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Background/Aims: The Flos Lonicera extract GCWB104 has been shown to have significant protective effects against gastritis and gastric ulcers in vivo. The aim of this study was to investigate the efficacy and safety of GCWB104 in subjects with functional dyspepsia (FD). Methods: In this single-center, double-blind, randomized clinical trial, 92 subjects diagnosed with FD using the Rome III criteria were allocated to either the test group (300 mg of GCWB104, containing 125 mg of Flos Lonicera extract, twice daily) or the placebo group (300 mg placebo, twice daily). The total score improvement on the Gastrointestinal Symptom Rating Scale (GSRS) for individual symptoms, changes in antioxidant levels, changes in dyspepsia-related quality of life according to the Nepean Dyspepsia Index (NDI), and adverse effects were compared before and after 8 weeks of treatment. Results: The differences in total GSRS scores and score improvements after 8 weeks of treatment were significant between the GCWB104 and control groups (p=0.0452 and p=0.0486, respectively). Thirteen of 15 individual symptoms on the GSRS improved in the GCWB104 group, while six symptoms improved in the control group. In addition, statistically significant changes in rumbling, loose stool, and stool urgency were observed in the GCWB104 group. Blood 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, known as antioxidants, showed significant reductions after 8 weeks of administration of GCWB104. There were no adverse events related to treatment with GCWB104. Conclusions: GCWB104 safely contributed to improvements in mild to moderate FD and irritable bowel syndrome symptoms. Antioxidant effects of GCWB104 were also suggested (Clinicaltrials.gov number NCT04008901).
Asunto(s)
Dispepsia/tratamiento farmacológico , Lonicera , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Adulto , Antioxidantes/análisis , Método Doble Ciego , Dispepsia/sangre , Femenino , Humanos , Síndrome del Colon Irritable/sangre , Síndrome del Colon Irritable/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Background/Aim: The purpose of this study was to establish a modified rat model with functional dyspepsia (FD) and analyze the changes in gastrointestinal motility and brain-gut peptide levels in serum and brain-gut axis. Materials and Methods: Male Wistar rats were divided into control group (Con) and FD model group. FD model was established by stimulating semi-starvation rats via tail damping, provocation, and forced exercise fatigue until gastrointestinal motility disorder appeared, and then levels of motilin, leptin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were detected in serum by enzyme linked immunosorbent assay and in duodenum, antrum, and hypothalamus by immunohistochemistry, reverse transcriptase-polymerase chain reaction, and Western blot. Results: The results showed rates of intestinal propulsion and gastric emptying slowed down markedly compared to Con (P < 0.05), the gastrointestinal electric activity attenuated, and migrating motor complex (MMC) interrupted in the model group. The levels of leptin and VIP markedly increased, but motilin decreased as compared to the Con (P < 0.05) in serum and in the above tissues. It is interesting that the level of CCK decreased in the antrum and duodenum but increased in the hypothalamus as compared to Con (P < 0.05). Conclusions: The modified rat model meets the diagnostic criteria of FD and can be used as a method for studying FD in animals.
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Dispepsia/sangre , Dispepsia/fisiopatología , Mucosa Gástrica/metabolismo , Hormonas Gastrointestinales/sangre , Motilidad Gastrointestinal/fisiología , Estómago/fisiopatología , Animales , Colecistoquinina/sangre , Modelos Animales de Enfermedad , Vaciamiento Gástrico/fisiología , Hipotálamo/metabolismo , Leptina/sangre , Masculino , Motilina/sangre , Ratas , Ratas Wistar , Péptido Intestinal Vasoactivo/sangreRESUMEN
BACKGROUND: Manual acupuncture (MA) manipulations are one of the key factors influencing acupuncture effects in traditional Chinese medicine theory. Different MA manipulations contain different stimulating parameters, thus generating different acupuncture responses or effects. Evidence has demonstrated that acupuncture is effective for functional dyspepsia (FD). However, the effects of different stimulating parameters of MA manipulations on FD remain unclear. METHODS/DESIGN: This study is a randomized controlled trial with a four-arm, parallel-group structure. Patients with FD with epigastric pain syndrome (EPS) will be included and randomly allocated into four groups: three MA manipulation groups (separately treated with a frequency of 1 Hz, 2 Hz, or 3 Hz) and a control group. All groups will receive omeprazole as a basic treatment and acupuncture: in the MA manipulation groups, the needles will be manipulated manually with three different frequencies on the basis when de qi is reached, while in the control group, the needles will be inserted without any manipulation. All patients will receive acupuncture treatment of five consecutive sessions per week for 2 weeks and be followed up at 4, 8, and 12 weeks. The primary outcomes of the study include patients' response to the treatment. The secondary outcomes include dyspeptic symptoms, quality of life, mental status, fasting serum gastrin, motilin, and ghrelin concentrations, and adverse events. The protocol was approved by the Ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (2016-K-057-01). DISCUSSION: The aim of this study is to evaluate the efficacy and safety of MA manipulations with different stimulating parameters (different frequencies) on EPS in patients with FD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-16008189 . Registered on 30 March 2016.
