Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame.

The use of artificial sweeteners has increased together with the epidemic growth of obesity. In addition to their widespread use in sodas, artificial sweeteners are added to nearly 6000 other products sold in the US, including baby foods, frozen dinners and even yogurts. It has been suggested that the use of nonnutritive sweeteners can lead to body weight gain and an altered metabolic profile. However, very few studies have evaluated the effects of maternal consumption of artificial non-caloric sweeteners on body weight, feeding behavior or the metabolism of offspring in adult life. In this study, we found that animals exposed to aspartame during the prenatal period presented a higher consumption of sweet foods during adulthood and a greater susceptibility to alterations in metabolic parameters, such as increased glucose, LDL and triglycerides. These effects were observed in both males and females, although they were more pronounced in males. Despite the preliminary nature of this study, and the need for further confirmation of these effects, our data suggest that the consumption of sweeteners during gestation may have deleterious long-term effects and should be used with caution.

Generalized thermodynamic and transport properties. I. Simple liquids.

We propose a method by which the generalized transport properties and coefficients at all wavelengths and frequencies can be obtained by inversion of an exact kinetic equation. The necessary data are the density-density, energy-energy, and density-energy time correlation functions, which can be obtained by molecular-dynamics simulation. In addition, also the coupling between viscous stress tensor and energy flux vector can be obtained without approximation. This allows one to check the validity of the Markov assumption in a straightforward way. As a first test case, the theory is applied to liquid argon in two thermodynamic states. For this system, we calculate and discuss generalized thermodynamic (enthalpy, specific heats, and thermal expansion) and transport properties (longitudinal viscosity, thermal conductivity).

Generalized thermodynamic and transport properties. II. Molecular liquids.

In the present paper, we extend the method described in paper I [D. Bertolini and A. Tani, preceding paper, Phys. Rev. E 83, 031201 (2011)] to molecular liquids, which allows us to solve the exact kinetic equation proposed by de Schepper et al. [Phys. Rev. A 38, 271 (1988)] without approximations. In particular, generalized thermodynamic properties (enthalpy, specific heat, and thermal expansion coefficient) and transport properties (longitudinal viscosity, thermal conductivity) have been calculated for three liquids of increasing complexity, namely dimethyl sulfoxide, hydrogen fluoride, and SPC/E water. All results have been obtained by the molecular formalism as well as the atomic one, corrected for intramolecular correlations that are due to the models adopted. As done for simple liquids, the coupling between the viscous stress tensor and the energy flux vector has been calculated exactly. We also show that the Markov assumption for the dynamics related to thermal conductivity can only be adopted with caution.

[Role of endoscopy in the management of obscure gastrointestinal bleeding]. / Rôle de l'endoscopie dans la prise en charge des saignements digestifs d'origine obscure.

Obscure gastrointestinal bleeding is defined as a blood loss in the digestive tract without etiology found at upper digestive endoscopy and colonoscopy. Small bowel lesions, in particular angiodysplasias, are the most frequent cause. Endoscopic examination of the small bowel can be performed using an enteroscope (with or without balloon) or a videocapsule. Videocapsule endoscopy is a minimally invasive procedure, and it allows complete small bowel exploration in 80% of cases (vs. 40-80% with balloon-aided enteroscopy). In practice, videocapsule endoscopy is the first line exam, followed by enteroscopy for biopsy sampling or treatment. In case of completely negative investigations and persistent bleeding, videocapsule endoscopy may be repeated, generally after repeat upper digestive endoscopy and colonoscopy.

Aspectos epidemiológicos da Leishmaniose Tegumentar Americana na região Noroeste do Estado do Paraná / Epidemiological aspects of American Cutaneous Leismaniasis in the northwest region of the state of Paraná

No Estado do Paraná, a primeira notificação de leishmaniose tegumentar americana ocorreu em 1917 e a partir de 1980 observou-se um aumento do número de casos, mantendo-se endêmica e acometendo pessoas de todas as faixas etárias e em ambos os sexos. Este estudo teve como objetivo realizar um levantamento epidemiológico sobre a ocorrência de LTA em pacientes atendidos no Laboratório de Ensino e Pesquisa em Análises Clínicas da Universidade Estadual de Maringá (LEPAC/UEM). Foi realizado um estudo retrospectivo e descritivo em base de dados secundário de 1986 a 2005, com 1656 pacientes segundo as variáveis: sexo, idade, ocupação, procedência, local de moradia, forma clínica e diagnóstico. A maioria dos pacientes era do sexo masculino (72,6%) e adquiriu a infecção no Estado do Paraná (97,8%), residia em área urbana (64,3%) dos quais 51,3% adquiriu a infecção durante atividades de lazer. O diagnóstico da maioria dos pacientes foi estabelecido nos dois primeiros meses de evolução das lesões (54,0%) e apresentando a forma cutânea da doença (88,9%). Uma parcela (34,4%) significativa dos pacientes que residiam em área rural adquiriu a infecção no domicílio ou peridomicílio. O estudo mostra a predominância da forma cutânea da leishmaniose tegumentar americana e sugere a atividade de lazer e o ambiente do domicilio como fatores preditivos importantes para a infecção.

