Comparative effects of organic and inorganic mercury on in vivo dopamine release in freely moving rats

The present study was carried out in order to compare the effects of administration of organic (methylmercury, MeHg) and inorganic (mercury chloride, HgCl 2 ) forms of mercury on in vivo dopamine (DA) release from rat striatum. Experiments were performed in conscious and freely moving female adult Sprague-Dawley (230-280 g) rats using brain microdialysis coupled to HPLC with electrochemical detection. Perfusion of different concentrations of MeHg or HgCl 2 (2 µL/min for 1 h, N = 5-7/group) into the striatum produced significant increases in the levels of DA. Infusion of 40 µM, 400 µM, or 4 mM MeHg increased DA levels to 907 ± 31, 2324 ± 156, and 9032 ± 70% of basal levels, respectively. The same concentrations of HgCl 2 increased DA levels to 1240 ± 66, 2500 ± 424, and 2658 ± 337% of basal levels, respectively. These increases were associated with significant decreases in levels of dihydroxyphenylacetic acid and homovallinic acid. Intrastriatal administration of MeHg induced a sharp concentration-dependent increase in DA levels with a peak 30 min after injection, whereas HgCl 2 induced a gradual, lower (for 4 mM) and delayed increase in DA levels (75 min after the beginning of perfusion). Comparing the neurochemical profile of the two mercury derivatives to induce increases in DA levels, we observed that the time-course of these increases induced by both mercurials was different and the effect produced by HgCl 2 was not concentration-dependent (the effect was the same for the concentrations of 400 µM and 4 mM HgCl 2 ). These results indicate that HgCl 2 produces increases in extracellular DA levels by a mechanism differing from that of MeHg.

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B4 (LTB4) production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group) with 1000 embryonated eggs containing third-stage (L3) T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB4 levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB4-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

Facilitatory effects of an auditory warning stimulus in a visual location identification task and a visual shape identification task

The occurrence of a weak auditory warning stimulus increases the speed of the response to a subsequent visual target stimulus that must be identified. This facilitatory effect has been attributed to the temporal expectancy automatically induced by the warning stimulus. It has not been determined whether this results from a modulation of the stimulus identification process, the response selection process or both. The present study examined these possibilities. A group of 12 young adults performed a reaction time location identification task and another group of 12 young adults performed a reaction time shape identification task. A visual target stimulus was presented 1850 to 2350 ms plus a fixed interval (50, 100, 200, 400, 800, or 1600 ms, depending on the block) after the appearance of a fixation point, on its left or right side, above or below a virtual horizontal line passing through it. In half of the trials, a weak auditory warning stimulus (S1) appeared 50, 100, 200, 400, 800, or 1600 ms (according to the block) before the target stimulus (S2). Twelve trials were run for each condition. The S1 produced a facilitatory effect for the 200, 400, 800, and 1600 ms stimulus onset asynchronies (SOA) in the case of the side stimulus-response (S-R) corresponding condition, and for the 100 and 400 ms SOA in the case of the side S-R non-corresponding condition. Since these two conditions differ mainly by their response selection requirements, it is reasonable to conclude that automatic temporal expectancy influences the response selection process.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

Hepatic inducible nitric oxide synthase expression increases upon exposure to hypergravity

Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

Influence of Immunopreventable Diseases and AIDS on the Demand of an Infectious Diseases Department in Rio de Janeiro State, Brazil, in the Course of Thirty Years (1965-1994)

Brazil's nosologic profile has been sustaining profound modifications. Some occurred because of massive immunization campaigns and socioeconomic and demographic trends. Some yet were pure nosologic transitions, such as the emergence of AIDS. In this demand study it is described how these changes reflected on the 8,630 admissions of an Infectious Diseases Department in Niterói, along a thirty year period. Brazilian rural endemic diseases were infrequent (3.45%). Men predominated (62%) all the time, in all age strata and in nearly all diseases. Children under fifteen predominated until 1983. There was, in the case of tetanus, a striking rise in age strata. Institutional mortality dropped from 31% in 1965 to 10% in 1984, but rose since then to 15% in 1994. However, if AIDS patients had not been computed, mortality would have kept descending till 8% at the end of the study period. The crescent unimportance of immunopreventable diseases paralleled with the growing prominence of AIDS. In less than a decade, AIDS ranked fifth among the most frequent diseases in the whole period of thirty years. As opposed to the immunopreventable diseases, neither meningitides nor pneumonia appear to be in decline. AIDS, by its exponential incidence, by its chronic character, and by the uncountable opportunistic infections it determines, imposes itself as a challenge for the coming years.

