Advances in new benzimidazole formulations and their anti- Echinococcus activities / 中华地方病学杂志

Echinococcosis is a serious zoonosis parasitic disease caused by the parasitic larva of Echinococcus. Surgical treatment, as the preferred treatment of echinococcosis, has disadvantages such as small scope of application, difficulty in complete resection, high postoperative recurrence rate and heavy burden on patients. Drug therapy is not only a necessary supplement to the preoperative, intraoperative and postoperative treatment of echinococcosis patients, but also the first choice when surgical treatment is not applicable. This article reviews the physicochemical and pharmacokinetic properties of benzimidazole drugs, and summarizes the anti- Echinococcus activities of different benzimidazole formulations, it will provide a reference for future exploration of echinococcosis treatment drugs.

A Case Of Primary Pulmonary Echinococcosis Presenting As Left Sided Gross Pleural Effusion

Invasion of the human lungs by the larvae of the dog tapeworm Echinococcus granulosus (pulmonary cystic echinococcosis, PCE) is an incapacitating disease, frequently found across a wide geographic area, CE is endemic in many parts of the world, particularly the Mediterranean countries, Central Asia including the Tibetan Plateau, Northern and Eastern Africa, Australia, and South America. [1] Global burden of the human AE is approximately 18,235 new cases per annum with the majority (91%) occurring in China. [2] We report a case of 17–year–old girl student who presented with complaints of left sided pleuritic chest pain, fever and dyspnoea. X–ray chest PA view revealed gross pleural effusion on left side that was exudative in nature and did not respond to antibiotics and anti–tuberculous therapy. HRCT chest revealed large loculated cystic lesion showing calcification in left upper lobe parenchymal region suggestive of ruptured hydatid cyst. IgG antibody for E granulosus was positive. Ultrasound scan of abdomen and pelvis were within normal limits. A diagnosis of Primary pulmonary echinococcosis was made. She was treated successfully with Albendazole 400 mg bid for 21 days; six such cycles 14 days apart

Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates

Manejo clínico de la equinococosis quística hepática, estadio CE3b, combinando tratamiento médico-estrategia de vigilancia y espera: a propósito de un caso / Clinical management of the hepatic cystic echinococcus, stage CE3b, combining medical treatment-surveillance strategy and waiting: a case report

La hidatidosis o equinococosis quística es una enfermedad zoonótica que tiene presentaciones clínicas muy heterogéneas. Los quistes sintomáticos y complicados habitualmente son resueltos mediante cirugía siguiendo las reglas de la WHO-IWGE. Sin embargo, en las formas transicionales (CE3) los criterios terapéuticos continúan en discusión. Asimismo, en quistes asintomáticos y en pacientes con alto riesgo quirúrgico, la opción del tratamiento médico con benzoimidazólicos y su combinación con la estrategia de vigilar y esperar puede ser una alternativa terapéutica segura. Se presenta un caso de hidatidosis hepática CE3b con características clínico-evolutivas excepcionales y alto riesgo quirúrgico en que se adoptó un manejo de vigilancia clínica y tratamiento con albendazol. Se analizan los beneficios y riesgos de esta terapéutica.

Cystic echinococcosis is a zoonotic disease with very heterogeneous clinical presentations. The possibility of symptomatic hepatic cysts be solved by surgery is the conduct of election. However, in asymptomatic cysts and in patients with high surgical risk, medical treatment with benzimidazolic combined with the strategy of watch and wait, may be an option to take into account. In the present work, we take as an example a case of hepatic hydatid disease with high surgical risk and analyze the potential benefits of establishing such therapeutic conduct and monitoring.