The first notification of American cutaneous Leishmaniasis (LTA) in the state of Paraná, Brazil, occurred in 1917 and an increasing number of cases has been reported since 1980. This parasitic skin disease, spread by the bite of infected sandflies, is still an endemic problem, with recurrence in both sexes and in all age groups. The objective of this study was to perform a survey on the occurrence of American cutaneous Leishmaniasis in patients attended at the Teaching and Research Clinical Analysis laboratory at the State University of Maringá (LEPAC/UEM). A retrospective and descriptive study was carried out, based on secondary data (1986-2005) on 1656 patients, relating to their sex, age and occupation and the origin, clinical forms and positive diagnosis of the disease. Most of the patients were male (72.6%), lived in the urban area (64.3%) and acquired the infection during outdoor leisure activities (51.3%) in the State of Paraná (97.8%). The cutaneous form of the infection predominated (88.9%) and the diagnosis was made in the first two months of development of the lesions (54.0%). A significant part (34.4%) of the patients who lived in the rural area acquired the infection inside or close to their homes. The study shows the predominance of the cutaneous form of American cutaneous Leishmaniasis and suggests that leisure activity and housing conditions could be useful predictive factors for the infection.

Hepatitis C: serological and molecular diagnosis and genotype in haemophilic patients at the Regional Hemocenter of Maringá, Maringá PR Brazil.

Prior to the process of viral inactivation in the 1980s most haemophilic patients were infected with hepatitis C virus, currently one of the disease's main causes. The prevalence of infection by hepatitis C virus in haemophilic patients enrolled in the Hemocenter of the Regional University Hospital maintained by the State University of Maringá is evaluated from social and epidemiologic data and from serum and molecular tests. Possible association between haemophilia's type and severity, type of treatment, data of start of treatment and hepatic enzyme rates of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) was verified. Sixty-nine haemophilic patients, 82.6% with haemophilia A and 17.4% with haemophilia B, in the 1 - 67 years age bracket, average age 22 years, were investigated. Whereas anti-HCV was investigated with third generation immunoenzymatic test and confirmed by HCV-RNA, LiPA technique determined genotypes. HCV-prevalence infection reached 37.7% and 21.7% respectively when antibody anti-HCV and HCV-RNA detection and associated significantly (p<0.05) with type of treatment, date of start of treatment and ALT and AST hepatic enzyme rates are taken into account. HCV genotype 1 predominated (53.3%) followed by genotype 3 (40.0%) and genotype 2 (6.7%). HCV predominance is high in haemophilic patients although infection has not been reported in patients under the age of 17.

[Functional bowel disorders: impact and limitations of evidence-based medicine]. / Troubles fonctionnels intestinaux: apports et limites de la médecine basée sur les preuves.

Although tremendous efforts have been carried out to explore the physiopathology, classification and therapeutic modalities of functional bowels disorders, these conditions still elude the classical anatomical-clinical approach. This article summarizes recent advances in the field, discusses critically their impact on daily clinical practice and provides some practical recommendations.

Prevalence of serological markers of hepatitis B virus in pregnant women from Paraná State, Brazil.

The prevalence of hepatitis B virus (HBV) in Brazil increases from South to North but moderate to elevated prevalence has been detected in the Southwest of Paraná State. The prevalence of serological markers of HBV was evaluated in 3188 pregnant women from different counties in Paraná State and relevant epidemiological features were described. The prevalence of HBV markers in pregnant women for the state as a whole was 18.5% (95% CI = 17.2-19.9), ranging from 7.2% in Curitiba to 38.5% in Francisco Beltrão. The endemicity of HBV marker prevalence in pregnant women was intermediate in Cascavel, Foz do Iguaçu, and Francisco Beltrão, and low in Curitiba, Londrina, Maringá, and Paranaguá. Multiple logistic regression showed that HBV marker prevalence increased with age, was higher among black women, among women of Italian and German descent, and among women who had family members in neighboring Rio Grande do Sul State. Univariate analysis showed that HBV marker prevalence was also higher among women with no education or only primary education, with a lower family income and whose families originated from the South Region of Brazil. Pregnant women not having positive HBV markers (anti-HBc, HBsAg or anti-HBs detected by ELISA) corresponded to 73.7% of the population studied, implying that HBV vaccination needs to be reinforced in Paraná State. The highest prevalence was found in three counties that received the largest number of families from Santa Catarina and Rio Grande do Sul, where most immigrants were of German or Italian ascendance. This finding probably indicates that immigrants that came to this area brought HBV infection to Southwestern Paraná State.

