Successful Regulatory T Cell-Based Therapy Relies on Inhibition of T Cell Effector Function and Enrichment of FOXP3+ Cells in a Humanized Mouse Model of Skin Inflammation.

BACKGROUND: Recent clinical trials using regulatory T cells (Treg) support the therapeutic potential of Treg-based therapy in transplantation and autoinflammatory diseases. Despite these clinical successes, the effect of Treg on inflamed tissues, as well as their impact on immune effector function in vivo, is poorly understood. Therefore, we here evaluated the effect of human Treg injection on cutaneous inflammatory processes in vivo using a humanized mouse model of human skin inflammation (huPBL-SCID-huSkin). METHODS: SCID beige mice were transplanted with human skin followed by intraperitoneal (IP) injection of 20-40 × 106 allogeneic human PBMCs. This typically results in human skin inflammation as indicated by epidermal thickening (hyperkeratosis) and changes in dermal inflammatory markers such as the antimicrobial peptide hBD2 and epidermal barrier cytokeratins K10 and K16, as well as T cell infiltration in the dermis. Ex vivo-expanded human Treg were infused intraperitoneally. Human cutaneous inflammation and systemic immune responses were analysed by immunohistochemistry and flow cytometry. RESULTS: We confirmed that human Treg injection inhibits skin inflammation and the influx of effector T cells. As a novel finding, we demonstrate that human Treg injection led to a reduction of IL-17-secreting cells while promoting a relative increase in immunosuppressive FOXP3+ Treg in the human skin, indicating active immune regulation in controlling the local proinflammatory response. Consistent with the local control (skin), systemically (splenocytes), we observed that Treg injection led to lower frequencies of IFNγ and IL-17A-expressing human T cells, while a trend towards enrichment of FOXP3+ Treg was observed. CONCLUSION: Taken together, we demonstrate that inhibition of skin inflammation by Treg infusion, next to a reduction of infiltrating effector T cells, is mediated by restoring both the local and systemic balance between cytokine-producing effector T cells and immunoregulatory T cells. This work furthers our understanding of Treg-based immunotherapy.

Prevalence of hypertension and its associated factors in contaminated areas of the Santos-São Vicente Estuarine region and Bertioga, Brazil: 2006-2009.

In Brazil, cardiovascular diseases account for 33% of deaths and the prevalence of hypertension is of approximately 22%. The Santos and São Vicente Estuarine System is the most important example of environmental degradation by chemicals from industrial sources. The aim of the present study was to evaluate the prevalence of hypertension and its associated factors in the population of this estuary in the period 2006-2009. A cross-sectional study was conducted to assess the aforementioned prevalence of hypertension in the evaluated areas, as well as risk factors for this disease in four contaminated areas located in the Estuary, and one area outside Estuary, the city of Bertioga. Associations between categorical variables were tested using Pearson's chi-square test incorporating Yates' correction, or Fisher's exact test. Single and multiple logistic regression models were applied to evaluate the risk factors for hypertension. The highest prevalence of hypertension was found in Continental São Vicente (28.4%). The risk factors for hypertension were the following: living in Center of Cubatão (OR: 1.3; IC95%: 1.0 - 1.6) and Continental São Vicente (OR: 1.4; IC95%: 1.1 - 1.8); illiterate (OR: 1.9; IC95%: 1.1 - 3.2); living in the area for more than 20 years (OR: 1.2; IC95%: 1.0 - 1.5); group of people aged 36-60 years (OR: 3.9; IC95%: 3.3 - 4.6) and who have had past occupational exposure (OR: 1.3; IC95%: 1.1 - 1.6). Results indicate that living in contaminated areas, especially for a longer time, is a risk factor for hypertension.

Prevalence of liver diseases as referred by people living in the Santos and São Vicente Estuary.

