RESUMEN

Background@#Teenage pregnancy is a public health concern because of its increasing incidence and its dire consequences. Numerous studies document the role of family in initiating sexual activity and teenage pregnancy, but there is a lack of studies that assess the effects of families and peers on teenage sexual behavior in the Philippines.@*Objective@#To determine the association between perceived family functionality as measured by the Family APGAR and teenage pregnancy in selected barangays in District 2, Quezon City, Philippines@*Methodology@#The study enrolled 233 women who are residents of Barangays Commonwealth and Payatas in Quezon City. Cases consisted of 133 women aged 18 to 24 years at the time of the interview who have become pregnant in 2011-2016, while they were 13 to 19 years old, while controls (N=100) were similar but had never been pregnant before age 20. Consecutive respondents who consented to participate in the study were enrolled and interviewed using the Filipino version of the Family APGAR. Respondents were then classified as having functional or dysfunctional families. Odds ratio was computed to determine the relationship between family functionality and teenage pregnancy.@*Results@#Family dysfunction based on the Family APGAR score was significantly associated with increased risk of teenage pregnancy with an OR 16.69, 1.93-144 (p=0.010) along with having both parents as caregivers with an OR of 29.69, 2.46-345, and teenage pregnancy in the mother with an OR of 15.87, 2.006-125.@*Conclusion@#Perception of dysfunction in the family based on the Family APGAR score, having both parents as caregivers and teenage pregnancy in the mother are associated with teenage pregnancy. Future researches should investigate the interactions of these factors but targeting family functionality may be key to curbing teenage pregnancies.

Asunto(s)

Embarazo , Femenino , Embarazo en Adolescencia

RESUMEN

Increased cholinergic stimulation and accelerated gastrointestinal (GI) transit may be produced by direct stimulation of the acetylcholine (ACh) receptor with an appropriate agonist by increased release of ACh from cholinergic nerve terminals or by a decreased removal or breakdown of ACh within cholinergic synapses. The acetylcholinesterase inhibitor, neostigmine, and the 5-HT(4) receptor partial agonist tegaserod, are two agents with known prokinetic activity which work by different mechanisms that result in increased levels of ACh at cholinergic synapses innervating intestinal smooth muscle. Here, we aimed to investigate the potential synergistic effect on colonic transit that may occur with concomitant use of these two agents. Colonic transit was indirectly assessed in rats via measurements of fecal pellet output every 30 min for 2.5 h following administration of neostigmine (0.003-0.1 mg kg(-1), i.p.), tegaserod (0.01-1.0 mg kg(-1), i.p.), or a combination of both compounds. When administered alone, neostigmine or tegaserod caused a dose-dependent increase in fecal pellet output. In combination, low doses of the two agents which did not produce statistically significant effects alone, compared to the vehicle, caused a significant increase in fecal pellet output. Combinations of higher doses of neostigmine and tegaserod did not display synergy. In summary, when combined at low doses, neostigmine and tegaserod produce synergistic effects manifested by a statistically significant increase in the expulsion of fecal pellets. A combination of an anticholinesterase agent with a 5-HT(4) receptor agonist may prove to be a useful therapeutic approach to treat conditions associated with slow GI transit.

Asunto(s)

Inhibidores de la Colinesterasa/farmacología , Colon/efectos de los fármacos , Tránsito Gastrointestinal/efectos de los fármacos , Indoles/farmacología , Neostigmina/farmacología , Agonistas del Receptor de Serotonina 5-HT4 , Agonistas de Receptores de Serotonina/farmacología , Animales , Colon/inervación , Defecación/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley

RESUMEN

BACKGROUND: The effects of tegaserod on gastric accommodation and postprandial satiety remain unclear. AIM: To compare the effects of tegaserod 6 mg twice daily vs. placebo on gastric volumes, postprandial symptoms, gastric emptying, small bowel transit and the surface electrogastrogram in female and male healthy volunteers. METHODS: Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of tegaserod 6 mg twice daily (n = 21) vs. placebo (n = 20) in healthy volunteers. Validated methods were used to study gastric emptying, myoelectrical activity, volumes and satiation postnutrient challenge. RESULTS: There were no significant effects of tegaserod on the primary endpoints assessing gastric function: emptying of solids or liquids, total gastric volumes or myoelectrical activity. Maximum tolerated volume and aggregate symptom score with nutrient challenge on placebo were 1,035 mL (+/-44) and 130 (+/-15) vs. 989 mL (+/-43) and 117 (+/-15) during tegaserod, respectively (all P = N.S.). Postprandial change in proximal gastric volume by single photon emission-computed tomography was decreased in females on tegaserod (246 +/- 30) vs. placebo (358 +/- 32) (P = 0.015). Proximal fasting volumes in females were increased on tegaserod (126 +/- 12) vs. placebo (92 +/- 13) (P = 0.066). CONCLUSIONS: While tegaserod decreased proximal gastric volume change after a meal, it does not appear to have significant effects on gastric motor and sensory function in healthy individuals. Further studies are required in patients with disturbances of gastric motor and sensory function.

Asunto(s)

Fármacos Gastrointestinales/administración & dosificación , Indoles/administración & dosificación , Agonistas de Receptores de Serotonina/administración & dosificación , Estómago/efectos de los fármacos , Administración Oral , Adulto , Sacarosa en la Dieta/administración & dosificación , Método Doble Ciego , Electromiografía/métodos , Ayuno/fisiología , Femenino , Alimentos Formulados , Vaciamiento Gástrico/efectos de los fármacos , Tránsito Gastrointestinal/fisiología , Humanos , Intestino Delgado/fisiología , Masculino , Periodo Posprandial , Respuesta de Saciedad , Estómago/fisiología

RESUMEN

BACKGROUND: Trials in functional dyspepsia report placebo response rates of 30% to 40%. AIM: We aimed to identify predictors of the placebo response. METHODS: Patients from primary, secondary and tertiary practices with functional dyspepsia defined by Rome II criteria were enrolled into one of four clinical trials; 220 patients were randomized to receive placebo. Scintigraphic assessment of gastric emptying at baseline was repeated at the end of the treatment in those with delayed emptying. After a 2 week run-in period, patients were followed for 8 weeks on placebo. Response was assessed on a weekly basis and a responder was defined as satisfactory relief of meal-related symptoms on at least 50% of weeks. RESULTS: The mean age was 44 years (range 18-82) and 74% were female; 76 (35%) were placebo responders. The predominant symptom was an unstable measure over the trial. Independent predictors of a lower placebo response were lower body mass index and a more consistent predominant symptom pattern (both P < 0.05). No association was seen with age, gender, centre type, baseline symptom score, baseline or change in gastric emptying, or baseline quality of life. CONCLUSION: In functional dyspepsia, a consistent predominant symptom pattern and lower body mass index may be associated with a lower placebo response rate.

Asunto(s)

Dispepsia/tratamiento farmacológico , Placebos/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Método Doble Ciego , Dispepsia/fisiopatología , Femenino , Vaciamiento Gástrico/fisiología , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

BACKGROUND: Proton-pump inhibitors effectively suppress stomach acidity. They are widely used for treating gastro-oesophageal reflux disease and related conditions. While generally safe, omeprazole and other proton-pump inhibitors can delay gastric emptying. AIM: To test the hypothesis that tegaserod can normalize or prevent omeprazole-induced delay in gastric emptying. METHODS: This was a randomized, double-blind, placebo-controlled, parallel group study in 40 healthy male volunteers. After informed consent and screening, qualified volunteers were treated with unblinded omeprazole 20 mg b.d. and either blinded tegaserod 6 mg t.d.s. (active treatment group) or placebo-matching tegaserod t.d.s. (control group) for 14 days. Gastric emptying was assessed before and after treatment, using a scintigraphy method. RESULTS: Omeprazole monotherapy significantly delayed gastric emptying expressed by duration of lag-phase (P < 0.007), time to gastric half-emptying (P < 0.003), and gastric retention of the meal at 60 (P < 0.002) and 120 min (P < 0.04) after its ingestion. Tegaserod taken together with omeprazole effectively prevented development of the above effects. Combined treatment was safe and well tolerated. CONCLUSION: Concomitant administration of tegaserod 6 mg t.d.s. prevented development of the delayed gastric emptying induced by omeprazole monotherapy.

