Transcranial direct current stimulation improves myofascial pain syndrome and chronic fatigue.

Not available.

The mGluR5 positive allosteric modulator, CDPPB, ameliorates pathology and phenotypic signs of a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin protein (htt), leading to motor dysfunction, cognitive decline, psychiatric alterations, and death. The metabotropic glutamate receptor 5 (mGluR5) has been implicated in HD and we have recently demonstrated that mGluR5 positive allosteric modulators (PAMs) are neuroprotective in vitro. In the present study we demonstrate that the mGluR5 PAM, CDPPB, is a potent neuroprotective drug, in vitro and in vivo, capable of delaying HD-related symptoms. The HD mouse model, BACHD, exhibits many HD features, including neuronal cell loss, htt aggregates, motor incoordination and memory impairment. However, chronic treatment of BACHD mice with CDPPB 1.5 mg/kg s.c. for 18 weeks increased the activation of cell signaling pathways important for neuronal survival, including increased AKT and ERK1/2 phosphorylation and augmented the BDNF mRNA expression. CDPPB chronic treatment was also able to prevent the neuronal cell loss that takes place in the striatum of BACHD mice and decrease htt aggregate formation. Moreover, CDPPB chronic treatment was efficient to partially ameliorate motor incoordination and to rescue the memory deficit exhibited by BACHD mice. Importantly, no toxic effects or stereotypical behavior were observed upon CDPPB chronic treatment. Thus, CDPPB is a potential drug to treat HD, preventing neuronal cell loss and htt aggregate formation and delaying HD symptoms.

Developmental ecdysteroid titers and DNA puffs in larvae of two sciarid species, Rhynchosciara americana and Rhynchosciara milleri (Diptera: Sciaridae).

Ecdysteroid titers, developmental landmarks and the presence of prominent amplifying regions (DNA puffs) have been compared during late larval to pupal development in four groups of Rhynchosciara americana larvae and in R. americana and Rhynchosciara milleri. Three prominent DNA puffs (B2, C3 and C8) expand and regress sequentially on the rising phase of the 20-hydroxyecdysone (20E) titer in R. americana as a firm, cellular cocoon is being constructed. A sharp rise in 20E coincides with the regression of these puffs. The shape of the 20E curve is similar in R. milleri, a species that does not construct a massive cocoon, but the behavior of certain DNA puffs and their temporal relationship to the curve differs. Regions corresponding to B2 and C3 can be identified in R. milleri by banding pattern similarity with R. americana chromosomes and, in the case of B2, by hybridization to an R. americana probe. A B2 puff appears in R. milleri as the 20E titer rises but remains small in all gland regions. A puff similar to the R. americana C3 puff occurs in posterior gland cells of R. milleri (C3(Rm)) after the B2 puff, but this site did not hybridize to R. americana C3 probes. C3(Rm) incorporated (3)H-thymidine above background, but showed less post-puff DNA accumulation than C3 of R. americana. R. americana C8 probes hybridized to a more distal region of the R. milleri C chromosome that did not appear to amplify or form a large puff. These differences can be related to developmental differences, in particular differences in cocoon construction between the two species.

Twelve chromatically opponent ganglion cell types in turtle retina.

The turtle retina has been extensively used for the study of chromatic processing mechanisms. Color opponency has been previously investigated with trichromatic paradigms, but behavioral studies show that the turtle has an ultraviolet (UV) channel and a tetrachromatic visual system. Our laboratory has been working in the characterization of neuronal responses in the retina of vertebrates using stimuli in the UV-visible range of the electromagnetic spectrum. In the present investigation, we recorded color-opponent responses from turtle amacrine and ganglion cells to UV and visible stimuli and extended our previous results that UV color-opponency is present at the level of the inner nuclear layer. We recorded from 181 neurons, 36 of which were spectrally opponent. Among these, there were 10 amacrine (5%), and 26 ganglion cells (15%). Morphological identification of color-opponent neurons was possible for two ganglion cell classes (G17 and G22) and two amacrine cell classes (A22 and A23b). There was a variety of cell response types and a potential for complex processing of chromatic stimuli, with intensity- and wavelength-dependent response components. Ten types of color opponency were found in ganglion cells and by adding previous results from our laboratory, 12 types of opponent responses have been found. The majority of the ganglion cells were R+UVBG- and RG+UVB-color-opponents but there were other less frequent types of chromatic opponency. This study confirms the participation of a UV channel in the processing of color opponency in the turtle inner retina and shows that the turtle visual system has the retinal mechanisms to allow many possible chromatic combinations.

