Acute and chronic effects of the organophosphate malathion on the pancreatic α and ß cell viability, cell structure, and voltage-gated K+ currents.

Studies indicate that the pesticide malathion may have a role in diabetes. Herein, we determined the effects of different concentrations of malathion on survival, ultrastructure, and electrophysiologic islet cell parameters. Acutely, high concentrations of malathion (0.5 or 1 mM) increased cell death in rat islet cells, while low concentrations (0.1 mM) caused signs of cell damage in pancreatic α and ß cells. Exposure of RINm5F cells to malathion for 24 or 48 h confirmed the reduction in ß-cell viability at lower concentrations (0.001-100 µM). Chronic exposure of mouse pancreatic α and ß cells to 3 nM of malathion led to increased voltage-gated K+ (Kv) currents in α-cells. Our findings show a time and concentration dependency for the malathion effect on the reduction of islet cell viability and indicate that pancreatic α cells are more sensitive to malathion effects on Kv currents and cell death.

Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum.

We evaluated whether hyaluronan (HA) levels in the sputum could be used as a noninvasive tool to predict progressive disease and treatment response, as detected in a computed tomography scan in non-small cell lung cancer (NSCLC) patients. Sputum samples were collected from 84 patients with histological confirmation of NSCLC, 33 of which were in early-stage and 51 in advanced-stage disease. Patients received systemic chemotherapy (CT) after surgery (n=36), combined CT and immunotherapy (IO) (n=15), or targeted therapy for driver mutation and disease relapse (N=4). The primary end-point was to compare sputum HA levels in two different concentrations of hypertonic saline solution with overall survival (OS) and the secondary and exploratory end-points were radiologic responses to treatment and patient outcome. Higher concentrations of HA in the sputum were significantly associated to factors related to tumor stage, phenotype, response to treatment, and outcome. In the early stage, patients with lower sputum HA levels before treatment achieved a complete tumor response after systemic CT with better progression-free survival (PFS) than those with high HA levels. We also examined the importance of the sputum HA concentration and tumor response in the 51 patients who developed metastatic disease and received CT+IO. Patients with low levels of sputum HA showed a complete tumor response in the computed tomography scan and stable disease after CT+IO treatment, as well as a better PFS than those receiving CT alone. HA levels in sputum of NSCLC patients may serve as a candidate biomarker to detect progressive disease and monitor treatment response in computed tomography scans.

Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum

We evaluated whether hyaluronan (HA) levels in the sputum could be used as a noninvasive tool to predict progressive disease and treatment response, as detected in a computed tomography scan in non-small cell lung cancer (NSCLC) patients. Sputum samples were collected from 84 patients with histological confirmation of NSCLC, 33 of which were in early-stage and 51 in advanced-stage disease. Patients received systemic chemotherapy (CT) after surgery (n=36), combined CT and immunotherapy (IO) (n=15), or targeted therapy for driver mutation and disease relapse (N=4). The primary end-point was to compare sputum HA levels in two different concentrations of hypertonic saline solution with overall survival (OS) and the secondary and exploratory end-points were radiologic responses to treatment and patient outcome. Higher concentrations of HA in the sputum were significantly associated to factors related to tumor stage, phenotype, response to treatment, and outcome. In the early stage, patients with lower sputum HA levels before treatment achieved a complete tumor response after systemic CT with better progression-free survival (PFS) than those with high HA levels. We also examined the importance of the sputum HA concentration and tumor response in the 51 patients who developed metastatic disease and received CT+IO. Patients with low levels of sputum HA showed a complete tumor response in the computed tomography scan and stable disease after CT+IO treatment, as well as a better PFS than those receiving CT alone. HA levels in sputum of NSCLC patients may serve as a candidate biomarker to detect progressive disease and monitor treatment response in computed tomography scans.

miRNA-34 and miRNA-210 target hexamerin genes enhancing their differential expression during early brain development of honeybee (Apis mellifera) castes.