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Dolor Abdominal/terapia , Dispepsia/terapia , Electroacupuntura/métodos , Dolor Abdominal/sangre , Dolor Abdominal/diagnóstico , Dolor Abdominal/fisiopatología , Adolescente , Adulto , Biomarcadores/sangre , China , Protocolos Clínicos , Método Doble Ciego , Dispepsia/sangre , Dispepsia/diagnóstico , Dispepsia/fisiopatología , Electroacupuntura/efectos adversos , Femenino , Gastrinas/sangre , Ghrelina/sangre , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Motilina/sangre , Dimensión del Dolor , Calidad de Vida , Proyectos de Investigación , Síndrome , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Comprehensive study of hepatospecific biochemical blood markers and haemostatic system in calves which recovered from gastrointestinal pathology at age 2-7 days, was con- ducted. Implementation of a complex of tests for evaluation of the liver's functional state and the efficiency of therapeutic regimens shown that the experimental animals compared to control at the 30th day of life demonstrated significantly increased conjugated bilirubin concentration (1.6 times), aspartate- and alanin aminotransferase activity (1.2 times), gamma-glutamyl transpeptidase (1.5 times) and alkaline phosphatase (1.4 times), and content of soluble fibrin monomer complexes (4 times). Such deviation from the norm of the mentioned parameters of liver's functional state suggests the need to monitor the liver state even 3 weeks after their clinical health is confirmed. To prevent the development of secondary hepatopathology it is recommended to conduct further medical correction of the functional state of the liver. It is found that to stimulate recovery of liver function in case of toxic dyspepsia in newborn calves, it is advisable to implement a phospholipid containing supplement Asunto(s)
Suplementos Dietéticos
, Dispepsia/fisiopatología
, Hemostasis/fisiología
, Hígado/fisiopatología
, Fosfolípidos/uso terapéutico
, Animales
, Animales Recién Nacidos
, Bovinos
, Dispepsia/sangre
, Dispepsia/tratamiento farmacológico
, Hígado/metabolismo
, Pruebas de Función Hepática
, Fosfolípidos/administración & dosificación
, Resultado del Tratamiento
RESUMEN
AIM: To evaluate the efficacy and safety of the Xiaoyao pill for treatment of functional dyspepsia (FD) associated with perimenopausal depression. METHODS: This was a double-blind, randomized, controlled trial including 180 patients with FD accompanied by depression that were divided into two groups of 90. Patients in the treatment group received oral administration of the Xiaoyao pill for soothing the liver and activating the spleen, and patients in the control group received a placebo. This trial included an 8-wk therapy period with a follow-up period of 6 mo. The total efficacy and degree of depression, as assessed by the Hamilton Rating Scale for Depression (HRSD), were evaluated. Plasma levels of motilin and gastrin were measured and a gastric emptying test was conducted in each participant. RESULTS: The Xiaoyao pill had a good therapeutic effect and improved the symptoms in patients with perimenopausal FD as assessed by the HRSD score, motilin and gastrin levels, and rate of gastric emptying. The total effective rate of the Xiaoyao pill in the treatment group was significantly superior to that of the placebo in the control group. In the control group, the initial HRSD score was 12.12 ± 2.29 and decreased to 7.14 ± 1.67 after therapy (P < 0.01). In the treatment group, the initial HRSD score was 11.44 ± 2.15, which significantly decreased to 6.20 ± 2.08 after therapy (P < 0.01). Moreover, the HRSD score in the treatment group was significantly lower than in control group after 8 wk (P < 0.01). Motilin and gastrin levels in both groups were significantly increased after the 8-wk therapy (P < 0.05). The gastric emptying rate was also improved in both groups after therapy (P < 0.05), and the improvement was significantly better in the treatment group compared to the controls (P < 0.05). These results confirm the therapeutic effects of the Xiaoyao pill in perimenopausal FD patients and indicate that it is worthy of clinical promotion. CONCLUSION: The Xiaoyao pill is effective and safe for the treatment of perimenopausal women with FD associated with depression.