Effects of mercury intoxication on the response of horizontal cells of the retina of thraira fish (Hoplias malabaricus).

Methyl mercury (MeHg) is highly neurotoxic, affecting visual function in addition to other central nervous system functions. The effect of mercury intoxication on the amplitude of horizontal cell responses to light was studied in the retina of the fish Hoplias malabaricus. Intracellular responses were recorded from horizontal cells of fish previously intoxicated with MeHg by intraperitoneal injection (IP group) or by trophic exposure (T group). Only one retina per fish was used. The doses of MeHg chloride administered to the IP group were 0.01, 0.05, 0.1, 1.0, 2.0, and 6.0 mg/kg. The amplitudes of the horizontal cell responses were lower than control in individuals exposed to 0.01 (N = 4 retinas), 0.05 (N = 2 retinas) and 0.1 mg/kg (N = 1 retina), whereas no responses were recorded in the 1.0, 2.0, and 6.0 mg/kg groups. T group individuals were fed young specimens of Astyanax sp previously injected with MeHg corresponding to 0.75 (N = 1 retina), 0.075 (N = 8 retinas) or 0.0075 (N = 4 retinas) mg/kg fish body weight. After 14 doses, one every 5 days, the amplitude of the horizontal cell response was higher than control in individuals exposed to 0.075 and 0.0075 mg/kg, and lower in individuals exposed to 0.75 mg/kg. We conclude that intoxication with MeHg affects the electrophysiological response of the horizontal cells in the retina, either reducing or increasing its amplitude compared to control, and that these effects are related to the dose and/or to the mode of administration.

Colour vision and contrast sensitivity losses of mercury intoxicated industry workers in Brazil.

We evaluated vision loss in workers from fluorescent lamp industries (n=39) who had retired due to intoxication with mercury vapour and had been away from the work situation for several years (mean=6.32 years). An age-matched control group was submitted to the same tests for comparison. The luminance contrast sensitivity (CSF) was measured psychophysically and with the sweep visual evoked potential (sVEP) method. Chromatic red-green and blue-yellow CSFs were measured psychophysically. Colour discrimination was assessed with the Farnsworth-Munsell 100-hue test, Lanthony D-15d test and Cambridge Colour Vision Test. Patient data showed significantly lower scores in all colour tests compared to controls (p<.001). The behavioural luminance CSF of the patients was lower than that of controls (p<.001 at all frequencies tested). This result was confirmed by the electrophysiologically measured sweep VEP luminance CSF except at the highest frequencies-a difference that might be related to stimulus differences in the two situations. Chromatic CSFs were also statistically significantly lower for the patients than for the controls, for both chromatic equiluminant stimuli: red-green (p<.005) and blue-yellow (p<.04 for all frequencies, except 2 cycles per degree (cpd), the highest spatial frequency tested) spatial gratings. We conclude that exposure to elemental mercury vapour is associated with profound and lasting losses in achromatic and chromatic visual functions, affecting the magno-, parvo- and koniocellular visual pathways.

Raman spectra of deuteriated taurine single crystals.

The polarized Raman spectra of partially deuteriated taurine [(ND3+)0.65(NH3+)0.35(CH2)2SO3-] crystals from x(zz)x and x(zy)x scattering geometries of the Ag and Bg irreducible representations of the factor group C2h are reported. The temperature-dependent Raman spectra of partially deuteriated taurine do not reveal any evidence of the structural phase transition undergone by normal taurine at about 250 K, but an anomaly observed in the 180 cm-1 band at approximately 120 K implies a different dynamic for this band (which is involved in a pressure-induced phase transition) in the deuteriated crystal.

IDDM and milk consumption. A case-control study in São Paulo, Brazil.

