Adjunctive ondansetron for schizophrenia: A systematic review and meta-analysis of randomized controlled trials.

The serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor has been implicated in the pathogenesis of schizophrenia. This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive ondansetron, a potent 5-HT3 receptor antagonist, in the treatment of schizophrenia. Only RCTs examining adjunctive ondansetron for schizophrenia were included. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan, Version 5.3. Study quality was evaluated with the Cochrane risk of bias and the Jadad scale. Data of 5 RCTs (n = 304) covering 149 patients on ondansetron (4-8 mg/day) and 155 patients on placebo were analyzed. Three RCTs reported "randomized allocation" with a specific description; the weighted Jadad score was 3.8. Adjunctive ondansetron outperformed placebo in the reduction of Positive and Negative Syndrome Scale (PANSS) total score [3 RCTs, n = 171; SMD: -1.06 (95%CI: -2.10, -0.02), p = 0.04, I2 = 85%], the negative [4 RCTs, n = 209; SMD: -0.96 (95%CI: -1.71, -0.22), p = 0.01, I2 = 80%], and general psychopathology symptom scores [3 RCTs, n = 171; SMD: -0.97 (95%CI: -1.91, -0.02), p = 0.04, I2 = 82%], but not in the positive (p = 0.05) and depressive symptom scores (p = 0.91). The difference in PANSS total score remained significant after excluding one outlying RCT [2 RCTs, n = 141; SMD: -0.50 (95%CI: -0.84, -0.16), P = 0.004, I2 = 0%]. Four RCTs examined the effect of ondansetron on cognition applying different instruments yielding conflicting findings. Ondansetron was superior over placebo in improving extrapyramidal symptoms, but no group differences were found in overall discontinuation rate and adverse drug reactions. In conclusion, adjunctive ondansetron appears to be efficacious and safe in improving negative symptoms and general psychopathology. The effect of ondansetron on cognitive impairment in schizophrenia needs to be further explored in large-scale RCTs.

Value of Two-Dimensional Shear Wave Elastography for Assessing Acute Liver Congestion in a Bama Mini-Pig Model.

BACKGROUND: To date, liver congestion is one of the most significant clinical diseases. However, few studies have profoundly investigated the development, pathology, and prognosis of the important problems associated with acute hepatic congestion. AIMS: To explore the value of noninvasive two-dimensional shear wave elastography (2D-SWE) for assessing acute liver congestion in an animal model. METHODS: Six healthy Bama mini-pigs were used for this research and randomly divided into the experimental group and control group. We measured the basal liver stiffness (LS) by 2D-SWE and then clamped the inferior vena cava (IVC). LS was measured after 1, 5, 10, and 15 min. We reopened the IVC of experimental group pigs and detected the LS again. All pigs were killed and obtained for a pathological microscopic examination. RESULTS: LS was distinctly increased from 7.03 ± 0.48 to 17.18 ± 3.40 kPa (p < 0.01) within 15 min and reversed to almost normal values of 7.59 ± 0.77 kPa (p < 0.01) within 5 min. In addition, two-dimensional ultrasound images demonstrated the interesting phenomenon of spontaneous echo contrast. Most importantly, the pathologic results of experimental group pigs showed the central veins of the hepatic lobules and hepatic sinusoids were enlarged and filled with numerous erythrocytes; central lobular hepatocytic necrosis and edema were noted. CONCLUSIONS: In conclusion, 2D-SWE is a valuable, reliable, and quantitative approach to successfully assess acute liver congestion, and it is well consistent with histopathological characteristics. Besides, acute liver congestion is an important factor influencing LS that increases LS in a reversible way.

Alteration of mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated heart failure with preserved ejection fraction.

BACKGROUND: Abnormalities of the mevalonate pathway, an important cellular metabolic pathway, are common in many diseases including cardiovascular disease. The mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated diastolic dysfunction remains largely unknown. This study aims to investigate whether the expression of mevalonate pathway related enzyme is altered during the progression of cardiac hypertrophy and associated diastolic dysfunction induced by pressure overload. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into two groups: the suprarenal abdominal aortic coarctation (AAC) group and the sham group. RESULTS: Histological and echocardiographic assessments showed that there was a significant cardiovascular remodeling in the AAC group compared with the sham group after 3 weeks post-operatively, and the left ventricular (LV) diastolic function was reduced at 8 and 14 weeks post-operatively in the AAC group, without any change in systolic function during the study. The tissue of the heart and the abdominal aorta proximal to the coarctation showed over-expression of several enzymes, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl diphosphate synthase (FDPS), farnesyltransferase-α (FNTA), farnesyltransferase-ß (FNTB), geranylgeranyltransferase type I (GGTase-I) and the activation of their downstream proteins was enhanced. CONCLUSIONS: AAC induced compensatory LV hypertrophy to decompensatory diastolic dysfunction, accompanied by altered expression of several key enzymes in the mevalonate pathway.