A hidatidose ou equinococose cística é uma doença zoonótica com apresentações clínicas muito heterogêneas heterogêneas. Os cistos sintomáticos e complicados de maneira geral são tratados por cirurgia de acordo com as indicações da WHO- IWGE. No entanto, nos casos de formas transicionais (CE3) os critérios terapêuticos continuam em discussão. Nos cistos assintomáticos e em pacientes com alto risco cirúrgico a opção do tratamento médico com benzoimidazolicos e sua combinação com a estratégia de vigilar e esperar, pode ser uma alternativa terapêutica segura. Apresenta-se um caso de hidatidose hepática CE3b, com características clínico-evolutivas excepcionais e alto risco cirúrgico, no qual utilizou- se um manejo de vigilância clínica e tratamento com albendazol. Os benefícios e os riscos desta terapêutica são analisados.

In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control / Suscetibilidade in vitro de fungos nematófagos à antiparasitários: interações e implicações para o controle biológico

Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animal's endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

Resumo O desenvolvimento rápido da resistência anti-helmíntica demonstrou a eficiência limitada no controle de endoparasitoses em animais, e promoveu a investigação em métodos de controles alternativos. O uso de produtos químicos no tratamento anti-helmíntico animal, em associação com fungos nematófagos utilizados para o controlo biológico, é uma estratégia que tem provado ser eficaz na redução da densidade da população de nematódeos em animais agrícolas. Este estudo teve como objetivo verificar a suscetibilidade in vitro dos fungos nematófagos Arthrobotrys oligospora, Duddingtonia flagrans e Paecilomyces lilacinus frente aos antiparasitários albendazol, tiabendazol, ivermectina, levamisol e closantel, usando a concentração inibitória mínima (MIC). Os MICs variaram entre 4,0 e 0,031 μg/mL para albendazol, tiabendazol e ivermectina, entre 0,937 e 0,117 μg/mL para o levamisol, e entre 0,625 e 0,034 μg/mL para closantel. Os resultados mostraram que todos os antiparasitários tiveram um efeito inibidor in vitro sobre os fungos nematófagos, o que poderia comprometer suas atividades como agentes de controle biológico. D. flagrans foi a espécie mais sensível a todas as drogas.

In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control

Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animals endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

Resumo O desenvolvimento rápido da resistência anti-helmíntica demonstrou a eficiência limitada no controle de endoparasitoses em animais, e promoveu a investigação em métodos de controles alternativos. O uso de produtos químicos no tratamento anti-helmíntico animal, em associação com fungos nematófagos utilizados para o controlo biológico, é uma estratégia que tem provado ser eficaz na redução da densidade da população de nematódeos em animais agrícolas. Este estudo teve como objetivo verificar a suscetibilidade in vitro dos fungos nematófagos Arthrobotrys oligospora, Duddingtonia flagrans e Paecilomyces lilacinus frente aos antiparasitários albendazol, tiabendazol, ivermectina, levamisol e closantel, usando a concentração inibitória mínima (MIC). Os MICs variaram entre 4,0 e 0,031 g/mL para albendazol, tiabendazol e ivermectina, entre 0,937 e 0,117 g/mL para o levamisol, e entre 0,625 e 0,034 g/mL para closantel. Os resultados mostraram que todos os antiparasitários tiveram um efeito inibidor in vitro sobre os fungos nematófagos, o que poderia comprometer suas atividades como agentes de controle biológico. D. flagrans foi a espécie mais sensível a todas as drogas.

Novos anticoagulantes orais (NOACs) na prevenção de acidente vascular encefálico (AVE) e fenômenos tromboembólicos em pacientes com fibrilação atrial / New oral anticoagulants (NOACs) in prevention of stroke brain and thromboembolic events in patients with atrial fibrillation