OBJECTIVE: To test the hypothesis that breast-feeding is a protective factor against IDDM and that early exposure to cow's milk is a risk factor for the disease. RESEARCH DESIGN AND METHODS: A case-control study was conducted in São Paulo, Brazil. A total of 346 diabetic children, aged < 18 years, were identified in two institutions in the city of São Paulo. Duration of exclusive breast-feeding and age of introduction to cow's milk products in infant diet were compared with 346 sex-, age-, and neighborhood-matched control children. All comparisons between diabetic and control children were done using paired tests. RESULTS: Statistically significant differences were found for the duration of exclusive breast-feeding (P = 0.007) and for the age of introduction to cow's milk products (P = 0.047). Control children had a longer time of exclusive breast-feeding and had received cow's milk later in their diet than the case children. CONCLUSIONS: The results suggest that a shorter duration of exclusive breast-feeding is a risk factor for IDDM (odds ratio [OR] 2.13; 95% CI 1.8-3.55) and that the introduction to cow's milk products before age 8 days is a risk factor for the disease.

Ethnicity and cancer risk in São Paulo, Brazil.

Data from the São Paulo Cancer Registry (Brazil) for the period 1969-1974 are used to investigate ethnic differentials in cancer risk. Risks for specific cancers were estimated for mulattos and blacks relative to whites, using a case-control approach with other cancers as controls. For both sexes, blacks and mulattos are at higher risk than whites for cancer of the esophagus, stomach, and liver and for myeloma; for prostate cancer in males; and for gall bladder, pancreas, and cervix uteri cancers in females. Blacks and mulattos are at lower risk than whites for cancer of the colon, lung, larynx (males only), bladder, bone, testis, breast, and corpus uteri and for melanoma and leukemia. Except for lung and colon cancers, for which life-style habits are the main risk factors, these ethnic differences are similar to those observed in the United States.

The isotype composition and avidity of naturally acquired anti-Plasmodium falciparum antibodies: differential patterns in clinically immune Africans and Amazonian patients.

A critical role has been proposed for cytophilic IgG1 and IgG3 subclass antibodies and monocytes and macrophages in antimalarial immunity. Here we compared the isotype composition and avidity of naturally acquired antibodies, as measured by enzyme immunoassay against a detergent-soluble extract of Plasmodium falciparum schizonts, in clinically immune Senegalese adults (n = 33) and semi-immune, adult Amazonian patients (n = 25). Plasma were collected during an acute symptomatic P. falciparum attack and two months later, and in the absence of recrudescence or reinfection. Specific IgG, IgM, IgA, and IgG subclass antibodies were assessed. The results are summarized as follows: 1) high-avidity cytophilic antibodies predominated in clinically immune Senegalese subjects; 2) acutely ill Amazonian patients produced high levels of low-avidity cytophilic antibody; 3) such a response was shortlived, since two months later, the concentrations of cytophilic antibodies were significantly lower; 4) however, affinity maturation of IgG antibodies was observed in Amazonian patients two months after the acute malaria attack. A considerable proportion (35-46%) of anti-P. falciparum IgG1 antibodies produced by African and Amazonian patients was shown to recognize periodate-sensitive carbohydrate epitopes. The potential impact of these findings on the design and evaluation of antimalarial vaccines is discussed.

Polyclonal B-lymphocyte stimulation in human malaria and its association with ongoing parasitemia.

To study the polyclonal B-lymphocyte stimulation or activation (PBA) phenomenon in human malaria, the numbers of immunoglobulin (G, A, and M)-secreting cells in the peripheral blood, serum levels of immunoglobulins, and the presence of antibodies directed against the DNA-autoantigen were evaluated in Plasmodium falciparum- and P. vivax-infected individuals. Individuals chronically exposed to the risk of infection or non-immune subjects who contracted malaria during first visits to endemic areas were studied. Numbers of immunoglobulin-secreting cells (IgSC) were increased dependent upon ongoing parasitemia. Levels of IgG and the anti-DNA activity were also augmented in malarious individuals from the endemic area. Study of the kinetics of PBA done in treated patients showed that PBA decreased during treatment and disappeared 5-15 days after the start of chemotherapy.

An AC constant-response method for electrophysiological measurements of spectral sensitivity functions.

A number of methods have been used in the past to measure spectral sensitivity (S(lambda)) functions of electric responses in the visual system. We present here a microcomputer based, AC, constant-response method for automatic on-line measurement of S(lambda) in cells with or without a sustained tonic response. It is based on feedback adjustment of light intensity to obtain constant peak-to-peak amplitudes of response to a flickering stimulus as the spectrum is scanned between 300 and 700 nm in 4 nm steps. It combines the advantages of: (1) on-line presentation of S(lambda) curves; (2) constant light adaptation; (3) sampling of many points; and (4) fast data collection time. The system can be applied to sensitivity or threshold (e.g., S(lambda), dark adaptation, receptive field) measurements of any electrically recorded visual response.

