Pharmacological research : the official journal of the Italian Pharmacological Society
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Meta Analysis Comparative Study
Etrolizumab versus infliximab in the treatment of induction phase of ulcerative colitis: A systematic review and indirect comparison.
There is still a need to develop new effective medications for the treatment of ulcerative colitis, particularly for patients who are intolerant or resistant to first line therapies. This article compared the efficacy and safety of etrolizumab and infliximab in moderate to severe ulcerative colitis. ⋯ Seven trials were sufficiently homogeneous to be used for indirect comparison of the induction phase of the treatment. There were no significant differences in clinical remission and serious adverse events between etrolizumab and infliximab. Moreover, adverse events of etrolizumab were significantly less than those of infliximab. However, further trials are required to compare other parameters of efficacy such as the clinical response and mucosal healing of etrolizumab with infliximab in anti-TNF alpha naïve patients.
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Risperidone, one of the second-generation antipsychotics, can efficiently target dopamine D2 and serotonin 5-HT2A receptors. There actually exists significant implication of CYP2D6 genetic polymorphisms on the metabolic kinetics of risperidone, little is known about the extent of CYP2D6 impacting human D2 and 5-HT2A receptor occupancies as well as the clinical efficacy and efficacy in schizophrenia treatment. Here we assessed the influences of CYP2D6 gene polymorphisms on human target occupancies/clinical outcomes and optimized the maintenance therapy of risperidone. ⋯ The predictions of human D2, 5-HT2A RO, PANSS and SAS changes for risperidone with CYP2D6 genetic polymorphisms were well in line with the reported values in clinic. 5.0, 4.0 and 2.5 mg/day were the equivalent dosages of risperidone for CYP2D6 PM, IM and EM, respectively. The optimized maintenance therapy of risperidone was provided through the Three-Step method and the dosage range was 2.5-5.0 mg/day for three CYP2D6 gene groups in the present study. Taken together, our findings demonstrate that this extended translational framework not only differentiates the effects of CYP2D6 genetic polymorphisms on target occupancies and clinical outcomes, but also constitutes a scientific basis to optimize the maintenance therapy of neuropsychiatric patients in clinic.
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Brigatinib is an FDA-approved oral anaplastic lymphoma kinase (ALK) inhibitor for treatment of metastatic non-small cell lung cancer (NSCLC). Using genetically modified mouse models, we investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, and the multispecific drug-metabolizing enzyme CYP3 A in plasma pharmacokinetics and tissue distribution of brigatinib. In vitro, brigatinib was exceptionally well transported by human ABCB1 and mouse Abcg2, and efficiently by human ABCG2. ⋯ ABCB1 and ABCG2 thus limit brain accumulation, toxicity, and systemic exposure of brigatinib, whereas CYP3 A also markedly restricts its oral availability. Unexpected toxicities should therefore be carefully monitored when brigatinib is coadministered with ABCB1/ABCG2 inhibitors in patients. Collectively, these insights may support the clinical application of brigatinib.
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Diabetes mellitus is an extremely prevalent endocrine disease and a major global public health concern. Diabetic complications, such as retinopathy, nephropathy, neuropathy and cardiovascular disease, are common and majorly impact a patient's quality of life. ⋯ Increasing evidence suggests that curcumin may offer protection against diabetic complications. The current review focuses on the possible molecular targets and pathways involved in diabetic complications and, in particular, the multi-target approach of curcumin in attenuating diabetic nephropathy, retinopathy, and neuropathy.
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Autism-spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and repetitive patterns of behavior. ASD is, however, often associated with medical comorbidities and gastrointestinal (GI) dysfunction is among the most common. Studies have demonstrated a correlation between GI dysfunction and the degree of social impairment in ASD. ⋯ This paper reviews the role of serotonin in ASD from the perspective of the ENS. A murine model that has been demonstrated to possess brain, behavioral and GI abnormalities mimicking those seen in ASD harbors the most common serotonin transporter (SERT) based mutation (SERT Ala56) found in children with ASD. Discussion of the gut-brain manifestations in the SERT Ala56 mice, and their correction with developmental administration of a 5-HT4 agonist, are also addressed in conjunction with other future directions for diagnosis and treatment.