Asunto(s)

Antiulcerosos/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Fármacos Gastrointestinales/farmacología , Indoles/farmacología , Omeprazol/farmacología , Adolescente , Adulto , Método Doble Ciego , Combinación de Medicamentos , Interacciones Farmacológicas , Humanos , Masculino

RESUMEN

While peripheral tissues and serum-shocked fibroblasts express rhythmic oscillations in clock gene expression, only the suprachiasmatic nucleus (SCN) is capable of endogenous, self-sustained rhythmicity and of functioning as a pacemaker by imposing rhythmic properties upon other cells. To differentially examine the molecular elements necessary for the distinctive rhythm-generating and pacemaking properties of the SCN, the effects of antisense inhibition of Clock expression on the rhythms in 2-deoxyglucose uptake and Per gene expression were compared in immortalized SCN cells and a fibroblast cell line. Similar to changes in molecular and physiological rhythmicity observed in the SCN of Clock mutant mice, the rhythmic pattern of Per2 expression was disrupted and the period of metabolic rhythmicity was increased in SCN2.2 cells subjected to antisense inhibition of Clock. NIH/3T3 fibroblasts cocultured with antisense-treated SCN2.2 cells showed metabolic rhythms with comparable increases in period and decreases in rhythm amplitude. Per2 expression in these cocultured fibroblasts exhibited a similar reduction in peak levels, but was marked by non-24 h or irregular peak-to-peak intervals. In serum-shocked NIH/3T3 fibroblasts, oscillations in Per2, Bmal1, and Cry1 expression persisted with some change in rhythm amplitude during antisense inhibition of CLOCK, demonstrating that feedback interactions between Clock and other core components of the clock mechanism may be regulated differently in SCN2.2 cells and fibroblasts. The present results suggest that CLOCK is differentially involved in the generation of endogenous molecular and metabolic rhythmicity within SCN2.2 cells and in the regulation of their specific outputs that control rhythmic processes in NIH/3T3 cells.

Asunto(s)

Relojes Biológicos/genética , Ritmo Circadiano/genética , Núcleo Supraquiasmático/metabolismo , Transactivadores/biosíntesis , Animales , Proteínas CLOCK , Línea Celular Transformada , Regulación de la Expresión Génica/fisiología , Ratones , Células 3T3 NIH , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Núcleo Supraquiasmático/citología , Transactivadores/genética

RESUMEN

BACKGROUND: Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation. AIM: : To determine the long-term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits. METHOD: A multicentre, open-label study with flexible dose titration of tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome. RESULTS: A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern-forming tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found. CONCLUSIONS: Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.

Asunto(s)

Enfermedades Funcionales del Colon/tratamiento farmacológico , Estreñimiento/tratamiento farmacológico , Fármacos Gastrointestinales/efectos adversos , Indoles/efectos adversos , Agonistas de Receptores de Serotonina/efectos adversos , Dolor Abdominal/inducido químicamente , Adolescente , Adulto , Anciano , Diarrea/inducido químicamente , Femenino , Estudios de Seguimiento , Fármacos Gastrointestinales/uso terapéutico , Humanos , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Agonistas de Receptores de Serotonina/uso terapéutico

RESUMEN

The capacity to generate circadian rhythms endogenously and to confer this rhythmicity to other cells was compared in immortalized cells derived from the suprachiasmatic nucleus (SCN) and a fibroblast line to differentiate SCN pacemaker properties from the oscillatory behavior of non-clock tissues. Only SCN2.2 cells were capable of endogenously generating circadian rhythms in 2-deoxyglucose uptake and Per gene expression. Similar to SCN function in vivo, SCN2.2 cells imposed rhythms of metabolic activity and Per gene expression on cocultured NIH/3T3 fibroblasts via a diffusible signal. The conferred rhythms in NIH/3T3 cells were phase delayed by 4-12 hr relative to SCN2.2 circadian patterns, thus resembling the phase relationship between SCN and peripheral tissue rhythms in vivo. Sustained metabolic rhythmicity in NIH/3T3 cells was dependent on continued exposure to SCN2.2-specific outputs. In response to a serum shock the NIH/3T3 fibroblasts exhibited recurrent oscillations in clock gene expression, but not in metabolic activity. These molecular rhythms in serum-shocked fibroblasts cycled in a phase relationship similar to that observed in the SCN in vivo; peak Per1 and Per2 mRNA expression preceded the rhythmic maxima in Cry1 and Cry2 mRNA levels by 4 hr. Despite these clock gene oscillations the serum-shocked NIH/3T3 cells failed to drive circadian rhythms of Per1 and Per2 expression in cocultures of untreated fibroblasts, suggesting that expression and circadian regulation of the Per and Cry genes are not sufficient to confer pacemaker function. Therefore, SCN-specific outputs are necessary to drive circadian rhythms of metabolic activity, and these output signals are not a direct product of clock gene oscillations.

