Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Doenças intestinais em cidades brasileiras: associação com elementos climáticos

Enteric fevers and dysenteries showed, during the period 1940-44, a summer prevalence in brazilian cities of the temperate zone. The distribu¬tion of the diseases by four-months periods, selected in acordance with the highest of lowest values of rainfall, mean temperature and absolute humidity induced to suppose that, in those cities, and also in tropical ones, both enteric fevers and dysenteries were closely associated with such climatic factors: enteric fevers mainly with absolute humidity and temperature, and dysenteries with humidity and rainfall. Correlation coefficients, statistically significant, have been obtained comparing monthly waves of climatic factors and corresponding waves of prevalence of the diseases. For enteric fevers, clear associations have been disclosed: with temperature variations in all temperate cities (coefficients ranging from + 0.42 to + 0.75, higher with mean temperature in the previous month) and in two of the four tropical cities (from + 0.26 to ± 0.30); with absolute humidity variations in cities of the first group (from + 0.51 to 0.71) and in the tropical city of Rio ( + 0.26 ± 0.12 and + 0.28 ± 0.12); and also with rainfall variations but only in two temperate cities (from + 0.28 to + 0.64). For dysenteric diseases, in cities of temperate zone similar associations have been found with absolute humidity (values of r, ranging from + 0.32 to + 0.45), with temperature (from + 0.26 to + 0.44); and with rainfall only in Curitiba ( + 0.25 ± 0.12). Recife (tropical city) yielded two significant values : r = — 0.27 ± 0.12 (correlation with mean temperature in the same month) and r = + 0.40 ± 0.11 and -h 0.37 ± 0.11 (between monthly morbidity rates and rainfall, respectively in the same month and in the previous one). Deaths by diarrhea and enteritis, in the cities of the temperate zone, prevailed in spring-summer seasons, also in four-months periods of highest temperature and humidity, for those cities and for the tropical ones, with the exception of Belem in which percentages were identical to those of opposite periods. Still with the exception of Belem, in all cities studied positive correla¬tion coefficients, statistically significant, have been obtained with temperature variations (ranging from + 0.25 to + 0.65 in tropical cities, and from + 0.47 to + 0.76 in temperate zone) and with humidity variations (from + 0.34 to + 0.44 in the first group, and from + 0.43 and + 0.74 in the second) . With rainfall, only Rio (in the tropical region) showed a significant value for r ( + 0.26 ±0:12); similarly in S. Paulo and Curitiba, the values ranged from + 0.46 to + 0.56, while in Porto Alegre there were found — 0.26 ± 0.12 and — 0.32 ± 012, for rainfall variations in the same and previous months.

Alterações do sistema nervoso central pelas toxinas do Clostridium perfringens

The progressive intoxication of dogs with Clostridium perfringens toxin promotes degenerative neural lesions analogous to that found in acute intoxication. In progressive intoxication, the neuroglia is more proliferative and the myeline sheats are altered. The alterations were not circunscribed to spinal cord and medulla but were extensive to other nervous organs.

A study of the endocervical columnar cells II - effects of physiological changes and of oathological lesions of the uterus on the specific numerical composition of the endocervical epithelium

In the second part of this paper we nalysed the correlation between the clinical pathological alterations and the sum of the types of columnar cells of 300 histological sections of cervix. Fifty histological sections of normal cervix of sexually mature women were selected and considered as normal in pattern. The specific counts of the columnar cells which line the endocervical mucosa and those of the glands of 50 normal cervices were compared with other similar counts made in 50 histological sections of cervices of old women and emphasized the differences. Comparisons were made also between 50 normal cervices and 50 sections of cervices with chronic inflammation, 50 cervices with epidermoid metaplasia and 50 cervices with myoma of the corpus. Counts were made from 50 cervices of patients who on the occasion of the surgical operation were in the proliferative phase of the menstrual cycle; these were compared with the counts of 50 cervices of uteri in the luteal phase. Finally, the numerical frequency of the following data encountered in the 300 cervices was recorded: 1. aspects of the ectocervical epithelium; 2. number of Nabothian cysts; 3. number of cervical glands; 5. number of deliveries and 6. aspect of the material within the cervical canal.