During the honeybee larval stage, queens develop larger brains than workers, with morphological differentiation appearing at the fourth larval phase (L4), just after a boost in nutritional difference both prospective females experience. The molecular promoters of this caste-specific brain development are already ongoing in previous larval phases. Transcriptomic analyses revealed a set of differentially expressed genes in the L3 brains of queens and workers, which represents the early molecular response to differential feeding females receive during larval development. Three genes of this set, hex70b, hex70c and hex110, are more highly transcribed in the brain of workers than in queens. The microRNAs miR-34, miR-210 and miR-317 are in higher levels in the queens' brain at the same phase of larval development. Here, we tested the hypothesis that the brain of workers expresses higher levels of hexamerins than that of queens during key phases of larval development and that this differential hexamerin genes expression is further enhanced by the repressing activity of miR-34, miR-210 and miR-317. Our transcriptional analyses showed that hex70b, hex70c and hex110 genes are differentially expressed in the brain of L3 and L4 larval phases of honeybee queens and workers. In silico reconstructed miRNA-mRNA interaction networks were validated using luciferase assays, which showed miR-34 and miR-210 negatively regulate hex70b and hex110 genes by directly and redundantly binding their 3'UTR (untranslated region) sequences. Taken together, our results suggest that miR-34 and miR-210 act together promoting differential brain development in honeybee castes by downregulating the expression of the putative antineurogenic hexamerin genes hex70b and hex110.

MicroRNA signatures characterizing caste-independent ovarian activity in queen and worker honeybees (Apis mellifera L.).

Queen and worker honeybees differ profoundly in reproductive capacity. The queen of this complex society, with 200 highly active ovarioles in each ovary, is the fertile caste, whereas the workers have approximately 20 ovarioles as a result of receiving a different diet during larval development. In a regular queenright colony, the workers have inactive ovaries and do not reproduce. However, if the queen is sensed to be absent, some of the workers activate their ovaries, producing viable haploid eggs that develop into males. Here, a deep-sequenced ovary transcriptome library of reproductive workers was used as supporting data to assess the dynamic expression of the regulatory molecules and microRNAs (miRNAs) of reproductive and nonreproductive honeybee females. In this library, most of the differentially expressed miRNAs are related to ovary physiology or oogenesis. When we quantified the dynamic expression of 19 miRNAs in the active and inactive worker ovaries and compared their expression in the ovaries of virgin and mated queens, we noted that some miRNAs (miR-1, miR-31a, miR-13b, miR-125, let-7 RNA, miR-100, miR-276, miR-12, miR-263a, miR-306, miR-317, miR-92a and miR-9a) could be used to identify reproductive and nonreproductive statuses independent of caste. Furthermore, integrative gene networks suggested that some candidate miRNAs function in the process of ovary activation in worker bees.

Seedling survival of Handroanthus impetiginosus (Mart ex DC) Mattos in a semi-arid environment through modified germination speed and post-germination desiccation tolerance.

Uniform rapid seed germination generally forms a great risk for the plant population if subsequent intermittent precipitation causes desiccation and seedling death. Handroanthus impetiginosus can be found commonly in a wide range of biomes within Brazil including those that are semi-arid. Germination and early growth was studied to understand how germinated seeds survive under these stringent conditions. Accessions were sampled from four seasonally dry biomes in Brazil. Precipitation at the start of the rainy season in the Caatinga, a semi-arid biome, is less predictable and the number of successive dry days per dry interval in the first four months of the rainy season was higher than in the other studied biomes. Plants from the Caatinga produced thicker seeds and this trait concurred with slow germination and stronger osmotic inhibition of germination across the accessions, forming a stress avoidance mechanism in the Caatinga. Post-germination desiccation tolerance was high in the Caatinga accession, could be re-induced in accessions from biomes with more regular precipitation (Cerrado and transition zone), but remained poor in the Cerradão accession; thus forming a stress tolerance mechanism. Production of adventitious roots ascertained survival of all tested individuals from all four locations, even if protruded radicles did not survive desiccation, forming an additional stress tolerance mechanism. A sequence of stress avoidance and stress tolerance mechanisms in seeds and germinated seeds was associated with precipitation patterns in different biomes. These mechanisms purportedly allow rapid seedling establishment when conditions are suitable and enable survival of the young seedling when conditions are adverse.

