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 ...

Appropriate candidates for statin use in heart failure

No abstract available.

Effects of intensive versus mild lipid lowering by statins in patients with ischemic congestive heart failure: Korean Pitavastatin Heart Failure (SAPHIRE) study

BACKGROUND/AIMS: This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear. METHODS: The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin. RESULTS: The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371). CONCLUSIONS: Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.

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.

Estudio de bioequivalencia de montelukast en tabletas masticables de 5 mg / Bioequivalence study of montelukast 5 mg chewable tablets

Introducción. La importancia de los medicamentos genéricos radica en la posibilidad de la disminución de los costos en el sistema nacional de salud, sin sacrificar la calidad del servicio ni la eficacia y la seguridad de los tratamientos. Es importante resaltar que los estudios de bioequivalencia pretenden demostrar que los perfiles farmacocinéticos del producto de prueba y del producto de referencia son similares e intercambiables. El montelukast sódico está indicado para la profilaxis y el tratamiento crónico del asma, en adultos y pacientes pediátricos de 12 meses de edad o más. En general, es bien tolerado y las reacciones adversas son un poco más frecuentes en los pacientes tratados con el fármaco que en los tratados con placebo. Objetivos. Comparar la biodisponibilidad de Amisped®, montelukast en tabletas masticables de 5 mg fabricadas por Sanofi-Aventis con la de Singulair®, montelukast en tabletas masticables de 5 mg elaboradas por Merck Sharp & Dohme. Materiales y métodos. Se comparó la magnitud y la velocidad de la absorción de montelukast en 18 voluntarios sanos, empleando un diseño cruzado completo al azar. El bioanálisis de las muestras se hizo por cromatografía líquida de alta resolución. Resultados. Los resultados para el genérico y el innovador, respectivamente, fueron: Tmax (horas) 2,17±0,73 y 2,28±0,88; Cmax (ng/ml) 607,42±122,92 y 627,69±134,17; AUC0-t (ng*h/ml) 3.316,39±861,57 y 3.545,40±1.070,07; AUC0-∞ (ng*h/ml) 3.450,92±904,89 y 3.722,03±1120,60; Ke (1/h) 0,25±0,05 y 0,23±0,04 en el intervalo de confianza de 0,99-1,00 para lnCmax y 0,94-1,06 para lnAUC0-∞. Conclusiones. La formulación ensayada de Amisped® de Sanofi-Aventis es bioequivalente a la formulación de referencia Singulair® de Merck Sharp& Dohme.

Introduction. The importance of generic drugs is the possibility of reduced costs in the national health system without sacrificing quality of service and the efficacy and safety of treatments. However, bioequivalence studies must show that the pharmacokinetic profiles of the test product and reference product are similar and interchangeable. Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age or older. It is generally well tolerated, although adverse reactions are more frequent in patients treated with the drug than in those treated with placebo. Objectives. To compare the bioavailability of Amisped® (5 mg montelukast chewable tablets) manufactured by Sanofi-Aventis and 5 mg chewable tablet montelukast (Singulair®) developed by Merck. Materials and methods. The magnitude and rate of absorption of montelukast was compared in 18 healthy volunteers using a randomized complete crossover design. The bioassay was performed by high performance liquid chromatography. Results. Results are indicated for the generic and innovator, respectively: Tmax (h) 2.17±0.73, 2.28±0.88; Cmax (ng/mL) 607.4±122.9, 627.7±134.2; AUC0-t (ng*h/ml) 3,316±861, 3,545±1,070; AUC0-∞ (ng*h/ml) 3,450±904, 3,722±1121; Ke (1/h) 0.25±0.05, 0.23±0.04 in the confidence range of 0.99-1.00 for lnCmax and 0.94-1.06 for lnAUC0-∞. Conclusions. The formula tested in Amisped® from Sanofi-Aventis is bioequivalent to the reference formulation of Merck Singulair®.

Montelukast Induced Hypertriglyceridemia.

Montelukast a LT4 receptor antagonist is a prophylactic agent used in chronic asthma, to improve asthma control and reduce the frequency of asthma exacerbation. Advantage of Montelukast is, it is well tolerated in both adult and children upto 6 years of age. Suspected adverse effect reported to U.K, CSM follow the launch of Montelukast are anaphylaxis, angioedema, urticaria, chest pain, vertigo, athralgia, fever. Further suspected side effects are nightmare, palpitation, and sweating and Churg Strauss syndrome. Hypertriglyceridemia associated with this agent is rarely found in any published medical report or literature. This is a case of a male patient who was suffering from chronic asthma since childhood, developed allergic rhinitis since November´10. He developed hypertriglyceridemia and associated lipid profile abnormality after taking Montelukast and was also receiving salbutamol inhalation since childhood. His lipid profile before Montelukast administration was normal. Routine investigation done 4 months following drug intake shows serum triglyceride to be 732mg/dl.Montelukast was immediately withdrawn, but salbutamol was continued The triglyceride level reaches near the base line 4 months following drug withdrawal. This case highlights a rare case of Montelukast induced hypertriglyceridemia. Physician should be vigilant of the fact that Montelukast can induce hypertriglyceridemia following therapy with it.

