Role of gastric acid inhibition, prostaglandins and endogenous-free thiol groups on the gastroprotective effect of a proteolytic fraction from Vasconcellea cundinamarcensis latex.

OBJECTIVES: The aim of this study was to extend our knowledge about the mechanism involved in the gastroprotective effect of P1G10, a proteolytic fraction rich in cysteine proteinases from Vasconcellea cundinamarcensis (syn. Carica candamarcensis) latex, which demonstrated gastric healing and protection activities in rats. METHODS: Wistar rats were submitted to gastric lesions by indomethacin and treated with P1G10 (10 mg/kg). Free thiol groups and prostaglandin E2 content were measured in gastric mucosal and gastrin levels in blood samples. To evaluate the participation of nitric oxide (NO) or proteolytic activity of P1G10 on its gastroprotective effect, animals were treated with an inhibitor of NO production (L-NAME) or the fraction inhibited by iodoacetamide, respectively. Gastric secretion study (acidity and pepsin activity) was also performed. KEY FINDINGS: P1G10 (10 mg/kg) inhibited the occurrence of gastric lesions by indomethacin, restored the free thiol groups content on gastric mucosa and increased moderately prostaglandin E2 levels (34%). Furthermore, the treatment decreased the gastrin levels (95%), suggesting a possible modulation of secretory activity. This effect was accordant with attenuation of gastric acidity (42%) and pepsin activity (69%) seen in animals subjected to pyloric ligation. The inhibition of NO production or the proteolytic activity of P1G10 does not affect the gastroprotective effect. CONCLUSIONS: These results can explain the gastroprotective activity of P1G10 and serve a basis for further studies of this active principle.

Postprandial proximal gastric acid pocket and gastroesophageal reflux disease.

An unbuffered layer of acidity that escapes neutralization by food has been demonstrated in volunteers and gastroesophageal reflux disease patients. This postprandial proximal gastric acid pocket (PPGAP) is manometrically defined by the presence of acid reading (pH<4) in a segment of the proximal stomach between nonacid segments distally (food) and proximally (lower esophageal sphincter or distal esophagus). The PPGAP may have important clinical implications; however, it is still poorly understood. Gastric anatomy and physiology seem to be important elements for PPGAP genesis. Gastric operations and acid suppression medications may decrease distal - proximal intragastric acid reflux and help control gastroesophageal reflux.

Obese patients have stronger peristalsis and increased acid exposure in the esophagus.

BACKGROUND: Obesity is a risk factor for GERD and a potential modulator of esophageal motility. AIM: To assess whether obese patients differ from non-obese patients in terms of esophageal motility and reflux. METHODS: Patients (n = 332) were categorized in GERD and controls after clinical assessment, esophageal manometry, and pH monitoring. Non-obese (BMI 16-29.9) and obese (BMI 30-68) were compared in regard of distal esophageal amplitude (DEA), LES pressure (LESP), manometric diagnosis, and esophageal acid exposure (EAE). RESULTS: Obese showed higher DEA in both controls (122 ± 53 vs. 97 ± 36 mmHg, p = 0.041) and GERD patients (109 ± 38 vs. 94 ± 46 mmHg, p < 0.001), higher LESP in GERD patients (20.5 ± 10.6 vs. 18.2 ± 10.6 mmHg, p = 0.049), higher frequency of nutcracker esophagus in controls (30 vs. 0%, p = 0.001), lower frequency of ineffective motility in GERD patients (6 vs. 20%, p = 0.001), and higher EAE in both controls [total EAE: 1.6% (0.7-5.1) vs. 0.9% (0.2-2.4), p = 0.027] and GERD patients [upright EAE: 6.5% (3.8-11.1) vs. 5.2% (1.5-10.6), p = 0.048]. Multiple linear regression showed that BMI was associated either with EAE (p < 0.001), DEA (p = 0.006), or LESP (in men, p = 0.007). CONCLUSIONS: Obese patients differed from non-obese in terms of esophageal motility and reflux, regardless of the presence of GERD. Obese patients showed stronger peristalsis and increased acid exposure in the esophagus.

