Type 2 Diabetes mellitus is a progressive metabolic disease characterized by relative insulin insufficiency and insulin resistance resulting in hyperglycemia. Despite the widespread use of metformin, there is considerable variation in treatment response; with approximately one-third of patients failing to achieve adequate glycemic control. Studies have reported the involvement of single nucleotide polymorphisms and their interactions in genetic pathways i.e., pharmacodynamics and pharmacokinetics. This study aims to investigate the association between 19 pharmacogenetics biomarkers and response to metformin treatment.
MassARRAY panels were designed and optimized by Inqaba Biotechnical Industries, to genotype 19 biomarkers for 140 type 2 diabetic outpatients.
The CT genotype of the rs12752688 polymorphism was significantly associated with increased response to metformin therapy after correction (OR=0.33, 95% CI [0.16–0.68], p-value=0.006). An association was also found between the GA genotype of SLC47A2 rs12943590 and a decreased response to metformin therapy after correction (OR=2.29, 95% CI [1.01–5.21], p-value=0.01).
This is the first study investigating the association between genetic variants and responsiveness to medication for diabetic patients from the indigenous Nguni population in South Africa. It is suggested that rs12752688 and rs12943590 be included in pharmacogenomics profiling systems to individualize metformin therapy for diabetic patients from African populations.
Cytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin.
Roma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay.
We found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics.
There were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.
Valproic acid (VPA) is an anticonvulsant used in several clinical scenarios. VPA has been increasingly associated with intentional or unintentional overdose. In patients presenting with severe VPA overdose, supportive care and airway protection are cornerstones of treatment, while levocarnitine is suggested in patients with hyperammonemia and hemodialysis is recommended in patients with VPA serum concentrations (SC) >1,300 mg/L and presence of cerebral edema or shock. Meropenem is a carbapenem antibiotic with a broad spectrum of activity. The pharmacological interaction between VPA and meropenem is characterized by a rapid decrease in VPA concentrations, which contraindicates concurrent use.
The following case report describes the use of meropenem to enhance the clearance of VPA in the case of severe VPA overdose. A patient with altered mental status was transported to the emergency department (ED) after VPA overdose. Meropenem was prescribed for significant elevated VPA SC. An important decline in SC was observed with short-term meropenem dosing, and an improvement in mental status occurred shortly after administration.
Carbapenem therapy has the potential to be used as last line strategy in the management of severe VPA overdose in patients where SC represent a significant risk of toxicity and clinical symptoms suggest difficulty managing the patient.
Coenzyme Q10 (CoQ10) has many vital functions in human body and its endogenous level can be affected either by various diseases or by administrated drugs. This study reveals the effect of atorvastatin, amlodipine and ethoxidol on the endogenous CoQ10 plasma concentration.
It was determined the total plasma concentration of endogenous CoQ10 in the plasma of 54 healthy individuals and 62 patients with cardiovascular diseases during treatment with various drugs using high performance liquid chromatography with mass spectrometric detection (HPLC-MS/MS).
It was found that CoQ10 plasma concentration in patients is statistically significantly lower (on average −49.0 Δ%) than in practically healthy individuals. The total CoQ10 plasma level in patients receiving atorvastatin in the complex therapy is statistically significantly lower (−15.2 Δ%), and in patients taking amlodipine or ethoxidol is statistically significantly higher (+18.2 and + 20.2 Δ%, respectively) than in patients of control groups (a group of patients who receive the same drugs, except for the studied one).
The study showed that in patients with CVDs treated with various drugs the CoQ10 plasma level is statistically significantly lower than in practically healthy individuals. So, to avoid the adverse reactions connected with low CoQ10 plasma levels, it is recommended to adjust the therapy to maintain its constant level.
Self-esteem is the degree to which the qualities and characteristics contained in one’s self-concept are perceived to be positive. The aim of this study was to evaluate the self-esteem scores in phenylketonuria (PKU) patients on “strict”, “loos” and “off diet”. Sixty PKU patients were divided in three equal groups.
