Conductometric determination of propranolol hydrochloride in pharmaceuticals

In this paper the conductometric titration of propranolol hydrochloride in pharmaceutical formulations using silver nitrate as titrant is proposed. The method was based on the formation of an insoluble salt (AgCl(s)) between the chloride of propranolol hydrochloride molecule and Ag(I) ions of the titrant AgNO3. The effect of the PROP-AgNO3 concentrations and the interval of time between the successive additions of the titrant on the shape of the titration curve were studied. The obtained recoveries for four samples ranged from 96.8 to 105%. The proposed method was successfully applied in the determination of propranolol hydrochloride in several pharmaceutical formulations, with results in close agreement at a 95 % confidence level with those obtained using official spectrophotometric method.

Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M3 receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury.

Epidemiologia do consumo de medicamentos em crianças de centro urbano da região sul do Brasil

Foram investigados os padrões do consumo de medicamentos em uma coorte de 4.746 crianças de Pelotas, RS, Brasil e as influências de variáveis socioeconômicas, biológicas e de utilização de serviços de saúde. O delineamento foi transversal aninhado em estudo longitudinal e o período investigado foi 15 dias. O consumo global alcançou 56% das crianças, sendo mais de 50% em todas as classes sociais. Os medicamentos mais utilizados foram ácido acetil salicílico, vitaminas com sais minerais, associações antigripais, mebendazole e estimulantes do apetite. Mais de 60,0% dos medicamentos eram indicados por médicos (inclusive dipirona e estimulantes do apetite). Os principais motivos do consumo foram gripe, febre e falta de apetite. Ser primogênito foi fator de risco para o consumo. As crianças com pouco apetite na semana anterior consumiam duas vezes mais do que aquelas com bom apetite. É preocupante o alto consumo de aspirina, principalmente devido à associação desse produto com a Síndrome de Reye em crianças. Outro ponto a ser questionado a respeito é a mensagem que talvez inadvertida ou inconscientemente possa estar sendo passada a essas crianças: o consumo de medicamentos é uma rotina e a resposta para qualquer problema. Nesse sentido, parece que se estará preparando o terreno para a dependência de medicamentos e drogas ilícitas.

Treatment of depression in older adults beyond fluoxetine

This review aimed to discuss the importance of the comprehensive treatment of depression among older adults in Brazil. The abuse of selective serotonin reuptake inhibitors, including fluoxetine hydrochloride, as antidepressants has been considered a serious public health problem, particularly among older adults. Despite the consensus on the need for a comprehensive treatment of depression in this population, Brazil is still unprepared. The interface between pharmacotherapy and psychotherapy is limited due to the lack of healthcare services, specialized professionals, and effective healthcare planning. Fluoxetine has been used among older adults as an all-purpose drug for the treatment of depressive disorders because of psychosocial adversities, lack of social support, and limited access to adequate healthcare services for the treatment of this disorder. Preparing health professionals is a sine qua non for the reversal of the age pyramid, but this is not happening yet.

A longitudinal study of enterobiasis in three day care centers of Havana City

Pinworm infection was prospectively studied during one year in 469 children attending three day care centers. Each child was examined at six months intervals using up to three perianal swabs with adhesive tape. Those found infected were treated with mebendazole. At the beginning of the study we found a prevalence of 28% that dropped to 13% and 12% in the following study periods. The reinfection rate was twice the incidence rate in both study periods. We also found a small percentage (10%) of the children reinfected in most or all study periods. There was a high correlation between reinfection and perianal itching. Our results add further knowledge to the epidemiology of intestinal parasites in day care centers.

Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice

Mebendazole, albendazole, levamisole and thiabendazole are well known as active drugs against several nematode species, and against cestodes as well, when the first two drugs are considered. None of the drugs have proven activity, however, against trematodes. We tested the effect of these drugs on the fecal shedding of schistosome eggs and the recovering of adult schistosomes, after portal perfusion in Schistosoma mansoni experimentally infected mice. Balb/c mice infected with 80 S. mansoni cercariae were divided into three groups, each in turn subdivided into four other groups, for each tested drug. The first group was treated with each one of the studied drugs 25 days after S. mansoni infection; the second group was submitted to treatment with each one of the drugs 60 days after infection. Finally, the third group, considered as control, received no treatment. No effect upon fecal shedding of S. mansoni eggs and recovering of schistosomes after portal perfusion was observed when mice were treated with either mebendazole or albendazole. Mice treated with either levamisole or thiabendazole, on the other hand, showed a significant reduction in the recovering of adult schistosomes after portal perfusion, mainly when both drugs were given during the schistosomula evolution period, i.e., 25 days after cercariae penetration, probably due to unspecific immunomodulation

Impact of antihelminthic treatment on infection by Ascaris lumbricoides, Trichuris trichiura and hookworms in Covas, a rural community of Pernambuco, Brazil

This work aims to evaluate the impact of drug treatment on infection by Ascaris lumbricoides (Al), Trichuris trichiura (Tt) and hookworms (Hook) in a rural community from the sugar-cane zone of Pernambuco, Brazil. Four parasitological surveys were carried out from March 2001 to March 2002. Individual diagnosis was based on eight slides (four by the Kato-Katz method and four by the Hoffman method) per survey. Infected subjects were assigned to two groups for treatment with either albendazole (n = 62) or mebendazole (n = 57). Prevalence of infection fell significantly (p < 0.05) one month after treatment: Al (from 47.7% to 6.6%); Tt (from 45.7% to 31.8%) and Hook (from 47.7% to 24.5%). One year after treatment, infections by Tt and Hook remained significantly below pre-control levels. A substantial decrease in single-infection cases and multiple infections was found. Egg-negative rate was significant for Al (94.0%), Hook (68.3%) but not for Tt (45.5%), and did not differ significantly between subjects treated with mebendazole or albendazole. Egg counts fell significantly in the individuals remaining positive for Tt. It is recommended that antihelminthic treatment should be selective and given at yearly intervals preferably with albendazole, due to its cost-effectiveness.

Study of enteroparasites infection frequency and chemotherapeutic agents used in pediatric patients in a community living in Porto Alegre, RS, Brazil

Parasitic infections caused by intestinal protozoan and helminths affect more than two billion people worldwide and chemotherapy is the most commonly used therapeutic procedure. Considering the problems created by parasitic infections and the incorrect use of drugs, the aim of this work was to detect the frequency of enteroparasites infection and to estimate the use of chemotherapeutic agents in children living in the periphery of the city of Porto Alegre, RS, Brazil. Ninety-six preschool age children, who had parasitological exams and who used antiparasitic drugs, were analyzed. The efficacy of treatment was evaluated by stool examination repeated six months after treatment. The same diagnostic test was used to evaluate parasitological cure, which was defined as absence of eggs and cysts in the stool. From these children, 79 (82.3%) were contaminated by some species of parasite, the most prevalent were Ascaris lumbricoides, Trichuris trichiura and Giardia lamblia. The most commonly used drugs were mebendazole (86% of prescriptions) and metronidazole (30.3%). The cure rate in the 79 children, examined 6 months after treatment, was 65.3% for A. lumbricoides and 66.1% for T. trichiura. This study suggests that a continuous education program regarding the prevention and treatment of parasitic infections is an essential tool for their eradication.