Glomerulonephritis in schistosomiasis with mesangial IgM deposits

Twenty one cases of hepatoesplenic schistosomiasis patients without clinical and laboratory evidence of renal disease, were studied by surgical biopsies using light microscopy and immunofluorescence. The cases were classified histologically as: normal pattern (6 cases); minimal changes (6 cases); and mesangial proliferative glomerulonephritis (9 cases). By the immunofluorescence microscopy using anti IgM, IgG, IgA and C3, the predominant finding in all biopsies, except the normal cases, was granular deposits of IgM in the mesangium along with C3. On the other hand, IgG was present in all cases including normal biopsies along the capillary walls. However IgG was also present in the mesangium only in cases with glomerular lesions. This finding may well be similar to that recently described as IgM mesangial nephropathy. According to our cases a mesangial proliferative glomerulonephritis, characterized by segmental cell proliferation and deposition of IgM in the mesangium, is probably the entity found in the early stages of mansonic schistosomiasis.

Lymph node cell responsiveness in BALB/C mice infected with Leishmania mexicana

In the present study we measured the blastogenic response of lymph node cells from BALB/c mice infected with Leishmania mexicana throughout the course of infection. Results showed that infected mice displayed normal blastogenic responses in the lymph nodes until twenty weeks of infection. Thereafter, there was a gradual suppression. Comparison of the immunoresponsiveness in the spleen and lymph nodes, revealed normal responses in the lymph nodes several weeks after suppression in the spleen had occurred. Suppression of blastogenic responses in the lymph nodes was related to an adherent macrophage-like cell which actively suppressed normal proliferative responses to mitogens.

T-cell response to my mycobacterial antigens in lepromatous and tuberculoid leprosy

We showed that a large fraction of lepromatous patients do harbor helper-type circulating T-cells that can be activated in vitro by Mycobacterium leprae. M. leprae and PPD triggered T-cell lines could be then obtained from both tuberculoid and lepromatous patients. The proliferative response of these helper T-cells is predominantly directed against epitopes shared by several species of mycobacteria, in lepromatous patients as well as in tuberculoid patients, but species specific T-cells are also present. When presented in the context of M. leprae, these cross reactive epitopes usually fail to stimulate the T-cell lines of lepromatous patients, because of the contamination of the lines by supressor T-cells actavable by M. leprae. In one lepromatous patient, PPD and M. leprae reactive T-cell lines and clones (of the CD4 phenotype), exhibited a strong cytotoxic activity to autologous target cells coated with antigen: the relevance of this phenomenon to the pathophysiology of lepromatous leprosy remains however unknown.

In vitro cell activating properties of the composite ribosomal vaccine D53

D53 (RibomuntyR) is a composite vaccine made of immunogenic ribosomes from 4 bacterial species (Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae) associated with a membrane proteoglycan from a non encapsulated strain of Klebsiella pneumoniae. D53 is a potent inducer of interleukin-1 production by mouse BALB/c spleen cells as shown by the C3H/HeJ thymocyte co-stimulation assay. Furthermore D53 triggers DNA synthesis by mouse spleen cells and induces the maturation of B lymphocytes into immunoglobulin secreting cells. Polyclonal B cell activation by D53 was readily achieved in the C3H/HeJ strain which is deficient in its response to E. coli lipopolysaccharide. The proliferative response to D53 was abrogated by removal of B cells from the spleen cell suspension, but it was not altered after depletion of T cells or adherent cells. D53 induced polyclonal B cell activation of spleen cells from athymic nude mice and from CBA/N mice. Each component of D53 induced polyclona B cell activation except ribosomes from Streptococcus pneumoniae. Each triggered Interleukin-1 synthesis except ribosomes from Klebsiella penumoniae. These in vitro properties may account for some of the in vivo immunostimulating properties of this composite vaccine.