The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals / Efecto de montelukast en un modelo de artritis gotosa inducido por cristales de monourato de sodio

Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p<0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

En artritis gotosa aguda las drogas antiinflamatorias no esteroideas son la primera línea terapéutica. Este tratamiento no es satisfactorio porque inhibe la ciclooxigenasa sin modificar la actividad de la lipooxigenasa, y puede acompañarse de numerosos efectos adversos. Investigamos el efecto de montelukast sobre el infiltrado celular inflamatorio en un modelo de artritis múrida inducida por cristales de monourato de sodio (MUS) en el modelo experimental de la bolsa de aire (air pouch). Siete grupos de ratones BALB/c (n = 4) fueron distribuidos en cinco grupos experimentales y dos grupos controles inflamatorios: positivo y negativo. Los grupos experimentales recibieron, montelukast (1 y 0,01 mg/Kg/p) y/o indometacina (2,5 mg/Kg/p) por vía oral, previo a la administración de MUS en la bolsa del aire. El conteo absoluto y diferencial de las células inflamatorias fue analizado después de 2, 6, 12 y 24 horas de tratamiento. El tratamiento con montelukast redujo significativamente el número total de células presentes en el infiltrado inflamatorio (p < 0,05), con un efecto mayor sobre polimorfonucleares que sobre las células mononucleares, y con un máximo efecto a las 12 horas después de la administración del medicamento. La combinación montelukast/indometacina mostró un efecto aditivo. Los resultados demuestran que montelukast tiene un efecto antiinflamatorio en el modelo de la artritis gotosa. Por lo tanto, los anti-leucotrienos podrían representar una nueva y eficaz terapia, aislada o en combinación con la terapéutica convencional, para la artritis gotosa.

A Case of Stenotrophomonas maltophilia Keratitis Effectively Treated with Moxifloxacin

A 70-year-old man with a long history of diabetes mellitus presented to our hospital (Department of Ophthalmology, Sahm Yook Medical Center, Seoul, Korea) complaining of severe ocular pain and visual disturbance in his left eye that had started three days prior to admission. A round 3.7 x 5.0 mm dense central stromal infiltrate with an overlying epithelial defect was noted on slit-lamp examination. Following corneal scrapings and culture, topical 0.5% moxifloxacin and 0.5% tobramycin were administered hourly. A few days later, Stenotrophomonas maltophilia was isolated in a bacterial culture from a corneal specimen. According to the results of susceptibility tests, topical 0.5% moxifloxacin was given every hour and 0.5% tobramycin was stopped. The patient's clinical features improved steadily with treatment. The corneal epithelium healed rapidly, and the infiltrate resolved within four weeks of the initiation of treatment. The patient's best corrected visual acuity improved from hand motion to 20 / 25.

A Case of Stenotrophomonas maltophilia Keratitis Effectively Treated with Moxifloxacin

A 70-year-old man with a long history of diabetes mellitus presented to our hospital (Department of Ophthalmology, Sahm Yook Medical Center, Seoul, Korea) complaining of severe ocular pain and visual disturbance in his left eye that had started three days prior to admission. A round 3.7 x 5.0 mm dense central stromal infiltrate with an overlying epithelial defect was noted on slit-lamp examination. Following corneal scrapings and culture, topical 0.5% moxifloxacin and 0.5% tobramycin were administered hourly. A few days later, Stenotrophomonas maltophilia was isolated in a bacterial culture from a corneal specimen. According to the results of susceptibility tests, topical 0.5% moxifloxacin was given every hour and 0.5% tobramycin was stopped. The patient's clinical features improved steadily with treatment. The corneal epithelium healed rapidly, and the infiltrate resolved within four weeks of the initiation of treatment. The patient's best corrected visual acuity improved from hand motion to 20 / 25.

Efficacy of montelukast and loratadine as treatment for allergic rhinitis in children.

