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.     

Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs clinical and immune correlates

Objective. To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high-dose dietary ω3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population. Methods. Sixty-six RA patients entered a double-blind, placebo-controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day). Patients took either 130 mg/kg/day of ω3 fatty acids or 9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum levels of interleukin-1β (IL-1β), IL-2, IL-6, and IL-8 and tumor necrosis factor α were measured by enzyme-linked immunosorbent assay at baseline and during the study. Results. In the group taking fish oil, there were significant decreases from baseline in the mean (±SEM) number of tender joints (5.3 ± 0.835; P < 0.0001), duration of morning stiffness (−67.7 ± 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (−0.33 ± 0.13; P = 0.017 and −0.38 ± 0.17; P = 0.036, respectively), and physician's evaluation of pain (−0.38 ± 0.12; P = 0.004). In patients taking corn oil, no clinical parameters improved from baseline. The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (−7.8 ± 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043). IL-1β decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (−7.7 ± 3.1; P = 0.026). Conclusion. Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL-1β from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare.     

Study of the 99mTc-labeling conditions of 6-hydrazinonicotinamide-conjugated peptides from a new perspective: Introduction to the term radio-stoichiometry

Specific tumor uptake of peptide radiopharmaceuticals depends on tumor binding affinity and their radiochemical purity. Several important parameters that influence the ^99mTc-labeling and consequently the radiochemical purity of 6-hydrazinonicotinamide (HYNIC)-conjugated peptide are radionuclide activity, the amount of peptide, the amount of coligands, and the amount of reducing agents (stannous ion). In this review article, we have attempted studying these parameters in the HYNIC-conjugated peptides (somatostatin, cholecystokinin/gastrin, bombesin, and RGD analogs) from a new perspective to obtain most used and optimized radio-stoichiometric relationships. One of the most important results in this review is that for ^99mTc-labeling of HYNIC-conjugated peptides, it is better to consider the most calculated mole ratio between technetium-99m and the peptide (mole ratio of technetium-99m to the peptide 1:200–400). The statistical results also show that among these ^99mTc-labeled peptides, the most used and favorable coligand is tricine/EDDA with two to one (2:1) mole ratio. These optimized radio-stoichiometric relationships, favorable coligand mole ratio, and applicable radiolabeling points can greatly improve the labeling process of the HYNIC-conjugated peptides, by reducing trial and error, increasing specific activity, and saving materials.     

Lack of association between paraoxonase 1 Q192R polymorphism and multiple sclerosis in relapse phase: A case-control study

ObjectivesThe aim of this study was to estimate the serum activity of paraoxonase 1(PON1) and assess the distribution of PON1 polymorphisms in MS patients in the relapse phase.Design and methodsPON1 and arylesterase (ARE) serum activities were measured in two equal groups (each group 63 cases) of relapsing–remitting MS patients and healthy individuals.ResultsMean values for serum PON1 and ARE activities were 90.3 ± 63.4 and 182.1 ± 128.7 IU/L for patients and 99.9 ± 73.3 and 190.8 ± 150.3 IU/L for controls. Those values were not statistically significant (p = 0.242 and p = 0.378), respectively. Comparing genotype distributions and allele frequencies in both groups for PON1 Q192R and PON L55M polymorphisms did not show any statistical difference.ConclusionIn a selected group of MS patients in relapsing phase no statistically significant difference in PON1 and ARE activities was detected but the mean values for the serum enzyme activities were lower in MS patients.     

Monitoring,Source Identification and Environmental Risk of Potentially Toxic Elements of Dust in Isfahan Province,Central Iran

Bulletin of Environmental Contamination and Toxicology - The aim of this study was to identify potentially toxic elements (PTEs) associated with airborne particulate matters (PMs) and their source...     

Ilioinguinal nerve excision in open mesh repair of inguinal hernia--results of a randomized clinical trial: simple solution for a difficult problem?

BACKGROUND: Inguinodynia is the second most common complication occurring after inguinal hernia repair. This study was undertaken to evaluate the effect of ilioinguinal nerve excision, a concept previously proposed to be performed during open hernia mesh repair, on postsurgical pain and hyposthesia. METHODS: A double-blind randomized clinical trial was performed on 121 patients undergoing open anterior mesh repair of inguinal hernia in 1 center from April 2005 through June 2006. The ilioinguinal nerve was excised in half of the patients and preserved in the other half. Pain and hyposthesia at POD 1, 1 and 6 months after surgery, and 1 year after surgery was evaluated in both groups using a visual analog scale. Results were compared using chi-square analysis. RESULTS: Of the total number of 121 patients who entered the study, with an age range of 18 to 86 years (mean +/- SD 45 +/- 18), 115 (95%) were male. Sixty-one were in the nerve-excision group, and 60 were in the nerve-preservation group. One hundred patients were followed-up until the end of the first year. Using the visual analog scale to detect pain severity on postsurgical day 1, mean scores in the nerve-excision and nerve-preservation groups were 2.2 +/- .8 (range 1 to 4) versus 2.8 +/- .7 (range 2 to 4.5), respectively (P < .001). At 1 month after surgery, these scores were .7 +/- .7 (range 0 to 3) versus 1.5 +/- .7 (range 0 to 3.5), respectively (P < .001). Between 6 months and 1 year after surgery, median scores of zero were detected in both groups. After postsurgical day 1, the median score of hyposthesia was near zero in both groups. Thirteen patients developed chronic inguinodynia (13%), 10 of whom were in the nerve-preservation group. Chronic postsurgical inguinodynia was seen in 6% of patients in the ilioinguinal nerve-excision and 21% of the patients in the ilioinguinal nerve-preservation group (P = .033). COMMENTS: Neurectomy decreases postsurgical pain after elective inguinal hernia repair. Although chronic inguinodynia was less frequent in our study than reported by many previous studies, it is still wise to recommend ilioinguinal neurectomy in patients undergoing anterior inguinal hernia mesh repair.     

Tumor targeting with 99mTc radiolabeled peptides: Clinical application and recent development

Targeting overexpressed receptors on the cancer cells with radiolabeled peptides has become very important in nuclear oncology in the recent years. Peptides are small and have easy preparation and easy radiolabeling protocol with no side‐effect and toxicity. These properties made them a valuable tool for tumor targeting. Based on the successful imaging of neuroendocrine tumors with ¹¹¹In‐octreotide, other receptor‐targeting peptides such as bombesin (BBN), cholecystokinin/gastrin analogues, neurotensin analogues, glucagon‐like peptide‐1, and RGD peptides are currently under development or undergoing clinical trials. The most frequently used radionuclides for tumor imaging are ^99mTc and ¹¹¹In for single‐photon emission computed tomography and ⁶⁸Ga and ¹⁸F for positron emission tomography imaging. This review presents some of the ^99mTc‐labeled peptides, with regard to their potential for radionuclide imaging of tumors in clinical and preclinical application.     

Serum levels of RHP and of unbound C1q in rheumatoid arthritis and systemic lupus erythematosus

RHP is a recently described serum protein which inhibits a number of physiologic functions of Clq unbound to Clr₂×Cls₂. In this report we show that sera from patients with rheumatoid arthritis contained elevated levels of RHP and of unbound Clq. Sera from patients with systemic lupus erythematosus contained normal levels of RHP and were characterized by deficits of Clq required to form Cl from existing levels of Clr and Cls.