Correlation of Plasma and Salivary Osteocalcin Levels with Nascent Metabolic Syndrome Components with and Without Pre/Diabetes Biochemical Parameters / Correlación de los niveles de osteocalcina en plasma y saliva con los componentes del síndrome metabólico naciente con y sin parámetros bioquímicos de prediabetes

Objectives: This study aimed to compare and correlate plasma and salivary levels of cardiometabolic risk biomarkers’ of pharmacotherapy (appraised using colorimetric assays), adiposity, and atherogenicity indices. Methods: 61 Nascent MetS subjects vs. 30 lean normoglycemic and healthy controls were recruited in Family Medicine outpatient clinics/Jordan University Hospital (a referral medical center). Fasting blood and saliva specimens were collected. Clinical and anthropometric variables were determined along with atherogenecity and adiposity indices. Results: Among nascent MetS (metabolic syndrome) recruits, almost half were normoglycemic, 43% were prediabetic and 8% were diabetic. Pronouncedly Glycemic (FPG and Alc) and lipid parameters (TG, HDL-C and non-HDL-C), adiposity indices (BMI, WHR, WtHR, Conicity-index, BAI, LAP, VAI) and atherogenicity indices (AIP, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C and TG/HDL-C) were higher in the nascent MetS group (P<0.05 vs. controls). Markedly among the plasma cardiometabolic risk biomarkers (P<0.05 vs. controls) in the nascent MetS group, adipolin, cathepsin S, ghrelin, irisin, LBP, leptin, and osteocalcin were higher but plasma FGF1 levels were oddly lower. Significantly (P<0.05 vs. controls) nascent MetS –linked salivary levels of adipolin and LBP were higher as opposed to the lower cathepsin S. Only osteocalcin, amongst 9 metabolic risk biomarkers studied, had remarkably significant correlation between plasma and saliva levels, in both total sample and MetS patients (P<0.05). Markedly in the nascent MetS only group, both plasma and salivary osteocalcin correlated with FPG and A1c (P<0.05); salivary osteocalcin correlated with BMI and LAP (P<0.05). Likewise, in the total sample plasma osteocalcin correlated significantly with BMI, BAI, WHt R, SBP, DBP, TG, LAP, VAI, TG/HDL-C and AIP (P<0.05), while salivary osteocalcin had substantial correlations only with FPG and A1c (P<0.05). Conclusion: Association of nascent MetS-related plasma and salivary osteocalcin levels and clinical characteristics and indices propagate salivary osteocalcin as a non-invasive marker for clinical control of MetS-/preDM.(AU)

Differential changes in maternal proinflammatory IL6 plasmalevels as a putatively surrogate marker of candidacy andclinical utility during mid- and late pregnancy hyperglycemia:interventional impact of clinical pharmacist on maternal andneonatal outcomes in a randomized clinical trial / Cambios diferenciales en los niveles plasmáticos de IL6 proinflamatoria materna como un marcador supuestamente sustituto de candidatura y utilidad clínica durante la hiperglucemia a mitad y final del embarazo: impacto intervencionista del farmacéutico clínico en los resultados maternos y neonatales en un ensayo clínico aleatorizado

Background/methods: The impact of clinical pharmacist on undiagnosed pregnancy hyperglycemia (PHG) in mid- and late- pregnancy as a major preventable cause of maternal and neonatal (M/N) complications is investigated. This longitudinal randomized controlled study of changes in plasma levels of predictive/prognostic/diagnostic biomarkers of oxytocin, thrombospondin, MCP1, IL6, MIF, insulin and LAR and undesirable M/N pregnancy outcomes in women with/out PHG (pregnancy normoglycemia; PNG) following the implementation of clinical pharmacist interventions were investigated. Results: A total of 68 PHG (36 intervention vs. 32 non-intervention) vs. 21 PNG participants were enrolled at 20–28 weeks and followed up till delivery. BMI of intervention PHG (unlike non-intervention) was greater (p=0.036) compared to PNG’s. LAR and insulin, oxytocin, thrombospondin1, adiponectin and MCP1 plasma levels and their differences between 2nd and 3rd pregnancy trimesters lacked discrepancies in participants. Both PHG groups in mid pregnancy had substantially greater HbA1c %, FPG and IL6 levels vs. PNG, while PHG non-intervention’ leptin was greater than PNG’s. In late pregnancy, greater SBP, IL6 and MIF levels between either PHG groups vs. PNG’s were observed. Unlike PHG non-intervention and PNG; IL6 level in PHG intervention group decreased (-2.54±6.61; vs. non-intervention PHG’s 4.26±5.28; p<0.001 and vs. PNG’s 2.30±4.27; p=0.023). None of the assessed M/N outcomes was found of differential significance between any of the three study groups. Conclusions: Proinflammatory IL6 as a robust and generalizable cardiometabolic risk-based and related pharmacotherapy biomarker in mid and late hyperglycemic pregnancy with likely implications of novel therapeutic targets was delineated by clinical pharmacist interventions.(AU)

