Structural parameters, molecular properties, and biological evaluation of some terpenes targeting schistosoma mansoni parasite

The use of natural products has a long tradition in medicine, and they have proven to be an important source of lead compounds in the development of new drugs. Among the natural compounds, terpenoids present broad-spectrum activity against infective agents such as viruses, bacteria, fungi, protozoan and helminth parasites. In this study, we report a biological screening of 38 chemically characterized terpenes from different classes, which have a hydroxyl group connected by hydrophobic chain or an acceptor site, against the blood fluke Schistosoma mansoni, the parasite responsible for schistosomiasis mansoni. In vitro bioassays revealed that 3,7-dimethyl-1-octanol (dihydrocitronellol) (10) was the most active terpene (IC50 values of 13­52 µM) and, thus, we investigated its antischistosomal activity in greater detail. Confocal laser scanning microscopy revealed that compound 10 induced severe tegumental damage in adult schistosomes and a correlation between viability and tegumental changes was observed. Furthermore, we compared all the inactive compounds with dihydrocitronellol structurally by using shape and charge modeling. Lipophilicity (miLogP) and other molecular properties (e.g. molecular polar surface area, molecular electrostatic potential) were also calculated. From the 38 terpenes studied, compound 10 is the one with the greatest flexibility, with a sufficient apolar region by which it may interact in a hydrophobic active site. In conclusion, the integration of biological and chemical analysis indicates the potential of the terpene dihydrocitronellol as an antiparasitic agent.

Comparative study of the accuracy of different technique for the laboratory diagnosis of schistosomiasis mansoni in areas of low endemicity in Barra Mansa City, Rio de Janeiro State, Brazil

Schistosomiasis constitutes a major public health problem, with an estimated 200 million people infected worldwide. Many areas of Brazil show low endemicity of schistosomiasis, and the current standard parasitological techniques are not sufficiently sensitive to detect the low-level helminth infections common in areas of low endemicity (ALEs). This study compared the Kato-Katz (KK); Hoffman, Pons, and Janer (HH); enzyme-linked immunosorbent assay- (ELISA-) IgG and ELISA-IgM; indirect immunofluorescence technique (IFT-IgM); and qPCR techniques for schistosomiasis detection in serum and fecal samples, using the circumoval precipitin test (COPT) as reference. An epidemiological survey was conducted in a randomized sample of residents from five neighborhoods of Barra Mansa, RJ, with 610 fecal and 612 serum samples. ELISA-IgM (21.4%) showed the highest positivity and HH and KK techniques were the least sensitive (0.8%). All techniques except qPCR-serum showed high accuracy (82­95.5%), differed significantly from COPT in positivity , and showed poor agreement with COPT. Medium agreement was seen with ELISA-IgG (Kappa = 0.377) and IFA (Kappa = 0.347). Parasitological techniques showed much lower positivity rates than those by other techniques. We suggest the possibility of using a combination of laboratory tools for the diagnosis of schistosomiasis in ALEs.

The first case of Angiostrongylus cantonesis eosinophilic meningitis diagnosed in the city of São Paulo, Brazil

Introduction: Angiostrongylus cantonensis is a natural parasite found in lung arteries of rats, which in humans may cause eosinophilic meningitis. Objective: To report the first case of eosinophilic meningitis caused by Angiostrongylus cantonensis in the city of São Paulo, Brazil. Case report: A male patient, 11 years old, living in the southern area of São Paulo, was admitted to the Pediatric Emergency Department with ongoing headaches for three days, but no fever or any other complaint. The presence of snails and rodents was reported in the peridomicile. The child was awake, lucid, oriented; muscular strength preserved, isochoric, photo reagent pupils and terminal nuchal rigidity - Glasgow Coma Scale (GCS) = 15. The laboratory tests showed a mild leukocytosis with 1736 eosinophils/mm3 and the CSF analysis disclosed 160 leukocytes/mm3 with 36% of eosinophils. The bacterial culture was negative. Computed Cerebral Tomography showed no alterations. The RT-PCR assay for detecting Angiostrongylus cantonensis larvae and DNA was negative. ELISA antibodies for IgG anti-A. cantonensis was negative in serum and undetermined in CSF and samples collected five days after the onset of symptoms. Seroconversion was observed in the sample collected 135 days later. Conclusion: the epidemiological and clinical data, the CSF alterations with eosinophilia and the seroconversion strongly suggest Angiostrongylus cantonensis eosinophilic meningitis.