Bioaccessible lead in soils, slag, and mine wastes from an abandoned mining district in Brazil.

We determined the amount of bioaccessible lead in samples of contaminated soils and in mining and refining wastes collected in the surroundings of a former smelter in a rural area in southeastern Brazil. Previous studies showed that some resident children and adults had blood Pb levels above recommended limits, but the contamination route was not established. The incidental ingestion of contaminated soils and dusts is considered to be a major route of lead uptake by humans. Bioavailability of heavy metals like Pb depends on solubility during digestion. We used in vitro tests that simulate human gastrointestinal (GI) media to measure the amount of soluble Pb under such conditions. Pb in soil and solid waste samples ranged from 0.03 to 4.1% and 1.2 to 15%, respectively. On average, 70% of the lead content was soluble in three different simulated gastric solutions (pH 1.5 and 1.7). For the same samples, lead solubility decreased to 2-22% when the pH was raised to pH 7 to approximate conditions found in the small intestine. These results indicate that if soils and dusts of the area are ingested, most of the lead will dissolve in the stomach, and part of it will remain soluble in the duodenum, i.e., would be potentially available for absorption. These findings may explain the high blood Pb levels previously reported.

Determinación del riesgo de desarrollo del síndrome de Mendelson en cirugía de coordinación / Determining the risk of development the syndrome of Mendelson in surgery of coordination

La aspiración pulmonar continúa siendo una de las complicaciones de mayor preocupación para el anestesiólogo. Un pH menor a 2,5 y un volumen gástrico mayor a 25 ml constituyen los "valores críticos" predisponentes para la producción del Síndrome de Mendelson.OBJETIVO: Determinar el riesgo de desarrollo de Síndrome de Mendelson en cirugía de coordinación.METODOLOGÍA: Se realizó un estudio prospectivo de una muestra de 22 pacientes de coordinación, sin patología gastroduodenal y que no estuvieran recibiendo fármacos con efectos gastrointestinales. Inmediatamente después de la intubación traqueal se colocó una sonda orogástrica y se extrajo el máximo contenido gástrico posible para medir su pH y volumen.RESULTADOS: Se obtuvieron medidas de volumen y pH gástrico en 16 pacientes. El tiempo de ayuno fue de 12.9 horas ± 2.4 horas (media ± desvío estándar). El pH hallado fue de 2.40 ± 2.01 (hombres 2.20 ± 2.16, y mujeres 2.66 ± 1.94). En 13 pacientes (81.3%) el pH fue menor a 2.5 (8 hombres y 5 mujeres). El volumen promedio extraído fue de 27.9 ml ± 23.2 ml (hombres 30.3 ml ± 30.2, y mujeres 24.7 ml ± 10.5 ml). 7 pacientes (43.8%) presentaron un volumen gástrico mayor a 25 ml (5 hombres y 2 mujeres). CONCLUSIONES: En la muestra estudiada encontramos un alto número de pacientes con un pH menor a 2.5 y un volumen gástrico mayor a 25 ml en el momento de la inducción anestésica, y por lo tanto con riesgo elevado, en caso de ocurrir una aspiración pulmonar, de desarrollar un Síndrome de Mendelson.

