Increased STAT3 Activation in Periodontitis Drives Inflammatory Bone Loss.

Periodontitis is one of the most prevalent human inflammatory diseases. It is characterized by periodontal tissue destruction, progressively driven by the host response. In this regard, cytokines associated with tissue destruction, such as interleukin (IL)-6 and IL-23, use a common signaling pathway mediated by STAT3. This transcription factor is also needed for IL-17A production, a key mediator in periodontitis pathogenesis. Although several studies have reported increased activation of STAT3 in experimental periodontitis, a detailed characterization of STAT3 activation in human gingival tissues and its involvement in alveolar bone loss has yet to be explored. Using a cross-sectional study design, we detected increased proportions of pSTAT3-positive cells during periodontitis compared with health, particularly in epithelial cells and T cells. Other cell types of hematopoietic and nonhematopoietic origin also display STAT3 activation in gingival tissues. We detected increased STAT3 phosphorylation and expression of STAT3-related genes during experimental periodontitis. Next, we evaluated the role of STAT3 in alveolar bone destruction using a mouse model of STAT3 loss of function (mut-Stat3 mice). Compared with controls, mut-Stat3 mice had reduced alveolar bone loss following ligature-induced periodontitis. We also evaluated pharmacologic inhibition of STAT3 in ligature-induced periodontitis. Like mut-Stat3 mice, mice treated with STAT3 small-molecule inhibitor had reduced bone loss compared with controls. Our results demonstrate that STAT3 activation is increased in epithelial and T cells during periodontitis and indicate a pathogenic role of STAT3 in inflammatory alveolar bone loss.

Predictors of C-reactive protein in Tsimane' 2 to 15 year-olds in lowland Bolivia.

Infectious disease is a major global determinant of child morbidity and mortality, and energetic investment in immune defenses (even in the absence of overt disease) is an important life-history variable, with implications for human growth and development. This study uses a biomarker of immune activation (C-reactive protein) to investigate an important aspect of child health among the Tsimane', a relatively isolated Amerindian population in lowland Bolivia. Our objectives are twofold: 1) to describe the distribution of CRP by age and gender in a cross-sectional sample of 536 2-15-year-olds; and 2) to explore multiple measures of pathogen exposure, economic resources, and acculturation as predictors of increased CRP. The median blood-spot CRP concentration was 0.73 mg/l, with 12.9% of the sample having concentrations greater than 5 mg/L, indicating a relatively high degree of immune activation in this population. Age was the strongest predictor of CRP, with the highest concentrations found among younger individuals. Increased CRP was also associated with higher pathogen exposure, lower household economic resources, and increased maternal education and literacy. The measurement of CRP offers a direct, objective indicator of immune activation, and provides insights into a potentially important pathway through which environmental quality may shape child growth and health.

Physical growth and nutritional status of Tsimane' Amerindian children of lowland Bolivia.

This study examines patterns of growth and nutritional status of indigenous Tsimane' children under 9 years of age (n = 199 boys and 210 girls), based on a cross-sectional sample from 58 villages from the Beni Deparment of lowland Bolivia. Compared with US children, Tsimane' children are quite short, with linear growth tracking at or below the US 5th centile in both sexes. The prevalence of low height-for-age ("stunting;" HA Z-scores

[Intraesophageal electrocardiography: an old technic under a new concept]. / Electrocardiografía intraesofágica: una técnica antigua bajo una nueva concepción.

Transesophageal recording of heart potentials is a fully accepted procedure for the electrical study of the heart. However, the intraesophageal ECG could be explored even better by using multipolar catheter electrodes and by considering various characteristics of the tracing such as amplitude, frequency and velocity. The authors describe their experience with the use of these electrodes and recording characteristics applied to the field of investigation and diagnosis of the electrical activity of supraventricular region. This objective can also by achieved by constructing esophagus-thoracic wall bipolar derivations.

[Transesophageal atrial stimulation]. / Estimulación auricular transesofágica.

Considering that catheterization of the esophagus is a relatively easy procedure, we studied the electrical transesophageal atrial stimulation in ninety patients (age range 15 to 75 years (mean 42 +/- 9 years). A multipolar electrode catheter was introduced through the nose into the esophagus of each patient and fixed in position at a site where the simultaneous recording of intraesophageal unipolar electrocardiographic derivations showed the greatest P wave potentials. Electrical atrial capture through the esophagus was obtained at frequency values higher than that of the heart, with lower voltages needed for atrial stimulation at the site in which the unipolar recording of the intraesophageal P wave was of highest amplitude. The difference of potential used was between 6 and 30 volts, with the highest values corresponding to patients with megaesophagus, whereas values below 15 volts were tolerated without major discomfort. Electric pulses of more than 10 ms duration did not significantly reduce the intensity of electric current needed to produce the atrial command. The stimulation bipole (area to be stimulated per pole, 0.72 cm2) had an interpolar distance of 22 or 30 mm, our overall experience showing that distances up to 44 mm did not require higher voltages. No cases of esophageal damage or severe arrhythmia were reported due to stimulation. In the present study, programmed transesophageal stimulation proved to be a good option for the evaluation of sinus node function and for the study and reversal of paroxysmal supraventricular tachycardia attacks by a reentry mechanism, representing in some cases an alternative approach for the study of atrioventricular conduction.