JUSTIFICATIVA E OBJETIVOS: Pacientes com fibrilação atrial (FA) estão mais propensos à ocorrência de eventos vasculares, como acidente vascular encefálico (AVE) e fenômenos tromboembólicos, sendo necessária anticoagulação oral. A varfarina, o anticoagulante mais utilizado, tem uma série de limitações referentes ao seu uso. Nesse contexto, foram desenvolvidos novos anticoagulantes orais (NOACs): inibidores da trombina (dabigatrana) e do fator Xa (rivaroxabana e apixabana). Essa revisão sistemática procurou elencar os principais resultados de Ensaios Clínicos Randomizados (ECRs) abordando o tema NOACs em pacientes com fibrilação atrial para a prevenção de acidente vascular encefálico e/ou fenômenos tromboembólicos. CONTEÚDO: Foram pesquisados Ensaios Clínicos Randomizados, cegos ou abertos, em indivíduos adultos, nas bases PubMed, Scopus, Web of Science, SciELO, LILACS e Cochrane CENTRAL. A avaliação da qualidade dos estudos foi feita utilizando a escala Downs & Black. Foram selecionados cinco Ensaios Clínicos Randomizados e descritos os seus resultados. A rivaroxabana se mostrou não inferior a varfarina no que diz respeito ao desfecho combinado embolismo sistêmico e acidente vascular encefálico, enquanto que a apixabana e a dabigatrana 150mg mostraram-se superiores. Todos os três medicamentos estiveram associados a menor incidência de hemorragia intracraniana quando comparado a varfarina. A apixabana mostrou perfil mais favorável em relação à ocorrência de qualquer sangramento. CONCLUSÕES: os Ensaios Clínicos Randomizados selecionados demonstraram a eficácia dos NOACs na prevenção de acidente vascular encefálicos e/ou embolismo sistêmico em pacientes com fibrilçao atrial. Contudo, são necessários mais estudos para preencher as lacunas do conhecimento quanto à eficácia e segurança desta nova classe de anticoagulantes orais.

BACKGROUND AND OBJECTIVES: Patients with atrial fibrillation (AF) are more likely to the occurrence of vascular events including stroke and thromboembolism systemic. Thus anticoagulation is necessary to prevent these events. Warfarin is the current gold standard but has a number of limitations regarding your use. In this context, new oral anticoagulants (NOACs) were developed: thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). The aim of this systematic review was to analyze the results of the main randomized clinical trials (RCTs) envolving NOACs in patients with atrial fibrillation for the prevention of stroke and/or thromboembolic events. CONTENTS: Double blinded or open label randomized clinical trials envolving patients with FA testing these drugs were researched in PubMed, Scopus, Web of Science, SciELO, LILACS and Cochrane CENTRAL. The quality assessment of studies used the Downs & Black Scale Five randomized clinical trials were selected, envolving 57.457 patients. Dabigatran, apixaban and rivaroxaban were at least non inferior to the warfarin in the outcome of stroke and systemic embolism. Apixaban and dabigatran 150mg were also superior than warfarin in efficacy. All three drugs were associated with a lower incidence of intracranial hemorrhage. Apixaban was related to lower risk of total bleeding. CONCLUSIONS: NOACs have efficacy to prevent AVE and systemic thromboembolism in patients with FA. However further studies are needed to resolve the issues that remain open and to provide more security to the use of these drugs in clinical practice.

Synthesis of Some New Phthalimides as Anti-metabolic Agents with Chemotherapeutic Effects.

A series of new phthalimides 1(a-f) were synthesized via reaction phthalic anhydride with different amino acids under fusion conditions. Esterification of N-phthaloyl acid derivatives 1(a-f) with methanol in the presence of SOCl2 to producing the corresponding esters 2(a-f). Which on reaction with hydrazine hydrate in boiling n-butanol afforded the corresponding N-phthaloyl acid hydrazides 4(a-f) Reaction of compound (4a) with different aldehydes and ketones yielded the corresponding hydrazone derivatives 5(a-d). Some new phthalimides linked to hetero cyclic moieties such as benzimidazoles, benzoxazines and quinazolines were synthesized. The structure of the synthesized compounds was confirmed from their analytical and spectral data such as, IR spectra, 1H-NMR and mass spectra. Antimicrobial against two types of bacteria and anticancer activity for some of the synthesized imides were evaluated. The results showed that most of them have a good antimicrobial and anticancer activities.