Pulmonary aspiration is still one of the most important concerns for the anesthesiologist. The "critical risk values" of aspirate to cause Mendelson's Syndrome are a gastric pH smaller than 2.5 and a gastric volume greater than 25 ml. OBJECTIVE: The aim of this study was to determinate the number of patients at risk of Mendelson's Syndrome in elective surgery. METHODS: A prospective study was conducted of a sample of 22 patients scheduled for elective surgery, without gastro-duodenal pathology, and who were not receiving drugs with gastrointestinal effect. After tracheal intubation an orogastric tube was placed and it was extracted the maximum gastric content possible to measure pH and volume RESULTS: Gastric volume and pH were measured in 16 patients. Mean fasting time was 12.9 hours ± 2.4 hours (mean ± SD). Mean pH value was 2.40 ± 2.01 (men 2.20 ± 2.16, and women 2.66 ± 1.94). In 13 patients (81.3%) pH was smaller than 2.5 (8 men and 5 women). Average volume was 27.9 ml ± 23.2 ml (men 30.3 ml ± 30.2, and women 24.7 ml ± 10.5 ml). Seven patients (43.8%) presented a gastric volume greater than 25 ml (5 men and 2 women). CONCLUSIONS: This study found that there was a high number of patients with gastric content with a pH smaller than 2.5 and a volume greater than 25 ml, and therefore with elevated risk in case of pulmonary aspiration to develop a Mendelson Syndrome.

Determinación del riesgo de desarrollo del síndrome de Mendelson en cirugía de coordinación / Determining the risk of development the syndrome of Mendelson in surgery of coordination

La aspiración pulmonar continúa siendo una de las complicaciones de mayor preocupación para el anestesiólogo. Un pH menor a 2,5 y un volumen gástrico mayor a 25 ml constituyen los valores críticos predisponentes para la producción del Síndrome de Mendelson.OBJETIVO: Determinar el riesgo de desarrollo de Síndrome de Mendelson en cirugía de coordinación.METODOLOGÍA: Se realizó un estudio prospectivo de una muestra de 22 pacientes de coordinación, sin patología gastroduodenal y que no estuvieran recibiendo fármacos con efectos gastrointestinales. Inmediatamente después de la intubación traqueal se colocó una sonda orogástrica y se extrajo el máximo contenido gástrico posible para medir su pH y volumen.RESULTADOS: Se obtuvieron medidas de volumen y pH gástrico en 16 pacientes. El tiempo de ayuno fue de 12.9 horas ± 2.4 horas (media ± desvío estándar). El pH hallado fue de 2.40 ± 2.01 (hombres 2.20 ± 2.16, y mujeres 2.66 ± 1.94). En 13 pacientes (81.3%) el pH fue menor a 2.5 (8 hombres y 5 mujeres). El volumen promedio extraído fue de 27.9 ml ± 23.2 ml (hombres 30.3 ml ± 30.2, y mujeres 24.7 ml ± 10.5 ml). 7 pacientes (43.8%) presentaron un volumen gástrico mayor a 25 ml (5 hombres y 2 mujeres). CONCLUSIONES: En la muestra estudiada encontramos un alto número de pacientes con un pH menor a 2.5 y un volumen gástrico mayor a 25 ml en el momento de la inducción anestésica, y por lo tanto con riesgo elevado, en caso de ocurrir una aspiración pulmonar, de desarrollar un Síndrome de Mendelson.

Pulmonary aspiration is still one of the most important concerns for the anesthesiologist. The critical risk values of aspirate to cause Mendelson's Syndrome are a gastric pH smaller than 2.5 and a gastric volume greater than 25 ml. OBJECTIVE: The aim of this study was to determinate the number of patients at risk of Mendelson's Syndrome in elective surgery. METHODS: A prospective study was conducted of a sample of 22 patients scheduled for elective surgery, without gastro-duodenal pathology, and who were not receiving drugs with gastrointestinal effect. After tracheal intubation an orogastric tube was placed and it was extracted the maximum gastric content possible to measure pH and volume RESULTS: Gastric volume and pH were measured in 16 patients. Mean fasting time was 12.9 hours ± 2.4 hours (mean ± SD). Mean pH value was 2.40 ± 2.01 (men 2.20 ± 2.16, and women 2.66 ± 1.94). In 13 patients (81.3%) pH was smaller than 2.5 (8 men and 5 women). Average volume was 27.9 ml ± 23.2 ml (men 30.3 ml ± 30.2, and women 24.7 ml ± 10.5 ml). Seven patients (43.8%) presented a gastric volume greater than 25 ml (5 men and 2 women). CONCLUSIONS: This study found that there was a high number of patients with gastric content with a pH smaller than 2.5 and a volume greater than 25 ml, and therefore with elevated risk in case of pulmonary aspiration to develop a Mendelson Syndrome.