MICROCIRCULATION AND CHAGAS' DISEASE: HYPOTHESIS AND RECENT RESULTS

This review focuses on studies that support the microvascular hypothesis, as well as on immunological and neurogenic mechanisms, and the role of the parasite itself, to explain further the pathology and clinical course of myocardial involvement in chagasic cardiomyopathy. The salient features of coronary microcirculation and Chagas' disease are discussed.

Evaluation of CD4+CD25+ T lymphocyte response time kinetics in patients with chronic Chagas disease after in vitro stimulation with recombinant Trypanosoma cruzi antigens

Introduction CD4+CD25+ T lymphocytes have been implicated in the regulation of host inflammatory response against Trypanosoma cruzi, and may be involved in the clinical course of the disease. Methods Peripheral blood mononuclear cells from patients with chronic Chagas disease were cultured in the presence of T. cruzi recombinant antigens and assayed for lymphocytes at distinct time points. Results It was possible to differentiate clinical forms of chronic Chagas disease at days 3 and 5 according to presence of CD4+CD25+ T cells in cell cultures. Conclusions Longer periods of cell culture proved to be potentially valuable for prospective evaluations of CD4+CD25+ T lymphocytes in patients with chronic Chagas disease.

Experience with the first Internet-based course at the Faculty of Medicine, University of São Paulo

PURPOSE: The Internet expands the range and flexibility of teaching options and enhances the ability to process the ever-increasing volume of medical knowledge. The aim of this study is to describe and discuss our experience with transforming a traditional medical training course into an Internet-based course. METHOD: Sixty-nine students were enrolled for a one-month course. They answered pre- and post-course questionnaires and took a multiple-choice test to evaluate the acquired knowledge. RESULTS: Students reported that the primary value for them of this Internet-based course was that they could choose the time of their class attendance (67%). The vast majority (94%) had a private computer and were used to visiting the Internet (75%) before the course. During the course, visits were mainly during the weekends (35%) and on the last week before the test (29%). Thirty-one percent reported that they could learn by reading only from the computer screen, without the necessity of printed material. Students were satisfied with this teaching method as evidenced by the 89% who reported enjoying the experience and the 88% who said they would enroll for another course via the Internet. The most positive aspect was freedom of scheduling, and the most negative was the lack of personal contact with the teacher. From the 80 multiple-choice questions, the mean of correct answers was 45.5, and of incorrect, 34.5. CONCLUSIONS: This study demonstrates that students can successfully learn with distance learning. It provides useful information for developing other Internet-based courses. The importance of this new tool for education in a large country like Brazil seems clear.

Nicolas Sanson and his Map: The Course of the Amazon River

One of the first scientific maps of the Amazon region, The Course of the Amazon River (Le Cours de La Rivière des Amazones), was constructed by Nicolas Sanson, a French cartographer of the seventeenth century, and served as the prototype for many others. The evaluation of this chart, until now, has been that it is a very defective map, a sketch based on a historical account, according to the opinion of La Condamine. Thus, the aim of the present work was to prove that the map of the Amazon River traced by Nicolas Sanson is a scientific work, a map that presents precise geographic coordinates considering its time, shows a well-determined prime meridian, and also employs a creative methodology to deduce longitudes from latitudes and distances that had been covered. To show such characteristics, an analysis of the accuracy of the map was made by comparing its latitudes and longitudes with those of a current map. We determined the prime meridian of this map and analyzed the methodology used for the calculation of longitudes. The conclusion is that it is actually a good map for the time, particularly considering the technology and the limited information that Sanson had at his disposal. This proves that the negative assertion of La Condamine is unfounded.