Mass treatment for intestinal helminthisis control in an Amazonian endemic area in Brazil

The objective of the present study was to estimate the prevalence of soil-transmitted helminthiasis and evaluate the sanitary conditions and the role of a mass treatment campaign for control of these infections in Santa Isabel do Rio Negro. A cross-sectional survey was carried out in 2002, to obtain data related to the sanitary conditions of the population and fecal samples for parasitological examination in 308 individuals, followed by a mass treatment with albendazole or mebendazole with coverage of 83% of the city population in 2003. A new survey was carried out in 2004, involving 214 individuals, for comparison of the prevalences of intestinal parasitosis before and after the mass treatment. The prevalences of ascariasis, trichuriasis and hookworm infection were 48%; 27% and 21% respectively in 2002. There was a significant decrease for the frequency of infections by Ascaris lumbricoides (p < 0.05; OR / 95% CI = 0.44 / 0.30 - 0.65), Trichuris trichiura (p < 0.05; OR / 95% CI = 0.37 / 0.22 - 0.62), hookworm (p < 0.05; OR / 95% CI = 0.03 / 0.01 - 0.15) and helminth poliparasitism (p < 0.05; OR / 95% CI = 0.16 / 0.08 - 0.32). It was also noticed a decrease of prevalence of infection by Entamoeba histolytica / dispar (p < 0.05; OR / 95% CI = 0.30 / 0.19 - 0.49) and non-pathogenic amoebas. It was inferred that a mass treatment can contribute to the control of soil-transmitted helminthiasis as a practicable short-dated measure. However, governmental plans for public health, education and urban infrastructure are essential for the sustained reduction of prevalences of those infections.

EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE

SUMMARY The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ.

Sintomatologia intestinal na fase crônica da esquistossomose mansoni

Com o objetivo de investigar os sintomas intestinais na fase crônica da esquistossomose mansoni, estudamos 102 indivíduos na faixa etária de nove a dezenove anos, dos 144previamente selecionados entre os moradores autóctones dos distritos de Lagoa Redonda e Menezes, portadores de Schistosoma mansoni. Todos foram submetidos a uma anamnese segmentar com a finalidade de detectara presença de cinco sintomas intestinais: dor abdominal, diarréia, muco e rajas de sangue nas fezes e enterorragia. Metade dos pacientes foi medicada com mebendazole e posteriormente com oxamniquine, constituindo-se no grupo caso, enquanto a outra metade, tratada apenas com mebendazole, constituiu-se no grupo controle. Os resultados mostram que a esquistossomose é provavelmente a responsável pelas queixas de muco e/ou rajas de sangue nas fezes, ocorrendo uma redução dessas queixas, estatisticamente significante, após a terapêutica específica.

Therapeutic trial in experimental tegumentary leishmaniasis caused by Leishmania (Leishmania) amazonensis. A comparative study between mefloquine and aminosidine

One hundred and eighty-two male inbred C57/BL/6 mice were infected with 3 x 106 Leishmania (Leishmania) amazonensis promastigotes of the MHOM/BR/PH8 strain by means of a subcutaneous injection in the right ear. The animals were separated in three groups: 1) oral mefloquine hydrochloride treatment (16mg/kg/day/10 days), 2) intramuscular aminosidine (Paromomycin®) treatment (20mg/kg/20 days) and 3) control. Twenty six mice of each treated group were sacrificed, one at the end of treatment (nine weeks after inoculation), and one six weeks later (fifteen weeks after inoculation). Control Group animals were sacrificed at weeks six, nine and fifteen after inoculation. There was no significant difference between Group 1 (mefloquine) and Group 3 (control) subjects. Group 2 animals (aminosidine) presented the smallest differences of all, both at the end of the treatment and six weeks later. The histopato-logical parameters have shown the following findings: a) there was no significant difference between the mefloquine treated group and the control group; the group treated with aminosidine showed fewer of vacuolated macrophages than the control group, at week 9 (end of treatment). b) both at the end of treatment and six weeks later, evaluation of tissue necrosis and tissue fibrosis revealed no differences between the treated groups. It was found that six weeks after the end of treatment, mice in the control group presented significantly more severe degrees of fibrosis than mice in the other groups. It can be concluded that mefloquine showed limited therapeutic effect in this experimental model, whereas aminosidine had a significant effect. Nevertheless, neither of them resulted in cure of the lesions.