Alteration in the expression of the chemotherapy resistance­related genes in response to chronic and acute hypoxia in pancreatic cancer.

Pancreatic cancer is currently one of the least curable types of human cancer and remains a key health problem. One of the most important characteristics of pancreatic cancer is its ability to grow under hypoxic conditions. Hypoxia is associated with resistance of cancer cells to radiotherapy and chemotherapy. It is a major contributor to pancreatic cancer genetic instability, which local and systemic resistance that may result in poor clinical outcome. Accordingly, identifying gene expression changes in cancer resistance genes that occur under hypoxic conditions may identify a new therapeutic target. The aim of the present study was to explore the association between hypoxia and resistance to chemotherapy and determine the alteration in the expression of cancer resistance-related genes in the presence of hypoxia. Pancreatic cancer cells (PANC-1) were exposed to 8 h hypoxic episodes (<1% oxygen) three times/week for a total of 20 episodes (chronic hypoxia) or 72 h hypoxic episodes twice/week for a total of 10 episodes (acute hypoxia). The alterations in gene expression were examined using reverse transcription-quantitative PCR array compared with normoxic cells. Chemoresistance of hypoxic cells toward doxorubicin was assessed using MTT cell proliferation assay. Both chronic and acute hypoxia induced chemoresistance toward doxorubicin in PANC-1 pancreatic cancer cell line. The greatest changes occurred in estrogen Receptor Alpha Gene (ESR1) and ETS Like-1 protein (ELK1) pathways, in nucleic transcription factor Peroxisome proliferator-activated receptors (PPARs) and in a cell cycle inhibitor cyclin dependent kinase inhibitor 1A (CDKN1A). The present study demonstrated that exposing cells to prolonged hypoxia results in different gene expression changes involving pleotropic pathways that serve a role in inducing resistance in pancreatic cancer.

Use of traditional and complementary medicine for COVID 19 prophylaxis among healthcare professionals and students in Jordan: A cross-sectional study.

INTRODUCTION: There is inadequate evidence to recommend the use of any traditional and complementary medicine (T&CM) methods such as vitamin, mineral, herbal or other dietary supplements to prevent or treat COVID 19. Members of the medical team are particularly at risk of exposure to high viral load of coronavirus. They have also the best access to professional information regarding disease treatment and prophylaxis and disseminate such knowledge. The aim of the study was to assess the prevalence of use of T&CM for the prophylaxis of COVID 19 among the healthcare professionals and students in Jordan, along with the most common types and the factors associated with T&CM use. METHODOLOGY: A cross-sectional study of T&CM use was conducted in Jordan using a snowball sampling method to distribute Google Forms and to enrol participants during coronavirus outbreak between June 10, 2021, and August 28, 2021. The study included healthcare professionals or students who consented to participate in the survey. The survey excluded those participants who had filled the questionnaire at least once or were pregnant/breast-feeding at the time of the study. The questionnaire consisted of 29 items, including screening, checkbox, dichotomous, matrix and open-ended questions. RESULTS: The response rate was 97.1%. Out of 560 study respondents, 359 (64.1%) reported using T&CM for COVID 19 prevention. Vitamins and nutrients were consumed by almost half (48.4%) of study participants, while nonpharmacological methods and herbal remedies were consumed by 35.2% and 25.2%, respectively. The most common source of information regarding T&CM use for COVID 19 prophylaxis included scientific publications (59.5%), followed by disease treatment guidelines (38.0%) and social media (32.3%). Adverse effects were reported by 8.5% and possible adverse effects were reported by another 8.5% of participants. The T&CM use was associated with working in contact with COVID 19 patients (OR: 1.625 (95% CI 1.047-2.523) (P = 0.03) and having a colleague as a source of information (OR: 1.720 (95% CI 1.026-2.883) (P = 0.04). CONCLUSIONS: The prevalence of T&CM use for COVID 19 prevention among healthcare professionals and students in Jordan is high, with a significant proportion of participants reporting adverse effects. There is an urgent need for further research toward efficacy and safety of T&CM in COVID 19 prophylaxis as well as development of appropriate public health policy on this issue specific to each country.

