- Retraction notice for: Therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis. [Braz J Med Biol Res (2018) 51(2): e6812]. [Journal Article]
- BJBraz J Med Biol Res 2018; 51(6):e6812retraction
- Pioglitazone abolishes autistic-like behaviors via the IL-6 pathway. [Journal Article]
- PlosPLoS One 2018; 13(5):e0197060
- Autism is characterized by social deficits, communication abnormalities, and repetitive behaviors. The risk factors appear to include genetic and environmental conditions, such as prenatal infections...
Autism is characterized by social deficits, communication abnormalities, and repetitive behaviors. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infections by gram-negative bacteria, induces autistic-like behaviors. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism. We selected pioglitazone to block or ease the impairments induced by LPS because although this drug was designed as an anti-diabetic drug (it has an insulin effect), it also exerts anti-inflammatory effects. Juvenile offspring were treated daily with pioglitazone, and the main behaviors related to autism, namely, socialization (play behavior) and communication (50-kHz ultrasonic vocalizations), were studied. Biomarkers linked to autism and/or pioglitazone were also studied to attempt to understand the mechanisms involved, namely, IL-6, TNF-alpha, MCP-1, insulin, and leptin. Prenatal LPS exposure induced social deficits and communicational abnormalities in juvenile rat offspring as well as elevated plasma IL-6 levels. Daily postnatal pioglitazone treatment blocked the impairments found in terms of the time spent on social interaction, the number of vocalizations (i.e., autistic-like behaviors) and the elevated plasma IL-6 levels. Thus, pioglitazone appears to be a relevant candidate for the treatment of autism. The present findings may contribute to a better understanding and treatment of autism and associated diseases.
- Comparative Efficacy and Acceptability of Anti-Diabetic Agents for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Network Meta-analysis. [Journal Article]
- DODiabetes Obes Metab 2018 May 23
- The current meta-analysis compares the efficacy (i.e., pro-cognitive effects) and acceptability of anti-diabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Libr...
The current meta-analysis compares the efficacy (i.e., pro-cognitive effects) and acceptability of anti-diabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials (RCTs) comparing anti-diabetic agents with placebo and/or another active anti-diabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4,855) evaluating the effects of six different anti-diabetic drugs (i.e., intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with anti-diabetic agents compared to placebo. Pioglitazone 15-30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of anti-diabetic agents in AD/MCI. Other anti-diabetic agents should also be investigated in future studies. This study is registered with PROSPERO (CRD42018085967). This article is protected by copyright. All rights reserved.
- Combination of metformin and pioglitazone and its effect in treatment of comorbid pathology. [Journal Article]
- WLWiad Lek 2018; 71(2 pt 2):278-280
- CONCLUSIONS: Conclusions: The proposed variant of the combination therapy has a positive effect on the clinical course of the coronary heart disease in patients with type 2 diabetes mellitus, well tolerated by the patients and can be considered as the pathogenetic factor in the treatment of these diseases.
- Efficacy and safety profile of once-weekly dulaglutide in type 2 diabetes: a report on the emerging new data. [Review]
- DMDiabetes Metab Syndr Obes 2018; 11:187-197
- Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist, which has been on the market in the USA since 2014. Dulaglutide has performed well in head-to-head studies against metformin, gl...
Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist, which has been on the market in the USA since 2014. Dulaglutide has performed well in head-to-head studies against metformin, glargine, and sitagliptin, where its A1c lowering ranged from -0.78% to -1.64% over 52-104 weeks, and it consistently outperformed each of these agents. As an add-on therapy, dulaglutide provided additional A1c lowering of -1.4% to -1.44% over monotherapy with glimepiride or glargine at 24 and 28 weeks, respectively. Dulaglutide outperformed exenatide when added to a regimen of metformin with pioglitazone as well as glargine when added to a regimen of metformin with glimepiride. Dulaglutide was shown to be non-inferior to liraglutide when added to metformin. In all AWARD studies other than when compared to liraglutide, dulaglutide at full strength resulted in significantly more patients achieving their A1c goal. Recent class-wide meta-analyses indicate that the incidence of commonly experienced gastrointestinal (GI) side effects is dose dependent, and nausea and vomiting are less common in longer-acting agents such as dulaglutide, but diarrhea may be more common. Pooled data have shown no increased risk of serious side effects such as pancreatitis or neoplasm with the use of dulaglutide. Given the evidence supporting liraglutide's cardiovascular benefits, the highly anticipated REWIND trial will have a significant impact on the future place in the therapy of dulaglutide.
- Repositioning of diabetes treatments for depressive symptoms: A systematic review and meta-analysis of clinical trials. [Review]
- PPsychoneuroendocrinology 2018 May 07; 94:91-103
- Depression is a common comorbidity in diabetes but conventional antidepressant treatments do not consistently improve outcomes. We tested whether established diabetes treatments can also improve depr...