Lower esophageal sphincter pressure in Chagas' disease.

It is known that lower esophageal sphincter (LES) pressure in patients with idiopathic achalasia is higher than in normal subjects, but in patients with Chagas' disease, who have esophageal disease with similar clinical, manometric, and radiologic results, studies of LES pressure show contradictory findings. We measured the LES pressure in 118 patients with chronic Chagas' disease, 14 patients with idiopathic achalasia, and 50 control subjects using a perfused catheter and the stationary pull-through (SPT) technique. The patients with Chagas' disease had normal esophageal radiologic examination (group A, N = 50), delay in esophageal clearance without dilatation (group B, N = 41), or delay in esophageal clearance with dilatation (group C, N = 27). The LES pressure of Chagas' disease patients of group A (18.6 +/- 9.1 mm Hg, mean +/- SD), group B (17.8 +/- 9.7 mm Hg), and group C (21.6 +/- 10.1 mm Hg) was lower (P less than 0.001) than the LES pressure of the controls (24.9 +/- 10.2 mm Hg). In patients with idiopathic achalasia, the LES pressure (40.7 +/- 17.8 mm Hg) was higher than in control subjects (P less than 0.01) and Chagas' disease patients (P less than 0.001). We conclude that the LES pressure of patients with Chagas' disease tended to be lower than that of control subjects and achalasia patients.

Effect of isosorbide dinitrate and atropine on the lower esophageal sphincter pressure in Chagasic patients.

The effect of isosorbide dinitrate (5 mg, sublingually) and of atropine (12 micrograms/kg i.v.) on the lower esophageal sphincter pressure of chagasic patients with esophageal involvement and of control subjects was studied by the manometric method. The pressure was measured at 5 minute intervals for 60 minutes after drug administration. When the effect of isosorbide dinitrate was studied, basal sphincter pressure (mean +/- SEM) was 15.3 +/- 1.9 mmHg in chagasic patients (N = 15) and 25.4 +/- 5.6 mmHg in controls (N = 9) (P greater than 0.05). Isosorbide dinitrate reduced sphincter pressure between 10 and 20 minutes and at 40 minutes in controls, and froM 5 to 60 minutes in chagasics (P less than 0.05). The reduction was more intense in chagasics throughout the time of measurement (P less than 0.05). When the effect of atropine was studied, basal sphincter pressure was 20.6 +/- 1.8 mmHg in chagasic patients (N = 14) and 23.7 +/- 2.5 mmHg in controls (N = 9) (P greater than 0.05). Atropine reduced sphincter pressure both in chagasics and controls, but more intensely so in controls during the first 30 minutes of the study (P less than 0.05). The action of the musculature itself may be the main factor in the maintenance of sphincter pressure in chagasics, with secondary participation of the cholinergic excitatory system.

Effect of isosorbide dinitrate and atropine on the lower esophageal sphincter pressure in Chagasic patients.

The effect of isosorbide dinitrate (5 mg, sublingually) and of atropine (12 micrograms/kg i.v.) on the lower esophageal sphincter pressure of chagasic patients with esophageal involvement and of control subjects was studied by the manometric method. The pressure was measured at 5 minute intervals for 60 minutes after drug administration. When the effect of isosorbide dinitrate was studied, basal sphincter pressure (mean +/- SEM) was 15.3 +/- 1.9 mmHg in chagasic patients (N = 15) and 25.4 +/- 5.6 mmHg in controls (N = 9) (P greater than 0.05). Isosorbide dinitrate reduced sphincter pressure between 10 and 20 minutes and at 40 minutes in controls, and froM 5 to 60 minutes in chagasics (P less than 0.05). The reduction was more intense in chagasics throughout the time of measurement (P less than 0.05). When the effect of atropine was studied, basal sphincter pressure was 20.6 +/- 1.8 mmHg in chagasic patients (N = 14) and 23.7 +/- 2.5 mmHg in controls (N = 9) (P greater than 0.05). Atropine reduced sphincter pressure both in chagasics and controls, but more intensely so in controls during the first 30 minutes of the study (P less than 0.05). The action of the musculature itself may be the main factor in the maintenance of sphincter pressure in chagasics, with secondary participation of the cholinergic excitatory system.