Asunto(s)

Relojes Biológicos/fisiología , Ritmo Circadiano/fisiología , Proteínas de Drosophila , Fibroblastos/metabolismo , Células Fotorreceptoras de Invertebrados , Núcleo Supraquiasmático/metabolismo , Células 3T3 , Animales , Relojes Biológicos/efectos de los fármacos , Proteínas Sanguíneas/farmacología , Comunicación Celular/efectos de los fármacos , Comunicación Celular/fisiología , Células Cultivadas , Ritmo Circadiano/efectos de los fármacos , Técnicas de Cocultivo , Criptocromos , Medio de Cultivo Libre de Suero/farmacología , Difusión , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Flavoproteínas/genética , Flavoproteínas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Ratones , Proteínas Circadianas Period , Periodicidad , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G , Núcleo Supraquiasmático/citología

RESUMEN

Studies in rats found that alcohol exposure during the early postnatal period, particularly during the brain-growth-spurt period, can result in cell loss in various brain regions and persistent behavioral impairments. Some investigators have speculated that the body's internal clock, which is located in the suprachiasmatic nuclei (SCN) in the brain, may also be affected by developmental alcohol exposure. For example, alcohol-induced damage to the SCN cells and their function could result in disturbances of the circadian timekeeping function, and these disturbances might contribute to the behavioral impairments and affective disorders observed in people prenatally exposed to alcohol. Preliminary findings of studies conducted in rats suggest that developmental alcohol exposure may indeed interfere with circadian clock function as evidenced by a shortened circadian sleep-wake cycle and changes in the release of certain brain chemicals (i.e., neuropeptides) by SCN cells.

Asunto(s)

Ritmo Circadiano/efectos de los fármacos , Etanol/farmacología , Trastornos del Espectro Alcohólico Fetal/fisiopatología , Animales , Animales Recién Nacidos , Ritmo Circadiano/fisiología , Femenino , Humanos , Masculino , Neuropéptidos/fisiología , Embarazo , Ratas , Fases del Sueño/efectos de los fármacos , Fases del Sueño/fisiología , Núcleo Supraquiasmático/efectos de los fármacos , Núcleo Supraquiasmático/fisiopatología

RESUMEN

The availability of reliable, portable computer-enhanced ultrasonography with high-frequency transducers has improved breast ultrasonography such that its role has increased dramatically. Diagnostic characteristics of breast lesions may be used to categorize these lesions according to their relative risk for malignancy. Furthermore, breast ultrasonography may be used to guide needle aspiration and biopsy of lesions so indicated by diagnostic evaluation. Results of ultrasound-guided aspiration and core biopsy accurately diagnose specific histopathology thereby avoiding unnecessary open biopsy for benign lesions and facilitating therapeutic planning for malignant lesions.

Asunto(s)

Enfermedades de la Mama/diagnóstico por imagen , Ultrasonografía Intervencional , Ultrasonografía Mamaria , Algoritmos , Biopsia con Aguja , Mama/patología , Enfermedades de la Mama/patología , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Humanos , Medición de Riesgo , Ultrasonografía Intervencional/estadística & datos numéricos , Ultrasonografía Mamaria/estadística & datos numéricos

RESUMEN

We evaluated the effects of dietary selenomethionine supplementation on colonic polyamine levels and the ability of L-selenomethionine supplementation to modulate the carcinogenic activity of azoxymethane (AOM) in the rat colon. Four-week-old male F344 rats were treated with 15 mg/kg body weight of AOM once a week for 2 weeks. Dietary selenomethionine at a concentration of either 1 or 2 ppm was administered in AIN-76A rodent diet to AOM-treated animals for 16 weeks. Aberrant crypt foci (ACF), precursor lesions of colon cancer, were investigated after the 16 week treatment course. Selenomethionine given in the diet at 2 ppm markedly reduced the number of aberrant crypt foci. The multiplicity of ACFs (i.e. the number of aberrant crypts/focus) and the percentage of microadenomas were also affected by selenomethionine in a dose dependent manner. However, evaluation of the colonic tissue polyamine levels between control and treated groups showed no significant difference. These results demonstrate that selenomethionine can modulate the development of AOM-induced premalignant lesions through a polyamine-independent mechanism.