Trypanosoma cruzi: experimental Chagas' disease in Rhesus monkeys. II. Ultraestructural and cytochemical studies of peroxidase and acid phosphatase activities

Ultrastructural and cytochemical studies of peroxidase and acid phosphatase were performed in skin, lymph node and heart muscle tissue of thesus monkeys with experimental Chagas's disease. At the site of inoculation ther was a proliferative reaction with the presence of immature macrophages revealed by peroxidase technique. At the lymph node a difuse inflammatory exudate with mononuclear cells, fibroblasts and immature activated macrophages reproduces the human patrtern of acute Chagas' disease inflamatory lesions. The hearth muscle cells present different degrees of degenerative alterations and a striking increase in the number of lysosomal profiles that exhibit acid hydrolase reaction product. A strong inflammatory reaction was present due to lymphocytic infiltrate or due to eosinophil granulocytes associated to ruptured cells. The present study provides some experimental evidences that the monkey model could be used as a reliable model to characterize histopathological alterations of the human disease.

Cellular immune response of humans to the circumsporozoite protein of Plasmodium vivax

The cellular immune response to the circumsporozoite (CS) protein of plasmodium vivax of individuals from malaria-endemic areas of Brazil was studied. We examined the in vitro proliferative response of the peripheral blood mononuclear cells (PBMC) of 22 individuals when stimulated with a CS recombinant protein (rPvCS-2) and two other synthetic peptides based on the sequenceof the P. vivax CS protein. Seven of the individuals from malaria-endemic area displayed an antigen specific in vitro proliferative responseto the recombinant protein PvCS-2 and one out of 6, proliferative response to the peptide 308-320. In contrast, none of the individuals displayed a proliferative reponse when stimulated with the D/A peptide which represent some of the repeated units present in this CS protein. Our study, therefore, provides evidence for the presence, withinthe major surface antigen of P. vivax sporozoites, of epitopes capble to induce proliferation of human PBMC.

Advances in pharmacological studies of silymarin

Silymarin is the flavonoids extracted from the seeds of Silybum marianum (L) Gearth as a mixture of three structural isomers: silybin, silydianin and silychristin, the former being the most active component. Silymarin protects liver cell membrane against hepatotoxic agents and improves liver function in experimental animals and humans. It is generally accepted that silymarin exerts a membrane-stabilizing action preventing or inhibiting membrane peroxidation. The experiments with soybean lipoxygenase showed that the three components of silymarin brought about a concentration-dependent non-competitive inhibition of the lipoxygenase. The experiments also showed an analogous interaction with animal lipoxygenase, thus showing that an inhibition of the peroxidation of the fatty acid in vivo was self-evident. Silybin almost completely suppressed the formation of PG at the highest concentration (0.3 mM) and proved to be an inhibitor of PG synthesis in vitro. In our experiments, silybin at lower dose (65 mg/Kg) decreased liver lipoperoxide content and microsomal lipoperoxidation to 84.5% and 68.55% of those of the scalded control rats respectively, and prevented the decrease of liver microsomal cytochrome p-450 content and p-nitroanisole-0-demethylase activity 24 h post-scalding. Effects of silymarin on cardiovascular systen have been studied in this university since 1980. O. O silymarin 800 mg/Kg/d or silybin 600 mg/Kg/d reduced plasma total cholesterol, LDL-C and VLDL-C. They however, enhanced HDL-C in hyperlipenic rats. Further studies showed that silymarin enhanced HDL-C in hyperlipemic rats. Further studies showed that silymarin enhanced HDL-C but didn't affect HDL-C, a property of this component which is beneficial to treatment of atherosclerosis. The results showed silymarin 80 mg or silybin 60 mg decreased in vitro platelet aggregation (porcentagem) in rats. The maximal platelet aggregation induced by ADP declined significantly, and time to reach maximal platelet aggregation and five-minute disaggregation didn't change. In our experiments, iv silybin 22,4 mg/kg lowered the amplitude and duration of diastolic blood pressure (DBP) more than those of systolic (SBP), but the descending aortic blood flow, cardiac contractility and ECG did not change significantly in anesthetized open-chest cats. The results indicated a reduction of peripheral resistance and dilatatory action on the resistant blood vessels. These effects are beneficial to coronary heart disease. We also observed the effects of silybin on morphological change, the release of glutamic oxaloacetate aminotrasferase (GOT) and lactate dehydrogenase (LDH) as well as the radioactivity of 3H-TdR incorporated into DNA in normal cardiac cells and cells infected by coxsackie B5, virus os newborn rats. The results showed that silynin did not affect the morphology of normal cell, and that the pathological change of cells infected by virus was delayed and reduced as compared to control. We have investigated the effect of silybin on synthesis and release of LTs in the cultured porcine cerebral basilar arteries (PCBA). Silybin 100 and 500 µmol/L declined the amounts of LTs released from the PCBA incubsated in the presence of A 23187, AA and indomenthacin. The result suggests that silybin can inhibit the activity of 5-lipoxygenase of cerebral blood vessel and may protect the brain from ischemia.