Natural course of subsequent pregnancy after peripartum cardiomyopathy

OBJECTIVE: To assess the effect of subsequent pregnancy after peripartum cardiomyopathy (PPCM) on maternal and fetal outcome. METHODS: Prospective study of 34 patients with the diagnosis of PPCM (mean age= 26years). At the time of first diagnosis 5 were in NYHA functional class (FC) II for heart failure, one in FC III and 28 in FC IV. After clinical treatment, patients were advised to avoid new pregnancies and a follow-up was obtained. RESULTS: There were 12 (35.3%) subsequent pregnancies in patients (pt) aged 19 to 44 years (mean 32), divided into two groups: GI: 6 pts who had normalized their heart size and GII: 6 pts with persistent cardiomegaly. GI had initially mild clinical manifestations ( 3 were in FC II, 1 in FC II and 2 in FC IV) and complete recovery of cardiac function (FC I). A new pregnancy was well-tolerated in 5 (83.3%); 1 pt presented with preeclampsia, and progressed to FC II. Presently, 5 pt are in FC I and 1 in FC II. GII pts had more severe heart failure at the onset of PPCM (1 pt in FC II and 5 in FC IV); during follow-up, 4 pt were in FC I and 2 in FC II. A new pregnancy was well tolerated in all of them, but the eldest, who had had 2 pregnancies and had a progressive worsening of clinical status, dying 8 years after the last pregnancy and 13 years after the diagnosis of PPCM. The remaining 5 pt are still alive, 3 in FC I and 2 in FC II, with worsening of FC in 1. Subsequent pregnancies occurred 3-7 years after clinical treatment of PPCM and no fetal distress was observed. CONCLUSION: Subsequent pregnancies are well-tolerated after PPCM, but not devoid of risk. No fetal distress was observed. A minimum interval of 3 years after the recovery of function seems to be safe for subsequent pregnancies.