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Depresión/psicología , Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Perimenopausia/psicología , Adulto , Biomarcadores/sangre , China , Depresión/diagnóstico , Depresión/etiología , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Dispepsia/sangre , Dispepsia/diagnóstico , Dispepsia/etiología , Dispepsia/fisiopatología , Dispepsia/psicología , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Gastrinas/sangre , Fármacos Gastrointestinales/efectos adversos , Humanos , Persona de Mediana Edad , Motilina/sangre , Escalas de Valoración Psiquiátrica , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the correlation between the pathogeneses of diarrhea-pre- dominant irritable bowel syndrome (D-IBS) complicated functional dyspepsia (FD) patients of Gan-stagnation Pi-deficiency Syndrome (GSPDS) and symptoms, psychological states, and gastrointestinal hormones. METHODS: A total of 111 patients with confirmed D-IBS complicated FD of GSPDS were recruited as the treated group by using Rome III standard and Chinese medical syndrome standard. And 30 healthy volunteers were recruited as the control group. The general condition, scoring for digestive symptoms, and the distribution of GSPDS subtype of all subjects were recorded by a questionnaire, and assessed by Symptom Checklist (SCL-90; a software for psychological test developed by Beijing Huicheng Adult Cor- poration). Meanwhile, plasma levels of 5-hydroxytryptamine (5-HT), somatostatin (SS), vasoactive intestinal peptide (VIP), endothelin (ET), interleukin 10 (IL-10), and interleukin 12 (IL-12) were measured in all subjects. RESULTS: (1) The subtype of D-IBS complicated FD of GSPDS was dominant in Pi-qi deficiency type (51/111,45.9%),Pi yang deficiency type (34/111,30.6%), and GSPDS. There was no statistical difference in the scoring of digestive symptoms among the 3 subtypes (P >0.05). (2) Compared with the control group, the anxiety factor score and the total score significantly increased in all three subtypes of D-IBS complicated FD of GSPDS, and the depression score of Pi yang deficiency type and Gan-depression type also significantly increased (P <0.05, P <0.01); the depression score of Gan-depression type was significantly higher than that of the Pi-qi deficiency type (P <0.01). Plasma 5-HT levels were obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities, and VIP and IL-10 levels were significantly lower than those in the control group (P <0.05). Plasma VIP levels were also obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities (P <0.01), and SS levels were significantly lower than those in the control group (P <0.05). There was no statistical difference in plasma ET or IL-12 levels in each patient group, when compared with the control group (P >0.05). (3) Compared with the.control group, plasma 5-HT levels significantly increased, plasma VIP and IL-10 levels significantly decreased in ach subtype of D-IBS complicated FD patients of GSPDS (P <0.05, P <0.01), and no significant change of SS, ET, or IL-12 occurred (P >0.05). Besides, plasma 5-HT levels were significantly higher in Gan-depression type than in Pi yang deficiency type, VIP levels were lower in Gan-depression type than in Pi-qi deficiency type (all P <0.05). CONCLUSIONS: Gan stagnation and Pi deficiency were dominant in D-IBS complicated FD patients of GSPDS. Psychological abnormalities, increased plasma 5-HT levels, and decreased plasma VIP levels were closely correlated with Gan stagnation subtype, which provided some reference for looking for objective indicators of Chinese medical syndromes in treating D-IBS complicated FD patients of GSPDS.
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Diarrea/etiología , Dispepsia/complicaciones , Síndrome del Colon Irritable/complicaciones , Adulto , Estudios de Casos y Controles , Dispepsia/sangre , Dispepsia/psicología , Hormonas Gastrointestinales/sangre , Humanos , Síndrome del Colon Irritable/sangre , Síndrome del Colon Irritable/psicología , Pruebas Psicológicas , Qi , Serotonina , Encuestas y Cuestionarios , Deficiencia YangRESUMEN
It has been reported that sevelamer hydrochloride, which is often used as a polymer phosphorus (P) binder for managing serum P concentration in dialysis patients, causes gastrointestinal adverse effects such as constipation, etc. The reason for this is thought to be that sevelamer hydrochloride has high water absorption, causing it to absorb water and swell in the gastrointestinal tract. In June 2012, the new polymer P binder bixalomer was launched in Japan. Since bixalomer has low swelling due to water absorption, it can be expected to alleviate adverse effects in the gastrointestinal system. In our study, for 21 cases of maintenance hemodialysis patients undergoing treatment with sevelamer hydrochloride at our hospital, the P binder was switched from sevelamer hydrochloride to the same dosage of bixalomer, and the concentrations of serum P, corrected calcium (Ca) and whole parathyroid hormone (PTH) before and one month after the switch were compared. In addition, gastrointestinal symptoms (acid reflux, abdominal pain, indigestion, diarrhea and constipation) were evaluated before and after the switch using a questionnaire based on the Japanese version of the Gastrointestinal Symptom Rating Scale (GSRS). By switching to bixalomer, serum P concentration was significantly reduced (P=0.024), but there were no significant changes observed for serum corrected Ca and whole PTH. Furthermore, there were no significant changes observed for all five of the evaluation items of the GSRS, before and after the switch. These results suggest that although bixalomer can more potently reduce the serum P concentration than sevelamer hydrochloride, there were no significant differences in the effects of both P binders on the gastrointestinal symptoms.