Depression is a common comorbidity in diabetes but conventional antidepressant treatments do not consistently improve outcomes. We tested whether established diabetes treatments can also improve depressive symptoms and examined biological correlates of response. We performed a multi-database systematic search of all clinical trials, which measured the effect of licensed diabetes treatments on depressive symptoms using a validated questionnaire. Results of randomised controlled trials (RCT's) were pooled for meta-analysis. Data were also collected on insulin resistance (HOMA-IR), C-reactive protein (CRP) and fasting blood glucose (FBG) as correlates of response. Nineteen studies (n = 3369 patients) were included in the qualitative synthesis, 9 testing thiazolidenediones, 5 metformin, 2 thiazolidenediones against metformin, 2 incretin-based therapies and 1 insulin. Most studies were of good quality. In random-effects meta-analysis of RCT's, pioglitazone improved depressive symptoms compared to controls (pooled effect size = -0.68 (95% C.I. -1.12 to -0.24), p = .003, Nstudies = 8, I2 = 83.2%). Conversely, metformin was comparable to controls overall (pooled effect size = +0.32 (95% C.I. -0.23 to 0.88), p = .25, Nstudies = 6, I2 = 94.2%), although inferior to active controls (pooled effect size = +1.32 (95% C.I. 0.31-2.34), p < 0.001, Nstudies = 3, I2 = 90.1%). In random-effects meta-regression, female sex (β = -0.023, (95% C.I.-0.041 to -0.0041), p = .016, Nstudies = 8) predicted reduction in depressive symptoms with pioglitazone, but baseline HOMA-IR, FBG and severity of depressive symptoms did not. In conclusion, pioglitazone was associated with improvement in depressive symptoms, an effect more marked in women and poorly explained by effects on glycaemia and insulin resistance. Metformin had no consistent benefit on depressive symptoms. Further mechanistc trials of diabetes treatments as potential antidepressants are needed, stratified by sex and including serial measures of innate inflammation.
- Effect of excipient properties, water activity, and water content on the disproportionation of a pharmaceutical salt. [Journal Article]
- IJInt J Pharm 2018 May 14
- Excipients are crucial components of most pharmaceutical formulations. In the case of a solid oral dosage formulation containing the salt form of a weakly ionizable drug, excipient selection is criti...
Excipients are crucial components of most pharmaceutical formulations. In the case of a solid oral dosage formulation containing the salt form of a weakly ionizable drug, excipient selection is critical, as some excipients are known to cause salt disproportionation (conversion of salt to the free form). Therefore, robust formulation design necessitates an in-depth understanding of the factors impacting salt disproportionation during processing or storage as this can negatively impact product quality and performance. To date, there is an incomplete understanding of key excipient properties influencing salt disproportionation. Specifically, the potential roles of amorphous excipient glass transition temperature and excipient hygroscopicity, if any, on salt disproportionation are still not well understood. Furthermore, the relationship between the compression and the extent of salt disproportionation is an unknown factor. Herein, by utilizing various grades of polyvinylpyrolidone (PVP), its copolymer, copovidone (PVPVA), and magnesium stearate, a systematic investigation on disproportionation was performed using pioglitazone HCl as a model salt of a weak base. It was observed that there was a poor correlation between excipient hygroscopicity and the rate and extent of disproportionation. However, powder compression into compacts enhanced the rate and extent of disproportionation. This work focused on disproportionation of the salt of a weak base, as basic drugs are more prevalent, however, salts of weak acids may have similar tendencies under relevant conditions. The knowledge gained from this study will help in understanding the role of various excipients with respect to salt disproportionation, paving the way for designing stable salt formulations.
- [Effects of peroxisome proliferator-activated receptor γ-toll-like receptor 4-tumor necrosis factor-α targeted pathway on hyperglycemia induced myocardium inflammation and oxidative stress]. [Journal Article]
- ZWZhonghua Wei Zhong Bing Ji Jiu Yi Xue 2018; 30(5):416-421
- CONCLUSIONS: 4 mg×kg-1×d-1 pioglitazone could activate PPARγ-TLR4-TNF-α targeted pathway, thus inhibit inflammatory and oxidative stress factors expression, and down-regulate hyperglycemia induced myocardium inflammatory and oxidative stress level, but the effect did not show a dose dependent manner.
- The Preventive Role of Pioglitazone in Glycerol-Induced Acute Kidney Injury in Rats during Two Different Treatment Periods. [Journal Article]
- IJIran J Med Sci 2018; 43(2):184-194
- CONCLUSIONS: These results indicate that pioglitazone might have nephroprotective effects in this injury model. Pioglitazone succeeded in producing this effect within 3 days. Doubling the drug administration period did not produce any significant superior benefit.
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- Identification of Potential Therapeutic Targets in the Liver of Pioglitazone-Treated Type 2 Diabetes Sprague-Dawley Rats via Expression Profile Chip and iTRAQ Assay. [Journal Article]
- JDJ Diabetes Res 2018; 2018:8120847
- The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats w...
The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats were randomly divided into the control, the diabetes model, and the pioglitazone-treated groups. After treatment with pioglitazone for 11 weeks, the effects on fasting blood glucose, body weight, and blood biochemistry parameters were evaluated. Microarray and iTRAQ analysis were used to determine the differentially expressed genes/proteins in rat livers. 1.5-fold changes in gene expression and 1.2-fold changes in protein were set as the screening criteria. After treatment with pioglitazone for 11 weeks, fasting blood glucose in pioglitazone-treated rats was significantly lower than that in the model group. There was a tendency for pioglitazone to reduce TC, TG, TP, ALB, BUN, and HDL-c levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) were applied to analyze differentially expressed genes/proteins. Furthermore, Western blotting and RT-qPCR were used to validate the results of microarray and iTRAQ. In conclusion, Cyp7a1, Cp, and RT1-EC2 are differentially expressed genes/proteins since they showed a similar trend in rats in the model group and the pioglitazone-treated group.