The Santos and São Vicente Estuary has suffered extensively over the years from irregular industrial deposits. The present study aimed to evaluate liver disease prevalence and potential associated risk factors in four of the Estuary's areas (Pilões and Água-Fria, Cubatão Center, Continental São Vicente, and Guarujá) and a reference area (Bertioga). This study consisted of a cross-sectional study design, in which a questionnaire was used to collect information in 820 households at each of the study areas. The proportion of total liver diseases, hepatitis, cirrhosis, and cancer (liver, biliary tract, and pancreas) per area were estimated. Pearson's chi-square test and two proportion differences test were applied in order to evaluate associations between disease occurrence and areas and to test differences between two proportions, respectively. Single and multiple logistic regression models were applied to assess associations between disease prevalence and the different study areas. Liver disease prevalence was 1.5 % among all inhabitants and 1.4 % among those without any type of exposure. Among those who reported the presence of liver disease, a higher percentage of the participants that reported hepatitis (27.7 %) or other liver disease (48.7 %) did not report occupational or alcohol exposures. Hepatitis (77.8 %) was the most reported disease, and a statistical association between living in Pilões and Água-Fria and the occurrence of hepatitis was observed (Pearson's χ (2): z = 18.1; p = 0.001). The consumption of locally-produced groceries (2.88; CI: 1.24-6.70) and water (5.88; CI: 2.24-15.45) were shown to be risk factors for the occurrence of liver disease. Thus, environmental exposure is still a public health problem present in the estuary region.

Selective B-cell expression of the MHV-68 latency-associated M2 protein regulates T-dependent antibody response and inhibits apoptosis upon viral infection.

To better understand the role of the M2 protein of the murine herpes virus strain 68 (MHV-68) in vivo, B-lymphocyte-restricted, M2-transgenic mice were constructed. The transgenic mice contained normal B-cell subpopulations in bone marrow, lymph nodes and spleen. After immunization with sheep red blood cells, spleens from M2-transgenic mice had increased germinal centres. Transgenic mice responded to the T-cell-dependent antigen keyhole limpet haemocyanin (KLH) with higher levels of secondary IgM and IgG2a antibodies than WT mice. Normal and M2-transgenic mice were infected with WT and M2 frame-shift mutant (M2FS) MHV-68 viruses. The pathogenesis of M2-transgenic mice infected with the M2-deficient mutant virus did not revert to that observed upon infection of normal mice with WT virus. However, the higher reactivation levels late after M2-transgenic mice were infected with WT virus reflected the importance of M2 as a target for the immune response, and thus with an impact on the establishment of latency. Finally, there was markedly less apoptosis in B-cells from M2-transgenic mice infected with either WT or M2FS mutant than from similarly infected WT mice, consistent with the published inhibitory influence of M2 on apoptosis in vitro. Thus, M2 provides a strategy to increase the pool of germinal centre B-cells through inhibition of apoptosis in the infected cell.

A novel TLR3 inhibitor encoded by African swine fever virus (ASFV).

African swine fever virus (ASFV) encodes proteins that manipulate important host antiviral mechanisms. Bioinformatic analysis of the ASFV genome revealed ORF I329L, a gene without any previous functional characterization as a possible inhibitor of TLR signaling. We demonstrate that ORF I329L encodes a highly glycosylated protein expressed in the cell membrane and on its surface. I329L also inhibited dsRNA-stimulated activation of NFκB and IRF3, two key players in innate immunity. Consistent with this, expression of I329L protein also inhibited the activation of interferon-ß and CCL5. Finally, overexpression of TRIF reversed I329L-mediated inhibition of both NFκB and IRF3 activation. Our results suggest that TRIF, a key MyD88-independent adaptor molecule, is a possible target of this viral host modulation gene. The demonstration of an ASFV host evasion molecule inhibiting TLR responses is consistent with the ability of this virus to infect vertebrate and invertebrate hosts, both of which deploy innate immunity controlled by conserved TLR systems.

Mycorrhizal morphotyping and molecular characterization of Chondrogaster angustisporus Giachini, Castellano, Trappe & Oliveira, an ectomycorrhizal fungus from Eucalyptus.

Chondrogaster angustisporus is a hypogeous ectomycorrhizal fungus described from fruiting bodies collected under Eucalyptus spp. in Brazil, Uruguay, and Australia. Due to its efficiency in promoting plant growth, we decided to characterize this fungus through mycorrhizal morphotyping and internal transcribed spacer (ITS) (rRNA) sequencing. DNA extracted from mycelium was amplified and sequenced using specific primers. Mycorrhizas were obtained aseptically and analyzed in terms of macroscopic and microscopic characteristics. When compared with other fungal DNA sequences available in the NBCI GenBank, the C. angustisporus sequence presented the highest similarity to an uncultured ectomycorrhizal fungus from the Seychelles. It also shows significant similarities to Gomphus, Ramaria, and Hysterangium species supporting the classification of Chondrogaster in the subclass Phallomycetidae in the gomphoid-phalloid group. The mycorrhizas were characterized by a narrow mantle with a single tissue layer densely arranged and organized as a net synenchyma with elongated hyphae. Interhyphal spaces were seen only in the external region where hyphae were more loosely organized. Bottle-shaped cystidia with bent necks were observed on the surface of the mantle. Emanating hyphae were larger than those in the mantle and presented a granular content. At regular intervals the hyphae were divided by septa with clamp connections. The Hartig net was of the common type, with typical palmetti and single hyphal rows and limited to the epidermal layer. The mycorrhizal description and the ITS sequence obtained are useful tools to identify this ectomycorrhizal fungus in culture and in association with Eucalyptus roots.