[Effect of isosorbide dinitrate on the lower esophageal sphincter pressure in patients with Chagas' disease]. / Efeito do dinitrato de isosorbitol na pressão do esfíncter inferior do esôfago de pacientes com doença de Chagas.

The effect of 5 mg of sublingual isosorbide dinitrate on the lower esophageal sphincter pressure of 28 chagasic patients with esophageal involvement, was studied by continuous perfusion manometry. The pressure was measured at 5 minute intervals for 60 minutes after drug administration. Isosorbide dinitrate reduced sphincter pressure from 5 to 60 minutes (p less than 0.01). Only two patients hadn't sphincter pressure reduced lower than 50% of initial value at 20 minutes after drug administration. These results indicate that isosorbide dinitrate may be useful to reduce lower esophageal sphincter pressure in chagasic megaesophagus.

Chronic Chagas' heart disease in the elderly: a clinicopathologic study.

A retrospective study of the medical records of our hospital from 1965 to 1985 was carried out to characterize for the first time chronic Chagas' heart disease in the elderly (more than 70 years old). A total of 25 patients (mean age = 76) were suitable for the study. Congestive heart failure, sudden cardiac death, thromboembolism and atypical chest pain were found in 68, 16, 8 and 8% of cases, respectively. Ventricular premature contractions (60%), right bundle branch block (32%), left anterior hemiblock (28%), atrial fibrillation (28%) and right bundle branch block associated with left anterior hemiblock (20%) were the ECG changes most frequently found. A morphological study was performed on 8 (32%) patients. All of them showed cardiac abnormalities, with apical aneurism being detected in 100% of cases. At autopsy, pulmonary embolism was observed in 3(37%) of these patients who presented with congestive heart failure, ventricular premature contractions and/or intraventricular conduction defect and/or atrial fibrillation. Thus, the characteristics of chronic Chagas' heart disease in the elderly are similar to those found in middle-aged patients. We suggest that these patients are important for the study of the pathogenesis of chronic Chagas' heart disease because they may have less aggressive pathophysiologic mechanisms than middle-aged patients.

Cholinergic innervation of the lower esophageal sphincter in Chagas' disease.

1. The effect of 12 micrograms/kg iv atropine on the lower esophageal sphincter (LES) pressure was studied by continuous perfusion manometry in 14 Chagasic patients, 9 controls, and 3 patients with achalasia, and the effect of 3 ml iv saline was studied in 7 Chagasic patients. 2. Resting LES pressure did not differ between Chagasic patients (11.5 +/- 4.1 mmHg) and controls (15.9 +/- 4.9 mmHg, P greater than 0.05). 3. Atropine caused a significant decrease in LES pressure in both Chagasics and controls, but the reduction in controls was significantly greater (56%) than in Chagasics (25%). 4. Saline did not change the LES pressure of Chagasics. Atropine caused a similar reduction of LES pressure in achalasia patients (49%) and in controls (56%). 5. These results suggest that the cholinergic excitatory nerves are impaired in Chagas' disease, but not in achalasia, where they were either normal or only minimally impaired.

Effect of CCK-OP and intraduodenal administration of essential amino acids on intraluminal pressures of sigmoid and rectum in patients with Chagasic megacolon.

The motility of the sigmoid colon and rectum was studied by manometry in patients with Chagasic megacolon and in control individuals using two different experimental procedures: (1) intravenous infusion of saline, followed by intravenous infusion of cholecystokinin octapeptide (OP-CCK) at the dose of 20 ng/kg/hr; and (2) intraduodenal instillation of saline followed by a solution of essential amino acids at a flow of 10 ml/min. CCK-OP induced an increase in motility index in the sigmoid colon (P less than 0.05) and rectum (P less than 0.05) in the controls, whereas intraduodenal infusion of amino acids produced a significant increase in motility index exclusively in the sigmoid colon (P less than 0.005). A significant increase (P less than 0.05) in sigmoid colon motility also occurred in the control group after duodenal saline infusion was interrupted. The release of other substances in addition to CCK must have been responsible for the different behavior of sigmoid colon and rectum in response to the stimuli used. Neither procedure caused significant changes in the motility of the sigmoid colon or the rectum of the Chagasic patients. The extensive intramural denervation occurring in Chagasic megacolon probably destroys the neural pathway through which OP-CCK and the substances released by the duodenum by the infusion of essential amino acids activate the motor cells of the human terminal intestine.

Effect of nifedipine on the lower esophageal sphincter pressure in chagasic patients.