Identification of Insulin Resistance Biomarkers in Metabolic Syndrome Detected by UHPLC-ESI-QTOF-MS.

Metabolic syndrome (MetS) is a disorder characterized by a group of factors that can increase the risk of chronic diseases, including cardiovascular diseases and type 2 diabetes mellitus (T2D). Metabolomics has provided new insight into disease diagnosis and biomarker identification. This cross-sectional investigation used an untargeted metabolomics-based technique to uncover metabolomic alterations and their relationship to pathways in normoglycemic and prediabetic MetS participants to improve disease diagnosis. Plasma samples were collected from drug-naive prediabetic MetS patients (n = 26), normoglycemic MetS patients (n = 30), and healthy (normoglycemic lean) subjects (n = 30) who met the inclusion criteria for the study. The plasma samples were analyzed using highly sensitive ultra-high-performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). One-way ANOVA analysis revealed that 59 metabolites differed significantly among the three groups (p < 0.05). Glutamine, 5-hydroxy-L-tryptophan, L-sorbose, and hippurate were highly associated with MetS. However, 9-methyluric acid, sphinganine, and threonic acid were highly associated with prediabetes/MetS. Metabolic pathway analysis showed that arginine biosynthesis and glutathione metabolism were associated with MetS/prediabetes, while phenylalanine, D-glutamine and D-glutamate, and lysine degradation were highly impacted in MetS. The current study sheds light on the potential diagnostic value of some metabolites in metabolic syndrome and the role of their alteration on some of the metabolic pathways. More studies are needed in larger cohorts in order to verify the implication of the above metabolites on MetS and their diagnostic value.

Painful subacute thyroiditis occurring after the administration of influenza vaccine and hyaluronic acid dermal filler: A case report.

RATIONALE: The occurrence of subacute thyroiditis (SAT) after vaccines or after hyaluronic acid skin fillers is very rare and might be related to genetic susceptibility. We suggest that the co-administration of both products could potentially increase the possibility of development of SAT. PATIENT CONCERNS: A 58-year-old Caucasian healthy female initially presented with chills, myalgia, dysphagia, sore throat, dry cough, fatigue, and intermittent fever of 38.5°C orally after simultaneous injection of an influenza vaccine and a dermal filler containing hyaluronic acid. Ten days later the patient developed palpitations and neck pain radiating to the left jaw. DIAGNOSIS AND INTERVENTIONS: She was diagnosed with SAT on day 16 after her first visit and responded promptly to etoricoxib treatment. OUTCOMES: The patient progressed clinically from hyperthyroidism to euthyroid state and eventually to hypothyroidism and further testing showed she had HLA B-35 haplotype. LESSONS: Physicians should be aware that SAT might be associated with the administration an influenza vaccine and this possible association might increase if the vaccine was co-administered with a dermal filler.

Serotonin reuptake inhibitors effect on fluconazole activity against resistant Candida glabrata strains.

OBJECTIVES: The study aimed to evaluate four selective serotonin reuptake inhibitors (SSRIs) as modifiers of fluconazole activity against resistant strains of Candida glabrata. METHODS: The effect of SSRIs on fluconazole activity was studied using the checkerboard method against C. glabrata strains (CBS 138, CBS 850821, DSY 562, DSY 565, ATCC 22553 and ATCC 90030); fractional inhibitory concentration index (FIC) was calculated and time-kill curve was used for the most prominent combination for further evaluation. RESULTS: All used SSRIs have antifungal activity against the C. glabrata strains tested. A combination of fluconazole with fluoxetine or fluvoxamine showed indifferent effects (fractional inhibitory concentration index [FICI] in all strains >1 but <4), whereas a paroxetine-fluconazole combination showed an additive effect against DSY565 and CBS138, known to express efflux pumps as well as on ATCC strain (0.5 < FIC < 1) with indifferent effect on other strains used. The most promising combination was that of fluconazole with sertraline (FICI ≤0.5), where a synergistic effect was observed against all resistant and susceptible dose-dependent strains, including those known to express efflux pumps. This synergistic effect was confirmed by time-kill curve assay against all resistant C. glabrata and ATCC strains with a >2-log10 CFU/mL reduction caused by combination compared with a single active agent of fluconazole after 24 hours of incubation. A sertraline-fluconazole combination produced an additive effect on the reference ATCC strain. CONCLUSION: Our data suggest that blocking active efflux pumps by sertraline may be considered the probable mechanism of synergism with fluconazole. The combination of sertraline with fluconazole could be a promising remedy for treatment of infections caused by resistant C. glabrata.