Prevalence of serological markers of hepatitis B virus in pregnant women from Paraná State, Brazil

The prevalence of hepatitis B virus (HBV) in Brazil increases from South to North but moderate to elevated prevalence has been detected in the Southwest of Paraná State. The prevalence of serological markers of HBV was evaluated in 3188 pregnant women from different counties in Paraná State and relevant epidemiological features were described. The prevalence of HBV markers in pregnant women for the state as a whole was 18.5 percent (95 percent CI = 17.2-19.9), ranging from 7.2 percent in Curitiba to 38.5 percent in Francisco Beltrão. The endemicity of HBV marker prevalence in pregnant women was intermediate in Cascavel, Foz do Iguaçu, and Francisco Beltrão, and low in Curitiba, Londrina, Maringá, and Paranaguá. Multiple logistic regression showed that HBV marker prevalence increased with age, was higher among black women, among women of Italian and German descent, and among women who had family members in neighboring Rio Grande do Sul State. Univariate analysis showed that HBV marker prevalence was also higher among women with no education or only primary education, with a lower family income and whose families originated from the South Region of Brazil. Pregnant women not having positive HBV markers (anti-HBc, HBsAg or anti-HBs detected by ELISA) corresponded to 73.7 percent of the population studied, implying that HBV vaccination needs to be reinforced in Paraná State. The highest prevalence was found in three counties that received the largest number of families from Santa Catarina and Rio Grande do Sul, where most immigrants were of German or Italian ascendance. This finding probably indicates that immigrants that came to this area brought HBV infection to Southwestern Paraná State.

Simultaneous micromechanical and electromagnetic detection of electron paramagnetic resonance

The peculiar advantages of simultaneous observation by electromagnetic and micromechanical methods in EPR spectroscopy are discussed. The development of a novel apparatus with the capability of this simultaneous detection is described. Experiments at 23 GHz show the performance of the apparatus. The problems related to the sensitivity and to the spatial resolution are analyzed. Future prospects are presented. Copyright 1999 Academic Press.

[The laboratory diagnosis and epidemiology of cutaneous leishmaniasis in Paraná State, southern Brazil]. / Observações sobre o diagnóstico laboratorial e a epidemiologia da leishmaniose tegumentar no Estado do Paraná, sul do Brasil.

Between 1986 and 1997 a total of 1418 patients were examined at the Clinical Analysis Teaching and Research Laboratory of Maringá State University (LEPAC/UEM) for cutaneous leishmaniasis by direct examination of stained smears made from the lesions, the Montenegro skin test and the indirect immunofluorescent antibody test. Nine hundred and fifty five patients (67.3%) were positive for at least one of the three tests and of these 804 (84.2%) were considered to have contracted the disease in Paraná State; 665 (69.6%) were between 15 and 49 years old; 658 (68.9%) were males; 523 (54.8%) sought medical advice during the first three months of their infections and 74 (7.7%) had mucosal lesions. Of the 83 counties of Paraná State, where the patients had most probably acquired their infections, 44.7% were from the counties of São Jorge do Ivaí (10.2%), Doutor Camargo (9.8%), Terra Boa (7.3%), Maringá (7.3%), Jussara (6.0%) and Cianorte (4.5%). Seventy seven strains of Leishmania (Viannia) braziliensis were isolated and 63.6% of these strains belong to serodema 1.

Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity.