The effect of 10 mg of sublingual nifedipine on the lower esophageal sphincter pressure (LESP) was studied by continuous perfusion manometry in 15 Chagasic patients and 9 controls. Resting LESP was lower in Chagasic patients (13.51 +/- 2.37 mmHg) than in controls (19.60 +/- 2.51 mmHg, P less than 0.02). Nifedipine caused a gradual decrease in the LESP in both Chagasics and controls. Maximal reductions occurred 50 minutes after the drug administration when LESP was reduced to 60% of the resting LESP in the control group and to 43% in the Chagasic group. These results indicate that the striking abnormalities found in the intramural plexuses of the alimentary canal of Chagasic patients do not affect the responsiveness of LESP to nifedipine, and that nifedipine may be useful to reduce LESP in Chagasic megaesophagus.

Dysphagia lusoria and segmental aperistalsis in the upper third of the esophagus.

An aperistaltic zone located in the upper third of the esophagus was present in a young woman with dysphagia, who had undergone surgical treatment for dysphagia lusoria 3 months before. The segmental absence of contraction in the upper third of the esophagus was the most probable cause for the persistence of dysphagia, and could have resulted from damage related to compression or to surgical intervention in the area.

Chronic Chagas' heart disease in children and adolescents: a clinicopathologic study.

A retrospective study of the medical records filed at the University Hospital from 1965 to 1983 and of 18456 autopsies carried out in the Department of Pathology of this Institution from 1953 to 1983, referring to patients aged less than 18 years was performed in an attempt to fully characterize chronic Chagas' heart disease in children and adolescents. Only 19 of these patients fulfilled the criteria for inclusion in the present study (12 cases with only clinical information and 7 cases with clinical and pathological information). We noted that the clinical manifestations of chronic Chagas' heart disease are congestive heart failure, thromboembolism and sudden death. Radiologic, electrocardiographic and anatomo-pathological findings demonstrated serious myocardial involvement. This set of alterations is also detected in adults with chronic Chagas' heart disease. Among adolescents, however, the disease exhibits relevant peculiarities such as rapid evolution to death within a short period of time (128 days), diagnostic difficulty related to the presence of significant mitral regurgitation (61% erroneous initial diagnosis), and low frequency of right bundle branch block (11% of cases). These findings suggest that among children and adolescents, chronic Chagas' heart disease may be of a peculiar type and therefore may be useful to clarify the pathogenetic mechanism of the disease.

Esophageal dysfunction in patients with progressive systemic sclerosis and mixed connective tissue diseases.

Esophageal motility was studied in 37 patients with progressive systemic sclerosis (PSS), 12 patients with mixed connective tissue disease (MCTD) and 40 controls by the manometry method, using an open tube and continuous perfusion, and by radiological examination. Radiology was normal in 17 patients with PSS and five patients with MCTD, and abnormal in 15 patients with PSS and three with MCTD. The most frequent abnormality was slow transit time of barium. Manometry of the esophageal body was normal in 20 patients with PSS and six patients with MCTD, and abnormal in 17 patients with PSS and six with MCTD. Lack of contraction in the middle lower segments of the esophagus was the abnormality most frequently observed. Lower esophageal sphincter pressure was significantly lower among patients with PSS and MCTD than among the controls. Dysphagia was reported by ten patients with PSS and by six patients with MCTD. Radiology and manometry showed similar changes in PSS and MCTD, but dysphagia was more frequent among patients with MCTD.

Plasma gastrin and gastric acid responses to insulin hypoglycemia in Chagas' disease.

Plasma gastrin and gastric acid responses to intravenous injection of insulin (0.2 IU/kg) were measured in 8 patients with Chagas' disease, which is known to be associated with extensive reduction of the intramural neurons of the digestive tract, and in 6 control subjects. All subjects developed hunger, sweating and tachycardia, and exhibited less than 50 mg/dl venous blood glucose. Plasma gastrin responses in Chagas' disease patients (median: 3.60 nmol L-1 min-1; range: 1:12 to 10.60 nmol L-1 min-1) were significantly higher than for control subjects (median: 0.52 nmol L-1 min-1; range: 0.25 to 1.09 nmol L-1 min-1). Gastric acid output was significantly lower in Chagas' disease patients (median: 3.5 mmol/h; range: 2.1 to 13.6 mmol/h) than in controls (median: 30.3 mmol/h; range: 7.3 to 38.2 mmol/h). These data show that chagasic patients have abnormally high gastrin release and low gastric acid secretion in response to insulin, and thus indicate that loss of intrinsic innervation of the stomach does not abolish the gastrin response to insulin hypoglycemia.