Group a: “on strict”, group b: “on loos” and group c: “off diet”. A special questionnaire for self-esteem scores was created for these patients.
Before psychological support, group a patients demonstrated 6/20 (30%) very high self-esteem, 9/20 (45%) high and 5/25 (25%) moderate. After support 14/20 (70%) were turned to very high, 5/20 (25%) represented high except one whose degrees remained an altered. group b 4/20 (20%) were very high, 7/20 (35%) were high, 3/20 (15%) moderate and the rest of them showed low self-esteem degrees, after support, 10/20 (50%) showed very high, 5/20 (25%) became high, 3/20 (15%) turned to moderate and 2/20 (10%) remained unaltered. Group c, 1/20 (5%) were very high self-esteemed, 7/20 (35%) were high, 6/20 (30%) were moderate and 6/20 (30%) with low self-esteemed, at the end of support, 6/20 (30%) become very high, 8/20 (40%) with high, 4/20 (20.0%), moderate self-esteem whereas the rest were unaltered.
Very high and high self-esteem degrees were demonstrated in patients who follow their PKU diet. Moderate and low self-esteem degrees were predominantly found in patients on loos and or off diet. Psychological supports commonly result in amelioration of self-esteem degrees.
Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning. The saliva, urine and blood samples were taken at the admission time. Consequently, concentration of tramadol and its major metabolites were measured.
A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96). Cases of tramadol poisoned evidenced seizure, hypertension, dizziness, nausea and vomiting symptoms participated.
Female cases showed higher N-desmethyltramadol (M2) tramadol concentrations than male cases: in urine (40.12 ± 124.53 vs. 7.3 ± 7.13), saliva (16.91 ± 26.03 vs. 5.89 ± 7.02), and blood (1.11 ± 1.56 vs. 0.3 ± 0.38) samples. Significant correlation between blood, saliva, and urine concentrations were found (r = 0.5). Based on the metabolic ratio of O-desmethyltramadol (M1) of male (0.53 ± 0.22) and female (0.43 ± 0.26), poisoning and severe symptoms like seizure in female occurs statistically fewer (13.04%) than in male (50.6%). Assessment of CYP2D6 phenotype showed all of the participants were extensive metabolizers (EM) and their phenotype was associated with clinical symptoms.
According to our results, M1 as a high potent metabolite has an important role in toxicity and the likelihood of poisoning in people with EM phenotype. Finally, tramadol metabolic ratio may justify the cause of various symptoms in human tramadol poisoning.
Present study was planned to investigate the efficacy of SLBSP vs. standardized BSE for symptomatic knee osteoarthritis (OA) treatment. It was prospective, randomized, double-blind, double-dummy, placebo-controlled, and single-centre clinical trial for symptomatic osteoarthritis of knee. Subjects were randomized to receive SLBSP capsule + BSE Placebo or BSE tablet + SLBSP placebo for two months. Patients were allowed to take rescue analgesics (Acelofenac 100 mg). Improvement in pain and function was assessed utilizing WOMAC, VAS. Level of CTX-II in urine and serum levels of inflammatory cytokines including IL-2, IL-4, IL-6, TNF-α, and IFN-γ were measured initially and at end of treatment. WOMAC and VAS score improved markedly in SLBSP as well as in BSE arm (p < 0.05). Difference in VAS and WOMAC scores between the two arms was not statistically significant. Most significant effect was observed in the need for rescue analgesics. SLBSP caused marked lowering of pro-inflammatory cytokines levels whereas a several fold increase was noted in the BSE arm (p < 0.05). Both groups showed marked improvement in pain, SLBSP being superior to BSE with respect to reducing the need for rescue analgesics in addition to modulating inflammatory cytokines.