Investigações sobre doenças de Psittacideos

The present paper colligates the notions acquired in previous investigations, already published, and new observations upon diseases of the psittacidae, liable to be confused with psittacosis of parrots. The author calls attention to the indifference with regard to this question shown by investigators, even by those who dealt with the study of this disease on the occasion of the latest outbreak of psittacosis, in flagrant contrast with the researches upon the alterations induced by pathogenic agents of other diseases transmissible to man, when these agents pass through animals or when the latter are depositaries of the virus. This remark considerably enhances the importance of the presence paper from a hygienic and epidemiologic point of view, representing moreover a contribution to general knowledge and to veterinary medicine. The researches carried out since the appearance of the latest outbreak of psittacosis,-which occurred simultaneously with an epizooty in parrots lodged in aviary of the park of Agua Branca (Directory of Animal Industry of the State São Paulo)-led to the verification of the frequent existence in these animals of various diseases liable to be confused with psittacosis. These diseases are due to two kinds of pathogenic agents: virus and bacteria. In the first group there are to be found the diseases occasioned by the virus of human psittacosis, discovered by Western, Bedson and Simpson, and the disease me with in parrots coming from traders in S. Paulo. The infections by bacteria of the genus Salmonella and by those of other genera belong to the second group. As differential characters of the two infections due to virus, delineated on the strength of notions drawn from a detailed experimental study and from the literature on this subject, the following are given: ¹ Samples of our virus were sent, for comparison, to various investigators of psittacosis. Amongst them, Prof. M. Rivers acceded to our request; he found its nature to be different from that of the virus of psittacosis studiedby him. We are very much obliged to him for the attention he paid to this verification. Virus of psittacosis - Infectiousness: man, monkey, rabbit, mouse, hen, canary. Neurotropic affinity. Inclusions: small, protoplasmic. Exsiccation: the virus has good power of preservation. Symptoms: inactivity, drowsiness, frequent diarrhoea, oculo-nasal discharge and cough, coma. Duration: 4 to 5 days. Bodily lesions: congestion of intestines, splenomegaly. Virus of S. Paulo - Infects only psittacidae, particularly those of the genus Amazona. No localization in the nervous system. Large, nuclear. Is rapidly destroyed. Inactivity, inappetency, adynamia (drooping of the wings, indifference, leaning its beak against the bars of the cage in order not to fall down); profuse diarrhoea, of whitish stools, at times enterorrhagia; prolonged coma. 2 to 8 days. Foci of yellowish necrosis in liver, spleen and lung. At times, congestion of intestines. Characteristic features common to the two viruses.-They act in great dilutions, filter through tight candles though being partly retained, are preserved under glycerine or Bedson's solution, are stable at 55°C. heat and are destroyed by physical and chemical agents. Both virus diseases are very seldom met with in psittacidae: only once, amongst numberless sick parrots, the author met with a disease of the virus differring from that of psittacosis. This disease, greatly transmissible to man, ought to be more frequent, if it were common in parrots. On the contrary, bacteria cause diseases in these animals with great frequency, presenting variable characters, from a severe epizootic form, rapidly mortal, to ambulatory or silent forms, for the most part developing towards a cure or assuming a chronic character. Amongst the bacteria which cause the infection of this group the salmonellae predominate and amongst them the bacterium discovered by Nocard, as well as a species which in the course of this study is characterized under the name of Salmonella nocardi. The author believes that in the epizooty from which Nocard isolated his bacterium there was association of the virus-disease inducing the epizooty of that epoch in Paris with the bacterial disease, as must have happened in Argentina, where the disease was transmitted to man, and Santillan, according to Barros, isolated from the sick parrots bacteria of the genus Salmonella. The diseases of the two groups, that due to virus and that due to bacteria, are differentiated: Virus-diseases - Evolution: rapid, nearly always followed by death. Symptoms: sadness, profuse diarrhoea, of whitish stools, at times enterorrhagia, complete inappetency, adynamia, indifference, prolonged coma. Clinical forms: acute and subacute. Lesions: Foci of necrosis in liver and spleen without cellular reaction around the focus, yellow liver, multiple serositis. Presence of protoplasmic or nuclear granulations. Bacteriology: Complete lack or inconstant presence of bacteria in the organs and blood. Infectiousness of the organs and blood after filtration: positive. Bacterial diseases - Varies from one week to a month or more, not always fatal. Sadness, partial inappetency, tremblings, intensive thirst, mucous or mucosanguineous diarrhoea, lack of adynamia (reacts to stimulations and moves well at any time of the disease, though showing little disposition to locomotion), soiling of feathers. Frustrate, acute, subacute and chronic. Hepatic and intestinal cogestion, foci of necrosis in liver, spleen and lung with cellular reaction around the focus. Lack of granulations. Constant presence of bacteria in the organs and blood. Negative. The analysis of the litterature shows that the characteristic features of the diseases in parrots referred to parrot psittacosis, more frequently approach the bacterial diseases here described of these animals, a hypothesis which is reinforced by the observation of the greater frequency of infections...

Studies on Trypanosoma rangeli Tejera, 1920: IX. Course of infection in different stages of Rhodnius prolixus

Frequent individual observations od different stages of Rhodnius prolixus exposed to Trypanosoma rangeli, revealed a higher susceptibility to infection in the bugs exposed during the two first instars. The mortality rate in infected bugs was significantly higher than in controls, indicating that the parasite was responsible for the majority of deaths. An analysis of the mortality distribution, per instar, is presented. Statistical analysis of deaths among the different infected instars, showed that T. rangeli produces its pathological effect in any stage of R. prolixus independently of its susceptibility to the parasite. The survival to adult decreased in all the infected instar bugs. A significant longer time to reach the adult stage was observed in the infected bugs when compared with controls, excepting for specimens exposed in the third instar. The epidemiological significance of the present results is discussed.

Sequential histological changes in Biomphalaria glabrata during the course of Schistosoma mansoni infection

Biomphalaria glabrata, highly susceptible to Schistosoma mansoni, were seen to shed less and less cercariae along the time of infection. Histological examination kept a close correlation with this changing pattern of cercarial shedding, turning an initial picture of no-reaction (tolerance) gradually into one of hemocyte proliferation with formation of focal encapsulating lesions around disintegrating sporocysts and cercariae, a change that became disseminated toward the 142nd day post miracidial exposure. Findings were suggestive of a gradual installation of acquired immunity in snails infected with S. mansoni.

Retinal fluorescein contrast arrival time of young patients with the hepatosplenic form of the Schistosomiasis mansoni

Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12%) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage.