99mTc‐(EDDA/tricine)‐HYNIC‐GnRH analogue as a potential imaging probe for diagnosis of prostate cancer

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC‐conjugated GnRH analogue and labeled it by ^99mTc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate ^99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys⁶]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN‐CaP and DU‐145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN‐CaP were superior to DU‐145 cells. The K_d values for LN‐CaP and DU‐145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of ^99mTc‐HYNIC‐Ahx‐[DLys⁶]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN‐CaP tumor‐xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor‐mediated. The lesion was visualized clearly using ^99mTc‐[DLys⁶]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of ^99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys⁶]GnRH peptide as a promising agent for GnRHR‐expressing tumor imaging.     

Endothelium-dependent vasodilation is related to the fatty acid composition of serum lipids in healthy subjects

The fatty acid (FA) composition of the serum lipids has been associated with cardiovascular disease (CVD). As an attenuated endothelium-dependent vasodilation (EDV) has been suggested as an early marker of atherosclerosis, we investigated the relationships between the proportion of FA in serum lipids (cholesterol esters and phospholipids) together with the levels of serum LDL- and HDL-cholesterol and triglycerides and EDV, as well as endothelium-independent vasodilation (EIDV). Fifty-six healthy subjects (31 men and 25 women), aged between 20 and 69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusion of 2 and 4 microg/min of metacholine (Mch, evaluating EDV), 5 and 10 microg/min of sodium nitroprusside (SNP, evaluating endothelium-independent vasodilation, EIDV) using venous occlusion plethysmography. An index of endothelial function was calculated as the ratio between EDV and EIDV. The proportion of palmitic (16:0) and palmitoleic (16:1) acids were inversely related (r=-0.35 and -0.35, P<0.01 for both), while linoleic acid (18:2 n6) and the HDL-cholesterol concentration were positively related (r=0.35 and 0.36, P<0.01 for both) to the endothelial function index. In multiple regression analysis also including age and gender, palmitoleic acid and HDL-cholesterol were significant independent predictors of endothelial function. Alfa-linolenic acid (18:3 n3) was positively correlated to both EDV and EIDV (r=0.40 and 0.43, P<0.01 for both), indicating a protective effect of this essential FA on vasodilation in general. It is concluded that the FA composition of serum lipids, partly reflecting the composition of dietary fat and previously associated with the development of CVD, was associated with endothelial function in apparently healthy subjects.     

Hepatic Hemodynamic Changes Following Stepwise Liver Resection

Aim

Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes.

Methods

To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups.

Results

Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %).

Conclusion

Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.

     

Polymorphisms of genes encoding interleukin-4 and its receptor in Iranian patients with juvenile idiopathic arthritis

As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value?=?0.03, and P value?=?0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses.     

Prognostic value of positive T wave in lead aVR in patients with non‐ST segment myocardial infarction

Background

Lead aVR provides prognostic information in various settings in patients with ischemia. We aim to investigate the role of a positive T wave in lead aVR in non‐ST segment myocardial infarction (NSTEMI).

Methods

In a prospective cohort study, we included 400 patients with NSTEMI. Presentation electrocardiogram (ECG) was investigated for presence of a positive T wave as well as ST segment elevation (STE) in aVR and study variables were compared. Predictors of primary outcome defined as hospital major adverse cardiovascular events (MACE) and secondary outcome, defined as three‐vessel coronary disease and/or left main coronary artery stenosis (3VD/LMCA) stenosis in angiography, were determined in multivariate logistic regression analysis.

Results

Patients with a positive T wave in aVR were significantly older and were more likely to be female. Left ventricular ejection fraction was significantly lower in patients of positive T group. Positive T group was more likely to have 3VD/LMCA stenosis (58.3% vs. 19.8%, p < .001). The prevalence of a positive T wave in aVR was significantly higher in MACE group (54.9 % vs. 24.8%, p < .001). However, in multivariate analysis, it was not an independent predictor of MACE (OR: 1.083 95% CI: [0.496–2.365], p: .841). Though, it was independently associated with presence of 3VD/LMCA stenosis (OR: 3.747 95% CI: [2.058–6.822], p < .001).

Conclusion

Though positive T wave in lead aVR was more common in patients with MACE; it was not an independent predictor. Additionally, a positive T wave in aVR was an independent predictor of 3VD/LMCA stenosis in NSTEMI.

     

Association Analysis Between the rs1899663 Polymorphism of HOTAIR and Risk of Psychiatric Conditions in an Iranian Population

Journal of Molecular Neuroscience - Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of a number of psychiatric disorders. In the current study, we...     

Endothelium-dependent vasodilation in normotensive subjects with a familial history of essential hypertension and in young subjects with borderline hypertension

OBJECTIVE: To investigate if young normotensive subjects with a familial history of essential hypertension (FHH) or young borderline-hypertensive (BHT) subjects have a defect endothelial function. METHODS: Fifteen young (26 +/- 4 years) healthy normotensive (115 +/- 8/71 +/- 6 mmHg) subjects with a FHH, 31 matched healthy normotensive subjects without FHH and seven BHT (143 +/- 12/92 +/- 2 mmHg), otherwise healthy, young males underwent evaluation of endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIDV), by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV) in the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. RESULTS: Although there was no significant difference between normotensive subjects with and without a FHH regarding FBF during vasodilation induced by MCh or SNP, the subjects with a FHH presented a significantly suppressed endothelial function index, calculated as the ratio between EDV and EIDV, when compared to subjects without FHH (1.04 +/- 0.15 vs. 1.24 +/- 0.23, p < 0.01). Also in the group of BHT subjects, the endothelial function index was suppressed (1.01 +/- 0.18, p < 0.01), in this case due to a significantly attenuated EDV (p < 0.05), when compared to male subjects without a FHH. CONCLUSION: The present findings suggest an early occurrence of endothelial dysfunction in the development of essential hypertension.