Seedling survival of Handroanthus impetiginosus (Mart ex DC) Mattos in a semi-arid environment through modified germination speed and post-germination desiccation tolerance / Sobrevivência de plântulas de Handroanthus impetiginosus (Mart ex DC) Mattos em ambiente semi-árido ocorre por modificação da velocidade de germinação e da tolerância à dessecação pós germinação

Abstract Uniform rapid seed germination generally forms a great risk for the plant population if subsequent intermittent precipitation causes desiccation and seedling death. Handroanthus impetiginosus can be found commonly in a wide range of biomes within Brazil including those that are semi-arid. Germination and early growth was studied to understand how germinated seeds survive under these stringent conditions. Accessions were sampled from four seasonally dry biomes in Brazil. Precipitation at the start of the rainy season in the Caatinga, a semi-arid biome, is less predictable and the number of successive dry days per dry interval in the first four months of the rainy season was higher than in the other studied biomes. Plants from the Caatinga produced thicker seeds and this trait concurred with slow germination and stronger osmotic inhibition of germination across the accessions, forming a stress avoidance mechanism in the Caatinga. Post-germination desiccation tolerance was high in the Caatinga accession, could be re-induced in accessions from biomes with more regular precipitation (Cerrado and transition zone), but remained poor in the Cerradão accession; thus forming a stress tolerance mechanism. Production of adventitious roots ascertained survival of all tested individuals from all four locations, even if protruded radicles did not survive desiccation, forming an additional stress tolerance mechanism. A sequence of stress avoidance and stress tolerance mechanisms in seeds and germinated seeds was associated with precipitation patterns in different biomes. These mechanisms purportedly allow rapid seedling establishment when conditions are suitable and enable survival of the young seedling when conditions are adverse.

Resumo A germinação rápida e uniforme geralmente pode apresentar riscos para a população de plantas caso a precipitação ocorra de maneira intermitente, provocando seca e morte das plântulas. Handroanthus impetiginosus pode ser encontrado em uma grande variedade de biomas no Brasil. A germinação e o crescimento inicial das plântulas de Handroanthus impetiginosus foram estudadas para compreender como as sementes germinadas sobrevivem nestas condições. Acessos de quatro biomas que apresentam secas sazonais foram amostrados. A precipitação, no início da estação chuvosa na Caatinga, um bioma semi-árido, é menos previsível e o número de dias secos consecutivos por intervalo de seca, nos primeiros quatro meses da estação chuvosa, foi maior do que nos outros biomas estudados. Plantas do bioma Caatinga produzem sementes mais espessas e essa característica está associada com uma germinação lenta e com a inibição osmótica maior da germinação através dos acessos, formando um mecanismo para evitar o estresse. Tolerância à dessecação em sementes germinadas foi superior no bioma Caatinga e que podem ser reinduzida em acesso com uma precipitação mais regular (Cerrado e na zona de transição), mas manteve-se baixa no acesso Cerradão, formando assim um mecanismo para evitar o estresse. Produção de raízes adventícias foi observada nos indivíduos estudados de todos os quatro biomas, mesmo quando as raízes primárias não sobreviveram à dessecação, formando um mecanismo adicional de tolerância ao estresse. Assim, foi observado estratégias para evitar o estresse e mecanismos de tolerância ao estresse em sementes e sementes germinadas associada com padrões de precipitação nos diferentes biomas estudados. Estes mecanismos podem favorecer o estabelecimento das plântulas de forma rápida quando as condições são adequadas e permitirem a sobrevivência de plântulas quando as condições são adversas.

Low temperature affects cattle tick reproduction but does not lead to transovarial transmission of Anaplasma marginale.