Asunto(s)

Anticarcinógenos/farmacología , Poliaminas Biogénicas/metabolismo , Neoplasias del Colon/prevención & control , Lesiones Precancerosas/prevención & control , Selenometionina/farmacología , Alanina Transaminasa , Animales , Azoximetano , Peso Corporal/efectos de los fármacos , Carcinógenos , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/metabolismo , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/metabolismo , Ratas , Ratas Endogámicas F344 , Selenio/sangre

RESUMEN

BACKGROUND: Many individuals with heartburn self-medicate with antacids for relief of their symptoms. AIM: To compare efficacy of effervescent ranitidine to as-needed calcium carbonate antacids in subjects who self-treat heartburn. METHODS: A total of 155 subjects with frequent antacid-responsive heartburn were randomized to receive effervescent ranitidine 150 mg tablets b.d., or as-needed calcium carbonate 750 mg for 12 weeks. Endoscopic oesophagitis severity and mucosal histology were assessed at baseline, and at weeks 6 and 12. Heartburn frequency, severity, and antacid consumption were recorded daily, and quality of life was assessed at baseline, and at weeks 6 and 12. RESULTS: Heartburn frequency and severity were significantly decreased after 1 day of ranitidine (P < 0.02). By week 6, ranitidine had significantly decreased rescue antacid consumption (7.3 tablets, P < 0.001) vs. antacids (14.1 tablets). Endoscopic oesophagitis healing (

Asunto(s)

Pirosis/tratamiento farmacológico , Ranitidina/uso terapéutico , Adulto , Anciano , Antiulcerosos/efectos adversos , Antiulcerosos/uso terapéutico , Esófago de Barrett/tratamiento farmacológico , Carbonato de Calcio/efectos adversos , Carbonato de Calcio/uso terapéutico , Método Doble Ciego , Esofagitis/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ranitidina/efectos adversos , Autoadministración , Resultado del Tratamiento

RESUMEN

Nonsteroidal antiinflammatory drugs are among the most promising chemopreventive agents for colorectal cancer. Although the mechanism by which nonsteroidal antiinflammatory drugs exert such effects remains to be further characterized, their best known pharmacological effect is inhibition of prostaglandin synthetase, which leads to decreases in tissue prostaglandin levels. We conducted a randomized, double-blind, controlled study to examine the effect of daily ibuprofen treatment on the rectal mucosal prostaglandin E2 (PGE2) levels in healthy subjects with a history of resected polyps. Study participants (n = 27) completed a 2-week run-in period and were then randomized to take a single, daily dose of ibuprofen (300 or 600 mg) or of a placebo for 4 weeks. Rectal biopsy specimens were taken before and after the run-in period and at 2 and 4 weeks after the ibuprofen/placebo treatment. Notably large between- and within-subject variability in the rectal mucosal PGE2 content was seen. The changes in PGE2 levels after ibuprofen/placebo treatment correlated with the baseline PGE2 content. After adjustment of the baseline values, 2 weeks of 300 mg/day of ibuprofen treatment resulted in significantly more suppression of PGE2 levels than that observed after the placebo treatment (55% versus 22% suppression from baseline; P = 0.033). Although other ibuprofen treatment schedules and doses appeared to result in suppression in the PGE2 levels, the suppression was not statistically significant because of the large variability in this measurement. Because lower doses are associated with fewer adverse effects, a dose of 300 mg of ibuprofen/day should be considered for future Phase II chemoprevention studies. Stratifying study participants, based on their baseline PGE2 levels and inclusion of a larger number of study subjects, are recommended for future trials where the rectal mucosal PGE2 level is to be used as a surrogate end point biomarker.