Introdução: Angiostrongylus cantonensis é um parasito natural das artérias de pulmões de ratos, que pode causar, em humanos, meningite eosinofílica. Objetivo: Relatar o primeiro caso de meningite eosinofílica causado por A. cantonensis na cidade de São Paulo, Brasil. Relato de caso: Paciente do sexo masculino, 11 anos, residente na zona sul de São Paulo, foi admitido no serviço de emergência pediátrica com história de cefaléia há três dias, sem febre ou outras queixas. Relato de presença de moluscos e roedores no peridomicílio. Ao exame físico, criança desperta acianótica, anictérica, hidratada; lúcido, orientado; força muscular preservada, isocórica, pupilas fotorreagentes e rigidez de nuca terminal - Glasgow Coma Scale = 15. Exames laboratoriais indicaram leve leucocitose com 1736 eosinófilos/mm3 e a análise do líquor revelou a presença de 160 leucócitos/mm3 com 36% de eosinófilos. Cultura para bactérias negativa. Tomografia cerebral sem alterações. Pesquisa direta de larvas e de DNA por PCR-RT para Angiostrongylus cantonensis foi negativa. ELISA para anticorpos IgG anti-A. cantonensis negativo no soro e indeterminado no líquor nas amostras coletadas após cinco dias do início dos sintomas. Soroconversão observada na amostra coletada após 135 dias. Conclusão: A história epidemiológica, dados clínicos, alterações liquóricas com presença de eosinofilia e a soroconversão sugerem fortemente o diagnóstico de meningite eosinofílica por A. cantonensis.

Mastocytosis: a rare case of anaphylaxis in paediatric age and literature review.

The term "mastocytosis" denotes a heterogeneous group of disorders characterised by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Symptoms result from MC chemical mediator's release, pathologic infiltration of neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal defects seem to contribute to an autonomous growth, but somatic c-kit D816V mutation is more frequently encountered, especially in systemic disease. We present a literature review of mastocytosis and a rare case report of an 18 month-old-girl with a bullous dermatosis, respiratory distress and anaphylaxis, as clinical manifestations of mastocytosis. The developments of accepted classification systems and novel useful markers allowed a re-evaluation and updating of the classification of mastocytosis. In paediatric age cutaneous forms of disease prevail and may regress spontaneously. SM is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow. The clinical course in these patients is variable. Today diagnostic criteria for each disease variant are reasonably well defined. There are, however, peculiarities, namely in paediatric age, that makes the diagnostic approach difficult. Systemic disease may pose differential diagnostic problems resulting from multiple organ systems involvement. Conversely, the "unexplained" appearance of those symptoms with no skin lesions should raise the suspicion of MC disease. This case is reported in order to stress the clinical severity and difficult diagnostic approach that paediatric mastocytosis may assume.

[Aedes albopictus in rural zone of Brazil and its implication in the wild yellow fever transmission]. / Aedes albopictus em área rural do Brasil e implicações na transmissão de febre amarela silvestre.

Larvae and adult forms of Aedes albopictus were found during ecological study of anopheline mosquitos in the rural zone of the state of Mato Grosso do Sul in Brazil. This occurrence was registered, for the first time in Brazil, in an enzoootic area if sylvatic yellow fever virus. This implies a potential risk of the transfer of this virus to an urban area infested with Aedes aegypti.

Life cycle of Trypanosoma cruzi (Y strain) in mice.

Since 1958, we have studied experimental Chagas' disease (CD) by subcutaneous inoculation of 1,000 blood forms of Trypanosoma cruzi (Y strain) in Balb/C. mice. Evolution of parasitemia remained constant, beginning on the 5th and 6th day of the disease, increasing progressively, achieving a maximum on about the 30th day. After another month, only a few forms were present, and they disappeared from the circulation after the third month, as determined from direct examination of slides and the use of a Neubauer Counting Chamber. These events coincided with the appearance of amastigote nests in the tissues (especially the cardiac ones), starting the first week, and following the Gauss parasitemia curve, but they were not in parallel until the chronic stage. In 1997, we began to note the following changes: Parasites appeared in the circulation during the first week and disappeared starting on the 7th day, and there was a coincident absence of the amastigote nests in the tissues. A careful study verified that young forms in the evolutionary cycle of T. cruzi (epi + amastigotes) began to appear alongside the trypomastigotes in the circulation on the 5th and 7th post-inoculation day. At the same time, rounded, oval, and spindle shapes were seen circulating through the capillaries and sinusoids of the tissues, principally of the hematopoietic organs. Stasis occurs because the diameter of the circulating parasites is greater than the vessels, and this makes them more visible. Examination of the sternal bone marrow revealed young cells with elongated forms and others truncated in the shape of a "C" occupying the internal surface of the blood cells that had empty central portions (erythrocytes?). We hypothesize that there could be a loss of virulence or mutation of the Y strain of Trypanosoma cruzi.

Santo Inácio revisited: protozoan diseases in an isolated village in northeastern Brazil after twenty years.