Anaplasma marginale is an obligate intracellular pathogen that infects the erythrocytes of calves, causing bovine anaplasmosis. This rickettsia is biologically transmitted by several species of ticks. In tropical and subtropical regions of the world, Rhipicephalus microplus is the main vector. Due to their mobility and longevity, the adult males play an important role in the transmission of A. marginale to calves. Some studies have demonstrated that A. marginale can be intrastadially and interstadially transmitted in R. microplus, but the transovarial transmission has not been demonstrated so far. In the present study, we investigated the effects of low temperature on both the A. marginale migration from infected females to their offspring and reproductive parameters of the tick R. microplus. The larvae of R. microplus fed on a calf infected with the strain Jaboticabal of A. marginale. At the end of the parasitic phase, fully engorged females were incubated at either 18°C or 28°C for oviposition. Although A. marginale was detected in the salivary glands of the females, demonstrating that the ticks were successfully infected, the presence of rickettsia was not detected in the offspring. However, the preoviposition period of the non-infected females maintained at 18°C was longer than that of those maintained at 28°C. In addition, the average weight of the mass of eggs as well as the egg production efficiency (ratio of the egg mass weight to the female weight) of the females maintained at 18°C were significantly lower than those of the females incubated at 28°C. There was no larval hatching from the eggs maintained exclusively at 18°C, even at 65 days after female detachment. Hatching occurred only when the eggs maintained at 18°C were transferred to 28°C at 20 days after female detachment (18°C/28°C). We also verified a significantly higher larvae conversion efficiency (ratio of the larvae mass weight to the egg mass weight) in the group of females maintained exclusively at 28°C compared to those from the 18°C/28°C group. Collectively, our results reinforce that low temperature exerts negative effects on female fertility and egg development in R. microplus, although it has no influence on A. marginale transmission to the progeny. In the field, the detrimental effects of temperatures on tick reproductive fitness lead to a reduction of tick population, which may cause a decrease in the incidence of bovine anaplasmosis.

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy.

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

Armazenamento de sementes de Alfavaca-cravo (Ocimum gratissimum L. ) / Storage of Clove Basil (Ocimum gratissimum L. ) seeds

A espécie Ocimum gratissimum L. é um subarbusto aromático, pertencente à família Lamiaceae, considerado como importante produtor de óleo essencial e largamente utilizado na medicina popular. Devido à escassez de informações sobre a conservação das sementes dessa espécie o presente estudo objetivou analisar a longevidade das sementes submetidas a diferentes condições de armazenamento, por 12 meses, através de avaliações do potencial germinativo e da capacidade de formação de plântulas normais. As sementes foram armazenadas em três tipos de embalagens: sacos de papel, sacos de papel aluminizado, e frascos de vidro, e nas seguintes condições ambientais: balcão de laboratório, geladeira, e câmara fria. Aos 6, 8, 10 e 12 meses de armazenamento foram avaliados os seguintes parâmetros: umidade, porcentagem de germinação, índice de velocidade de germinação e porcentagem de plântulas normais. Durante o período de armazenamento a manutenção da umidade nas sementes foi mantida, bem como a porcentagem de germinação e de plântulas normais em todos os tratamentos avaliados. As sementes armazenadas apresentaram maiores valores de IVG quando comparadas com as recém-colhidas.

The Ocimum gratissimum L. species is an aromatic subshrub that belongs to the Lamiaceae family and is considered as an important producer of essential oil, widely used in folk medicine. Because of the lack of information about the conservation of O. gratissimum seeds, we aimed to evaluate the longevity of the seeds on different storage conditions for 12 months through the germination and seedling formation percentage in this study. The seeds were stored in three types of packages: paper bags (permeable), aluminized paper bags (semipermeable) and glass flasks (impermeable), in the settings of laboratory bench, refrigerator and cold room over the 12 month period. The germination tests were performed on the 6th, 8th, 10th and 12th month, when moisture, germinability, germination velocity index and percentage of normal seedlings were evaluated. During the storage period, moisture, germinability and percentage of normal seedling were kept in each storage condition. The stored seeds showed increased values of GSI compared to the newly- harvested ones.

Use of the Larval Tarsal Test to determine acaricide resistance in Rhipicephalus (Boophilus) microplus Brazilian field populations.