The Effect of Antipsychotics and Their Combinations with Other Psychotropic Drugs on Electrocardiogram Intervals Other Than QTc among Jordanian Adult Outpatients.

The ECG changes produced by antipsychotics and other psychotropic medications are studied mostly regarding QTc interval prolongation. This study aimed to investigate ECG changes beyond long QTc interval produced by psychotropic medications. A cross-sectional study was conducted to assess the effect of these agents on RR, PR, TpTe intervals and TpTe/QT ratio among Jordanian outpatients. The RR interval was significantly shorter among patients on TCAs versus those not receiving TCAs and among patients on polytherapy versus those on monotherapy (p < 0.05 for both comparisons), when adjusted for age, gender, BMI, caffeine intake, smoking, presence of diabetes mellitus, cardiovascular disease and medications known to produce heart rate changes. Positive correlations were found between the PR interval and age in patients treated with SGAs, SSRIs, citalopram, polytherapy and in the total sample (p < 0.01 for all). Inverse correlations were found between the RR interval and the number of psychotropic medications among patients treated with SSRIs and in the whole study sample (p < 0.01 for both). In conclusion, various ECG changes beyond QTc interval prolongation are observed in patients on antipsychotics and other psychotropic medications, in those on polytherapy. It is recommended to obtain an ECG before starting patients on psychotropic drugs known to produce electrocardiographic changes and their combinations.

Pharmaceutical Care in the Treatment of Substance Use Disorders in Jordan: A Randomized Controlled Trial.

BACKGROUND: Substance Use Disorder is a chronic relapsing disease that is characterized by compulsive drug seeking and use, despite harmful consequences. The aim of this study was to evaluate the impact of clinical pharmacist intervention/recommendation on the treatment of patients admitted to addiction rehabilitation centers in Jordan. METHODS: A randomized controlled trial was conducted in two public addiction treatment centers in Amman. Patients (n = 93) were randomized into 2 groups (control and intervention). Medication review was conducted for both groups at baseline, during stay and at discharge. Treatment related problems (TRPs) were identified by the clinical pharmacist and recommendations provided to the therapeutic team in the intervention group. Additionally, quality of life and quality of sleep were assessed at baseline and 2 weeks later. RESULTS: A total of 392 TRPs were identified during the study period. The mean number of TRPs ± SD was 4.22 ± 2.58 per patient. The clinical pharmacist intervention led to a reduction in the mean number of TRPs at discharge by 2.2 ± 0.85 (p < 0.001) in comparison to the control group (by 0.23 ± 0.27, p = 0.066). After 2 weeks of admission, there was an improvement of physical health (p = 0.035) and of the overall sleep status (p = 0.048) in the intervention vs. control groups. CONCLUSION: Clinical pharmacy services provided to patients with substance use disorder reduced the number of TRPs and improved other outcomes such as physical health and quality of sleep during detoxification. Long term studies with larger sample sizes are needed.

The Effect of Psychotropic Medications and Their Combinations on the QTc Interval Among Jordanian Outpatients: A Cross-Sectional Study.