Diminished retention of food in the proximal stomach correlates with increased acidic reflux in patients with gastroesophageal reflux disease and dyspeptic symptoms.

This work aimed at evaluating the intragastric distribution of food in patients with GERD and dyspepsia and its relationship to acidic reflux episodes. Gastric emptying and food retention in the proximal stomach were evaluated by scintigraphy in 12 healthy subjects and 19 patients with GERD and dyspepsia after a liquid test meal. Patients also underwent 24-hr esophageal pH monitoring, which included a 2-hr postprandial period following a similar test meal. Total gastric emptying was similar in patients and controls, whereas proximal gastric retention (AUCprox/AUCtot) was significantly decreased in patients (mean +/- SD: 0.48 +/- 0.07 vs. 0.56 +/- 0.06; P = 0.02). Within the GERD-dyspepsia group, a significant negative correlation was found between proximal gastric retention and the number of acidic reflux episodes. We concluded that abnormally decreased retention of gastric contents in the proximal stomach after a liquid meal may contribute to the pathogenesis of acidic reflux episodes in patients with GERD and dyspepsia.

Mechanisms of gastroesophageal reflux in healthy premature infants.

OBJECTIVES: The aim of this study was to characterize the motor events responsible for gastroesophageal reflux (GER) and esophageal acid clearance in a cohort of healthy preterm infants. STUDY DESIGN: Esophageal motility was recorded for 2 to 3 hours after a feeding in 24 preterm infants, 31 to 38 weeks' postmenstrual age, by using a sleeveside hole micromanometric assembly incorporating a pH probe. RESULTS: Sixty acid GER episodes were recorded by pH probe, and 133 non-acid GER episodes were recorded manometrically by the presence of esophageal common cavities. Of the 193 GER episodes, 159 (82%) were associated with transient lower esophageal sphincter relaxation (TLESR). TLESRs were significantly longer in duration than single swallows (15.1 seconds vs 5.6 seconds, P < .001) and had lower nadir pressures (0.8 mm Hg vs 2.3 mm Hg, P < .001). A total of 3216 esophageal body pressure waves were analyzed; 70% of swallow-induced pressure waves were peristaltic in sequence compared with 5% of swallow-unrelated pressure waves. During periods of esophageal acidification (pH below 4), peristaltic esophageal body pressure wave sequences cleared acid refluxate more effectively than nonperistaltic pressure wave sequences. CONCLUSIONS: In healthy preterm infants, TLESRs are the predominant mechanism underlying GER, and esophageal clearance mechanisms are well developed by at least 31 weeks' postmenstrual age.

[Gastric Acid]. / El ácido gástrico.

Gastric acid, a product of parietal cells secretion, full fills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressive lyactivated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms.

La importancia clínica de Helicobacter pylori y el diagnóstico de laboratorio de las enfermedades que ocasiona al humano / The importance of clinic diagnostic of Helicobacter pylory and diseases cause

H. pylori es una bacteria curva o helicoidal que se establece y multiplica en la mucosa gástrica ÄÄbasándose en algunos de sus diversos factores de patogenicidadÄÄ y, aunque no invade los tejidos, provoca la progresiva degradación de la capa de moco que protege al epitelio estomacal, exponiéndolo a la acción lesiva del ácido clorhídrico, aún cuando éste no alcanza las concentraciones comunes, ya que el microorganismo también afecta a las células parietales (que son las responsables de la liberación del HCI). De esa manera, H. pylori promueve la ocurrencia de las gastritis y las úlceras gástricas, aunque también se acepta que desempeña un importante papel en las úlceras duodenales, e inclusive, se le relaciona con la aparición de adenocarcinoma gástrico. El diagnóstico de laboratorio de las gastritis y las úlcera gástricas contempla métodos invasivos y no invasivos, considerando que, en el caso de los primeros, las muestras apropiadas son las biopsias obtenidas mediante endoscopía, en tanto que, los segundos, se basan en la detección-cuantificativa de anticuerpos séricos anti-H. pylory

Gastric residual volume in infants and children following a 3-hour fast.