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Enfermedades Gastrointestinales/inducido químicamente , Hiperfosfatemia/tratamiento farmacológico , Poliaminas/efectos adversos , Diálisis Renal/efectos adversos , Dolor Abdominal/sangre , Dolor Abdominal/inducido químicamente , Anciano , Calcio/sangre , Quelantes/uso terapéutico , Estreñimiento/sangre , Estreñimiento/inducido químicamente , Diarrea/sangre , Diarrea/inducido químicamente , Dispepsia/sangre , Dispepsia/inducido químicamente , Femenino , Reflujo Gastroesofágico/sangre , Reflujo Gastroesofágico/inducido químicamente , Enfermedades Gastrointestinales/sangre , Humanos , Hiperfosfatemia/sangre , Hiperfosfatemia/etiología , Japón , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Hormona Paratiroidea/sangre , Fósforo/sangre , Poliaminas/sangre , Poliaminas/uso terapéutico , Sevelamer , Encuestas y CuestionariosRESUMEN
BACKGROUND: Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). METHODS: FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. KEY RESULTS: Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. CONCLUSIONS & INFERENCES: Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/tratamiento farmacológico , Dolor/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Dispepsia/sangre , Femenino , Ghrelina/sangre , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Functional dyspepsia (FD) is a common health problem currently without any optimal treatments. Acupuncture has been traditionally sought as a treatment for FD. The aim of this study is to investigate whether acupuncture treatment helps improve symptoms of FD. METHODS/DESIGN: A two-center, randomized, waitlist-controlled trial will be carried out to evaluate whether acupuncture treatment improves FD symptoms. Seventy six participants aged 18 to 75 years with FD as diagnosed by Rome III criteria will be recruited from August 2013 to January 2014 at two Korean Medicine hospitals. They will be randomly allocated either into eight sessions of partially individualized acupuncture treatment over 4 weeks or a waitlist group. The acupuncture group will then be followed-up for 3 weeks with six telephone visits and a final visit will be paid at 8 weeks. The waitlist group will receive the identical acupuncture treatment after a 4-week waiting period. The primary outcome is the proportion of responders with adequate symptom relief and the secondary outcomes include Nepean dyspepsia index, EQ-5D, FD-related quality of life, Beck's depression inventory, state-trait anxiety inventory questionnaire, and level of ghrelin hormone. The protocol was approved by the participating centers' Institutional Review Boards. DISCUSSION: Results of this trial will help clarify not only whether the acupuncture treatment is beneficial for symptom improvement in FD patients but also to elucidate the related mechanisms of how acupuncture might work. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01921504.
Asunto(s)
Terapia por Acupuntura , Dispepsia/terapia , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Protocolos Clínicos , Dispepsia/sangre , Dispepsia/diagnóstico , Dispepsia/psicología , Femenino , Ghrelina/sangre , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Inducción de Remisión , República de Corea , Proyectos de Investigación , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Dyspeptic symptoms are frequently induced, or exacerbated, by fatty food ingestion. Excessive release of, and/or hypersensitivity to, cholecystokinin (CCK) may explain the exaggerated response to lipid in patients with functional dyspepsia (FD). Thus far, plasma CCK response has been evaluated. However, stimulation of CCK1 receptors on duodenal vagal afferents occurs in a paracrine manner, suggesting that mucosal CCK concentrations are relevant to quantify. Apolipoprotein A-IV stimulates mucosal CCK release. AIM: To investigate the hypothesis that fat-induced release of CCK and apolipoprotein A-IV (apoA-IV) is enhanced in the duodenum of FD patients. PATIENTS AND METHODS: Sixteen symptomatic FD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with intralipid 20%, 2 kcal/min, for 60 min. Symptoms were scored and blood samples were collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosal concentrations of CCK and apoA-IV were quantified. RESULTS: Abdominal discomfort (P=0.001), nausea (P=0.05), and fullness (P=0.005) in response to duodenal lipid increased significantly only in FD patients. Following lipid infusion, the mean mucosal CCK concentration was lower in FD patients compared with HV (P<0.0001). Fasting concentrations and plasma response of CCK were comparable in FD patients and HV. Plasma apoA-IV response appeared to differ between patients and HV, whereas mucosal apoA-IV concentrations were similar. CONCLUSION: Our results suggest excessive local release of CCK in response to duodenal lipid in FD. This likely causes exaggerated stimulation of duodenal vagal afferents, explaining dyspeptic symptom generation. The mechanisms underlying elevated mucosal CCK release warrant further investigation.