Objective: To investigate the effect of psychotropic drugs and their combinations on the QTc interval as well as the prevalence of long QTc (LQTc) among ambulatory patients with psychiatric illness in Jordan. Methods: A cross-sectional study that included patients treated in an outpatient psychiatric clinic was conducted. The QTc duration was calculated using a combined QT correction (Bazett's formula for heart rate 60-100 and the Framingham formula for extremes of HR). Results: Among 307 patients, about 60% received multiple psychotropic drugs. The LQTc frequency was 1.2%. QTc interval prolongation was observed in patients receiving selective serotonin reuptake inhibitors (SSRIs) (P = .011), tricyclic antidepressants (TCAs) (P = .033), citalopram (P = .044), or psychotropic polytherapy (P = .005). The addition of SSRIs to second-generation antipsychotics (SGAs) also lengthened the QTc interval (P = .029). There was a correlation between the number of psychotropic medications and the QTc length (P = .018). All patients with LQTc carried at least one risk factor for it other than the use of psychotropic medication(s), 3 of 4 patients had a combination therapy, all patients were prescribed SSRIs, and 2 of them had comorbid conditions. Conclusion: There is a high prevalence of psychotropic drugs polytherapy, and it is clearly associated with LQTc. Citalopram, SSRIs, and TCAs prolong QTc interval. It is recommended to assess non-pharmacological factors for LQTc and, if necessary, to obtain an electrocardiogram before starting patients on psychotropic drugs known to prolong the QTc interval.

A Pre-Post Study of Vitamin D Supplement Effects on Urinary Megalin: The Emerging Predictive Role of Megalin in Diabetic Nephropathy Progression.

INTRODUCTION: Megalin is a renal proximal tubular protein that reabsorbs vitamin D from glomerular filtrates. Previous studies found significantly higher levels of urinary megalin in chronic microvascular complications of diabetes with associated metabolic derangements. This study aimed at testing the effect of vitamin D supplements on urinary megalin levels in diabetic nephropathy (DN) patients with vitamin D hypovitaminosis. METHODS: Sixty-three participants with vitamin D deficiency and diabetic nephropathy (DN) were enrolled in the pre-post study; urinary megalin levels with various clinical parameters and serum levels of vitamin D3 were measured and compared to the baseline at 3- and 6-month intervals. RESULTS: Interestingly, a supplementation related increase in serum vitamin D3 levels at 3- and 6- month interventions affected a constellation of ameliorations in the DN progression of clinical and metabolic factors. There was a decrease in ACR with a concomitant decrease in urinary megalin and a decrease in blood pressure, fasting plasma glucose (FPG), and low-density lipoprotein - cholesterol (LDL-C) - but an increase in glomerular filtration rate (GFR). Principally, pellet urinary megalin associated positively (p < 0.05) with vitamin D hypovitaminosis and the albumin-to-creatinine ratio (ACR) but negatively (p < 0.05) with Ca2+ and body mass index (BMI). CONCLUSION: Vitamin D supplementation could elucidate underlying pathophysiological mechanisms and a prognostic significance of urinary megalin association with DN, obesity/MetS-related dyslipidemia, and hyperglycemia modification. Megalin is a putative sensitive and precise predictive marker and an emerging therapeutic target of renal anomalies.

Patterns of Substance Use among Patients in Addiction Rehabilitation in Jordan.

Background: This study aimed to identify pattern of substance use among patients at two public addiction rehabilitation centers in Amman. It provided a description of substance use career and assessment of addiction severity, quality of life and quality of sleep among participants.Methods: A quantitative cross-sectional study using a structured data collection form consisting of 4 parts: 1. General data including the demographic characteristics, medical history and career of drug abuse. 2. Severity of addiction using the severity of dependence scale (SDS). 3. Quality of life measured by the EQ-5D and 4. Quality of sleep measured by the insomnia severity index (ISI) scale.Results: A total of 93 patients from 2 treatment settings were recruited over 5 months. The total number of actively used substances was 196, with an average of 2 substances per patient. Alcohol and synthetic cannabinoids were the two most commonly used substances (39.8% and 38.7% respectively) followed by benzodiazepines (33.4%). A notable drop in heroin use was observed (5.4%, 5 out of 23 opioid user) compared to the years 2007-2009. The mean SDS score among patients was 11.43 (SD ± 3.48) indicating high dependence. Sleep problems were reported by 45% of patients. Data showed a significant role of community pharmacies in supplying drugs of abuse for users.Conclusion: Pattern of substance use changed significantly in Jordan with synthetic cannabinoids being of the top substances used and heroin use dropping. Actions should be taken to reframe the legalization of dispensing certain drugs by pharmacists without a prescription.

Correlates of zinc finger BED domain-containing protein 3 and ghrelin in metabolic syndrome patients with and without prediabetes.

