rhinitis. Individually both drugs have been found to be effective in allergic rhinitis. Fixed dose combination of montelukast 10 mg plus fexofenadine 120 mg is available in India is also used in the treatment of allergic rhinitis. Objective: To evaluate the efficacy and safety of montelukast and fexofenadine fixed dose combination in the management of patients with allergic rhinitis. Material and methods: Post marketing observational study was conducted in 809 patients from all over India. All the patients were treated with montelukast 10 mg plus fexofenadine 120 mg fixed dose combination once daily for 14 days. The primary outcome criteria was the change in total symptom score (Sum of total nasal symptom score and total ocular symptom score) at the end of study compared to baseline. The secondary outcome criteria included change in total nasal symptom score (nasal congestion, rhinorrhea, nasal itching, and sneezing) and total ocular symptom score (Itching/burning eyes, tearing/ watering eyes and eye redness) at the end of study compared to baseline and physician’s and patient’s global assessment for efficacy and tolerability. The patients were evaluated at baseline, day 7 and day 14 for efficacy evaluation while the safety parameters were assessed at screening and day 14. Results: The fixed dose combination of fexofenadine plus montelukast was significantly effective in reducing total symptom score, total nasal symptom score and total ocular symptom score (p<0.0001 for all parameters). The global assessment of efficacy evaluation by both patient and investigators demonstrated “excellent to good” efficacy in >95% of patients. Most of the study population reported “good” tolerability with the fixed drug combination. No adverse events were reported in the study. Conclusion: The fixed dose combination of fexofenadine plus montelukast was found to be efficacious and well tolerated in allergic rhinitis in Indian adult patients.

Síntesis y evaluación preliminar de la posible actividad antimalárica y antineoplásica de derivados 7-cloroquinolina-4-sustituidos / Synthesis and preliminary evaluation of antimalarial and antineoplastic possible activity of 7-chloroquinoline-4-substituted derivatives

En el presente trabajo se describe la síntesis y la evaluación de la posible actividad Antimalárica y Antineoplásica de una serie de derivados 7-cloroquinolina-4-sustituidos. La estrategia empleada para la síntesis comienza con las obtención de los intermediarios clave 1-(3 ó 4-(7-cloroquinolin-4-ilamino)fenil)etanona (2 y 3) mediante una sustitución nucleofílica aromática entre la 4,7-dicloroquinolina y la 3 y/o 4-amino acetofenona. Los derivados (E)-1-(3 ó 4-(7-cloroquinolin-4-ilamino)fenil)-3-(fenilsustituido)prop-2-eno-1-ona (4 y 5), se sintetizaron a través de una condensación aldólica de Claisen-Schmidt entre los intermediarios clave y diferentes benzaldehídos sustituidos. Los derivados 7-cloro-N-(3 ó 4-(4,5-dihidro-5-(fenilsustituido)-1H-pirazol-3-il)fenil)quinolin-4-amina (6 y 7) y los 1-(3 ó 4-(7-cloroquinolin-4-ilamino)fenil)-3-(fenilsustituido)propano-1-ona (8 y 9) se diseñaron por modificación molecular de la cetona a,b-insaturada de los compuestos finales 4 y 5, (metodología clásica de la Química Medicinal) para obtener dichos derivados rígidos 6 y 7, mediante la formación de un anillo D2-pirazolina y flexibles 8 y 9, a través de su reducción. La síntesis de los derivados 6 y 7 se realizó mediante una reacción de ciclo-condensación con hidrazina monohidratada y los derivados 8 y 9, se obtuvieron a través de una hidrogenación catalítica. En la evaluación de la actividad Antimalárica in vitro se evidenció que los derivados 4, 5, 6 y 7, mostraron actividades inhibitorias la formación de la b hematina importantes (superior al 70 %), siendo los más activos: 4l, 5g, 5c, 5g y 6e, 6f con valores comparable al de la CQ. En la evaluación Antimalárica in vivo se encontró que el derivado 4e fue el más activo con 26,4 días de sobrevivencia post-infección (230 % de incremento) y una parasitemia de 2,4 % (96 % de reducción). Con respecto a los resultados obtenidos en el efecto de estos derivados sobre la viabilidad y proliferación de las líneas celulares neoplásicas Jurkat E6.1, HL60, MCF-7 y A549, los compuestos 4a, 4g, 4l, 4m y 6e mostraron la mayor actividad inhibitoria del crecimiento de las células leucémicas HL60 después de 24h de tratamiento con valores de CI50 de 1,19 µM, 1,08 µM, 0,59 µM, 0,43 µM y 0,94 µM (hasta 3 y 100 veces más activos que la doxorubicina y que la CQ, respectivamente). En lo referente a la evaluación de la actividad proapoptótica en las líneas celulares neoplásicas Jurkat E6.1, HL60, MCF-7 y A549, se evidenció que los derivados 4, 5 y 6, al igual que los controles, generaron un aumento en el porcentaje de células positivas para la Anexina V/FITC dependiente de la dosis (apoptosis temprana y tardía). Ninguno de estos derivados indujo el proceso de necrosis en estas células.

The present investigation describes the synthesis and evaluation of the Antimalarial and Antineoplastic activity possible a series of derivatives of 7-substituted-4-chloro-quinoline. The strategy employed for the synthesis begins with preparation of the key intermediate 1-(3 or 4-(7-chloroquinolin-4-ylamino) phenyl)ethanone (2and 3) by a nucleophilic aromatic substitution between 4,7-dichloroquinoline and the 3 and/or4-amino acetophenone. The derivatives (E)-1-(3 or 4-(7-chloroquinolin-4-ylamino) phenyl)-3-(substitutedphenyl)prop-2-en-1-one (4and 5), were synthesized a through aldol condensation Claisen-Schmidt among different key intermediates and substituted benzaldehydes. The resulting 7-chloro-N-(3 or 4-(4,5-dihydro-5-(substitutedphenyl)-1H-pyrazol-3-yl)phenyl)quinolin-4-amine (6 and 7) and 7-chloro-4-[(3 or 4-(substituted phenyl)ethylcarbonyl)phenyl]aminoquinoline(8 and 9) were designed for the molecular modification , -unsaturated ketone of the final compounds 4and 5 (classic methodology Medicinal Chemistry) for said rigid derivatives 6and 7, through the formation of a 2-pyrazoline ring flexible and 8and 9, through its reduction. The synthesis of derivatives 6and 7were performed using a cycle-condensation reaction with hydrazine monohydrate and 8and 9derivatives were obtained via a catalytic hydrogenation. In the assessment of antimalarial activity in vitro was demonstrated that derivatives 4, 5, 6and 7showed inhibitory activities forming the major hematin (above 70%), being more active: 4l, 5g, 5c, 5g, 6eand 6f,with values comparable to that of CQ. In vivoantimalarial evaluation found that the derivative 4ewas most active with survival 26.4 dayspost-infection (230% increase) and a parasitemia of 2.4% (96% reduction). With regard to the results on the effect of these derivatives on the viability and proliferation of neoplastic cell lines Jurkat E6.1, HL60, MCF-7 and A549, compounds 4a, 4g, 4l,4mand 6eshow greater activity growth inhibitory HL60 leukemia cells after 24 h of treatment with IC50values of 1.19µM, 1.08µM, 0.59µM, 0.43µMand 0.94 M (to 3 and 100 times more active than doxorubicin and the CQ, respectively). Regarding the evaluation of pro-apoptotic activity on neoplastic cell lines Jurkat E6.1, HL60, MCF-7 and A549, was demonstrated that derivatives 4, 5and 6, like the controls, an increase in generated percentage of cells positive for Annexin V/FITC dose dependent (early andlate apoptosis). None of these derivatives induced necrosis process in these cells.

Comparision of efficacy of levocetirizine with montelukast and levocetirizine alone in persistent allergic rhinitis

To compare the efficacy of levocetirizine with montelukast and levocetirizine alone in patients with persistent allergic rhinitis in our setup. Patients with symptoms of AR attending ENT clinic were registered and divided into two groups based on drug given. Patients with odd numbers were included in group A receiving levocetirizine 5mg with montelukast 10mg once daily while patients with even numbers were included in group B receiving only levocetirizine 5mg once daily. Data was collected at visit 1 prior to medication, visit 2 one week after medication and visit 3 two weeks after medication. Medication history review, nasal symptom assessment and anterior rhinoscopy were done at each visit. Patients were evaluated for rhinorrhea, sneezing, nasal itching and nasal obstruction on a scale. Total symptom complex score [TSCS] was calculated by adding scores of all four variables under study using proforma. Lower the score more effective will be the drug. One hundred twenty four patients were included in study; 63 were male and 61 were female. TSCS was 9 -10 in 73.3% patients at visit 1 in levocetirizine + montelukast group that improved to 4-5 in 28.3% and 3- 4 in 65% patients at visit 2 and 3 respectively. Patients receiving levocetirizine alone had TSCS of 9 to 10 in 52.9% at visit 1 with an improvement to 3-4 in 9.4% and 49.1% at visit 2 and visit 3 respectively. Levocetirizine with montelukast is superior to levocetirizine alone in controlling overall symptoms of AR.

Streptococcus pneumoniae: sensibilidade a penicilina e moxifloxacina / Streptococcus pneumoniae: susceptibility to penicillin and moxifloxacin

OBJETIVO: Determinar a concentração inibitória mínima (CIM) de penicilina parenteral e moxifloxacina contra cepas de Streptococcus pneumoniae isoladas em um centro hospitalar. Métodos: Estudo in vitro prospectivo de 100 isolados de S. pneumoniae coletados de pacientes tratados entre outubro de 2008 e julho de 2010 no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, em São Paulo (SP). Os isolados foram obtidos de culturas do trato respiratório e de amostras de sangue não relacionadas a infecções meníngeas e foram testados quanto à suscetibilidade a penicilina e moxifloxacina por E test. As interpretações categóricas de CIM foram baseadas em padrões atualizados. RESULTADOS: Todos os isolados foram suscetíveis a penicilina parenteral (CIM < 2 µg/mL) e, consequentemente, eram também suscetíveis a amoxicilina, ampicilina, cefalosporinas de terceira e quarta geração e ertapenem. Quanto à moxifloxacina, 99 por cento das cepas de S. pneumoniae também foram suscetíveis, e somente uma teve CIM = 1,5 µg/mL (intermediário). Conclusões: Nossos resultados mostraram altas taxas de sensibilidade a penicilina parenteral e moxifloxacin nos isolados de S. pneumoniae não relacionados a meningite, o que difere de relatos internacionais. Relatos sobre resistência a penicilina devem ser baseados em pontos de corte atualizados para isolados não relacionados a meningite a fim de guiar a escolha terapêutica antimicrobiana e melhorar a predição dos desfechos clínicos.

OBJECTIVE: To determine the minimum inhibitory concentrations (MICs) of parenteral penicillin and moxifloxacin against Streptococcus pneumoniae strains isolated at a hospital center. METHODS: In-vitro, prospective study involving 100 S. pneumoniae isolates collected from patients who had been treated, between October of 2008 and July of 2010, at the Hospital das Clínicas complex of the University of São Paulo School of Medicine, located in the city of São Paulo, Brazil. The isolates were obtained from respiratory tract cultures or blood samples unrelated to meningeal infections, and they were tested for penicillin and moxifloxacin susceptibility by E-test. The MIC category interpretations were based on updated standards. RESULTS: All isolates were fully susceptible to parenteral penicillin (MIC < 2 µg/mL), and, consequently, they were also susceptible to amoxicillin, ampicillin, third/fourth generation cephalosporins, and ertapenem. Of the S. pneumoniae strains, 99 percent were also susceptible to moxifloxacin, and only one strain showed an MIC = 1.5 µg/mL (intermediate). CONCLUSIONS: Our results showed high susceptibility rates to parenteral penicillin and moxifloxacin among S. pneumoniae isolates unrelated to meningitis, which differs from international reports. Reports on penicillin resistance should be based on updated breakpoints for non-meningitis isolates in order to guide the selection of an antimicrobial therapy and to improve the prediction of the clinical outcomes.