Asunto(s)
Colecistoquinina/metabolismo , Duodeno/metabolismo , Dispepsia/diagnóstico , Mucosa Intestinal/metabolismo , Fosfolípidos , Aceite de Soja , Adulto , Apolipoproteínas A/metabolismo , Biomarcadores/sangre , Biomarcadores/metabolismo , Biopsia , Estudios de Casos y Controles , Colecistoquinina/sangre , Regulación hacia Abajo , Dispepsia/sangre , Dispepsia/metabolismo , Emulsiones/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Fosfolípidos/administración & dosificación , Valor Predictivo de las Pruebas , Aceite de Soja/administración & dosificación , Factores de TiempoRESUMEN
BACKGROUND/AIMS: Functional dyspepsia (FD) is a common disease but there is no established treatment. Rikkunshito is a traditional Japanese medicine that is widely used for treating upper gastrointestinal symptoms and its effect on ghrelin is of great interest. The aim of this study was to investigate the effect of rikkunshito on upper gastrointestinal symptoms and the levels of acylated ghrelin (AG) in patients with FD. METHODOLOGY: This study was a paralleled, randomized controlled trial. Patients were treated with either rikkunshito (group R) or domperidone (group D) for 4 weeks. The overall change in dyspeptic symptoms was evaluated by the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire score. RESULTS: 27 patients were enrolled. There was a significant improvement in dyspeptic symptoms in both groups, based on the GSRS score. AG levels increased significantly in plasma in group R at 2 weeks after treatment (paired t-test, p<0.05). The improvements of reflux (Pearson's correlation test, r=-0.73, p=0.04) and indigestion (r=-0.76, p=0.03) symptoms in group R showed a good correlation with the increase of AG. CONCLUSIONS: Rikkunshito improves upper gastrointestinal symptoms in patients with FD, accompanied by an increase in the levels of AG.
Asunto(s)
Domperidona/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Ghrelina/sangre , Acilación , Adulto , Anciano , Peso Corporal/efectos de los fármacos , Dispepsia/sangre , Dispepsia/diagnóstico , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
Ghrelin is a peptide hormone produced mainly by the stomach and has widespread physiological functions including increase in appetite. The stimulation of the ghrelin system represents a potential therapeutic approach in various disorders characterized by deficient ghrelin signaling or by low appetite. This stimulation may be achieved via pharmacological targeting of the ghrelin receptor with synthetic ghrelin or ghrelin mimetics or via increased endogenous ghrelin production. Recently, it was demonstrated that gastric electrical stimulation (GES) with Enterra parameters results in increased ghrelin production in rats. Furthermore, recent data revealed putative role of ghrelin-reactive immunoglobulins in the modulation of the ghrelin signaling which can be also stimulated by GES. Here, we review the links between GES and ghrelin in existing GES experimental and clinical applications for treatment of gastroparesis, functional dyspepsia or obesity and discuss if GES can be proposed as a non-pharmacological approach to improve ghrelin secretion in several pathological conditions characterized by low appetite, such as anorexia nervosa or anorexia-cachexia syndrome.
Asunto(s)
Regulación del Apetito/fisiología , Ingestión de Alimentos/fisiología , Terapia por Estimulación Eléctrica/métodos , Mucosa Gástrica/metabolismo , Ghrelina , Inmunoglobulinas/uso terapéutico , Receptores de Ghrelina/metabolismo , Animales , Anorexia Nerviosa/sangre , Anorexia Nerviosa/fisiopatología , Anorexia Nerviosa/terapia , Regulación del Apetito/efectos de los fármacos , Caquexia/sangre , Caquexia/fisiopatología , Caquexia/terapia , Dispepsia/sangre , Dispepsia/fisiopatología , Dispepsia/terapia , Electrodos Implantados , Gastroparesia/sangre , Gastroparesia/fisiopatología , Gastroparesia/terapia , Regulación de la Expresión Génica/efectos de los fármacos , Ghrelina/sangre , Ghrelina/genética , Ghrelina/metabolismo , Humanos , Hambre/efectos de los fármacos , Inmunoglobulinas/administración & dosificación , Obesidad/sangre , Obesidad/fisiopatología , Obesidad/terapia , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Ratas , Receptores de Ghrelina/genética , Respuesta de Saciedad/efectos de los fármacos , Estómago/efectos de los fármacos , Estómago/fisiopatologíaRESUMEN
AIM: To evaluate the effects of ginger on gastric motility and emptying, abdominal symptoms, and hormones that influence motility in dyspepsia. METHODS: Eleven patients with functional dyspepsia were studied twice in a randomized double-blind manner. After an 8-h fast, the patients ingested three capsules that contained ginger (total 1.2 g) or placebo, followed after 1 h by 500 mL low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires, and blood was taken for measurement of plasma glucagon-like peptide-1 (GLP-1), motilin and ghrelin concentrations, at intervals throughout the study. RESULTS: Gastric emptying was more rapid after ginger than placebo [median (range) half-emptying time 12.3 (8.5-17.0) min after ginger, 16.1 (8.3-22.6) min after placebo, P≤0.05]. There was a trend for more antral contractions (P=0.06), but fundus dimensions and gastrointestinal symptoms did not differ, nor did serum concentrations of GLP-1, motilin and ghrelin. CONCLUSION: Ginger stimulated gastric emptying and antral contractions in patients with functional dyspepsia, but had no impact on gastrointestinal symptoms or gut peptides.
Asunto(s)
Dispepsia/tratamiento farmacológico , Dispepsia/fisiopatología , Motilidad Gastrointestinal/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Zingiber officinale/química , Método Doble Ciego , Dispepsia/sangre , Vaciamiento Gástrico/efectos de los fármacos , Motilidad Gastrointestinal/fisiología , Ghrelina/sangre , Péptido 1 Similar al Glucagón/sangre , Humanos , Motilina/sangre , Dimensión del Dolor , Placebos , Estómago/anatomía & histología , Estómago/efectos de los fármacos , Estómago/fisiopatologíaAsunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/tratamiento farmacológico , Fitoterapia , Adulto , Animales , Dispepsia/sangre , Medicina Basada en la Evidencia , Ghrelina/sangre , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To observe the long-term efficacy and safety on functional dyspepsia treated with electroacupuncture and Zhizhu Kuanzhong capsule and explore the therapeutic mechanism. METHODS: Three hundreds and twenty patients with confirmed diagnosis as functional dyspepsia were randomly divided into 4 groups: an electroacupuncture group, a Zhizhu Kuanzhong capsule group, a combined therapy group and a western medication group, 80 cases in each group. In electroacupuncture group, acupuncture was applied to Zusanli (ST 36), Zhongwan (CV 12), Neiguan (PC 6), Taichong (LR 3) and Gongsun (SP 4), twice per day, continuously for 5 days each week. In Zhizhu Kuanzhong capsule group, Zhizhu Kuanzhong capsule, 1.29 g was administered for oral application, three times each day. In combined therapy group, the therapeutic programs in the above-mentioned groups were applied in combination. In western medication group, Mosapride 5 mg, three times per day; Omeprazole 20 mg, twice per day and Amitriptyline 25 mg, twice per day were administered for oral application. Six weeks treatment was required in each group. The symptoms score, the Nepean Dyspepsia Symptom Index (NDSI), the Nepean Dyspepsia Life Quality Index (NDLQI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), electrogastrography, plasma motilin, gastric emptying by B-sonography and adverse reactions were observed before and after treatment, as well as 4 weeks after treatment separately. RESULTS: Compared with those before treatment, the symptom score and NDSI decreased apparently after treatment (all P < 0.01), NDLQI, SF-36, electrogastrographic frequency, plasma motilin and gastric emptying were up-regulated apparently (all P < 0.01) after treatment in each group. The results of the above-mentioned indices in combined therapy group were superior to the other groups (all P < 0.05). As compared with the condition at the end of treatment, in 4 weeks after treatment, the above indices were not rebound apparently in electroacupuncture group and combined therapy group (all P > 0.05). But they were rebound obviously in Zhizhu Kuanzhong capsule group and western medication group (all P < 0.05). The short-term and long-term efficacies in combined therapy group were significantly higher than the total effective rates in the other groups (P < 0.05, P < 0.01). No serious adverse reaction was reported in each group. CONCLUSION: Electroacupuncture and Zhizhu Kuanzhong capsule all up-regulate plasma motilin and electrogastrographic frequency, promote gastric emptying, alleviate the symptom of functional dyspepsia and improve NDLQI. But the combined medication achieves much better efficacy and presents better safety and long-term therapeutic effect.