Pathogenesis of hepatic septal fibrosis associated with Capillaria hepatica infection of rats

Septal fibrosis is a common form of hepatic fibrosis, but its etiology and pathogenesis are poorly understood. Rats infected with the helminth Capillaria hepatica constitute a good experimental model of such fibrosis. To investigate the pathogenetic contribution of the several parasitic factors involved, the following procedures were performed in rats: a) regarding the role of eggs, these were isolated and injected either into the peritoneal cavity or directly into the liver parenchyma; b) for worms alone, 15-day-old infection was treated with mebendazole, killing the parasites before oviposition started; c) for both eggs and worms, rats at the 30th day of infection were treated with either mebendazole or ivermectin. Eggs only originated focal fibrosis from cicatricial granulomas, but no septal fibrosis. Worms alone induced a mild degree of perifocal septal fibrosis. Systematized septal fibrosis of the liver, similar to that observed in the infected controls, occurred only in the rats treated with mebendazole or ivermectin, with dead worms and immature eggs in their livers. Thus, future search for fibrogenic factors associated with C. hepatica infection in rats should consider lesions with both eggs and worms.

Capillaria hepatica-induced septal fibrosis in rats: a contribution to the study of liver fibrogenesis

INTRODUCTION: Septal fibrosis of the liver regularly develops in rats infected with the nematode Capillaria hepatica. Curative treatment of the infection prevents the development of septal fibrosis when intervention occurs up to postinfection day (PID) 15, but not later. The present investigation aimed to demonstrate which parasitic factors are present when the process of septal fibrosis can no longer be prevented by curative treatment. METHODS: Wistar rats were infected with 600 embryonated eggs of C. hepatica administered by gavage and treated with ivermectin and mebendazole in separate groups at PIDs 10, 12, 15, 17 or 20. Rats from each group and their nontreated controls, were killed and examined 40 days after the end of treatment. RESULTS: Findings by PID 15 were compatible with the stage of complete maturation of infection, when worms and eggs were fully developed and a complex host-parasite multifocal necroinflammatory reaction showed greater intensity, but with no signs of septal fibrosis, which appeared from PID 17 onward. CONCLUSIONS: Since the worms spontaneously died by PID 15, not only septal fibrosis production, but also its maintenance and further development appeared dependent on the presence of eggs, which were the only parasitic factor remaining thereafter.

Quality of essential drugs in tropical countries: evaluation of antimalarial drugs in the Brazilian Health System

INTRODUCTION: The emergence of drug resistance is one of the main problems concerning malaria treatment. The use of counterfeit and/or substandard antimalarial drugs can contribute to the development of parasite resistance. Thus, the aim of this study was to evaluate the quality of antimalarial drugs distributed in Brazil. METHODS: Samples containing chloroquine phosphate, mefloquine hydrochloride, primaquine phosphate, and quinine sulfate tablets were delivered to the Rio de Janeiro central storeroom (CENADI), state storerooms (SS), and Basic Health Units (BHUs) in the north region of Brazil - a total of 10 sample sets. After 5 months of storage, the samples were collected, and in vitro quality control analyses according to official and published methods were performed. RESULTS: Inadequate drug storage conditions were found in two SS and in all BHUs evaluated. There were no quality deviations found in the chloroquine samples. The quinine samples exhibited weight variation above the allowed limits. The primaquine samples were found to have packaging deficiency. The release of mefloquine in samples from some regions showed a statistically significant difference when compared with the CENADI samples. CONCLUSIONS: It is important to periodically evaluate the quality and storage conditions of essential drugs. The quality deviations found with the primaquine and quinine samples are not related to storage conditions and must be addressed urgently. The decreased mefloquine release from tablets is related to formulation problems or influenced by inadequate storage conditions, prompting further investigation. Even with the mentioned problems, the samples would probably not contribute to resistant parasite selection.