Amazonian plant crude extract screening for activity against multidrug-resistant bacteria.

Antimicrobial resistance is a subject of great concern in public health and also in the designing of strategies for current therapeutic protocols all over the world. New drugs, including those necessary for a reserve armamentarium and exhibiting less side effects deserve special attention. In rural areas, particularly in Brazil, a huge number of natural products, in different artisanal preparations, mainly from plants, have been used by traditional populations to cure diseases. Despite some of these plants have been studied, many of them are awaiting to have their compounds chemically characterized and investigated their pharmacodynamics properties. Further, as well known, the environment plays a crucial role in the metabolism of these plants, yielding different and varied molecular complexes depending on the period of collection, climate conditions, kind of soil and also the plant speciation. In this report, ethanol crude extract of 10 different botanical specimens from the Amazon region of Brazil, in the Amapa State, were screened for antibacterial activity of 7 clinical resistant microorganisms utilizing as control ATCC bacterial species by the Kirby-Bauer method. Plant extracts of Geissospermum argenteum, Uncaria guianensis, Brosimum acutifolium, Copaifera reticulate, Licania macrophylla, Ptycopetalum olacoides and Dalbergia subcymosa yielded activity against Staphylococcus aureus and Pseudomonas aeruginosa, both multidrug resistant, and Staphylococcus aureus ATCC strain.

Chronic salt loading and cardiovascular-associated changes in experimental diabetes in rats.

1. High-sodium intake may increase blood pressure and diabetes is a salt-sensitive condition. In the present study, we evaluated cardiovascular changes and their neurohumoral mechanisms in streptozotocin (STZ)-diabetic rats that underwent chronic salt loading. 2. We studied male Wistar rats (150-280 g) 14 days after the injection of either STZ (50 mg/kg, i.v.; D; n = 18) or citrate buffer (C; n = 16). After the induction of diabetes, animals were maintained for 14 days with free access to standard rat chow and tap water (C and D groups) or 1% NaCl solution (C-S and D-S groups). We conducted two experiments. Experiment 1 consisted of basal arterial pressure (AP) measurement (30 min) followed by the evaluation of AP responsiveness to phenylephrine and sodium nitroprusside. One day later, with the rats anaesthetized, a blood sample was collected to test for glycaemia, plasma angiotensin-converting enzyme (ACE) activity and renin. Kidneys were removed for the determination of tissue ACE activity. Experiment 2 comprised 24 h urine collection followed by 3 days of cardiovascular records, which consisted of a 30 min basal AP measurement, followed by injection of blockers of the vasopressin system, the renin-angiotensin system (RAS) and the sympathetic system. Basal haemodynamic data, baroreflex evaluation and AP responses to blockade of the vasopressin system with vasopressin V(1) receptor antagonist (aAVP; 10 mg/kg, i.v.), the RAS by losartan (10 mg/kg, i.v.) and the sympathetic system by hexamethonium (20 mg/kg, i.v.) were determined. 3. Glycaemia was similar between C and C-S (P = 0.612) and between D and D-S (P = 0.552), but higher in diabetic compared with non-diabetic rats (P < 0.0001). The D-S rats had an increment of 24% in mean AP compared with D (120 +/- 4 vs 97 +/- 2 mmHg, respectively; P = 0.0001), which was not seen in C-S compared with C rats. A positive association was noted between urinary sodium and mean AP (r = 0.37; P = 0.04). Plasma renin was undetectable in D-S rats. The response to acute drug blockade of vasopressin and the RAS was similar among groups, but hexamethonium elicited a more pronounced decrease in AP in D-S compared with D rats (P = 0.001). 4. The main neurohumoral mechanisms of salt-induced cardiovascular changes in STZ-diabetes are increased sodium and vascular sensitivity to adrenergic stimuli, which act in combination to produce a final result of higher AP levels, a finding not observed in control rats. Baroreflex derangements induced by diabetes were not affected by salt overload.

Tuberculosis treatment default among Brazilian children.