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Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/terapia , Electroacupuntura , Adolescente , Adulto , Cápsulas , Terapia Combinada , Dispepsia/sangre , Dispepsia/tratamiento farmacológico , Dispepsia/fisiopatología , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Motilina/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To compare the effects of electroacupuncture (EA) of Shu-acupoint "Weishu" (BL 21), Mu-acupoint "Zhongwan" (CV 12) and BL 21 + CV 12 on serum large molecular metabolites in functional dyspepsia (FD) rats. METHODS: A total of 50 Wistar rats were randomly divided into control, model, BL 21, CV 12 and BL 21 + CV 12 groups (n = 10/group). FD model was established by clamping the rats' tails for 30 min, once every 3 h, 4 times daily for 7 days. EA was applied to BL 21,CV 12, or BL 21 + CV 12, respectively for 20 min, once daily for 10 days. The rats' venous blood was collected for detecting large molecular metabolites by 1H nuclear magnetic resonance (NMR) spectrometer (Varian UnityInova, 600 MHz). Segmental integral calculus (0.04 ppm per segment) was performed from 6.0-0 ppm (longitudinal eddy-delay, LED) as defaulted 1H spectra values by using the VNMR software. Data was saved as text or excel files after normalization and then used for pattern recognition analyses. All the data were analyzed by principal component analysis (PCA) using the SIMCA-P 10.04 software (Umetrics AB, Umea, Sweden), and orthogonal signal correction and partial least squares discriminant analysis (OSC-PLS-DA). RESULTS: The rat serum proton-LED-1H NMR spectra revealed different metabolic spectra among control,model, BL 21, CV 12, and BL 21 + CV 12 groups. PCA and OSC-PLS-DA showed that compared with the normal control group, FD rats in model group displayed serum N-acetylglucoprotein (NAc) content was reduced considerably, high density lipoprotein (HDL) level decreased to a certain degree, while very low density lipoprotein (VLDL)/LDL increased significantly. In comparison with model group, VLDL/LDL was decreased in BL 21, CV 12 and BL 21 + CV 12 groups, while NAc content increased. Compared with BL 21 and CV 12 groups respectively, HDL level in BL 21 + CV 12 increased to a certain degree. CONCLUSION: EA of BL 21, CV 12 and BL 21 + CV 12 groups can reverse or relieve FD induced increase of VLDL/LDL and decrease of serum NAc level in rats, which may contribute to its function in improving symptoms of FD patients.
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Puntos de Acupuntura , Dispepsia/sangre , Dispepsia/terapia , Electroacupuntura , Lipoproteínas/sangre , Animales , Modelos Animales de Enfermedad , Dispepsia/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Radiografía , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
AIM: The aim of the study was to explore the potential of phytotherapy with artichoke leaf extract in the management of functional dyspepsia symptoms, a disorder notoriously recalcitrant to pharmacotherapy. METHODS: A cohort of outpatients with a clinical diagnosis of functional dyspepsia and deemed suitable candidates for non-pharmacologic treatment was prospectively observed for 60 days by 33 physicians. Treatment consisted of Cinarepa, a commercial mixture of dry extracts of artichoke leaf (Cynara scolymus) 15% of chlorogenic acid (150 mg per capsule), dandelion radix (Taraxacum officinalis) 2% of inulin, turmeric rhizome (Curcuma longa) 95% of curcumin and rosemary bud essential oil microencapsulated (Rosmarinum officinalis). The severity of 8 dyspepsia symptoms was self-evaluated on a 10-point scale. Blood chemistry testing of lipid profile and liver function was discretionary. RESULTS: Of the 311 patients in the cohort, the data from 305 (98%) were included in the analysis of dyspepsia symptoms and the data from 50-73 (16-23%) were entered into the analysis of blood chemistry results. A statistically significant gradual reduction in symptom severity was noted at day 30 and further improvement was observed at day 60. Global clinical response, defined as a 50% reduction in the total scores of all symptoms, was recorded in 38% of patients at 30 days and in 79% at 60 days. At 60 days, total cholesterol, LDL and triglyceride levels had decreased by 6-8% over baseline values (P < or = 0.001); transaminase (AST, ALT), and gamma GT concentrations had diminished by 13-20 U/L (P<0.01) in patients with relatively elevated baseline values. CONCLUSION: Phytotherapy with Cinarepa holds promise as an alternative option in the relief of functional dyspepsia symptoms and merits further investigation in controlled studies.