Immunological profiles of patients from endemic areas infected with Schistosoma mansoni

Crude extracts of eggs (SEA) adult worms (SWAP) or cercariae (Cerc) have been used to stimulate Peripheral Blood Mononuclear cells (PBMC) and have provided rather distinct profiles of responses in different types of patients. In genenral it is clear that patients with early infections respond strongly to SEA while response to SWAP are developed more slowly. As infection progresses into the more chronic phases, a general pattern is seen whic leads to lower anti-SEA proliferative responses in the face of higher responses to SWAP and variable anti-cerc responsiveness. Cured not re-exposed patients express very high levels of anti-SEA proliferation. It has recently been seen that those individuals who live in endemic areas and have continued water contact, but are reapeatedly stool-negative (who are presumed to have self-cured or be putatively resistant; endemic normals) are strongly responsive to antigenic extracts, particularly to SEA. Furthermore, our results show that endemic normal individuals have significantly higher IFN gamma production upon PBMC stimulation with schistosome antigens than infected individuals. With the emergence of more studies it is becoming apparent that both the intensity and the prevalence of a given area may influence or shape the general responsiveness of the population under study.

A modified assay for measuring thymocyte co-stimulatory activity

The observation that murine thymocytes increase their proliferation to interleukin 1 (IL-1) in the presence of phytohemagglutinin (PHA) when pre-incubated with interleukin 2 (IL-2) allowed the introduction of a modified assay for the measurement of IL-1 or the search of thymocyte-inducing proliferative activities in biological samples. Pre-incubation of thymocytes for 24 hr with 50 u/ml IL-2, followed by washings, elicited their maximal response to IL-1 in the usual lymphocyte activating factor (LAF) assay. This suggests that sequential events lead to thymocyte activation. The responsiveness is three to five fold greater than, and the total time of assay is the same as that of the LAF assay. Interestingly, pre-incubation with IL-2 renders thymocytes more sensitive than responsive to crude monocyte conditioned media. The use of the MTT colorimetric method for the assessment of thymocyte proliferation, and of the lectin jacalin as a co-mitogen are suggested as alternatives to be used in co-stimulatory assays.

Laboratory evaluation on pathogenic potentialities of Vibrio furnissii

Sixteen strains of Vibrio furnissii recovered from 16 Brazilian patients with diarrhea were screened for virulence-associated factors. All strains were non-invasive, non-fimbriated, and did not produce either enterotoxins or cholera-like toxin. In contrast, most were hemolytic on blood agar and their broth-culture supernatants damaged HeLa cell monolayers. These cytolysins, as accepted for other enteropathogenic members of the family Vibrionaceae, might be determinants of pathogenicity in V. furnissii-mediated enteritis.

Vibrio fluvialis attachs to but does not enter Hela cell monolayers

Considering the possibility that invasiveness could be a neglected factor of virulence in Vibrio fluvialis-linked enteritis, since a dysenteric form of the disease was seen in Bangladesh, we studied 12 Brazilian strains of the organism, six clinical and six environmental, to determine whether they might be able to enter into HeLa cell monolayers or would carry plasmids incidentally involved in invasiveness. Four human and two environmental isolates attached to but did not enter into the cells. Though five strains harbored plasmids,no relationship was found between the carriage of these genetic elements and adhesiveness.