Novel coumarin-benzimidazole derivatives as antioxidants and safer anti-inflammatory agents

Inspired from occurrence of anti-inflammatory activity of 3-substituted coumarins and antiulcer activity of various 2-substituted benzimidazoles, novel compounds have been designed by coupling coumarin derivatives at 3-position directly or through amide linkage with benzimidazole nucleus at 2-position. The resultant compounds are expected to exhibit both anti-inflammatory and antioxidant activities along with less gastric toxicity profile. Two series of coumarin-benzimidazole derivatives (4a-e and 5a-e) were synthesized and evaluated for anti-inflammatory activity and antioxidant activity. Compounds 4c, 4d and 5a displayed good anti-inflammatory (45.45%, 46.75% and 42.85% inhibition, respectively, versus 54.54% inhibition by indomethacin) and antioxidant (IC50 of 19.7, 13.9 and 1.2 µmol/L, respectively, versus 23.4 µmol/L for butylatedhydroxytoluene) activities. Evaluation of ulcer index and in vivo biochemical estimations for oxidative stress revealed that compounds 4d and 5a remain safe on gastric mucosa and did not induce oxidative stress in tissues. Calculation of various molecular properties suggests the compounds to be sufficiently bioavailable.

Clinical analysis of 4 cases of Fasciola gigantica infection from Binchuan County, Yunnan Province / 中华传染病杂志

Objective To explore the epidemiological characteristics,clinical manifestations,diagnosis and treatment of Fasciola gigantica infection,and to provide reference for future diagnosis and treatment.Methods Four cases of confirmed Fasciola gigantica infection were analyzed retrospectively for epidemiological information,clinical manifestations,laboratory results,imaging findings,diagnosis and treatment outcomes.Results Four Fasciola gigantica infection cases were farmers from Binchuan County,Yunnan Province.All presented with fever,hepatalgia,percussion pain,hepatomegaly,eosinophilia,hyperglobulinemia,neutrophilia and anemia.Computed tomography (CT) scans showed multiple low density shadows scattered in the liver parenchyma.Eggs of Fasciola gigantica were detected in feces of the patients,and results of antibody against Fasciola gigantica detected by enzyme-linked immunosorhent assay (ELISA) were positive.Triclabendazole treatment was effective.Conclusion Human Fasciola gigantica infection is rare,without specific clinical manifestations,and triclabendazole is the first choice of treatment.

A Comparison Study of Combined Medication of Telmisartan with Amlodipine on the Reversal Left Ventricular Remodeling in Renal Hypertensive Rats / 天津医药

Objective To compare the effects of telmisartan and (or) amlodipine on the reversal left ventricular re-modeling in two-kidney one clip hypertensive rats. Methods A total of 50 healthy male SD rats were randomly divided into 5 groups (n=10):two-kidney one clip renal hypertensive (2KIC) model group, sham group, telmisartan (10 mg/kg) group, am-lodipine (2.5 mg/kg) group and telmisartan (10 mg/kg)+amlodipine(2.5 mg/kg) group. The model of two-kidney one clip re-nal hypertensive rats was established. The tail arterial blood pressure was detected once a week. After 20 weeks, rats were sacrificed and specimens were collected. The left ventricular mass index (LVMI) was assessed. The myocardial ultrastructur-al changes were observed by electron microscope. Values of plasma renin activity (PRA), angiotensionⅡ(AngⅡ) and atrial natriuretic peptide (ANP) were measured by enzyme linked immunosorbent assay (ELISA).Results Compared with sham group, the levels of systolic blood pressure (SBP), LVMI, PRA, AngⅡand ANP were significantly higher in 2KIC group (P＜0.01). Compared with 2KIC group, values of SBP, LVMI, PRA and ANP were significantly lower in telmisartan group and am-lodipine group (P＜0.01), but the value of AngⅡwas significantly higher (P＜0.01). The levels of SBP, LVMI, AngⅡand ANP were significantly lower in combined medication group than those of single drug medication group (P＜0.01). There was no significant difference in the plasma PRA level between those groups (P>0.05). Results of myocardial electron microsco-py showed that the left ventricular remodeling was significantly improved in combined treatment group. Conclusion Telmisartan and amlodipine can effectively improve the left ventricular remodeling induced by hypertension. There was more effective therapy using both medications together.

Benzimidazole: A short review of their antimicrobial activities.

Benzimidazole is the heterocyclic compound formed from benzene and imidazole ring containing nitrogen, oxygen sulphor and its derivatives are of wide interest because of their diverse biological activity and clinical applications, they are remarkably effective compounds both with respect to their inhibitory activity and their favourable selectivity ratio. Reported nucleus is a constituent of vitamin-B12. Benzimidazoles are regarded as a promising class of bioactive heterocyclic compounds that exhibit a range of biological activities like anti-microbial, anti-viral, anti-diabetic, anti-cancer activity, numerous anti-oxidant, anti-parasitic, anti-helmintics, anti-proliferative, anti-HIV, anti-convulsant, anti-inflammatory, anti-hypertensive, anti-neoplastic, proton pump inhibitor and anti-trichinellosis. Benzimidazoles exhibit significant activity as potential antitumor agents, smooth muscle cell proliferation inhibitors, a treatment for intestinal cystitis, and in diverse area of chemistry. Some of the important benzimidazole derivatives have been reported as thyroid receptor agonist gonadotropin releasing hormone receptor antagonists, non-nucleoside HIV-1 reverse transcriptase inhibitors and interestingly alkynylbenzimidazoles as modulators of metabotropic glutamate receptors. The imidazole core is a common moiety in a large number of natural products and pharmacologically active compounds. The synthesis of novel benzimidazole derivatives remains a main focus of medicinal research. This comprehensive overview summarizes the chemistry of different derivative of substituted benzimidazole along with their anti-microbial activity containing anti-malarial anti-fungal, anti-bacterial, anti-viral activities.

Benzimidazole: A short review of their antimicrobial activities.

Benzimidazole is the heterocyclic compound formed from benzene and imidazole ring containing nitrogen, oxygen sulphor and its derivatives are of wide interest because of their diverse biological activity and clinical applications, they are remarkably effective compounds both with respect to their inhibitory activity and their favourable selectivity ratio. Reported nucleus is a constituent of vitamin-B12. Benzimidazoles are regarded as a promising class of bioactive heterocyclic compounds that exhibit a range of biological activities like anti-microbial, anti-viral, anti-diabetic, anti-cancer activity, numerous anti-oxidant, anti-parasitic, anti-helmintics, anti-proliferative, anti-HIV, anti-convulsant, anti-inflammatory, anti-hypertensive, anti-neoplastic, proton pump inhibitor and anti-trichinellosis. Benzimidazoles exhibit significant activity as potential antitumor agents, smooth muscle cell proliferation inhibitors, a treatment for intestinal cystitis, and in diverse area of chemistry. Some of the important benzimidazole derivatives have been reported as thyroid receptor agonist gonadotropin releasing hormone receptor antagonists, non-nucleoside HIV-1 reverse transcriptase inhibitors and interestingly alkynylbenzimidazoles as modulators of metabotropic glutamate receptors. The imidazole core is a common moiety in a large number of natural products and pharmacologically active compounds. The synthesis of novel benzimidazole derivatives remains a main focus of medicinal research. This comprehensive overview summarizes the chemistry of different derivative of substituted benzimidazole along with their anti-microbial activity containing anti-malarial anti-fungal, anti-bacterial, anti-viral activities.