Electrophysiological measurements of spectral sensitivities: a review.

Spectral sensitivities of visual systems are specified as the reciprocals of the intensities of light (quantum fluxes) needed at each wavelength to elicit the same criterion amplitude of responses. The review primarily considers the methods that have been developed for electrophysiological determinations of criterion amplitudes of slow-wave responses from single retinal cells. Traditional flash methods can require tedious dark adaptations and may yield erroneous spectral sensitivity curves which are not seen in such modifications as ramp methods. Linear response methods involve interferometry, while constant response methods involve manual or automatic adjustments of continuous illumination to keep response amplitudes constant during spectral scans. In DC or AC computerized constant response methods, feedback to determine intensities at each wavelength is derived from the response amplitudes themselves. Although all but traditional flash methods have greater or lesser abilities to provide on-line determinations of spectral sensitivities, computerized constant response methods are the most satisfactory due to flexibility, speed and maintenance of a constant adaptation level.

Contrast sensitivity threshold measured by sweep-visual evoked potential in term and preterm infants at 3 and 10 months of age.

Although healthy preterm infants frequently seem to be more attentive to visual stimuli and to fix on them longer than full-term infants, no difference in visual acuity has been reported compared to term infants. We evaluated the contrast sensitivity (CS) function of term (N = 5) and healthy preterm (N = 11) infants at 3 and 10 months of life using sweep-visual evoked potentials. Two spatial frequencies were studied: low (0.2 cycles per degrees, cpd) and medium (4.0 cpd). The mean contrast sensitivity (expressed in percentage of contrast) of the preterm infants at 3 months was 55.4 for the low spatial frequency (0.2 cpd) and 43.4 for the medium spatial frequency (4.0 cpd). At 10 months the low spatial CS was 52.7 and the medium spatial CS was 9.9. The results for the term infants at 3 months were 55.1 for the low spatial frequency and 34.5 for the medium spatial frequency. At 10 months the equivalent values were 54.3 and 14.4, respectively. No difference was found using the Mann-Whitney rank sum T-test between term and preterm infants for the low frequency at 3 or 10 months or for the medium spatial frequency at 3 or 10 months. The development of CS for the medium spatial frequency was equally fast for term and preterm infants. As also observed for visual acuity, CS was equivalent among term and preterm infants, suggesting that visual experience does not modify the development of the primary visual pathway. An earlier development of synapses in higher cortical visual areas of preterm infants could explain the better use of visual information observed behaviorally in these infants.

Characterization of convulsions induced by a hexanic extract of Spilanthes acmella var. oleracea in rats.

To characterize the convulsions induced by a hexanic extract of Spilanthes acmella var. oleracea, male Wistar rats were injected ip with 50 to 150 mg/kg of the extract and EEG and behavior were observed for periods as long as 2 h. Following the lower doses (50 and 75 mg/kg) only minor behavioral changes such as grooming and wet dog shakes were observed. Higher doses (100 to 150 mg/kg) induced full tonic-clonic convulsions in a dose-dependent manner which were accompanied by typical electrographic seizures in the EEG. These results confirm that the hexane extract of Spilanthes acmella var. oleracea is able to induce generalized convulsions in rats and can be used as a tool in the development of new models of epilepsy.

HLA compatibility and graft survival in 502 kidney transplants.

The survival of 502 kidney grafts (458 first-grafts and 44 second-grafts) performed at Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, was analyzed in relation to the degree of HLA compatibility. The actuarial graft survival for first-transplants, at 1 and 5 years, was a follows: a) HLA-identical donor: 90 and 83%; b) one-haplotype identical donor: 68 and 54%; c) unrelated living donor: 61 and 37.5% and d) cadaver donor: 52.5 and 32%. These survival data are similar to those reported by other transplantation groups and confirm the important role of the HLA antigens in the outcome of renal transplantation.

Reproducibility of alkaline antigens of Leishmania major-like and Leishmania (V.) braziliensis evaluated by IgG-ELISA. Comparison of antigens added of a protein inhibitor (PMSF) or not.