The effect of a 3-hour versus a 10-hour preoperative fasting interval on the gastric residual volume and gastric pH of pediatric patients was evaluated. Forty-four healthy infants, 1 month to 5 years of age, were randomly assigned to one of two groups. The 3-hour nil per os (NPO) group consisted of 19 infants kept NPO for 3 hours following ingestion of up to 4 ounces of 5% dextrose in water (D5W). The control group consisted of 25 infants who remained NPO an average of 10 hours prior to surgery. Gastric residual volume was calculated using the dye-dilution technique. After the dye marker was injected into the stomach, complete aspiration of the stomach (including the volume of dye marker plus residual gastric contents) was attempted as another method to measure gastric residual volume. There were no significant differences in gastric residual volume between the 3-hour and the 10-hour NPO groups using either the dye-dilution or aspiration methods. However, there were significant differences between the two measuring techniques. Gastric residual volume was significantly greater in volume when measured by the dye-dilution technique than it was when measured by the aspiration technique in both the 10-hour (p less than 0.009) and the 3-hour (p less than 0.0009) NPO groups. Complete aspiration of a known volume of fluid injected through the orogastric tube was not possible in 23 of the 44 (52.4%) infants. Mean gastric pH was less than 2.0 in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Motor responses of the upper esophageal sphincter and body to intraluminal acid.

1. It is known that contraction of the upper esophageal sphincter (UES) and secondary peristalsis protect the airway and clear the esophagus of refluxed gastric contents. However, the exact nature of the stimulus and the role of acid remain controversial. 2. Secondary peristalsis and UES responses were measured following the intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar NaCl solutions in seven normal volunteers. The protocol consisted of three phases: infusion of increasing volumes (1, 3, 5 and 7 ml per min), infusion of a given volume (7 ml per min) at different stimulation sites and balloon distension. 3. At the proximal esophagus the UES response to both solutions was similar, rising from a basal resting pressure of 30 mmHg to 70 mmHg for both HCl (range 60-85 mmHg) and NaCl (55-85 mmHg). The magnitude of the response decreased as the distance from the UES increased. The level of response decreased to 40 mmHg for both NaCl and HCl (range 30-60 mmHg) at the distal esophagus. These responses were also volume dependent. When the solutions were infused at 7 ml/min into either the proximal or distal esophagus, the sphincter pressure increased with increased volume to 65 mmHg for HCl (range 50-85 mmHg) and 60 mmHg for NaCl (range 50-80 mmHg). Secondary peristalsis was also induced by the two solutions. The level of response again decreased as the distance from the UES increased. This response was also volume dependent. Esophageal distension by a balloon positioned 10 cm below the sphincter induced secondary peristalsis and sphincter response identical to those induced by the infusion of fluid. 4. These results indicate that the principal stimulus for recruitment of the esophageal motor clearance mechanism is intraluminal distension and not necessarily the pressure of intraluminal acid.