Candesartan early or late treatment reduced advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mice kidney / 中国医师杂志

Objective The effects of candesartan,an angiotensin Ⅱ type 1 receptor blocker (ARB) were investigated on advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mouse kidneys.MethodsKK/Ta mice(n=72)were random divided into three groups(n=24) and it was treated with candesartan [4 mg/(kg·d)] or vehicle from 6 or 12 to 28 weeks of age.BALB/c mice(n=24) treated with vehicle were used as controls.Body weight,blood pressure,blood glucose,urinary microalbumin,urinary creatinine and serum creatinine were measured every four weeks.At 28 weeks,renal expressions of carboxymethyllysine and RAGE were evaluated by immunohistochemistry and/or competitive RT-PCR.Results KK/Ta mice developed high body weight,high blood glucose,and high urinary microalbumin/creatinine ratio in KK/Ta mice at 28 weeks of age,and it was significantly higher than that of BALB/c mice [(427.49±89.37)mg/g vs (9.54±3.25)mg/g,P＜0.01 ].Protein and mRNA expressions of RAGE were upregulated in KK/Ta kidneys with increased immunostaining intensities of carboxymethyllysine.Candesartan treatment has markedly reduced urinary microalbumin/creatinine ratio [Early treatment group (32.18±9.41)mg/g,Late treatment group (53.20±7.26)mg/g,P＜0.01 ].Treatment with candesartan down-regulated the protein and mRNA expressions of RAGE and reduced the accumulation of carboxymethyllysine.There were no significant differences between the two treatment groups (from 6 or 12 weeks).ConclusionsThe results suggest that candesartan,an ARB,reduces advanced glycation end-products accumulation and subsequent albuminuria by down-regulating RAGE expression in type 2 diabetic KK/Ta mouse kidneys.

Synthesis and Antimicrobial studies of novel Benzimidazole derivatives.

Two series of novel benzimidazole derivatives were synthesized. The first one comprise of 2-methyl, the second one comprise of 2-phenyl substitution on benzimidazole moiety. Seven novel benzimidazole derivatives were synthesized successfully in appreciable yields and characterized physicochemically. The structures of all the synthesized derivatives were confirmed by IR and 1HNMR. Furthermore, the synthesized compounds were screened for antimicrobial activity (antibacterial activity and antifungal activity) by tube dilution method. Some of the synthesized compounds showed appreciable antifungal activity.

One-pot synthesis of 2-ARYL-1-ARYLMETHYL-1H-1,3-benzimidazole derivatives using sulfonic acid functionlized silica (SiO2-Pr-SO3H) under solvent free conditions.

2-Aryl-1-arylmethyl-1H-1,3-benzimidazoles were synthesized by the reaction of o-phenylendiamine with different types of aromatic aldehydes in the presence of Sulfonic acid functionlized silica (SiO2-Pr-SO3H) as solid acid catalyst under solvent free condition at room temperature in good to excellent yields.

The efficacy analysis of domestic pantoprazole in the treatment of non-steroidal anti-inflammatory drugs associated ulcer bleeding / 中华消化杂志

Objective To compare the efficacy, adverse reactions and cost-effectiveness between domestic pantoprazole (Pan Li Su) and imported omeprazole (Losec) in the treatment of non-steroidal anti-inflammatory drugs (NSAID) associated ulcer bleeding.Methods Fifty-eight hospitalized patients with NSAID associated ulcer bleeding were randomly divided into pantoprazole group (n=31)and omeprazole group (n= 27) according to random number table.Pantoprazole group was given 40 mg domestic pantoprazole dissolved 100 ml 0.9% sodium chloride solution intravenously every 12 hours.Omeprazde group was given 40 mg omeprazole dissolved in 100 ml 0.9% sodium chloride solution intravenously every 12 hours.The two groups were both treated for seven days.Finally, the efficacy and adverse effect were observed, and cost-effectiveness was analyzed with pharmacoeconomics.Results The total effective rate of pantoprazole group was 93.5%, omeprazole group was 96.3% .The drugs of the two groups could effectively stop bleeding, the difference was not statistically significant (P= 1.00).The rate of adverse effect was 3.2 % and 7.4 % in the two groups accordingly.The cost-effectiveness ratio (C/E) was 7.76 and 20.73 respectively.Compared with pantoprazole group, the incremental cost-effectiveness ratio of omeprazole group was 454.Conclusions Domesic pantoprazole is an effective, safety and economical medicine for NSAID associated ulcer bleeding.