OBJECTIVES: To study the prevalence and time of tuberculosis (TB) treatment default among children and to compare defaulters with those who completed treatment. METHODS: Retrospective cohort study at the Hospital Municipal Jesus, Rio de Janeiro, Brazil, among TB patients aged <15 years followed from 1998 to 2002. The group that completed treatment was compared with those that defaulted. RESULTS: The records of 248 patients were studied. The default rate was 24.2% and was more frequent in the first 2 months of treatment (43.3%) and among those aged <1 year (42.4%). The following variables were associated with default: previous default (relative risk [RR] 1.99, 95%CI 1.12-3.54, P = 0.035), father not living with the child (RR 1.85, 95%CI 1.06-3.21, P = 0.030) and father using illicit drugs (RR 2.93, 95%CI 1.44-5.97, P = 0.002). CONCLUSIONS: Health professionals responsible for treating children with TB should pay special attention to children aged <1 year, those with a history of previous default, and those whose father is absent or an illicit drug user.

Inoculum production of the ectomycorrhizal fungus Pisolithus microcarpus in an airlift bioreactor.

Many important tree species in reforestation programs are dependent on ectomycorrhizal symbiosis in order to survive and grow, mainly in poor soils. The exploitation of this symbiosis to increase plant productivity demands the establishment of inoculum production methods. This study aims to propose an inoculum production method of the ectomycorrhizal fungus Pisolithus microcarpus (isolate UFSC-Pt116) using liquid fermentation in an airlift bioreactor with external circulation. The fungus grew as dark dense pellets during a batch fermentation at 25.5 degrees C and air inlet of 0.26-0.43 vvm. The maximum biomass (dry weight) achieved in the airlift bioreactor was approximately 5 g.l(-1) after 10-11 days. The specific growth rate (micro(x)) in the exponential phase was 0.576 day(-1), the yield factor (Y(X/S)) 0.418, and the productivity (P(X)) 0.480 g.l(-1).day(-1). This specific growth rate was higher than that observed by other authors during fermentation processes with other Pisolithus isolates. The method seems to be very suitable for biomass production of this fungus. However, new studies on the fungus growth morphology in this system, as well as on the efficiency of the process for the cultivation of other ectomycorrhizal fungi, are necessary. It is also necessary to test the infectivity and efficiency of the inoculum towards the hosts.

Cardiopulmonary reflex impairment in experimental diabetes in rats.

The aim of the present study was to evaluate the sensitivity of the cardiopulmonary receptors in experimental diabetes induced by streptozotocin by the use of 2 different methods: (1) administration of increasing doses of serotonin to analyze peak changes of arterial pressure and heart rate for each given dose in conscious intact normal and diabetic rats; (2) expanding blood volume with the use of dextran (6%) to produce similar increases in left ventricular end-diastolic pressure to quantify the arterial pressure, heart rate, and renal sympathetic nerve activity in sinoaortic, denervated, anesthetized normal and diabetic rats. Blood samples were collected to measure blood glucose. Diabetic rats showed hyperglycemia (22+/-0. 7 versus 7+/-0.2 mmol/L), reduced body weight (226+/-12 versus 260+/-4 g) and heart rate (294+/-14 versus 350+/-10 bpm), and similar arterial pressure (104+/-4 versus 113+/-4 mm Hg) when compared with control rats. Serotonin induced significant bradycardia and hypotension, which were similar and proportional to the dose injected in both groups. Mean arterial pressure and heart rate decreases in response to volume overload were significantly lower in diabetic than in control rats. The reflex reduction of the renal sympathetic nerve activity as expressed by percentage changes in nerve activity in response to increasing left end-diastolic pressure was abolished in diabetic animals (1.9+/-0.8% versus -14+/-4%/mm Hg in controls). These results showed an impairment of cardiopulmonary reflex control of circulation in diabetes during acute volume expansion. The normal responses to serotonin administration indicated that the cardiopulmonary reflex is still preserved in diabetic rats.

Hemodynamics of chemoreflex activation in unanesthetized rats.