Asunto(s)

Antiinflamatorios no Esteroideos/farmacología , Dinoprostona/análisis , Ibuprofeno/farmacología , Pólipos Intestinales/complicaciones , Recto/efectos de los fármacos , Adulto , Anciano , Biomarcadores/análisis , Quimioprevención , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Mucosa Intestinal/química , Mucosa Intestinal/efectos de los fármacos , Pólipos Intestinales/cirugía , Masculino , Persona de Mediana Edad , Neoplasias del Recto/prevención & control , Recto/química

RESUMEN

BACKGROUND: The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas. METHODS: We randomly assigned 1429 men and women who were 40 to 80 years of age and who had had one or more histologically confirmed colorectal adenomas removed within three months before recruitment began to a supervised program of dietary supplementation with either high amounts (13.5 g per day) or low amounts (2 g per day) of wheat-bran fiber. The primary end point was the presence or absence of new adenomas at the time of follow-up colonoscopy. Subjects and physicians, including colonoscopists, were unaware of the group assignments. RESULTS: Of the 1303 subjects who completed the study, 719 had been randomly assigned to the high-fiber group and 584 to the low-fiber group. The median times from randomization to the last follow-up colonoscopy were 34 months in the high-fiber group and 36 months in the low-fiber group. By the time of the last follow-up colonoscopy, at least one adenoma had been identified in 338 subjects in the high-fiber group (47.0 percent) and in 299 subjects in the low-fiber group (51.2 percent). The multivariate adjusted odds ratio for recurrent adenoma in tile high-fiber group, as compared with the low-fiber group, was 0.88 (95 percent confidence interval, 0.70 to 1.11; P=0.28), and the relative risk of recurrence according to the number of adenomas, in the high-fiber group as compared with the low-fiber group, was 0.99 (95 percent confidence interval, 0.71 to 1.36; P=0.93). CONCLUSIONS: As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas.

Asunto(s)

Adenoma/prevención & control , Neoplasias Colorrectales/prevención & control , Fibras de la Dieta/administración & dosificación , Recurrencia Local de Neoplasia/prevención & control , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Neoplasias Colorrectales/cirugía , Método Doble Ciego , Grano Comestible , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cooperación del Paciente , Insuficiencia del Tratamiento , Triticum

Asunto(s)

Reflujo Gastroesofágico/epidemiología , Pirosis/epidemiología , Calidad de Vida , Enfermedad Crónica , Determinación de la Acidez Gástrica , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/terapia , Conocimientos, Actitudes y Práctica en Salud , Pirosis/diagnóstico , Pirosis/etiología , Pirosis/terapia , Humanos , Concentración de Iones de Hidrógeno , Estados Unidos/epidemiología

Asunto(s)

Antiácidos/uso terapéutico , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/tratamiento farmacológico , Conocimientos, Actitudes y Práctica en Salud , Pirosis/etiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Apoyo Social

RESUMEN

Prostaglandin E2 (PGE2) has served as a surrogate end point biomarker in colorectal tumor progression. Colonic mucosa PGE2 levels of patients with colorectal adenomas or carcinomas have been shown to be higher than in control subjects. Our dose-finding study on piroxicam, a nonsteroidal anti-inflammatory drug with chemopreventive effects in preclinical colon carcinoma models, suggested that 7.5 mg/day was well tolerated and associated with significant depression of rectal mucosa PGE2 concentrations in comparison with baseline values. We therefore conducted a randomized Phase IIb cancer prevention clinical trial to investigate the chemopreventive properties of piroxicam in patients with a history of resected colorectal adenomatous polyps. After a 2-month run-in period, 47 participants were randomized to piroxicam at a dose of 7.5 mg/day, and 49 were randomized to a placebo. Rectal biopsy specimens were taken at the initial visit, at 2 months later during the run-in period, and at 6, 12, and 24 months after the start of the interventions. Mean PGE2 concentrations in the rectal mucosa of the piroxicam-treated patients differed significantly between visits (P < 0.001), and the values at the 6-month visit (P < 0.001) and 12-month visit (P = 0.005) differed significantly from the average baseline value. Unfortunately, we observed an incidence of adverse gastrointestinal side effects in patients treated with 7.5 mg/day of piroxicam similar to that seen for arthritis patients treated with 20 mg/day. Consequently, the gastrointestinal toxicities appear to override the potential benefit that piroxicam may offer as a long-term colon cancer chemopreventive agent.