We report molecular cloning and initial functional characterization of a novel member of the low density lipoprotein receptor (LDLR) gene family. The cDNA was isolated from a human osteoblast cDNA library and encoded a 1,615 amino acids protein designated as LR3. It has, in the extracellular region, a cluster of three LDLR ligand binding repeats at a juxtamembrane position and four EGF precursor homology domains separated by YWTD spacer repeats. The entire ectodomain shares the same modular organization with the middle portion of the extracellular regions of two LDLR family members, LDLR-related protein (LRP), and gp330/megalin. LR3 mRNA was expressed in most of the adult and fetal tissues examined. The highest expression level was seen in aorta. In human osteosarcoma cells examined, LR3 mRNA was highly enriched in TE85 cells, moderately expressed in MG63 cells and primary human osteoblasts, and undetectable in SaOS-2 cells. NIH 3T3 cells transfected with either full length LR3 or its ectodomain showed significantly increased proliferation, whereas transfection of intracellular domain had no proliferative effect. We predict that LR3 is a multi-functional protein with potential mitogenic activity.

17Beta-hydroxysteroid dehydrogenases in human bone cells.

Interconversion of estrogens by osteoblasts may play a role in regulating bone mass. As a first step toward exploring this possibility, we investigated the expression and activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in cultured human osteoblasts (HOB) and osteoblast-like osteosarcoma cells (MG63, TE85, and SaOS-2). Significant 17beta-HSD activity was detected in cell-free extracts of all bone cells with oxidation of estradiol to estrone predominating over reduction. Reverse transcription-polymerase chain reaction (RT-PCR) experiments showed that the mRNA for 17beta-HSD I was detectable only in MG63 cells, albeit at low levels, while 17beta-HSD II was present in MG63, TE85, and HOB, but not SaOS-2, and 17beta-HSD III was absent from each bone cell type. 17Beta-HSD IV was the only isoform present in all bone cells analyzed. Further analysis of the expression of 17beta-HSD IV in these bone cells by immunoblotting revealed both the full-length 83 kDa protein and the proteolytic 38 kDa form. The kinetic parameters for estradiol oxidation by purified recombinant 17beta-HSD IV (Km = 49.7 microM, Vmax = 79.4 nmol/minute/mg of protein) and its HSD-domain (Km = 79.4 microM, Vmax = 476 nmol/minute/mg of protein) were significantly higher than previously reported, but consistent with the values obtained with crude cell-free extracts of SaOS-2 cells (Km = 98.8 microM, Vmax = 0.07 nmol/minute/mg of protein) which contain only 17beta-HSD IV based on RT-PCR. These studies show that bone cells have the capacity to interconvert circulating estrogens and suggest that bone cell 17beta-HSDs serve primarily to attenuate the continuing actions of estradiol through conversion to its less potent form, estrone, under certain conditions.

Morphological and structural characteristics of the proximal femur in human and rat.

Because the ovariectomized rat model of postmenopausal osteoporosis is the most commonly used small animal model to investigate consequences of bone loss on bone structure and strength, or to assess benefits of the various therapeutic strategies to improve bone mass and strength, the attempt was made to compare histoanatomical and structural characteristics of the femoral neck between human and rat models. In addition to different biomechanics, there is a significant difference in gross- and microanatomy of the proximal femur between humans and rats. Percent of the cortical bone component is much higher in rats (72.5%) relative to humans (12.5%). Also, cortical bone at the femoral neck in rats is evenly distributed, whereas in humans there is a considerable difference in the amount of the cortical bone between the superior half of the femoral neck with cortical thickness being only 0.3 mm, and the inferior half of the neck having 6-mm-thick cortex. Humans have far more cancellous bone at the femoral neck (22.7% average) relative to rats (6.8%). In addition, cancellous bone at the femoral neck in humans is unevenly distributed between the bone center and its periphery. Human samples exhibited striking differences in the cancellous bone structure between weight-bearing and tensile trabecular groups exhibiting clear trabecular orientation consisting of plates and rods, and trabeculae around the neutral bone axis with little mechanical activity exhibiting rod-like trabeculae only. Although humans and rats have a periosteum covering the femoral neck, and each lacks the muscular attachment at intracapsular portions of the femoral neck, rats, in contrast to humans, have the ability to quickly adapt cortical thickness and increase inertia to meet mechanical needs via modeling-dependent periosteal apposition.

Anti-arthritic activity of hydroxamic acid-based pseudopeptide inhibitors of matrix metalloproteinases and TNF alpha processing.