Motor responses of the upper esophageal sphincter and body to intraluminal acid

1.It is known that contraction of the upper esophageal sphincter (UES) and secondary peristalsis protect the airway and clear the esophhagus of refluxed gastric contents. However, the exact nature of the stimulus and the role of acid remain controversial. 2. Secondary peristalsis and UES responses were measured following the intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar NaCl solutions in seven normal volunteers. The protocol consisted of three phases: infusion of increasing volumes (1, 3, 5 and 7 ,l per min), infusion of a given volume (7 ml per min) at different stimulation sites and balloon distension. 3. At the proximal esophagus the UES response to both solutions was similar, rising from a basal resting pressure of 30 mmHg to 70 mmHg for both HCL (range 60-85 mmHg) and NaCl (55-85 mmHg). The magnitude of the response decreased as the distance from the UES increased. The level of response decreased to 40 mmHg for both NaCl and HCl (range 30-60 mmHg) at the distal esophagus. These responses were also volume dependent. When the solutions were infused at 7 ml/min into either the proximal or distal esophagus, the sphincter pressure increased with increased with volume to 65 mmHg for HCL (range 50-85 mmHg) and 60 mmHg for NaCl (range 50-80 mmHg). Secondary peristalsis was also induced by two solutions. The level of response agaim decreased as the distance from UES increased. This response was also volume dependent. Esophageal distension by a balloon positioned 10 cm below the sphincter induced secondary induced secondary peristalsis and sphincter response identical to those induced by the infusion of fluid. 4. These results indicate that the principal stimulus for recruitment of the esophageal motor clearance mechanism is intraluminal distension and not necessarily the pressure of intraluminal acid

Aspectos patogénicos en la úlcera duodenal por cisteamina: rol de las glándulas de Brunner (G B)

Se estudió en ratas Wistar el factor ácido, el mecanismo dopaminérgico periférico y el rol de las GB en la prevención o agravación de la UDC. Se halló que Bromocriptina, un agonista dopaminérgico DA2, actuó en la prevención de la UDC y en la depleción PAS de las GB. En cambio, las drogas antidopaminérgicas periféricas SCH 23390, Domperidona y SAM e agravaron la UDC y ni impidieron la depleción PAS de las GB. El efecto antidopaminérgico de Cisteamina mas SAME provocaron siempre úlceras duodenales perforadas y que fue totalmente impedido por al ligaudra del píloro. En conclusión, se postuló al factor ácido, al mecanismo dopaminérgico periférico y a las GB en la patogenia de la UDC

Aspectos patogénicos en la úlcera duodenal por cisteamina: rol de las glándulas de Brunner (G B)

Se estudió en ratas Wistar el factor ácido, el mecanismo dopaminérgico periférico y el rol de las GB en la prevención o agravación de la UDC. Se halló que Bromocriptina, un agonista dopaminérgico DA2, actuó en la prevención de la UDC y en la depleción PAS de las GB. En cambio, las drogas antidopaminérgicas periféricas SCH 23390, Domperidona y SAM e agravaron la UDC y ni impidieron la depleción PAS de las GB. El efecto antidopaminérgico de Cisteamina mas SAME provocaron siempre úlceras duodenales perforadas y que fue totalmente impedido por al ligaudra del píloro. En conclusión, se postuló al factor ácido, al mecanismo dopaminérgico periférico y a las GB en la patogenia de la UDC (AU)

[Pathogenic aspects of duodenal ulcers by cysteamine. Role of the Brunner glands]. / Aspectos patogénicos en la úlcera duodenal por cisteamina. Rol de las glándulas de Brunner (GB).

In Wistar rats, the acid factor, the peripheral dopaminergic mechanism and the role of Brunner gland (BG), in the prevention of the Cysteamine duodenal ulcer (CDU) were studied. It was found that Bromocriptine; a peripheral dopaminergic neuronal receptor agonist (DA2), produced prevention of the CDU and blocked of PAS depletion of the BG; in contrast, SCH23390, a peripheral dopaminergic vascular receptor antagonist (DA1), and SAMe, a peripheral and central antidopaminergic; induced aggravation of CDU and total depletion of the BG. In conclusion, the HCl factor, a peripheral dopaminergic mechanism and impaired Brunners gland secretion of PAS mucus, in the pathogenesis of the CDU was postulated.