Acaricide resistance of the cattle tick Rhipicephalus (Boophilus) microplus is widespread in most of the countries where this parasite is present. Bioassays are used to diagnose the level and pattern of resistance in tick populations. In the present study, we describe a detailed protocol of the Larval Tarsal Test (LTT) using simplified equipment and data on the resistance of 17 tick field populations originating from 5 Brazilian states. Nine acaricidal compounds from 5 major classes were tested: organophosphates (OP), synthetic pyrethroids (SP), macrocyclic lactones (ML), phenylpyrazols (PYZ) and amidines. For comparison, four of the tick populations were also tested with the Larval Packet Test (LPT) with one compound per class. The most common resistances were to SP, amitraz and OP, with frequencies of 94%, 88% and 82%, respectively. Resistance to PYZ was also found to be widespread (65%), suggesting a rapid development of fipronil resistance in Brazil. One case of ML resistance and 2 cases of suspected ML resistance were identified with the LTT. The LTT led to higher resistance ratios to all compounds than the LPT, reflecting its high sensitivity to detect resistance. Finally, the LTT allowed testing a larger number of compounds and doses with reduced labour in comparison to the LPT and turned out to be a reliable bioassay to detect resistance in field populations.

Schistosomiasis mansoni: ultrasound-evaluated hepatic fibrosis and serum concentrations of hyaluronic acid.

Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north-eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A-F, according to the World Health Organization's 'Niamey protocol'. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 µg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.

Occurrence of Ornithodoros brasiliensis Aragão (Acari: Argasidae) in São Francisco de Paula, RS, Southern Brazil.

There have been no reports of the endemic Ornithodoros brasiliensis (Aragão) in Rio Grande do Sul, southern Brazil, since the 1950s. In January 2007, 21 O. brasiliensis ticks were collected in a rural area named "Cruzinha" in the municipality of São Francisco de Paula, RS, and another population was sampled later that year (October) in Vargem do Cedro, another rural area of São Francisco de Paula, following reports of human parasitism by ticks. The reappearance of this tick is a reason for concern in terms of public health.

Diagnoses of fipronil resistance in Brazilian cattle ticks (Rhipicephalus (Boophilus) microplus) using in vitro larval bioassays.

Fipronil is a phenylpyrazolic insecticide that is widely used in agriculture and has been recently used to control the cattle tick, Rhipicephalus (Boophilus) microplus. Because of the serious problems associated with resistance to the available acaricides, this product has been used as an important alternative to control acaricide-resistant ticks. The objective of this work was to analyse the fipronil sensitivity of ticks that were collected from farms with a history of fipronil use by larval bioassays. A total of 11 Brazilian tick populations were studied: one population from Rio Grande do Sul, one population from Mato Grosso do Sul and nine populations from São Paulo. To validate the assays, susceptible reference strains, POA (Porto Alegre, Brazil) and Mozo (Dilave, Uruguay), and ticks from six different farms that never used fipronil were tested. The resistance of various tick populations to technical grade fipronil (95.3%) was primarily evaluated using the larvae immersion test (LIT) and the larval packet test (LPT), when a sufficient number of larvae was collected. Using the LIT, the resistance ratios (RR(50)) of the tick populations from Rio Grande do Sul and Mato Grosso do Sul were 14.9 and 2.6, respectively, and the populations derived from São Paulo had RR(50)s ranging from 2.5 to 6.9. Four populations were evaluated with the LPT, and two populations displayed lower RR(50), while other populations displayed higher RR(50) than those determined by the LIT. This article reports the first cases of fipronil resistance in Brazil and highlights the LIT as a more sensitive technique for the evaluation of fipronil resistance in R. (B) microplus ticks. We suggest the use of the LIT as an evaluation tool for monitoring fipronil resistance in the control programmes of R. (B) microplus.

Chondroitin sulfate and kallikrein in saliva: markers for glossodynia.