OBJECTIVE AND DESIGN: The effects of two hydroxamate inhibitors of metalloproteinase and tumor necrosis factor alpha (TNF alpha) processing on endotoxin-induced plasma TNF alpha and arthritic lesions in adjuvant-induced arthritic (AA) rats were determined. MATERIAL AND TREATMENT: BB-1101 and BB-1433 were administered orally twice daily to AA Lewis rats with an established disease (days 13 to 22). AA rats (day 16) or normal rats were injected with bacterial endotoxin and plasma levels of TNF alpha were also determined. METHODS: Hindpaw swelling was measured plethysmographically. Bone degradation was determined by radiography and bone mineral densitometry. TNF alpha was quantified using a sandwich ELISA. RESULTS: The hydroxamic-acid pseudopeptides inhibited plasma. TNF alpha levels in vivo and significantly reduced swelling and bone degradation of the tibiotarsal joints of AA rats in the range of 10-50 mg/kg given orally (p < 0.01 by Student's t-test). CONCLUSIONS: Thus, these novel compounds offer a new disease modifying therapy for arthritis and the results also suggest that inhibition of TNF alpha production may contribute, at least in part, to their anti-arthritic activity.

[Frequency of anti-Cysticercus cellulosae antibodies in individuals from five counties in the Northern region of Brazil]. / Freqüência de anticorpos anti-Cysticercus cellulosae em indivíduos de cinco municípios da região Norte do Estado do Paraná-Brasil.

An epidemiological and serological study was carried out on a sample of 2,180 individuals, in five counties in the north of Paraná State-Brazil, using the indirect immunofluorescence test to detect anti-Cysticercus cellulosae antibodies. These individuals, 69 (3.2%) showed significant titers of antibodies. No single significant difference between the proportion of reactivity in Sarandi (6.6%) and in Marialva (4.7%) was observed (Z = 1,319, P = 0.0936), but it was significantly higher than that observed in Mandaguaçu, Paiçandu and Maringá (P < 0.01). Of these individuals, 47.9% were within 21-49 years old and 79.4% were of female sex. "Headache" (70.6%), "faintness" (57.4%), and "convulsions" (7.4%) were among the most frequent by reported, moreover, cases of Taenia infections (22.1%) and the custom of eating uncooked beef (41.2%) or pork (27.9%) and meat containing cysticerci (25.0%) were also related.

Pharmacologic evaluation of the calcitonin analogue SB 205614 in models of osteoclastic bone resorption in vitro and in vivo: comparison with salmon calcitonin and elcatonin.

The activity of a novel calcitonin SB 205614 was compared with salmon calcitonin (sCT) and (Asu1,7)-eel calcitonin (ELC) in six different models of osteoclastic bone resorption in vitro and in vivo. SB 205614 is an ELC analogue that has an acetylenic bridge instead of the natural disulphide bridge, rendering the molecule more stable biologically than sCT and equally stable to ELC. Our aim was to determine whether this structural change compromised biologic activity, and if not, whether the increased stability could be used to exploit novel modes of administration. In the in vitro assays of pit formation by disaggregated rat osteoclasts on cortical bone slices (DROcA) and PTH stimulation of 45Ca-release from prelabeled fetal rat bone, no significant differences in activity were observed between the three calcitonins. In the DROcA, IC50s of 0.003, 0.015 and 0.064 pg/ml for sCT, ELC, and SB 205614, respectively, were determined, with total or near complete inhibition observed at 1 pg/ml (0.3 pM). In the assay of PTH-stimulation of 45Ca release, IC50s were measured of 5.5, 4.8, and 12.9 pM for sCT, ELC, and SB 205614, respectively; in every case maximal inhibition (ca. 80%) was observed at 30 and 100 pM. The internationally approved U.S. Pharmacopoeia bioassay of hypocalcemia in the rat following intravenous (IV) administration indicated that SB 205614 had a greater potency than ELC or sCT. More important, a full dose-hypocalcemic response curve demonstrated significantly increased potency compared to sCT or ELC, as the doses causing 15% lowering of serum calcium (approximately 50% of the maximum effect) were 33.9, 25.2, and 12.9 mg/kg for sCT, ELC, and SB 205614, respectively. As a preliminary means of investigating alternative delivery forms of calcitonin, the time course of the hypocalcemic effect was investigated in the rat and rabbit following IV administration, and was compared with that following intranasal (IN) administration (rat and rabbit), and following intracolonic administration (rat only). Maximal effects were similar, whereas in general the hypocalcemic effect of SB 205614 was of a longer duration than the other two calcitonins; this was reflected in a larger area over the curve (AOC). However, following IN administration in the rabbit, where an aerosol delivery device similar to that used in the clinic was used to administer the calcitonins, SB 205614 (100 IU/kg) induced a highly significant two-fold increase in the AOC compared to ELC or sCT. The calcitonins were also compared in assays designed to measure therapeutic efficacy in the rat.(ABSTRACT TRUNCATED AT 400 WORDS)