Drug-related problems in patients with rheumatoid arthritis

Shu Ning Ma,1 Hasniza Zaman Huri,1,2 Fariz Yahya3 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Clinical Investigation Centre, University of Malaya Medical Centre, Kuala Lumpur, Malaysia; 3Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background: Rheumatoid arthritis (RA) patients are at risk of acquiring drug-related problems (DRPs). However, there has been a lack of studies on DRPs in patients with RA up to now. Method: This retrospective study was conducted in a tertiary hospital in Malaysia from January 2012 to December 2017 with the purpose of assessing DRPs in RA patients and factors associated with its occurrence. A total of 200 patients who had received pharmacological treatment for RA were enrolled in this study. Assessment of DRPs was based on the Pharmaceutical Network Care Europe tool version 5.01. Results: A total of 289 DRPs with an average of 1.5±1.0 problems per patient were identified, in which 78.5% of the population had at least one DRP. The most common DRPs encountered were adverse reactions (38.8%), drug interactions (33.6%), and drug-choice problems (14.5%). Factors that had significant association with the occurrence of DRPs were polypharmacy (P=0.003), multiple comorbidities (P=0.001), hyperlipidemia (P=0.009), osteo (P=0.040), and renal impairment (P=0.044). These data indicated that the prevalence of DRPs was high among RA patients. Conclusion: Early identification of types of DRPs and associated factors may enhance the prevention and management of RA. Keywords: RA drugs, DRPs, factor associated, prevention and managemen

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from Litsea costalis: an in vitro study

Maryam Abbaspour Babaei,1 Hasniza Zaman Huri,1,2 Behnam Kamalidehghan,3,4 Swee Keong Yeap,5,6 Fatemeh Ahmadipour1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Clinical Investigation Centre (CIC), University of Malaya Medical Centre, Kuala Lumpur, Malaysia; 3Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Medical Genetics Department, National Institute for Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran; 5Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 6Xiamen University Malaysia, Sepang, Malaysia Abstract: Litsea is considered as an evergreen genus distributed in tropical and subtropical Asia; this genus belongs to the large family of Lauraceae. In this study, the cell-death metabolism of biseugenol B was investigated. Nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and release of cytochrome c have been detected in human prostate cancer cell line (PC3) treated with biseugenol B by high content screening (HCS). Fluorescent analysis was conducted to examine the reactive oxygen species formation. To determine the mechanism of cell death, the levels of Bcl-cell lymphoma (Bcl)-2 proteins, Bcl-2-associated X (Bax) protein and anti-apoptosis heat-shock protein 70 were tested by applying reverse transcription polymerase chain reaction and Western blot. Bioluminescent assays were also performed to assess the level of caspases such as 3/7, 8 and 9 during treatment. Furthermore, the involvement of nuclear factor kappa-B (NF-κB) was examined by Western blot and HCS. Biseugenol B showed significant cytotoxicity toward PC3 with no toxicity toward normal prostate cells (RWPE-1), which indicates that biseugenol B has qualities that induce apoptosis in tumor cells. The treatment of PC3 cells with biseugenol B provoked apoptosis with cell-death-transducing signals. Downregulation of Bcl-2 and upregulation of Bax regulated the MMP, which in turn caused the release of cytochrome c from mitochondria into cytosol. The release of cytochrome c activated caspase-9, which consequently activated caspase-3/7 with the cleaved poly(ADP-ribose) polymerase protein, thereby resulting in apoptosis alteration. Involvement of an extrinsic apoptosis pathway was exhibited by the increase in caspase-8, while the increase in caspase-3/7 and caspase-9 demonstrated involvement of an intrinsic apoptosis pathway. Meanwhile, no significant increase was observed in caspases 3/7, 8 or 9 in normal prostate cells (RWPE-1) after treatment with biseugenol B. Prevention of NF-κB translocation from the cytosol to the nucleus occurred in PC3 after treatment with biseugenol B. The results of our study reveal that biseugenol B triggers the apoptosis of PC3 cells via intrinsic and extrinsic apoptosis pathways and inhibition of NF-κB signaling pathway. Our findings suggest that biseugenol B is a potentially useful agent for prostate cancer treatment. Keywords: biseugenol B, apoptosis, mitochondria, caspase, intrinsic, extrinsic, NF-κ

Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects.

A soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.We assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).Fasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.Serum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c

Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects.

BACKGROUND:Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV). METHOD:Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels. RESULTS:Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects. CONCLUSIONS:DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects

Comparison of fasting serum levels of sCD26/DPP-IV and active GLP-1 between normal, non-diabetic metabolic syndrome, type 2 diabetes mellitus subjects with and without metabolic syndrome and total type 2 diabetes mellitus.

<p>The results presented represent geometric means (SD), adjusted for age, race and gender.</p><p>^avs control group</p><p>^bvs non-diabetic metabolic syndrome group</p><p>^cvs type 2 diabetes mellitus without metabolic syndrome which evaluated using univariate (General Linear Model).</p><p>Bold values are significant. MetS: metabolic syndrome.</p><p>Comparison of fasting serum levels of sCD26/DPP-IV and active GLP-1 between normal, non-diabetic metabolic syndrome, type 2 diabetes mellitus subjects with and without metabolic syndrome and total type 2 diabetes mellitus.</p

Association of fasting serum levels of sCD26/DPP-IV with diabetic and metabolic parameters among normal subjects.

<p>The results are presented as unstandardized coefficients; B, r² and (P-value) assessed using hierarchical linear regression adjusted for, age, race, and gender. Bold values are significant. B: coefficient for the relationship between the dependent variable “metabolic syndrome and T2DM parameters” and the independent variable “DPP-IV level.” The positive sign of the coefficient implies a direct relationship, and the negative sign implies an inverse relationship.</p><p>Association of fasting serum levels of sCD26/DPP-IV with diabetic and metabolic parameters among normal subjects.</p

Correlation between of fasting serum levels of sCD26/DPP-IV and active GLP-1 among normal, non-diabetic metabolic syndrome, type 2 diabetes mellitus subjects with and without metabolic syndrome.

<p>The results are presented as r_s and (P-value) assessed by Spearman partial correlation adjusted for, age, race and gender. Bold values are significant.</p><p>Correlation between of fasting serum levels of sCD26/DPP-IV and active GLP-1 among normal, non-diabetic metabolic syndrome, type 2 diabetes mellitus subjects with and without metabolic syndrome.</p

Demographic and standard biochemical parameters among normal control, non-diabetes metabolic syndrome, type 2 diabetes mellitus subjects with and without metabolic syndrome.

<p>The results presented represent geometric means (SD)</p><p>^a<i>vs</i> normal control group</p><p>^b<i>vs</i> non-diabetes MetS group</p><p>^c<i>vs</i> type 2 diabetes mellitus without metabolic syndrome evaluated using ANOVA.</p><p>Demographic and standard biochemical parameters among normal control, non-diabetes metabolic syndrome, type 2 diabetes mellitus subjects with and without metabolic syndrome.</p

Association of fasting serum levels of sCD26/DPP-IV with MetS and A1c levels among type 2 diabetes patients.

<p>The results are presented as unstandardized coefficients; B and (P-value) assessed using multiple linear regression adjusted for, age, race, gender, and duration of diabetes. Bold values are significant. B: coefficient for the relationship between the dependent variable “DPP-IV level” and the independent variable “diabetic and metabolic biomarker”. The positive sign of the coefficient implies a direct relationship, and the negative sign implies an inverse relationship.</p><p>Association of fasting serum levels of sCD26/DPP-IV with MetS and A1c levels among type 2 diabetes patients.</p