Assessment of oltipraz in schistosomiasis mansoni clinical trial

Seventy three children (6-15 years) and 75 adults (18-47 years) with active schistosomiasis mansoni were treated with oltipraz. All cases had at least 100 eggs per gram of feces as determined by the Kato-Katz technique. Children and adults were divided in two groups receiving respectively 25 or 30 mg/kg, as a single oral dose. Clinical examination, laboratories tests (haemogram, urinalysis, hepatic and kidney functions tests, glycemia, cholesterol, triglicerides, lipoprotein — HLD and LDL) and ECG were performed before, 3 or 7 days and 1 month after treatment. Parasitological control with 3 daily coprological examinations, was done on the 1st, 3rd j 6th month after drug administration. Giddiness, somnolence, headache, nausea, vomiting and abdominal distress were the most frequent side effects. Pain in the finger tips that need further investigations also occurred. No significant alteration in complementary tests were observed, whereas eosinophilia 1 month after treatment was detected, probably indicating worm death. The cure rate in children was 81.8% and 74.2% with 25 and 30 mg/kg respectively, and in adults 75.0% and 81.2% of the patients. No statistical significant difference was observed between cure rate and side effects at different dosages employed, neither between adults nor children. In all groups the percentage of egg reduction in feces in the non cured patients was higher than 96.0%. Further investigation with this new compound is necessary to accomplish the real value of oltipraz in the schistosomiasis chemotherapy.

Tratamento da cisticercose subcutânea co praziquantel: um novo agente cestoidicida

Twenty adult patients presenting dermal cysticercosis without cerebral or ocular involvement were treated with praziquantel. The first eleven cases received 60 mg/kg/day and the last nine cases 30 mg/kg/day. In both groups the daily dose was split into three oral intakes 4 to 6 hours apart and the drug administration lasted for 6 consecutive days. The latter group of patients also got dexamethasone, 3 mg daily, from one day before until four days after the treatment period with praziquantel. The drug proved to be 100% efficacious as demonstrated histopathologically by the death of the cysticerci of Taenia solium (Cysticercus cellulosae) in serial biopsies taken from the 2nd week on after the end of treatment, as well as clinically by the steady disappearence of the dermal nodules during the 6 months following the therapy. Tolerance of praziquantel was good as the incidence and severity of side-effects were not relevant. The drug safety was confirmed through laboratory tests which failed to detect any abnormal findings related to the hematopoietic, liver and kidney functions.

Treatment of patients with Schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine

A double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects — mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea — were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls — three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs — despite their different chemical structures, pharmacological properties and mechanisms-of-action — induce similar side-effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations.

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.

Acquisition and data analysis related to changes in some forest soils properties after prescribed fire action

Controlled fires in forest areas are frequently used in most Mediterranean countries as a preventive technique to avoid severe wildfires in summer season. In Portugal, this forest management method of fuel mass availability is also used and has shown to be beneficial as annual statistical reports confirm that the decrease of wildfires occurrence have a direct relationship with the controlled fire practice. However prescribed fire can have serious side effects in some forest soil properties. This work shows the changes that occurred in some forest soils properties after a prescribed fire action. The experiments were carried out in soil cover over a natural site of Andaluzitic schist, in Gramelas, Caminha, Portugal, that had not been burn for four years. The composed soil samples were collected from five plots at three different layers (0-3cm, 3-6cm and 6-18cm) during a three-year monitoring period after the prescribed burning. Principal Component Analysis was used to reach the presented conclusions.

Schistosoma mansoni: preclinical studies with 9-acridanone-hydrazones in Cebus monkeys experimentally infected

Derivatives of acridine (9-Acridanone-hydrazones) were tested in Cebus monkeys experimentally infected with Schistosoma mansoni, at the dosages of 50, 25, and 12.5 mg/kg (p.o., single dose). At least, four compounds seemed to be very promising, promoting alterations in the oogram and reducing the worm burden drastically, even at the lowest dose (12.5 mg/kg). No side effects could be detected after drug administration.

A farmacogenética e a medicina personalizada

A farmacogenética tem por objetivo a identificação de diferenças genéticas entre indivíduos que possam influenciar a resposta à terapêutica farmacológica, melhorando a sua eficácia e segurança. Associado à farmacogenética surge a “medicina personalizada”, ou seja, em oposição à existência de um fármaco que consiga tratar todos os pacientes, o tratamento individualizado parece o caminho mais promissor, uma vez que reduz o risco de reações adversas por toxicidade (segurança), adequa a dose ao indivíduo, evitando excessos ou défices (dose) e evita a metodologia de tentativa erro na escolha do fármaco (eficácia). A farmacogenética é relevante para a resposta individual ao fármaco por duas vias distintas: a farmacocinética e a farmacodinâmica. A variabilidade genética pode afetar a forma como um fármaco pode ser absorvido, ativado, metabolizado ou excretado, podendo conduzir assim a uma variabilidade na resposta. De entre o número infindável de possíveis exemplos, nesta revisão apresentam-se exemplos relacionados com os genes do Citocromo P450, do gene NAT2 e do gene da Colinesterase. As diferenças genéticas entre os indivíduos podem ainda afetar a resposta ao fármaco pela sua farmacodinâmica, ou seja, a resposta específica do alvo ao fármaco. De entre a multiplicidade de alvos de fármacos existentes serão apresentados exemplos do gene da G6PD e do VKORC1. Apesar de alguns dados científicos indicarem benefício para o paciente, ainda está longe de a farmacogenética fazer parte da prática clínica de rotina, talvez porque os custos-benefícios ainda não foram avaliados de forma precisa.