Antimicrobial peptides are natural substances that have played a role in the development of the adaptive immune system, and are currently involved in the prevention of infections, through their direct antimicrobial and immunomodulatory properties. While the amino acid composition and spatial structure vary, most antibacterial peptides have a positive surface charge, which allows them to bind to the negative bacterial membranes. Buforin II is a widely studied antimicrobial peptide first obtained through the structural modification of buforin I, a peptide isolated from Bufo gargarizans. The peptide showed significant antibacterial activity against Gram-positive and Gram-negative bacterial strains. The mechanism of action of buforin II differs from that of other antimicrobial peptides, as it binds directly to bacterial DNA and RNA. The aim of our study was to obtain recombinant buforin II with a ubiquitin fusion partner, through heterologous expression in Escherichia coli Rosetta™ (DE3)pLysS cells, using a laboratory scale biore-actor. The incubation of expression host cells in a bioreactor allowed the constant monitoring and control of the process parameters, leading to high biomass levels and an increased production rate of the peptide. The parameters used during incubation were: 37°C, pH=6.9 and dissolved oxygen level above 40%. Purification of the recombinant protein was accomplished by affinity chromatography using a Ni-chelate solid phase to which the 10xHistag of our construct showed affinity. Method optimisation consisted in the use of gradient and linear elution, of which the latter was found to be more effective. Digestion of the fusion partner from the target peptide was performed with ubiquitin carboxyl-terminal hydrolase enzyme. The expression and purification protocols developed in our experiment allow the production of a significant amount of buforin II, allowing its use for further research. Furthermore, the presented methods could be suitable for industrial production of the recombinant peptide..
Aim. The aim of this study is to evaluate the efficiency of proton pump inhibitors in the treatment of gastric and duodenal ulcers as based on literature.
Materials and methods: The materials of this research are the results of 86 original studies on the effectiveness of proton pump inhibitors analysis.
Methods. Descriptive, statistical, retrospective.
Results and Conclusion. According to the clinical random researches, Omeprazole preparations are not included in the list due to proven better effectiveness of Esomeprazole drugs. Moreover, lansoprazole drugs are not included according to proven short-acid inhibitory effect. In addition, the brand of mentioned above preparation does not exist on the pharmaceutical market of Ukraine. Furthermore, rabeprazole preparations are presented in the research by Pariet (brand) and by the effective generic Barol, while pantoprazole preparations are represented in the research by Kontrolok (brand) and by the generic Pultset, as well as by Nolpaza. Herein, the Pantosan effect was not significantly different from the effect of Pultset and Nolpaza, but the preparation is much more expensive. In terms of efficiency (%), 4 week repair of mucosal defects was carried out by way of the following treatment regimens: Barol + Amoxicillin + Clarythromycin (90.9±6.2), Pariet + Amoxicillin + Clarythromycin (83±2.6), Kontrolok + Amoxicillin + Clarythromycin (100±1.3), Pultset + Amoxicillin + Clarythromycin (88±4.1), Nolpaza + Amoxicillin + Clarythromycin (72±4.1), Ezolonh + Amoxicillin + Clarythromycin (87.7±3.8), Neksium + Amoxicillin + Clarythromycin (96.1±3.1).
Increased multidrug resistance prompted researchers to search for a new drug that has the ability to overcome antibiotic resistant pathogens. Essential oils have been used in folk medicine for centuries, therefore, they could be employed as an effective alternative to antibiotics without having secondary side effects.
The aim of the present study was to test the antibacterial and antibiofilm activity of the essential oil of Achillea santolina and to ascertain its mode of action.
Minimum Biofilm Inhibitory Concentration (MBIC) susceptibility assays were performed using a biofilm inoculator with a 96-well plate with peg led. Minimum Inhibitory Concentration (MIC) was performed in normal microtitre plates using a twofold dilution series.
Achillea santolina essential oil (ASEO) was able to overcome the resistance of all tested bacteria. The MIC values were in the range of 250-1000 µg/ml, while the MBC values were in the range of 500-2000 µg/ml. ASEO increased leakage of potassium ions from the cell membrane and increased release of cellular materials – suggesting that the cell membrane is the target and site of action of ASEO. Moreover, ASEO was able to inhibit initial adherence of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300) at sub-inhibitory concentrations through alterations to cell membrane.