This paper deals with the analysis of 10 batches of L.major-like and L. (V.) braziliensis antigens added or not of a proteases inhibitor evaluated by means of an IgG-ELISA on three consecutive days using positive standard sera from patients with diagnosis of American Leishmaniasis previously tested for the presence of IgG antibodies by means of ELISA. The statistical analysis showed that for L. (V.) braziliensis the PMSF-containing antigen did not show any difference among batches or days of testing; the L. (V.) braziliensis antigen without PMSF showed statistical significance for differences among batches and a two-way ANOVA showed significant differences between antigens. L.major-like antigen prepared with or without PMSF showed differences among batches; all 3 days of testing displayed differences for the PMSF antigen but only for days 1 and 2 for the antigen without inhibitor. A two-way ANOVA showed differences among batches of the antigens but not for antigens with and without the protein inhibitor. According to the statistical analysis the L.major-like antigen added or not of PMSF has shown that it is the choice antigen for mucocutaneous leishmaniasis serology.

Evaluation of Leishmania antigens preparation and storage for use in enzyme immunoassays.

The influence of time and temperature on the storage of an alkaline antigen of L. major-like and L.(V.) braziliensis promastigotes added or not of a proteases inhibitor (PMSF) was evaluated by means of an IgG-ELISA. Antibodies in assays using L. major-like antigen stored at -20 degrees C for 6 months had a statistically lower geometric mean titer (GMT) and different 95% confidence interval limits (CL) than antigens stored otherwise, as assessed by the "t" statistic. The PMSFL. major-like antigen after storage for 6 months at a temperature of 4 degrees C had the same GMT and 95% CL displayed at time zero as well as when storage for 4 and 6 months at -20 degrees C. Significant differences were not found when L.(V.) braziliensis antigens were stored at times and temperatures mentioned; the PMSF antigen stored for 2 months at -70 degrees C resulted in a lower serum GMT and 95% CL than any other, as assessed by the "t" statistic. Antigen performance did not show any statistical difference associated to the addition of PMSF within the same species; the largest difference between antigens was that between PMSF-L. (V.) braziliensis and L. major-like without PMSF.

[The evolution over time of the in-vitro resistance of Plasmodium falciparum to antimalarial drugs in 2 areas of the Brazilian Amazonia with distinct socioeconomic and geographic characteristics]. / Evolução temporal da resistência in vitro do Plasmodium falciparum às drogas antimaláricas em duas áreas da Amazônia Brasileira com distintas características sócio-econômicas e geográficas.

We evaluated the temporal progression of in vitro P. falciparum resistance to chloroquine, amodiaquine, quinine and mefloquine in two areas with distinct socioeconomical and geographical characteristics: Lourenço, in Amapá state and Paragominas, in Pará state. The former region is essentially an "open" gold mining camp, whereas the latter is one currently undergoing a colonization settlement process, in addition to expanding economical activities which mainly include cattle raising and wood exploitation. Our results show high resistance rates to chloroquine in the two study areas: 79.8% and 68.4% in Lourenço and Paragominas, respectively. Variations in the response of P. falciparum to both amodiaquine and quinine were recorded throughout the study period. On the other hand, no mefloquine P. falciparum resistant strains could be identified, despite the tact we had noted a decrease in sensitivity to this antimalarial drug throughout the study period.

[Assessment of the response to reduced treatment schemes for vivax malaria]. / Avaliação da resposta aos esquemas de tratamento reduzidos para malária vivax.

Relapses may occur with long standard treatment of vivax malaria, and these are caused by incomplete patient's compliance. The use of reduced schedules may further better patient compliance, while maintaining the same efficacy, tolerance and minimal adverse reactions. The objective of this study was to test two schedules with reduced doses of chloroquine for vivax malaria and comparing these with the classical schedule. The authors studied 120 outpatients, with vivax malaria, aged over 12 years, submitted to three therapeutic schemes: scheme I: chloroquine phosphate (150 mg) in a dose of 25mg/kg/day for three days (10mg/kg/ day in the first day, 7.5mg/kg/day in the second and third day), plus primaquine (15 mg) in a dose of 0.25mg/kg/day for fourteen days; scheme II: chloroquine, in a single dose of 10mg/kg, plus primaquine in a dose of 0.5mg/kg/day for seven days; scheme III: chloroquine, 10mg/kg in a single dose plus primaquine in a dose 0.5mg/kg/ day for five days. The clinical response to all three therapeutic schemes was satisfactory. The disappearance of malarial symptoms occurred after a maximum 96 hours of treatment, while the asexual parasitaemia clearance occurred within 72 hours, in all therapeutic schemes.