Glossodynia or burning mouth syndrome is a multifunctional disorder. The oral mucosa is apparently normal but patients report burning and dried mouth and painful tongue and lips. The present study reports biochemical and physiological markers in saliva of patients presenting glossodynia compared to normal subjects. Saliva-buffering capacity and contents of protein and hyaluronic (HA) acid were similar in both groups. In contrast, chondroitin sulfate (CS) concentration was decreased in the saliva of patients with glossodynia when compared to control group (p=0.0036). On the other hand glandular kallikrein showed increased activity in the saliva of patients compared to normal subjects (p<0.0001). The data suggest involvement of the kinin system, possibly related to the low levels of CS. Depression could explain the low level of serotonin in patient serum (p=0.0478).

Ticks (Ixodidae) on humans in South America.

Twenty eight species of Ixodidae have been found on man in South America (21 Amblyomma, 1 Boophilus, 2 Dermacentor, 2 Haemaphysalis, 1 Ixodes and 1 Rhipicephalus species). Most of them are rarely found on man. However, three species frequently parasitize humans in restricted areas of Argentina (A. neumanni reported from 46 localities), Uruguay (A. triste from 21 sites) and Argentina-Brazil (A. parvum from 27 localities). The most widespread ticks are A. cajennense (134 localities in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Paraguay, Suriname and Venezuela), A. ovale (37 localities in Argentina, Brazil, Ecuador, French Guiana, Guyana, Paraguay, Suriname and Venezuela) and A. oblongoguttatum (28 sites in Brazil, Colombia, French Guiana, Guyana, Suriname and Venezuela). Amblyomma aureolatum (18 localities in Argentina, Brazil, French Guiana and Paraguay), A. cajennense, and A. triste are vectors of rickettsioses to man in South America. A better understanding of the respective roles of these and other tick species in transmitting pathogens to humans will require further local investigations. Amblyomma ticks should be the main subjects of these studies followed by species of Boophilus, Dermacentor, Haemaphysalis and Rhipicephalus species. In contrast with North America, Europe and Asia, ticks of the genus Ixodes do not appear to be major players in transmitting diseases to human. Indeed, there is only one record of an Ixodes collected while feeding on man for all South America.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease.

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87 percent accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100 percent), but with reduction in diagnostic sensitivity (64 percent). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70 percent). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

Pentoxifylline (PTX)--an alternative treatment in Graves' ophthalmopathy (inactive phase): assessment by a disease specific quality of life questionnaire and by exophthalmometry in a prospective randomized trial.

PURPOSE: To investigate the effect of pentoxifylline (PTX) in subjects with inactive Graves' ophthalmopathy (GO) through a specific quality of life (QOL) questionnaire and exophthalmometry readings. METHODS: Eighteen females were randomly divided in two groups. Group A (n=9) was treated with PTX 1200 mg orally/day for 6 months. Group B (n=9) received placebo during the initial 6 months and then PTX for another 6 months. Proptosis measurements were carried out every 3 months and a questionnaire graded from 0 to 10 according to the severity of the symptoms was performed at baseline and after placebo and PTX administration. RESULTS: At baseline, Group A questionnaire score values were 5.5 (median; range 3.5 to 8.0), and 5.0 after 6 months (3.0 to 6.0; p=0.01). In Group B, baseline values were not significantly different after 6 months of placebo: 6.0 (4.5 to 7.0) and 5.5 (4.5 to 7.0), respectively. However, a significant change was observed 6 months after PTX: 4.0 (2.0 to 5.0; p<0.001). Patients in Group A had a progressive improvement of proptosis during PTX: at baseline, 23 mm (median; range 20 to 32); after 3 months, 23 mm (18 to 30; p=0.02); and after 6 months, 23 mm (18 to 30; p=0.005). In Group B, proptosis remained stable during placebo: at baseline, 23 mm (21 to 25); after 3 months, 23 mm (20 to 25); and after 6 months, 23.5 mm (20 to 25). A significant change was observed after 3 and 6 months of PTX: 22 mm (19 to 24; p=0.0006) and 20.8 mm (17 to 25; p=0.0003), respectively. CONCLUSIONS: Pentoxifylline seems to improve the QOL of patients in the inactive phase of GO. The objective findings of the proptosis readings corroborate to suggest that PTX may be an effective and promising drug in the inactive phase of GO.