Drug susceptibility of Plasmodium falciparum in the western Amazon region, state of Acre, Brazil

Field studies in the western Amazon region (state of Acre, Brazil) indicate that the 4-aminoquinolines, as well as the combined regimen with sulfadoxine-pyrimethamine, can no longer be recomended for the treatment and prophylaxis of P. falciparum infections in this region. Quinine remains an effective drug when used correctly. However, compliance problems arise due to the often occurring side-effects during a ten day regimen. Prospects of overcoming these constraints by combining a short course of quinine with other drugs are limited, because of the lack of suitable partner compounds. For this reason quinine/clindamycin appears to be a more practical therapy of P. falciparum malaria. In vitro data from this study suggest that mefloquine is another effective alternative for the treatment of falciparum malaria in this Amazon region.

A comprehensive high-throughput FTIR spectroscopy-based method for evaluating the transfection event: estimating the transfection efficiency and extracting associated metabolic responses

Reporter genes are routinely used in every laboratory for molecular and cellular biology for studying heterologous gene expression and general cellular biological mechanisms, such as transfection processes. Although well characterized and broadly implemented, reporter genes present serious limitations, either by involving time-consuming procedures or by presenting possible side effects on the expression of the heterologous gene or even in the general cellular metabolism. Fourier transform mid-infrared (FT-MIR) spectroscopy was evaluated to simultaneously analyze in a rapid (minutes) and high-throughput mode (using 96-wells microplates), the transfection efficiency, and the effect of the transfection process on the host cell biochemical composition and metabolism. Semi-adherent HEK and adherent AGS cell lines, transfected with the plasmid pVAX-GFP using Lipofectamine, were used as model systems. Good partial least squares (PLS) models were built to estimate the transfection efficiency, either considering each cell line independently (R 2 ≥ 0.92; RMSECV ≤ 2 %) or simultaneously considering both cell lines (R 2 = 0.90; RMSECV = 2 %). Additionally, the effect of the transfection process on the HEK cell biochemical and metabolic features could be evaluated directly from the FT-IR spectra. Due to the high sensitivity of the technique, it was also possible to discriminate the effect of the transfection process from the transfection reagent on KEK cells, e.g., by the analysis of spectral biomarkers and biochemical and metabolic features. The present results are far beyond what any reporter gene assay or other specific probe can offer for these purposes.

A randomized clinical trial with high dose of chloroquine for treatment of Plasmodium falciparum malaria in Brazil

This clinical trial compared parasitological efficacy, levels of in vivo resistance and side effects of oral chloroquine 25 mg/Kg and 50 mg/Kg in 3 days treatment in Plasmodium falciparum malaria with an extended followed-up of 30 days. The study enroled 58 patients in the 25 mg/Kg group and 66 in the 50 mg/Kg group. All eligible subjects were over 14 years of age and came from Amazon Basin and Central Brazil during the period of August 1989 to April 1991. The cure rate in the 50 mg/Kg group was 89.4% on day 7 and 71.2% on day 14 compared to 44.8% and 24.1% in the 25 mg/Kg group. 74.1% of the patients in the 25 mg/Kg group and 48.4% of the patients in the 50 mg/Kg group had detectable parasitaemia at the day 30. However, there was a decrease of the geometric mean parasite density in both groups specially in the 50 mg/Kg group. There was 24.1% of RIII and 13.8% of RH in the 25 mg/Kg group. Side effects were found to be minimum in both groups. The present data support that there was a high level resistance to chloroquine in both groups, and the high dose regimen only delayed the development of resistance and its administration should not be recommended as first choice in malaria P. falciparum therapy in Brazil.

Predicting Xerostomia induced by IMRT treatments: A logistic regression approach

Radiotherapy is one of the main treatments used against cancer. Radiotherapy uses radiation to destroy cancerous cells trying, at the same time, to minimize the damages in healthy tissues. The planning of a radiotherapy treatment is patient dependent, resulting in a lengthy trial and error procedure until a treatment complying as most as possible with the medical prescription is found. Intensity Modulated Radiation Therapy (IMRT) is one technique of radiation treatment that allows the achievement of a high degree of conformity between the area to be treated and the dose absorbed by healthy tissues. Nevertheless, it is still not possible to eliminate completely the potential treatments’ side-effects. In this retrospective study we use the clinical data from patients with head-and-neck cancer treated at the Portuguese Institute of Oncology of Coimbra and explore the possibility of classifying new and untreated patients according to the probability of xerostomia 12 months after the beginning of IMRT treatments by using a logistic regression approach. The results obtained show that the classifier presents a high discriminative ability in predicting the binary response “at risk for xerostomia at 12 months”