The objective of this study was to compare the effectiveness of montelukast combined with loratadine once daily to loratadine alone for a 2-week treatment course of allergic rhinitis in a randomized, double-blind placebo controlled trial which enrolled 115 children, 6- 15-years-old. The patients were randomly assigned to receive montelukast and loratadine (treatment group) or placebo and loratadine (control group). The primary outcome was the mean percent change of the total daytime nasal symptom scores (PDTS) and secondary outcomes were the mean percent changes of the nighttime nasal, daytime eye and composite symptom scores (PNTS, PES, PCS), as well as the nasal secretion, turbinate swelling and nasal congestion scores (PNSS, PTSS, PNCS). There were no significant differences in the PDTS of the 2 groups. The change in the night time nasal congestion score (PNTS-congestion) was higher in the treatment group, but not statistically significant (p = 0.077). Only the mean percent change in decreased turbinate swelling was significantly greater in the montelukast and loratadine group than the loratadine alone group (-22 +/- 7 vs. -1 +/- 5, p < 0.05).

Efficacy of Artequick versus artesunate-mefloquine in the treatment of acute uncomplicated falciparum malaria in Thailand.

To determine the efficacy, safety and tolerability of an alternative short-course, artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum malaria, we compared Artequick--a fixed-dosed combination of artemisinin (80 mg), piperaquine (400 mg), and primaquine (4 mg), per tablet--with a standard regimen of artesunate-mefloquine. A total of 130 patients were randomly assigned to treatment with an orally administered, once-daily, 3-day regimen of either Artequick (Group A: 3.2 mg/Kg/day of artemisinin, 16 mg/Kg/day of piperaquine, and 0.16 mg/Kg/day of primaquine) or artesunate-mefloquine (Group B: artesunate, 4 mg/Kg/day, with mefloquine, 8 mg/Kg/day). Patients receiving each regimen had a rapid clinical and parasitological response. All treatments were well tolerated, and no serious adverse effects occurred. No significant differences were found in fever- and parasite-clearance times between the two study groups. The 28-day cure rates were similarly high, at 98.5% and 100%, in groups A and B, respectively. We conclude that Artequick was as effective and well tolerated as artesunate-mefloquine and could be used as an alternative treatment for multidrug-resistant Plasmodium falciparum malaria in Southeast Asia.

Infectious keratitis secondary to Histoplasma capsulatum: the first case reports in humans

The authors report an unusual case of fungal keratitis caused by Histoplasma capsulatum in a male immunocompetent patient. PCR confirmed the presence of the fungus DNA in the material studied. To our knowledge this is the first reported case in humans described all over the world.

Dose ranging studies of new artemisinin-piperaquine fixed combinations compared to standard regimens of artemisisnin combination therapies for acute uncomplicated falciparum malaria.

To determine the optimum dose of artemisinin-piperaquine combination therapies for acute uncomplicated Plasmodium falciparum malaria, we examined 7 candidate regimens in 411 patients admitted to the Bangkok Hospital for Tropical Diseases. The studies were performed from May 2005 to October 2005 and November 2005 to June 2006. We compared 3-day courses of artesunate-mefloquine, artemether-lumefantrine (Coartem) and of dihydroartemisinin-piperaquine (Artekin) as reference antimalarial treatments, with candidate regimens using 2-3 day courses of artemisinin-piperaquine, Artequick. Initially, patients receiving each of the regimens had a rapid clinical and parasitological response. All treatments were well tolerated and no serious adverse effects occurred. The 28-day cure rates were < 80% for the 2-day treatments with artemisinin-piperaquine at 2.4 mg/kg and 14.4 mg/kg, respectively, in the first study period and artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg, respectively, but > 98% for the 3-day regimens. These results suggest that a 3-day course of artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg, respectively, deserve further evaluation as an alternative treatment for multidrug-resistant P. falciparum malaria.

An open randomized clinical trial of Artekin vs artesunate-mefloquine in the treatment of acute uncomplicated falciparum malaria.

Malaria remains a major cause of morbidity and mortality in tropical countries and subtropical regions in the world. Southeast Asia has the most resistant malaria parasites in the world, which has limited treatment options in this region. In response to this situation, short-course artemisinin-based combination therapies (ACTs) have been developed. The combination of dihydroartemisinin (DHA) and piperaquine (PQP) in the form of Artekin has been developed as an alternative to established combinations, such as artesunate-mefloquine, primarily to reduce treatment costs and toxicity. We conducted a study comparing a standard treatment for acute uncomplicated falciparum malaria (artesunate 4 mg/kg/day together with mefloquine 8 mg/kg/day oral route once a day for 3 days) (Group A) and a combination of dihydroartemisinin 40 mg and piperaquine 320 mg in the form of Artekin given once a day for 3 days (Group B) to determine safety, efficacy, and tolerability. One hundred and eighty patients were randomly enrolled at the ratio of 1:2 into groups A:B. All patients had rapid initial clinical and parasitological responses. There were no significant differences in fever clearance time or parasite clearance time between both groups. The 28-day cure rates were high, at 100% and 99%, in groups A and B, respectively. We conclude that Artekin was as effective and well-tolerated as artesunate-mefloquine, and can be used alternatively as the current treatment for multidrug-resistant P. falciparum malaria.