Experiments were performed on unanesthetized rats (n=6) to determine the systemic hemodynamics during chemoreflex activation by intravenous KCN. Rats chronically instrumented with ultrasonic flow probes in the ascendant aorta were submitted to KCN injections (30 microg/kg) before and after sequential administration of the autonomic blockers atropine and propranolol. In the control period KCN injections produced a 60% reduction in heart rate (HR) and a 46% elevation in blood pressure (BP), while cardiac output (CO) decreased 76%, stroke volume (SV) decreased 40%, and calculated total peripheral resistance (TPR) increased 900%. Atropine administration increased resting HR, whereas no change was observed in CO or BP. Chemoreflex-induced bradycardia was markedly attenuated (26%), and the pressor response was potentiated (59%) after atropine administration. CO and TPR responses were both attenuated after atropine administration (68% and 718%, respectively). Sequential administration of propranolol decreased HR but did not change the cardiovascular responses to KCN injections compared with the responses observed after atropine administration. In conclusion, CO is greatly reduced during KCN-evoked chemoreflex. Besides the intense bradycardia, a decrease in SV contributed to this reduction. Bradycardic response was most dependent on the cardiac parasympathetic activation, and the reduction in SV was probably most dependent on the increased cardiac afterload due to the sudden increase in BP.

Hepatic damage during acute pancreatitis in the rat.

We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I) and to five other groups corresponding to 2, 4, 12, 24 and 48 h after the induction of acute pancreatitis by the injection of 5% sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4) and in the presence of ADP (activated respiration, state 3). Serum amylase, transaminases (ALT and AST) and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4 h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h) there was an increase in state 4 respiration (45.65 +/- 1.79 vs 28.96 +/- 1.50) and a decrease in respiration control rate (3.53 +/- 0.09 vs 4.45 +/- 0.08) and in the ADP/O ratio (1.77 +/- 0.02 vs 1.91 +/- 0.01) compared to controls (P < 0.05). These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min) showed that arterial blood pressure remained normal up to 24 h (111 +/- 3 mmHg) while a significant decrease occurred in the 48-h group (91 +/- 4 mmHg). These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an initial uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related to ischemic damage.

Hepatic damage during acute pancreatitis in the rat

We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I) and to five other groups corresponding to 2,4, 12,24 and 48 h after the induction of acute pancreatitis by the injection of 5 per cent sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4) and in the presence of ADP (activated respiration, state 3). Serum amylase, transaminases (ALT and AST) and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h) there was an increase in state 4 respiration (45.65 + 1.79 vs 28.96 + 1.50) and a decrease in respiration control rate (3.53 + 0.09 vs 4.45 + 0.08) and in the ADP/O ratio (1.77 + 0.02 vs 1.91 + 0.01) compared to controls (P<0.05). These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min) showed that arterial blood pressure remained normal up to 24 h (111 + 3 mmHg) while a significant decrease occurred in the 48-h group (91 + 4 mmHg). These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an inital uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related to ischemic damage.

Disseminated herpesvirus infection during pregnancy.

A case of disseminated herpes simplex virus infection during pregnancy is reported, and 26 similar cases are reviewed. The present case was unusual in that it occurred in the 12th week of gestation, whereas all but one of the other cases occurred in the second or third trimester. This rare complication is generally preceded by a flu-like prodrome with or without oral or genital lesions. The clinical presentation is (1) encephalitis without hepatic involvement, (2) hepatitis with or without central nervous system findings, or (3) disseminated skin lesions. When the liver is involved, rapidly progressive hepatic necrosis and severe coagulopathy are common and the mortality is high. Early diagnosis and early institution of antiviral chemotherapy with acyclovir greatly improve the outcome for both mother and infant.

Renal denervation normalizes pressure and baroreceptor reflex in high renin hypertension in conscious rats.

High renin hypertension is usually accompanied by impairment of the baroreceptor reflexes. This feature has been mostly ascribed to overactivity of the renin-angiotensin system. However, renal nerves could also modulate the baroreceptor reflexes. In the present experiments, the effect of renal denervation on the depressed baroreceptor reflexes was studied in rats subjected to aortic ligation between the renal arteries. Renal denervation of the ischemic kidney was performed at the same time as aortic ligation. The resulting effects on arterial pressure, heart rate, plasma renin activity, and baroreceptor reflex control of heart rate were studied 10-12 days after ligation and denervation. Aortic ligation induced high levels of mean arterial pressure (166 +/- 6 versus 110 +/- 3 mm Hg in controls), heart rate (380 +/- 9 versus 352 +/- 8 beats per minute in controls), and plasma renin activity (44 +/- 5 versus 6 +/- 1.2 ng angiotensin I/ml/hr). The baroreceptor reflex sensitivity for bradycardia and tachycardia was significantly reduced (-0.18 +/- 0.04 and -0.18 +/- 0.05, respectively, versus -2.3 +/- 0.01 and -2.4 +2- 0.1 beats per minute per mm Hg in controls). Denervation of the ischemic kidney attenuated the development of hypertension in aortic-ligated rats (122 +/- 3 mm Hg), lowering heart rate (319 +/- 8 beats per minute) and normalizing baroreceptor reflex sensitivity to bradycardia (-2.0 +/- 0.2 beats per minute per mm Hg) and to tachycardia (-4.0 +/- 0.1 beats per minute per mm Hg). Plasma renin activity was also normalized (4.3 +/- 2.4 ng angiotensin I/ml/hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Early depression of the baroreceptor sensitivity during onset of hypertension.