Regional Difference of Antibiotic Resistance of Helicobacter pylori Strains in Korea / 대한소화기학회지

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.

Regional Difference of Antibiotic Resistance of Helicobacter pylori Strains in Korea / 대한소화기학회지

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.

Flora conjuntival y sensibilidad antibiótica en pacientes a ser sometidos a cirugía de catarata y LASIK / Antibiotic susceptibility of bacterial conjunctival flora isolated from patients undergoing LASIK and cataract surgery

Objetivo: Conocer y proveer de evidencia acerca de la sensibilidad de la flora bacteriana normal de la superficie ocular aislada en dos diferentes grupos sociales y etáreos de pacientes prontos a someterse a cirugía de Catarata y LASIK en nuestro país. Materiales y Métodos: Se cultivaron muestran conjuntivales de 221 pacientes previo a LASIK y de 180 pacientes de un grupo de Cataratas. De haber un cultivo positivo se realizó aislamiento e identificación bacteriana utilizando la técnica de difusión en disco de Kirby-Bauer para doce antibióticos. El análisis estadístico se hizo con chi-cuadrado y el test exacto de Fisher. Resultados: Hubo 66,8 por ciento de cultivos positivos, más frecuentemente gran positivos. SCN fue el aislado en mayor porcentaje (92,2 por ciento) y mostró una alta sensibilidad a Cloramfenicol, Tobramicina, Moxifloxacino y Gatifloxacino, intermedia para Levofloxacino, Gentamicina y Ciprofloxacino y menor para Eritromicina, Oxacilina, Cefalotina y Ceftriaxona (p<0,01). Todos los cultivos fueron sensibles a Vancomicina. No hubo diferencia estadísticamente significativa entre ambos grupos. Conclusiones: 1. Por primera vez nuestros resultados muestran que la flora y sensibilidad antibiótica son similares en pacientes a ser sometidos a LASIK y Catarata, siendo los SCN los más frecuentemente encontrados en ambos grupos de pacientes. 2. Las bacterias más comúnmente aisladas permanecen altamente sensibles a Cloramfenicol, Tobramicina, Moxifloxacino y Gatifloxacino.

Purpose: To know and provide a background on antibiotic susceptibility of normal ocular surface bacterial flora isolated from two different social and age groups of patients undergoing LASIK and cataract surgery in our country. Material and Methods: Conjunctival samples of 221 patients in a LASIK group and 180 patients in a cataract surgery group were cultivated. When there were a positive cultures, isolation and identification of the bacteria were made and antibiotic susceptibility tests were carried out, using the Kirby-Bauer disc diffusion technique for twelve antibiotics. Statistical analysis was performed using chi-square and exact Fisher test. Results: There were 66.8 percent of positive cultures, most of them gram positives. The most frequently isolated bacteria were the CNS (92,2 percent) that showed high sensitivity for Chloramphenicol, Tobramycin, Moxifloxacin and Gatifloxacin, intermedia for Levofloxacin, Gentamicin and Ciprofloxacin and lowest for Erytomycin, Oxacillin, Cefalotin and Ceftriaxone (p<0,01). All the cultures were susceptible to Vancomycin. There was not statistically difference between LASIK and cataract group. Conclusions: 1. For the first time, our results have shown that the conjunctival flora and its sensitivity to antibiotics are similar in the conjunctival flora of the patients undergoing LASIK surgery and Cataract, being CNS the bacterium most frequently found in both different groups of patients. 2. The most frequently isolated conjunctival bacteria remained highly sensitive to Chloramphenicol, Tobramycin, Moxifloxacin and Gatifloxacin.