Yttrium (III) chloride: A mild and efficient catalyst for the synthesis of benzimidazoles.

A simple and efficient synthesis of benzimidazole derivatives from orthophenylene diamine and aldehydes by using a Lewis acid catalyst yttrium (III) chloride has been described. Compared with classical benzimidazole synthesis, this method has advantage of excellent yields and short reaction times. All the reactions were carried out using the catalyst in 10 mol %, in acetonitrile at room temperature.

Effects of preoperative intravenous different doses of pantoprazole on acidity of gastric fluid / 中华麻醉学杂志

Objective To investigate the effects of preoperative iv different doses of pantoprazole on acidity of gastric fluid in patients undergoing elective surgery. Methods Sixty ASA Ⅰ -Ⅲ patients aged 38-80 yr,weighing 44-72 kg undergoing elective surgery were randomly allocated into 3 groups (n = 20 each): group Ⅰ control (group C); group Ⅱ pantoprazole 40 mg(group P1) and group Ⅲ pantoprazole 80 mg(group P2). The patients received intravenous normal saline (NS) 100 ml, pantoprazole 40 and 80 mg in NS 100 ml respectively in group C, P1 and P2 at 30 min before surgery. Gastric content was aspirated using a gastric tube on the patients'arrival in the operating room and at 1,2 h and the end of surgery. The pH of the gastric fluid was measured. The adverse effects including dizziness, diarrhea, PONV and incidence of stress ulcer were recorded. Results The pH was significantly increased in group P1 and P2 as compared with control group but there was no significant difference in pH between group P1 and P2 . There were no significant difference in the incidence of stress ulcer and pH of the gastric fluid≤2.5 among the 3 groups. Conclusion Preoperative intravenous pantoprazole 40 mg can effectively increase pH of gastric juice and is helpful in reducing the incidence of stress ulcer and the risk of acid aspiration.

Effects of Pantoprazole on Stress-Induced Gastric Mucosal Lesions in Rats / 天津医药

Objective: To investigate the effects of Pantoprazole on the expression of TFF1 in stress-induced gastric mucosal lesions in rats, and the mechanism thereof. Methods: Fifty-six rats were randomly divided into seven groups, normal group, model groups (3 groups) and model therapy groups (3 groups). The rat model of water immersion- restraint stress (WRS) was established in model groups, model group1(the immediately after establishing models), model group 2 (4 h after establishing models) and model group 3(8 h after establishing models). The model therapy groups were divided into model therapy group 1 (immediately after establishing models), model therapy group 2 (4 h after establishing models), and model therapy group 3 (8 h after establishing models). The ulcer index (UI) and histological changes were observed after WRS in rats. The expression of TFF1 was detected by immunohistochemistry. Results: After WRS, the gastric mucosa was widely damaged in rats. UI were increased and the expression of TFF1 was decreased in model groups. After intervention with Pantoprazole, UI was lower in model therapy group than those in model groups (model group 1 vs model therapy group 1,69.13±1.97 vs 23.38±1.30, P ＜ 0.01; model group 2 vs model therapy group 2, 57.50±8.81 vs 10.38±3.02, P ＜ 0.01; model group 3 vs model therapy group 3, 43.50±6.76 vs 5.88±1.25, P ＜ 0.01). The staining scores of TFF1 were increased (model group 1 vs model therapy group 1, 0.55±0.11 vs 0.92±O.15, P＜ 0.01; model group 2 vs model therapy group 2, 0.76±0.24 vs 1.36±0.21, P＜ 0.01; model group 3 vs model therapy group 3, 1.12±0.16 vs 1.65±0.11, P ＜ 0.01). Conclusion: TFF1 may participate in the protection of gastric mucosa and promote ulcer recovery. Pantoprazole may participate in the defense of gastric mucosa through mediating the up-regulation of TFFI expression.