Consumo de Fitoterápicos no Distrito de Viana do Castelo

A fitoterapia é umas das Medicinas Alternativas e/ou Complementares mais utilizadas pela população no quotidiano. Esta terapêutica é constituída por misturas de compostos químicos, que são responsáveis pelas suas ações no organismo. Estes compostos não atuam de forma independente, mas sim por efeito aditivo, antagónico ou sinérgico, resultando numa interação dos vários constituintes e dos diversos locais de ação. Nos últimos anos ressurgiu o interesse por esta terapia nos países desenvolvidos, principalmente devido aos efeitos secundários que os medicamentos convencionais podem provocar, e também pelo uso descontrolado e abusivo de certos fármacos. Deste modo, o número de estudos científicos com plantas e seus compostos tem vindo a aumentar ao longo dos anos, fornecendo evidências científicas quanto à sua segurança, aceitabilidade, eficácia, e mostrando menos efeitos secundários que os medicamentos convencionais. Com este projeto pretende-se caraterizar o conhecimento e o consumo de fitoterápicos pela população do distrito de Viana do Castelo. Aplicou-se um estudo observacional, descritivo do tipo transversal e analítico. A população alvo do estudo é a população em geral, residente no distrito de Viana do Castelo, com mais de 18 anos de idade. Para a recolha de informação foi realizado um questionário anónimo, confidencial e voluntário, a 914 individuos. A amostra é constituída maioritariamente por indivíduos do género feminino (58,3%). A faixa etária mais frequente é dos 18 aos 25 anos (19,7%) distribuída por todos os concelhos do distrito. Verificou-se que mais de 40% da população tem doença crónica, e mais de 60% recorreu a produtos fitoterápicos no último ano, havendo uma relação entre quem recorre a esta terapia e a existência de uma patologia crónica associada. Observou-se ainda que mais da 80% da população que utiliza estes produtos se encontra satisfeita com os resultados, sendo que mais de 85% dos utilizadores de fitoterápicos pretende voltar a utilizá-los.

Etiological drug treatment of human infection by Trypanosoma cruzi

Forty-nine American Trypanosomiasis (Chagas' disease) patients, with xenodiagnosis proven parasitemia were treated by the authors. Forty-one of these patients were given benznidazole, at dosages ranging from 5mg/kg/day to 8mg/kg/day, during a pre-established period of 60 days. In this group, 17 patients had an undetermined form of the disease, whereas 22 had cardiologic disease and 4 had digestive disease (two patients had a mixed form of the disease). Side effects were frequent, and led to the discontinuation of treatment in 17 patients. The follow-up period ranged from 1 to 20 years (mean follow-up period of 6 yrs. 7 mo). 26 (63.4%) of the patients became parasitemia-negative. The other eight patients were treated with nifurtimox, during 120 days, following a variable dose regime of 5mg/kg/day (initial dose) to 17 mg/kg/day (final dose). Six of them had severe side effects, and only one patient remained parasitemia-negative throughout the observation period (ranging from 1 to 18 years). Benznidazole proved to be better tolerated and more effective in the management of parasitemia when compared to nifurtimox, although more effective and less toxic drugs are still desirable.

Hepatic fascioliasis: case report and review

A well documented case of hepatic fascioliasis (HF), successfully treated with triclabendazole, is reported. Predominant clinical manifestations were fever, marked eosinophilia and abdominal pain. Triclabendazole was given as two single oral doses of 10 mg/kg each. Neither side effects nor clinical or parasitological relapses were seen after three months of follow up Based on this experience and few other similar reports in the literature, triclabendazole might be a valid therapeutical alternative in the treatment of human fascioliasis.

IMMUNOGENICITY OF LOW-DOSE INTRAMUSCULAR AND INTRADERMAL VACCINATION WITH RECOMBINANT HEPATITIS B VACCINE

The study is a randomized trial using recombinant DNA vaccine to determine whether an intramuscular 10 µg dose or intradermal 2 µg induces satisfactory anti-HBs levels compared to the standard dose of intramuscular 20 µg. participants were 359 healthy medical and nurse students randomly allocated to one of the three groups: Group I - IM 20 µg; Group II - IM 10 µg; Group III - ID 2 µg at 0, 1 and 6 months. Anti-HBs titres were measured after complete vaccine schedule by ELISA/Pasteur. Baseline variables were similar among groups and side effects were mild after any dose. Vaccinees in the IM-10 µg group had seroconversion rate and geometric mean titre (GMT 2344 IU L-1), not significant different from the IM-20 µg group (GMT 4570 IU L-1). On the contrary, 21.4% of the ID - 2 µg recipients mount antibody concentration below 10 IU L1 and GMT of 91 IU L-1, a statiscally significant difference compared with the standard schedule IM-20 µg (p < 0.001). A three dose regimen of half dosse IM could be considered an appropriate schedule to prevent hepatitis B in young health adults which is of relevance to the expansion of hepatitis B vaccine programme