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Biomarcadores/sangre , Cynara scolymus , Dispepsia/sangre , Dispepsia/tratamiento farmacológico , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Colagogos y Coleréticos/uso terapéutico , Colesterol/sangre , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Cinamatos/uso terapéutico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Italia , Masculino , Persona de Mediana Edad , Hojas de la Planta , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Transaminasas/sangre , Transaminasas/efectos de los fármacos , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
Functional dyspepsia (FD) is a common gastrointestinal disorder with multiple pathogenic mechanisms seen in clinical practice, and acupuncture may potentially be an alternative therapy for it. In order to investigate the biological effects of FD and the effect of acupuncture on metabolism, (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques have been used to compare the plasma metabolic profiles of six female FD patients with those of six female healthy control subjects. Plasma metabolic profiles of FD patients treated by acupuncture at the Foot-Yangming Meridian were also collected and compared. Data obtained from NMR spectroscopy were subjected to principal components analysis (PCA). The results show that there are relatively higher levels of glucose, acetate, high-density lipoprotein (HDL), and phosphatidylcholine (PtdCho), and lower levels of lactate, leucine/isoleucine, N-acetyl glycoprotein (NAc), and low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) in FD patients than in healthy controls. Acupuncture treatment of FD patients significantly changed the levels of leucine/isoleucine, lactate and glucose, and slightly changed lipids level towards those of the healthy controls, demonstrating its therapeutic effects on the relief of FD symptoms. Due to the limited number of subjects, the present work is just a proof-of-principle study and further researches with larger number of subjects are needed. Our work shows the potential of an NMR-based metabonomic approach in the study of biological effects of acupuncture.
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Terapia por Acupuntura , Dispepsia/sangre , Dispepsia/terapia , Espectroscopía de Resonancia Magnética/métodos , Metabolómica/métodos , Adulto , Biomarcadores/sangre , Femenino , Humanos , Protones , Adulto JovenRESUMEN
OBJECTIVE: To compare the therapeutic effects of transcutaneous electrical point stimulation and medication on functional dyspepsia. METHODS: Two hundred and fifty cases were randomly divided into an observation group and a control group, 125 cases in each group. The observation group was treated with transcutaneous electrical acupoint stimulation and oral administration of placebo, transcutaneous electrical stimulated at Zusanli (ST 36), Liangmen (ST 21), Taichong (LR 3) etc. The control group was treated with oral administration of Mosapride citrate dispersible tablets, Domperidone and Omeprazole and the placebo treatment of transcutaneous electrical acupoint stimulation, the stimulated position was 3-4 cm to the selected points of the observation group, the amount of the stimulation did not reach the treatment amount. The symptom score, the plasma motilin (MTL) concentration and the somatostatin (SS) concentration were observed before and after treatment of 3 courses. RESULTS: All symptom scores after treatment were lower than that before treatment in the two groups, the scores of the upper abdominal pain, acid regurgitation, belching and abdominal distention in the observation group were significantly lower than that in the control group (P < 0.05, P < 0.01); the treatments of both two groups can increase the plasma MTL concentration and decrease the SS concentration (both P < 0.001), and the plasma MTL concentration in the observation group was significantly higher than that in the control group (P < 0.01), and the SS concentration was significantly lower than that in the control group (P < 0.05). CONCLUSION: Transcutaneous electrical point stimulation can more reduce the symptoms of upper abdominal pain, acid regurgitation, belching and abdominal distention, etc. in the functional dyspepsia patients than medication treatment, and can increase the concentration of the plasma MTL and decrease the SS concentration, thus to improve the gastrointestinal motility.
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Puntos de Acupuntura , Dispepsia/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Adulto , Anciano , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Domperidona/administración & dosificación , Domperidona/uso terapéutico , Dispepsia/sangre , Dispepsia/fisiopatología , Femenino , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Morfolinas/administración & dosificación , Morfolinas/uso terapéutico , Motilina/sangre , Omeprazol/administración & dosificación , Omeprazol/uso terapéutico , Somatostatina/sangre , Resultado del TratamientoRESUMEN
Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.