The northeastern highlands of Brazil are endemic for several tropical diseases, especially American trypanosomiasis (Chagas' disease) and schistosomiasis. Twenty years ago, we measured the seroprevalence of protozoan diseases in Santo Inácio, a village of approximately 1,000 inhabitants located 1,000 m above sea level. We detected small numbers of sera with antibodies against Trypanosoma cruzi and Toxoplasma gondii, and the area had a low prevalence both of American trypanosomiasis (3.54%) and toxoplasmosis (27.43%) compared with nearby Brazilian areas. This was attributed to a specific triatomine vector and local housing conditions. Twenty years later, we again determined the prevalences of both diseases and compared these results with those from Iraquara, a larger town with the same ethnic and social background but with a higher prevalence of rural activities. The incidence of Chagas' disease in San Inácio showed the same low level, i.e., 3.78% (5 of 132) with only adult males affected in contrast with Iraquara, which had an incidence of 34.5%, but a low prevalence of only one of 22 among children up to 14 years of age. Santo Inácio maintained a low (25.8%) seroprevalence for toxoplasmosis. Housewives presented a higher incidence of toxoplasmosis during both periods, probably due to related risk factors. Cats were found less frequently in Santo Inácio than in Iraquara, which showed an incidence of 65.5% seropositivity for Toxoplasma gondii. These results suggest that the environmental conditions of Santo Inácio were preserved after 20 years, with a low incidence of these selected protozoan diseases.

Soluble CD30, dehydroepiandrosterone sulfate and dehydroepiandrosterone in atopic and non atopic children.

Elevated levels of soluble CD30-sCD30 (possibly related to Th2) are seen in atopy and other diseases. Dehydroepiandrosterone (DHEA) may regulate Th1/Th2 balance. The aim was to study the relationship between the levels of sCD30, DHEAS and DHEA in atopic (A) and non atopic (B) children, to assess immune-endocrine interactions. We studied 36 children (8-15 years), 18 (A) monosensitised to Dermatophagoides Pteronyssinus (Dpt.), and 18 (B) with isolate rhinitis (R) or asthma (BA) and R (33.3%) without differences in age and sex. They were all HIV negative and free from any medication. It was determined sCD30, DHEAS and DHEA. There was no statistically significant differences between A and B for the levels of DHEAS, DHEA suggesting that the role of this regulation in Th2 type is not important in patients with allergic disease in this age group. sCD30: A-mean 121.1U/ml; B-mean 53.9U/ml. This difference is statistically significant-p = 0.02. sCD30 in patients only with R showed also significant differences-p = 0.01. These results could reflect the Th2 profile. There is an overlap of the values (for R < 80 U/ml; for BA + R < 140 U/ml). Due to this only values > 80 U/ml for R and > 140 U/ml for BA + R could be considered discriminating for atopy.

Atopy and enteroparasites.

UNLABELLED: There are not many studies about the intestinal parasitosis (IP) and atopic asthma (AA) relationship, and these show discordant results, possibly due to different studies design and differences in population selection. On the basis of personal results obtained by an epidemiological inquiry designed to estimate the prevalence of enteroparasitoses in asthmatic children and vice vesa, the aim of this study was to compare the prevalence of IP in AA and in a control group (CG) by a cross sectional study using clinical and laboratorial parameters, applied to 63 children (47 with AA and 16 in CG) aged 6 to 11 years, 37 males and 26 females, Caucasians, with the same socioeconomical conditions, consecutively selected in our Hospital. The results showed: The IP in AA children was 21.3%; the IP in CG was 25%; in the group with AA and IP, 40% of them had symptomology of IP; in the CG with IP, 100% had symptoms. CONCLUSIONS: The IP prevalence in AA was not statistically different from the IP in CG (p > 0.05) More data are needed to clarify the significant differences between the symptomatology rates of IP in asthmatic and non asthmatics; the reduced number of patients with symptoms in AA may reflect modulation of IP in AA and/or different parasite load.

ALATOP-RIA in the screening of atopy in a non Caucasian population.

UNLABELLED: ALATOP is an "in vitro" radioimmunoassay screening test for atopy, previously validated in a caucasian population. The aim of the study was to assess the usefulness of a screening test of atopy in a non caucasian population. We select a non caucasian population (n = 208), from hospital immunoallergy consultations, Cape Verde Republic (Africa). It was determined the sensitivity, specificity and predictive values comparing with skin prick tests (SPT) results for the 208 patients, and with clinical data (Clin) in 115 patients. It was also determined the levels of total IgE, done by IRMA. RESULTS: Using different corrections factors, 0.85 gives the best results: ALATOP/SPT-Sensitivity-88.5% +/- 4.34; Specificity-73.8% +/- 8.41; Positive predictive value-66.9%; Negative predictive value-91.4%; Efficiency of the test-79.3%. ALATOP/CLIN-Sensitivity-95.2% +/- 3.89; Specificity-71.2% +/- 12.07; Positive predictive value-65.6%; Negative predictive value-96.2%; Efficiency of the test-80.0%. The mean values of total IgE were-406 IU/ml. CONCLUSIONS: The mean value of total IgE was significantly increased even in the ALATOP-/SPT-not saw in caucasian populations. The use of a different correction factor (0.85) for ALATOP, optimize the test, showing a good negative predictive value, but raises the question of adapted compositions of screening tests for different populations.