Trial of Moxifloxacin-containing Triple Therapy after Initial and Second-line Treatment Failures for Helicobacter pylori Infection / 대한소화기학회지

BACKGROUND/AIMS: Proton-pump inhibitor (PPI)-based triple therapy for Helicobacter pylori eradication is widely used with considerable failure rate. Bismuth-based, second-line therapy is also associated with failures in more than 20% of cases in Korea. Our aim was to evaluate the efficacy and tolerability of third-line therapy containing moxifloxacin as a rescue in Korea. METHODS: The subjects consisted of 201 patients infected with H. pylori, who were treated with PPI-based therapy, 42 patients treated with bismuth-based after failure of initial PPI triple therapy, and 10 patients treated with moxifloxacin-containing triple therapy after failure of successive initial and second-line therapy. Eradication rate, compliance and side effect rates were compared. RESULTS: The eradication rates of initial, second-line, and third-line therapy were as follows: 67.2%/83.3%, 54.8%/76.7%, 80.0%/88.9% by intention-to-treat and per protocol analysis, respectively. The compliance of patients for each treatment was 98.2%, 90.9%, 100%, respectively. The side effect rate was significantly higher in the bismuth triple therapy than in the PPI- or moxifloxacin-containing triple therapy (p<0.05). CONCLUSIONS: Moxifloxacin-containing triple therapy shows high eradication rate with fewer side effects and good compliance. Thus, this regimen could be used as a rescue therapy.

Effects of antileukotriene among asthmatic patients.

STUDY OBJECTIVE: To determine the effect of antileukotriene (montelukast) 10 mg once daily for the treatment of mild to moderate asthma. DESIGN: Open label, prospective. PATIENTS: Thirty asthmatic patients > or = 18 years of age with baseline FEV1 > 60 per cent and < or = 80 per cent of predicted values and evidence of reversible airway obstruction, as defined by an increase in FEV1 of > or = 20 per cent. INTERVENTIONS: Montelukast 10 mg once daily orally for 12 weeks, back up beta-2 agonist inhaler was available. MEASUREMENT AND RESULTS: Spirometry was performed during the screening period, and every month after starting antileukotriene. Subjects recorded asthma-related symptoms and use of supplement beta-2 agonists daily on diary cards. Over 12 weeks of treatment, the FEV1 increased 10 per cent, 14 per cent and 19 per cent respectively, compared to the baseline (p < 0.05). The physician and patients evaluation scores were quite good in the study. CONCLUSION: Oral montelukast once daily gave a favorable effect in management of mild to moderate asthmatic patients.

Antinociceptive activity of chromophoric chain substituted hemicyaninocolourants.

Some of the chromophoric chain substituted hemicyaninocolourants (CCHCs) were synthesized and confirmed on the basis of nitrogen analysis. These were tested for their antinociceptive activity in albino rats against tail flick technique and sodium chloride induced writhing test. Test compounds were given in graded doses (10, 20 and 50 mg/kg, intraperitoneally) and compared with morphine and aspirin as standard controls. Two compounds CCHC-1 and CCHC-2 showed antinociceptive activity in a dose-dependent manner in both the experimental models. The compound CCHC-3 did not exhibit antinociceptive activity to any significant extent.

The effect of mefloquine-sulfadoxine-pyrimethamine vs quinine on patients with complicated falciparum malaria.

Sixty-six patients with complicated falciparum malaria (defined as anaemia, hyperpyrexia, jaundice, or more than 2% of RBC parasitised) were studied. Patients with cerebral signs and symptoms were not included in the study. Patients were randomised in pairs to receive either mefloquine 750 mg, sulfadoxine 1500 mg and pyrimethamine 75 mg (MSP) single oral dose or quinine (10 mg/kg tds X 7 days oral therapy). All the patients were admitted in hospital for 7 days and were followed on days 14, 21 and 28. All patients survived. The parasite clearance times in MSP treated patients were significantly shorter then those treated with quinine. There was no difference in fever clearance time in the two groups of patients. One patient was resistant to MSP at RII level and 5 patients were resistant at RI level. Among patients treated with quinine 3 patients were resistant at RI level.