Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Prescription pattern & adverse drug reactions of prokinetics

Background & objectives: Prokinetics are extensively prescribed leading to several adverse events (AEs). The aim of this study was to assess the prescription pattern in patients receiving prokinetics, and characteristics of adverse drug reactions (ADRs) in an outpatient department set up in a tertiary care hospital in western India. Methods: Patients attending outpatient departments of a tertiary care hospital and who had received prokinetic agent for at least seven days over the last one month were enrolled. Causality assessment of AEs was done and assessed for severity, preventability, seriousness and predictability. Results: A total of 304 patients [161 males (52.96%); 143 females (47.04%)] were enrolled. Most prescriptions (299/304, 98%) included domperidone, most commonly prescribed as fixed-dose combination (FDC) with pantoprazole (274/304, 90%). Prokinetic dose was not mentioned in 251/304 (83%) prescriptions, and 18/304 (6%) did not mention frequency. Of the 378 AEs reported from 179 patients (47.35%), 306 (81%) were mild, all non-serious; 272 (72%) not preventable and 291 (77%) predictable in nature. Decreased appetite (n=31, 8.2%) and fatigue (n=27,7.14%) were most commonly reported. Causality assessment by the World Health Organization-Uppsala Monitoring Centre scale showed that 180 AEs were related to suspected drug (17 probable and 163 possible ADRs). Significant correlation was observed for AEs with increasing number of drugs per prescription (Spearman's R=+0.8, P =0.05) and with increasing therapy duration (Spearman's R=+1.00, P <0.001). Interpretation & conclusions: Our findings showed that prokinetics were often prescribed as FDCs, with incomplete prescriptions. Domperidone was found to be associated with multiple AEs. It is suggested that regular prescription monitoring should be done in hospitals to encourage rational use of drugs.

Sobrecrecimiento bacteriano intestinal y pseudoobstrucción intestinal crónica: una relación poco conocida / Small intestinal bacterial overgrowth and chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIP) is the most severe intestinal motility disorder. Small intestinal bacterial overgrowth (SIBO) is frequently associated to dysmotility. In spite of this association, there is scare data on the relation between CIP and SIBO. To establish occurrence of CIP in SIBO patients in inter-crisis periods. To compare clinical and manometric characteristics of SIBO and non-SIBO patients. Retrospective analysis of 40 CIP patients (average age: 41 years; range: 18-76 years; 75 percent women). The following elements were registered: symptoms (such as pain, distention, vomit, constipation, diarrhea and weight loss); findings of the intestinal manometry (neuropathic, miopatic and mix pattern; intestinal motility index); and SIBO using lactulose H2 breath test, defined as an increase > 20 ppm in 2 or more figures in the first 60 minutes. Statistical analysis: t-test y and comparison of two ratios. SIBO was observed in 60 percent of the patients with CIP. Three or more symptoms were observed in 70.8 percent of the patients with SIBO 50 percentwithout SIBO (p = NS). In patients with SIBO, the most frequent symptom was abdominal pain (70.8 percent p= 0.032). There were no differences between SIBO patients and the different motility patterns, however, the intestinal motility index was lower for the SIBO group (9.7 +/- 44 12.3 +/-7; p < 0.001). : There is a high prevalence of SIBO in CIP patients. This is associated to a major compromise of intestinal motility assessed by the intestinal motility index...

Introducción: La pseudoobstrucción intestinal crónica (POIC) es el trastorno más grave de la motilidad intestinal. El sobrecrecimiento bacteriano intestinal (SBI) se asocia frecuentemente a estados de dismotilidad. A pesar de esta asociación existen escasos datos sobre la relación entre POIC y SBI. Objetivo: Determinar SBI en pacientes con POIC en período inter-crisis. Comparar características clínicas y manométricas de pacientes con y sin SBI. Material y Método: Análisis retrospectivo de 40 pacientes con POIC (edad promedio: 41 años, rango: 18-76 años; 75 por ciento mujeres). Se registraron síntomas (dolor, distensión, vómitos, constipación, diarrea, baja de peso), hallazgos en manometría intestinal (patrón neuropático, miopático o mixto, índice de motilidad intestinal (IMI)) y SBI con test de H2 con lactulosa, definido como la elevación > 20 ppm en 2 o más cifras en los primeros 60 min. Análisis estadístico: t-test y comparación de 2 proporciones. Resultados: Se observó SBI en 60 por ciento de los pacientes con POIC. Tres o más síntomas se presentaron en 70,8 por ciento de los pacientes con SBI vs 50 por ciento en POIC sin SBI (p = NS). El síntoma dolor abdominal fue más frecuente en pacientes con SBI (70,8 por ciento vs 31,2 por ciento, p = 0,032). No hubo diferencias entre pacientes con SBI y los distintos patrones de motilidad, sin embargo, el IMI fue menor para el grupo con SBI (9,7 +/- 1,44 vs 12,3 +/- 1,7, p < 0,001). Conclusiones: Existe una alta prevalencia de SBI en pacientes con POIC. Esto se relaciona con mayor compromiso de la motilidad intestinal evaluado por el IMI.