Background Ghrelin and zinc finger BED domain-containing protein 3 (ZBED3) are distinctively cross linked with prediabetes (preDM) and metabolic syndrome (MetS). Materials and methods In a cross-sectional design with 29 normoglycemic MetS and 30 newly diagnosed drug naïve preDM/MetS patients vs. 29 lean and normoglycemic controls; ghrelin and ZBED3 were evaluated using colorimetric enzymatic assays. Results While ZBED3 mean circulating levels (ng/mL) in both MetS groups (normoglycemic and preDM) invariably lacked discrepancy vs. controls; Appreciably ghrelin levels (ng/mL) in preDM/MetS (but not normoglycemic MetS) participants were markedly higher vs. controls. Except for fasting plasma glucose (FPG) and glycosylated-hemoglobin (HbA1C); no further intergroup discrepancy could be identified between the MetS arms. Remarkably adiposity indices (body mass index (BMI), body adiposity index (BAI), and lipid accumulation product (LAP), but not conicity index (CI) or visceral adiposity index (VAI)); atherogenicity index of plasma (but not non-high-density lipoprotein-cholesterol (non-HDL-C/HDL-C) ratio, or total cholesterol (TC)/HDL-C ratio) or any of hematological indices (red cell distribution width (RDW-CV%), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR) and platelet (PLT) to lymphocyte ratio (PLR)) were substantially higher in both MetS (non- and preDM) groups vs. those of controls. Exceptionally low-density lipoprotein -cholesterol (LDL-C)/HDL-C ratio, and waist circumference (WC)/hip circumference (HC) ratio were much more pronounced in MetS-preDM vs. normoglycemic MetS recruits. In the MetS pool (both normoglycemic and preDM, n = 58), neither biomarker could relate to each other, or any of clinical parameters, adiposity or atherogenecity indices. Exceptionally ghrelin correlated significantly and inversely with age. ZBED3 correlated significantly and directly with RDW-CV% in the same pool of MetS recruits (n = 59). Conclusions Both biomarkers can not be ruled out as putative predictive/surrogate prognostic tools for metabolic anomalies prevention and pharmacotherapy.

Glycated LDL-C and glycated HDL-C in association with adiposity, blood and atherogenicity indices in metabolic syndrome patients with and without prediabetes.

BACKGROUND: The aim of the study was to compare and correlate glycated high-density lipoprotein (GHDL-C) and glycated low-density lipoprotein (GLDL-C) plasma levels with adiposity indices [weight/hip ratio (WHR) and body adiposity index (BAI)], lipid ratios and hematological indices [platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR)]. METHODS: This was a cross-sectional study of 30 nondiabetic metabolic syndrome (MetS) patients, 30 prediabetic or type 2 diabetes mellitus (T2DM) patients and 30 normoglycemic controls. RESULTS: Remarkably both GHDL-C and GLDL-C levels lacked any intergroup statistically significant discrepancy in either MetS or MetS-pre/T2DM versus control (p > 0.05). Unlike GLDL-C/LDL-C ratios for either MetS groups; there were highly significant intergroup differences in the means of GHDL-C/HDL-C ratios when comparing both nondiabetic MetS and MetS-pre/T2DM groups versus controls (p = 0.001). In MetS patients; GHDL-C and GLDL-C proportionally correlated with WHR (p < 0.05). Also, MetS GHDL-C correlated inversely with MLR and monocytes (p < 0.05). In MetS-pre/T2DM; GLDL-C directly correlated with BAI, platelet count and PLR (p < 0.05). CONCLUSION: GLDL-C and GHDL-C are dysfunctional glucolipotoxicity lipoproteins and may present putatively surrogate biomarkers for prediction/prevention of metabolic disturbances.

Increased malondialdehyde vs. reduced sirtuin 1 in relation with adiposity, atherogenicity and hematological indices in metabolic syndrome patients with and without prediabetes.