We studied the correlation of changes in gain sensitivity of the baroreceptors and the development of resetting of the baroreceptors 2 and 6 days after the onset of hypertension produced by subdiaphragmatic aortic constriction in rats. Mean arterial pressure of anesthetized rats was maintained at approximately the same level as that of conscious rats, and baroreceptor function curves were studied on a beat-to-beat basis by computer. After 2 days of hypertension, the difference between the systolic pressure threshold and the control diastolic pressure was -13 +/- 2 mm Hg (125 +/- 3 versus 138 +/- 4 mm Hg). Individual values showed that in seven of nine hypertensive rats, the difference was less than 15 mm Hg, indicating complete resetting. After 6 days of hypertension, all rats exhibited complete resetting, when the systolic pressure threshold was similar to control diastolic pressure (143 +/- 4 versus 141 +/- 2 mm Hg), indicating that more than 2 days of hypertension is necessary for full displacement of the pressure thresholds when all hypertensive rats are considered. Slopes of the baroreceptor curves after 2 and 6 days of hypertension showed that baroreceptor gain was depressed by 25% and 34%, respectively. The difference was not statistically significant (1.07 +/- 0.054% versus 0.94 +/- 0.049% and 1.43 +/- 0.075% in controls). When changes in pressure were circumscribed to a more physiological range, a depression of 25% in response to +10 mm Hg and 37% in response to -10 mm Hg was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid resetting of the baroreceptors in renal hypertensive rats.

The characteristics and extent of rapid or acute resetting of the aortic baroreceptors were studied in long-term renal hypertensive rats during 30 minutes of sustained hypertension produced by phenylephrine infusion. The aortic baroreceptors of hypertensive rats exhibited complete resetting to hypertension because during the control period the systolic threshold pressure for activation of the baroreceptors was similar (137 +/- 5 vs. 142 +/- 4 mm Hg) to the control diastolic pressure. Five minutes after onset of hypertension, a resetting of 32% (percent change of mean pressure threshold divided by total change of mean pressure) was demonstrable. The extent of resetting was 39%, 38%, and 41% after 10, 20, and 30 minutes of hypertension, respectively. When the percent change of systolic threshold pressure divided by total change of control diastolic pressure was used to calculate the extent of resetting, similar results were obtained. The extent of displacement of the entire baroreceptor pressure-response curves was similar to that of pressure thresholds. Reversibility of the resetting process was not complete within 30 minutes of pressure normalization after the administration of phenylephrine was interrupted. These data indicate that the characteristics and extent of rapid resetting of the baroreceptors of renal hypertensive rats, which were reset to operate at hypertensive levels, are similar to those previously described in normotensive rats.

Complicacoes do megacolon e megaesofago chagasicos observadas em necropsia. / Complications of Chagas' megacolon and megaesophagus in necropsy

182 casos autopsiados de megaesofago e/ou megacolon chagasicos foram estudados quanto as complicacoes nao relacionadas (pelo menos diretamente) ao tratamento. As complicacoes do megacolon se traduziram por: a) ulceras, com frequencias levando a peritonite aguda, por perfuracao ou mesmo na ausencia desta: b) volvo com peritonite.No megaesofago, foram escassas as complicacoes, representadas por: a) ulceracoes, como parte de esofagite cronica, sem mediastinite ou perfuracao; b) absceso pulmonar. De 85 casos de megaesofago (isolado ou associado a outros megas), em apenas dois houve, concomitantemente, carcinoma de esofago. Analisam-se as complicacoes relativamente a cor, idade, sexo e "causa mortis" dos pacientes

[Treatment of inflammatory dermatoses with difluocortolone valerate]. / Behandlung entzündlicher Dermatosen mit Diflucortolonvalerianat

The authors investigated the therapeutic effect of diflucortolone valerate as an ointment in 40 patients with inflammatory dermatoses of various etiology. They described the antiphlogistic and antipruritic effect of the preparation as excellent and practically devoid of any side effects and cosmetic problems.