Asunto(s)

Pólipos Adenomatosos/cirugía , Antiinflamatorios no Esteroideos/uso terapéutico , Anticarcinógenos/uso terapéutico , Neoplasias Colorrectales/cirugía , Dinoprostona/análisis , Mucosa Intestinal/efectos de los fármacos , Piroxicam/uso terapéutico , Recto/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/efectos adversos , Anticarcinógenos/efectos adversos , Femenino , Humanos , Mucosa Intestinal/química , Masculino , Persona de Mediana Edad , Piroxicam/efectos adversos , Recto/química

RESUMEN

The central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates the generation of mammalian circadian rhythms, including an oscillation in pacemaker sensitivity to photic signals conveyed by the retinohypothalamic tract. Because brain-derived neurotrophic factor (BDNF) has been implicated in the functional regulation of neural input to other targets of visual pathways, the present study examined whether changes in BDNF expression or blockade of its action in the SCN affect circadian pacemaker responses to light. In rats receiving infusion of exogenous BDNF into the SCN, the free-running rhythm of activity in constant darkness was characterized by large phase advances in response to light exposure during the midsubjective day, when the circadian pacemaker is normally insensitive to photic perturbation. In contrast, SCN infusion of BDNF did not potentiate either phase-delaying or phase-advancing effects of light on the rat activity rhythm during the subjective night. In heterozygous BDNF mutant mice, deficits and damped rhythmicity in SCN levels of this neurotrophin were accompanied by marked decreases in the amplitude of light-induced phase shifts during the subjective night. In agreement with the effects of decreased BDNF expression, SCN infusion of the tyrosine kinase inhibitor K252a blocked or strongly inhibited both the phase-delaying and -advancing effects of light during the subjective night. Collectively, these findings suggest that BDNF-mediated signaling may play an important role in the circadian regulation of SCN pacemaker sensitivity to light.

Asunto(s)

Relojes Biológicos/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/farmacología , Ritmo Circadiano/efectos de los fármacos , Luz , Núcleo Supraquiasmático/efectos de los fármacos , Animales , Relojes Biológicos/fisiología , Factor Neurotrófico Derivado del Encéfalo/genética , Carbazoles/farmacología , Ritmo Circadiano/fisiología , Alcaloides Indólicos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Proteína Quinasa C/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Núcleo Supraquiasmático/fisiología

RESUMEN

Gastric acid-related disorders are common clinical problems associated with a wide range of symptoms. Important advances have occurred over the last 20 yr that have improved our understanding of these disorders as well as our approach to treatment. Today, control of gastric acid secretion represents the cornerstone of effective management of both peptic ulcer disease and gastroesophageal reflux disease (GERD). A variety of acid-reducing strategies are now available to clinicians to manage symptoms and control or resolve disease. Antacids offer rapid symptomatic relief but probably have little effect on overall disease progression. Histamine-2 receptor antagonists can also provide good initial symptomatic treatment in peptic ulcer disease and in mild to moderate GERD. However, problems with postmeal acid control and tachyphylaxis may detract from their long-term usefulness. The availability of proton pump inhibitors (PPIs), which block the final process in H+ ion secretion, has revolutionized our approach to the management of patients with acid secretory disorders. The currently available PPIs, omeprazole and lansoprazole, enable us to control symptoms effectively and safely, hasten healing, and minimize disease recurrence. New PPIs, such as rabeprazole and pantoprazole, will further expand our treatment options and may offer even greater possibilities with regard to rapid symptomatic relief and disease resolution.

Asunto(s)

Ácido Gástrico/metabolismo , Reflujo Gastroesofágico/tratamiento farmacológico , Úlcera Péptica/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Úlcera Péptica/microbiología , Inhibidores de la Bomba de Protones

RESUMEN

We report a convenient method for the synthesis of dinorbile acids (23,24-dinor-5beta-cholan-22-oic acids, pregnane-20-carboxylic acids) in fair to good yields from norbile acid nitriles in one step by oxidative hydrolysis with oxygen in the presence of potassium-t-butoxide. The method results in stepwise overall removal of two carbon atoms in bile acid side chains in two steps. Dinorbile acids corresponding to several common bile acids have been prepared and their structures confirmed by spectroscopic methods. This simple method for synthesis of dinorbile acids may facilitate their study metabolically.

Asunto(s)

Ácidos y Sales Biliares/síntesis química , Ácidos Carboxílicos/síntesis química , Cromatografía de Gases , Hidrólisis , Espectroscopía de Resonancia Magnética , Oxidación-Reducción