BACKGROUND: Sirtuin 1 (SIRT 1) and malondialdehyde (MDA) were implicated in metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) pathophysiology. AIMS AND METHODS: This cross-sectional study aimed to investigate both SIRT 1 and MDA in 30 lean healthy control, 31 normoglycemic MetS subjects and 30 MetS-Pre/T2DM drug naïve. C orrelation studies were established for both biomarkers with adiposity indices [conicity index (CI), waist circumference (WC), weight-to-height (WHtR) ratio, weight-to-hip (WHR) ratio, hip circumference (HC), and body adiposity index (BAI)], hematological indices [red cell distribution width (RDW), mean platelet volume (MPV), platelet-to-lymphcyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR)] and atherogenicity indices (atherogenicity index of plasma (AIP = log10TG/HDL-C ratio), TC/HDL-C and LDL-C/HDL-C ratios]. RESULTS: SIRT1 levels (ng/mL) were markedly lower in both MetS groups (2.12 ±â€¯0.06 and 2.32 ±â€¯0.19, respectively, vs. controls 4.73 ±â€¯0.15; P < 0.05). Conversely, a gradual increase in MDA levels (µM) was attained (MetS 72 ±â€¯3.3 and MetS pre-T2DM 81 ±â€¯6.1 vs. controls 62 ±â€¯3.5; P > 0.05). A significant inverse MDA-SIRT1 relationship was observed (P = 0.006). SIRT1 correlated inversely with all the studied adiposity (WC: P < 0.001, HC: P < 0.001, WHR: P < 0.001, C-index: P < 0.001, BAI: P < 0.001) and atherogenicity indices (AIP: P < 0.001, TC/HDL-C: P < 0.001, LDL-C/HDL-C: P < 0.001) as well as MPV (P < 0.01). Whereas MDA directly with WHtR, CI and BAI (WC: P < 0.01, HC: P < 0.05, BMI: P < 001, WHtR: P < 0.001, C-index: P < 0.005, BAI: P < 0.01). CONCLUSION: The substantial variations and correlations emphasize a potential molecular role of SIRT1 and MDA in the pathophysiology of MetS and pre/T2DM.

Evaluation of four calcium channel blockers as fluconazole resistance inhibitors in Candida glabrata.

OBJECTIVES: The aim of this study was to evaluate the ability of four calcium channel blockers (CCBs), namely verapamil, diltiazem, nicardipine (NIC) and nifedipine (NIF), to enhance the susceptibility of Candida glabrata strains to fluconazole (FLC). METHODS: Synergistic antifungal effects of the CCBs with FLC were examined by the chequerboard method, and fractional inhibitory concentration indices (FICIs) were determined. The time-kill curve method was used for the most promising combination to further evaluate the synergetic effects. RESULTS: NIC showed an additive effect with FLC against FLC-resistant and FLC-susceptible-dose-dependent strains (DSY 565 and CBS 138) known to express efflux pumps, but not against FLC-susceptible strains. NIF exhibited an additive effect with FLC both by the chequerboard method (0.5

Association of Oxytocin with Glucose Intolerance and Inflammation Biomarkers in Metabolic Syndrome Patients with and without Prediabetes.

OBJECTIVES: The aim of this study was to explore the differences in OXT levels in metabolic syndrome (MetS) subjects, newly diagnosed type 2 diabetes mellitus (T2D), and prediabetes subjects vs. MetS subjects without glucose intolerance (non-diabetic MetS). It was also intended to determine the relationship between plasma OXT levels and inflammatory markers in those subjects. METHODS: Along with 45 lean and normoglycemic controls, a total of 190 MetS subjects (61 men, 129 women) were enrolled. Colorimetric enzymatic assays of the following components were performed: plasma OXT, high-sensitivity C-reactive protein (hs-CRP), macrophage chemoattractant protein 1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), matrix metalloproteinase 9 (MMP-9), resistin, adiponectin, leptin, macrophage migration inhibitory factor (MIF), tumor necrosis factor α (TNF-α), thrompospondin 1 (TSP-1), interleukin 10 (IL-10), interleukin 6 (IL-6), and glucagon. RESULTS: hsCRP, PAI-1, resistin, leptin-to-adiponection-ratio (LAR), TNF-α, TSP-1, and MIF were significantly higher in both MetS groups (prediabetic and T2DM) than in MetS-only subjects. Leptin and MMP-9 were significantly higher in the MetS-T2DM group (but not in MetS-prediabetics) vs. MetS-only subjects. Conversely adiponectin, OXT, MCP-1, and IL-10 were significantly lower in both MetS groups (prediabetic and T2DM) than in MetS-only subjects. There was no marked discrepancy in either glucagon or IL-6 levels among the three MetS groups. In the entire MetS study population, OXT correlated substantially and proportionally with MCP-1, IL-10, and IL-6; it correlated negatively with HbA1c, fasting plasma glucose (FPG), PAI-1, MMP-9, TNF-α, TSP-1, resistin, adiponectin, leptin, LAR, and MIF. No association could be observed between OXT and glucagon. CONCLUSIONS: OXT may be a substantial surrogate predictive/prognostic tool and putative pharmacotherapeutic target in metabolic anomalies and related disorders.

