Serum Alkaline Phosphate Level Associates with Metabolic Syndrome Components Regardless of Non-Alcoholic Fatty Liver; A Population-Based Study in Northern Iran.

Background: Serum alkaline phosphatase (ALP) is an indicator of hepatobiliary disorders, such as metabolic syndrome (MetS). To assess the association between serum ALP levels and MetS, with or without non-alcoholic fatty liver disease (NAFLD), in a cohort study in northern Iran. Methods: Data from approximately 5257 subjects aged more than 18 years participating in the Amol cohort were used. We extracted the required data and investigated the correlation between liver enzyme levels and MetS. Multiple logistic regression analyses based on the serum ALP quartiles were performed. Results: Of them, 2860 were male with a mean age of 42.11±16.1 years. A positive linear trend was observed between serum ALP levels and the number of MetS components in both sexes. In both sexes, systolic blood pressure, waist circumferences, and high-density lipoprotein (HDL) had a significant association with ALP. After adjusting for age, both sexes with NAFLD showed an increased risk of developing MetS. The risk of NAFLD increased in individuals with>2nd quartile of ALP. Furthermore, higher ALP levels were associated with an increased risk of MetS in males (1.1014 [0.782-1.315]) and females (1.441 [1.085-1.913]). Conclusion: There is a significant association between serum ALP levels and MetS, independent of fatty liver changes, suggesting that this marker can be considered as a feasible predictor of MetS.

Akt-targeted therapy as a promising strategy to overcome drug resistance in breast cancer - A comprehensive review from chemotherapy to immunotherapy.

Breast cancer is the most frequently occurring cancer in women. Chemotherapy in combination with immunotherapy has been used to treat breast cancer. Atezolizumab targeting the protein programmed cell death-ligand (PD-L1) in combination with paclitaxel was recently approved by the Food and Drug Administration (FDA) for Triple-Negative Breast Cancer (TNBC), the most incurable type of breast cancer. However, the use of such drugs is restricted by genotype and is effective only for those TNBC patients expressing PD-L1. In addition, resistance to chemotherapy with drugs such as lapatinib, geftinib, and tamoxifen can develop. In this review, we address chemoresistance in breast cancer and discuss Akt as the master regulator of drug resistance and several oncogenic mechanisms in breast cancer. Akt not only directly interacts with the mitogen-activated protein (MAP) kinase signaling pathway to affect PD-L1 expression, but also has crosstalk with Notch and Wnt/ß-catenin signaling pathways involved in cell migration and breast cancer stem cell integrity. In this review, we discuss the effects of tyrosine kinase inhibitors on Akt activation as well as the mechanism of Akt signaling in drug resistance. Akt also has a crucial role in mitochondrial metabolism and migrates into mitochondria to remodel breast cancer cell metabolism while also functioning in responses to hypoxic conditions. The Akt inhibitors ipatasertib, capivasertib, uprosertib, and MK-2206 not only suppress cancer cell proliferation and metastasis, but may also inhibit cytokine regulation and PD-L1 expression. Ipatasertib and uprosertib are undergoing clinical investigation to treat TNBC. Inhibition of Akt and its regulators can be used to control breast cancer progression and also immunosuppression, while discovery of additional compounds that target Akt and its modulators could provide solutions to resistance to chemotherapy and immunotherapy.

Left ventricular torsional parameters before and after atrial fibrillation ablation: a velocity vector imaging study.

BACKGROUND AND AIM: Effects of atrial fibrillation (AF) and its ablative treatment on LV torsion have not yet been fully investigated. This study aimed to examine whether AF patterns of LV contraction and its ablative correction can exert a significant impact on LV torsion by velocity vector imaging (VVI). METHODS: This case-control study conducted in Rajaie Cardiovascular, Medical and Research Center between October 2012 and June 2013. Study participants were 30 consecutive patients with symptomatic paroxysmal AF who met the inclusion criteria. The control group included 24 healthy participants with no history of cardiovascular disease. All individuals were in sinus rhythm at the time of echocardiography before and after the ablation procedure. Two-dimensional (2D) and Doppler echocardiography on a commercially available ultrasound system was performed for all the patients. Scanning was done by a wide-band ultrasound transducer with the frequency range between 2.5-3.5 MHz. The two short-axis views at basal and apical levels were subsequently processed off-line by VVI XStrain software. In order for data analysis, SPSS 16 utilized using paired and independent t-test. p-value ≤0.05 was considered significant. RESULTS: LV torsion (°/cm) mean ± SD was significantly lower in paroxysmal AF patients before ablation (0.8±0.3) than the control group (1.5±0.4) (p<0.001) and increased significantly after ablation (1.1±0.5) compared with before ablation (p=0.004), but still significantly lower than the control group (p=0.003). LV Twist, twist rate and untwist rate mean ± SD were significantly lower in paroxysmal AF patients before ablation than the control group and increased significantly after ablation compared with before ablation, but still significantly lower than the control group. CONCLUSION: Subclinical LV dysfunction may be detected in paroxysmal AF rhythm by measuring torsional parameters through VVI which improves after AF ablation.

Hypo and hyperglycemia among tramadol overdose patients in Loghman Hakim Hospital, Tehran, Iran.

Tramadol is a synthetic and centrally active analgesic. Hypoglycemia as another possible major side effect among abusers has not been known well. Our objective is evaluation of the Blood Glucose Level (BGL) among tramadol-overdosed patients. This prospective cross-sectional study was performed from Feb to June 2013; BGL was measured at the time of admission, 8 and 12 hours later. All patients with hypoglycemia received infusion of 0.5-1 gr/kg of hypertonic dextrose and their BGL was checked every hour until normal BGL. Patients' demographic, clinical and paraclinical data were collected. Totally, 128 patients with a mean (SD) age of 24.5 (6.9) years were recruited; 127 (99.2%) were male. Seizure occurred in 59.4% cases. Mean ± SD admission BGL was 94.88 ± 21.5mg/dL. Fourteen patients experienced hypoglycemia within 12 hours period. Hyperglycemia was experienced in 8 patients (6.25%) on admission day. There was no significant relation between the dose of tramadol and BGL. In conclusion, hypoglycemia must be considered as an important side effect of tramadol-overdose. It is suggested that serial BGL monitoring in cases of Tramadol-overdose should be done for early recognition of hypoglycemia and its timely management. Also hyperglycemia may be revealed.

Single beat determination of intraventricular systolic dyssynchrony in patients with atrial fibrillation and systolic dysfunction.

BACKGROUND: Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. However, diagnosis of intraventricular dyssynchrony in patients with AF is difficult due to beat-to-beat variation. Additionally, evaluation of mechanical dyssynchrony in the traditional method is based on average of 5 to 10 beats, which is exhausting and time consuming. Single-beat evaluation of a beat with equal subsequent cardiac cycles has been proposed as an accurate method in patients with AF. OBJECTIVES: We proposed to evaluate intraventricular mechanical dyssynchrony by measuring time-to-peak systolic velocity between basolateral and basoseptal segments (septum to lateral wall delay) using Tissue Doppler Study (TDI) by two different methods. MATERIALS AND METHODS: 31 patient (68 ± 10.3 years) with heart failure (EF < 35%) and AF rhythm, R-R cycle length more than 500 msec were evaluated. We found a target beat in which preceding R-R (R-R1) to pre-preceding R-R (R-R2) ratio was 1(RR1/RR2 = 1) then measured the intraventricular dyssynchrony in that cycle. Intraventricular dyssynchrony was also determined and averaged for 8 consecutive cardiac cycles. The values at RR1/RR2 = 1 were compared with the average of intraventricular dyssynchrony in eight cycles and the relationship between dyssynchrony were evaluated by paired T-test, linear Pearson correlation (r2), linear regression analysis. RESULTS: The average of dyssynchrony in eight cycles showed a positive correlation with dyssynchrony in target beat RR1/RR2 = 1. Average of dyssynchrony in target beat was 46.77 msec, and average of 8 cycle was = 47.701, (P value = 0.776, Pearson linear correlation 0.769). CONCLUSIONS: Measurement of intraventricular dyssynchromy in basoseptal and basolateral segments in AF and heart failure patients in a single beat with RR1/RR2 = 1 , were very similar to the average value of eight cardiac cycle.

Lack of association between the C677T single nucleotide polymorphism of the MTHFR gene and glaucoma in Iranian patients.

Glaucoma is a major cause of blindness worldwide. A single nucleotide polymorphism of the MTHFR gene (C677T) has been associated with susceptibility to this disease, although this is controversial in the last decade. In this study, the possible association between the MTHFR C677T polymorphism and the risk of developing primary open angle (POAG) and pseudoexfoliation glaucoma (PEXG) was investigated. For this, a prospective study consisting of 73 POAG, 85 PEXG and 90 matched controls was undertaken in an Iranian population. Genomic DNA was extracted from whole blood. Genotyping of all individuals for the MTHFR C677T polymorphism was conducted using the PCR-RFLP technique. Our findings revealed no significant association between the MTHFR C677T polymorphism in POAG and PEXG compared with controls. Consistent with several other studies, our analysis suggests that the MTHFR C677T polymorphism is unlikely to be a factor contributing to the risk of developing specific forms of glaucoma.