Effect of metformin combined with lifestyle modification versus lifestyle modification alone on proinflammatory-oxidative status in drug-naïve pre-diabetic and diabetic patients: A randomized controlled study.

BACKGROUND: Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction. METHODS: 64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline. RESULTS: Except for HbA1c, baseline values did not differ significantly between the two groups. The post 3-months relative reductions in BMI (P=0.014) and HbA1c (P=0.037) in metformin combined with TLC intervention were significantly greater than those in TLC alone group. TNFα plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (-22.90±46.76%, P=0.01). Conversely, TLC alone basically worsened proinflammatory status (42.40±40.82 %), P<0.001. Metformin with TLC treatment effected a therapeutic decrement of the oxidative stress (-15.44±35.32%, P=0.029 vs. baseline) unlike TLC alone (61.49±122.66%, P=0.01 vs. baseline). Both interventions' effects were sustained in the 6-month follow up periods. CONCLUSION: In both intervention groups, the relative changes in plasma TNFα were significantly correlated (P<0.01) with systolic blood pressure and the relative changes in oxidative stress were markedly correlated (P<0.05) with total cholesterol.

The correlation between plasma levels of oxytocin and betatrophin in non-diabetic and diabetic metabolic syndrome patients: A cross sectional study from Jordan.

BACKGROUND: Oxytocin (OXT) is a neurohypophyseal hormone that has been recently shown to possess a number of beneficial effects in diabetes and obesity. Betatrophin is a protein expressed in fat and liver that regulates lipid metabolism and promotes pancreatic ß-cell proliferation. It is not investigated yet whether OXT and betatrophin levels correlate in metabolic syndrome (MS) or diabetes patients. METHODS: The aim was to assess correlations between plasma betatrophin and OXT levels in MS-diabetic or prediabetic (N=89) as compared to MS-non-diabetic (N=69) patients. Competitive binding ELISA was used to evaluate betatrophin and OXT plasma concentrations. Correlations of the above biomarkers and patient clinical characteristics were also detected. RESULTS: As compared to the control MS participants (0.32±0.25ng/mL); betatrophin plasma levels were increased (P<0.001) in the MS-pre/T2DM patients (1.23±0.68ng/mL). On the contrary, OXT concentrations were decreased (P<0.001) in the MS-pre/T2DM patients (1222.46±514.55pg/mL) as compared to the MS control subjects (2323.42±848.68pg/mL). OXT concentration correlated negatively (r=-0.492, P<0.001), while HbA1c and FPG correlated positively with betatrophin plasma levels (P<0.001), but were inversely correlated with OXT levels (P<0.001) in the total sample. CONCLUSION: Betatrophin levels are increased, while OXT levels are decreased in MS-pre/T2DM. We found an inverse correlation between the levels of the two biomarkers in addition to correlation between their levels and the degree of glycemic control.

Effects of Genetic Polymorphism in CYP3A4 and CYP3A5 Genes on Tacrolimus Dose Among Kidney Transplant Recipients.

INTRODUCTION: This study aimed to evaluate the effects of single nucleotide polymorphisms CYP3A4*1B and CYP3A5*3 on tacrolimus dose requirement among kidney transplant recipients. MATERIALS AND METHODS: Blood levels of tacrolimus were measured using microparticle enzyme immunoassay. Genotyping analysis utilized specific polymerase chain reaction-restriction fragment length polymorphism methods for 137 kidney transplant recipients. RESULTS: The median tacrolimus dose was significantly lower in the CYP3A4*1/*1 carriers (0.06 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d) as compared to the CYP3A4*1B/*1B carriers (0.1 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d; P = .001). Patients with at least 1 CYP3A5*1 wild-type allele required higher median doses of tacrolimus (median, 0.08 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d) as compared to the CYP3A5*3 carriers (median, 0.05 mg/kg/d; range, 0.007 mg/kg/d  to 0.17 mg/kg/d; P = .002). CONCLUSIONS: This study showed that tacrolimus dose requirement is lower in Jordanian kidney transplant recipients compared to other populations. Moreover, we found a correlation between genetic variations in CYP3A4 and CYP3A5 enzymes and tacrolimus blood levels among our kidney transplant recipients.