Pharmacokinetics of positron-labeled 1,3-bis(2-chloroethyl)nitrosourea in human brain tumors using positron emission tomography

The nitrosoureas are widely used in the chemotherapy of brain tumors, two of the most common being 1,3-bis(2-chloroethyl)nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. However, we do not understand how these compounds work, nor do we know which part of the molecule has antitumor activity. In six patients with brain tumor, we measured the kinetic behavior of positron-labeled 1,3-bis(2-chloroethyl)nitrosourea in both the tumor and the normal brain with the aid of positron emission tomography; we also analyzed the distribution of radioactivity in plasma. We found the clearance of total radioactivity from the tumor to be significantly slower than from the contralateral brain and plasma, indicating a different rate of 1,3-bis(2-chloroethyl)nitrosourea decomposition in the tumor than in normal brain.     

Unraveling the impact of interval length between neoadjuvant chemoradiotherapy and surgery on perioperative and postoperative complications in rectal cancer patients

European Surgery - The optimal timing for surgery following neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients and its impact on perioperative and postoperative complications remain...     

Novel Extracorporeal Dialysis Circuit to Improve the Removal Efficiency of High and Middle Molecular Weight Toxins

A new extracorporeal circuit for hemodialysis was designed with the goal of improving the middle and high molecular weight toxins removal. A recirculation pathway was added to the hemodialysis circuit and relevant pressure regulation was performed along the circuit in order to keep the ultrafiltration rate as zero. The influence of increasing the recirculation to dialysate flow rate ratio on the removal of urea, vitamin B12, and hemoglobin was investigated. This removal was also modeled by an analytical method and solved by MATLAB software. A significant increase in removal of vitamin B12 (34%) and especially hemoglobin (228%) was achieved using the recirculation flow in an adjusted hemodialysis circuit. The model showed an acceptable agreement with the experimental results which shows its applicability for prediction of different toxin removal in this circuit.     

An effective method for establishing animal models of azoospermia and oligospermia

The current study aims to develop a validated animal model to predict successful spermatogenesis retrieval in azoospermia and oligospermia men. Thirty-two mice were equally divided into 4 groups: control, scrotal hyperthermia (15 times), scrotal hyperthermia group (10 times), scrotal hyperthermia group (5 times). In the scrotal hyperthermia groups, their scrotum exposed to water at a temperature of 43°C for 20 min every other day. Then, the mice were euthanised and sperm samples were collected for sperm parameters analysis, and blood samples were obtained for hormonal assay. The testis samples were taken for histopathology experiments, immunofluorescence staining and Western blot in order to examine the protein expression together with RNA extraction in order to examine the gene expression of germ cell markers. The results of sperm analysis and histopathology of testicular tissue as well as the results of gene expression and Western blot showed that hyperthermia can significantly impair spermatogenesis. In conclusion, we have developed a novel model of azoospermia and oligospermia in mouse, which uses a high temperature to suppress spermatogenesis process through demolition of germ cells subsequent cell cycle arrest and apoptosis. The model will contribute to understanding azoospermia in human, oligospermia pathophysiology and the development of treatment.     

Effect of sour tea supplementation on liver enzymes,lipid profile,blood pressure,and antioxidant status in patients with non‐alcoholic fatty liver disease: A double‐blind randomized controlled clinical trial

The aim of this study was to evaluate the efficacy of sour tea supplementation in patients with nonalcoholic fatty liver disease (NAFLD). Seventy NAFLD patients were enrolled in this randomized, double‐blind, placebo‐controlled clinical trial. Participants received sour tea in the form of a 450 mg capsule or a placebo capsule daily for 8 weeks. Anthropometric indices, liver enzymes, lipid profile, blood pressure, and antioxidant status were evaluated at the baseline and at the end of the study. Sixty‐one participants completed the study. After 8 weeks, sour tea administration significantly decreased serum triglyceride (TG) (p = .03), alanine aminotransferase (ALT) (p = .01), and aspartate aminotransferase (AST) (p = .004) levels compared with the placebo. In addition, sour tea supplementation resulted in a significant reduction in systolic blood pressure (SBP) (p = .03) and diastolic blood pressure (DBP) (p = .04), and a significant increase in serum total antioxidant capacity (TAC) levels (p ? .001) compared with the placebo. However, no significant changes in anthropometric measures, total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐c), and high‐density lipoprotein cholesterol (HDL‐c) levels were observed after sour tea supplementation compared with the placebo (p > .05). Sour tea supplementation may be effective in improving serum TG, liver enzymes, and blood pressure in patients diagnosed with NAFLD. Further studies are needed to address the exact mechanism of action of these effects.     

MiR-339 and especially miR-766 reactivate the expression of tumor suppressor genes in colorectal cancer cell lines through DNA methyltransferase 3B gene inhibition

It is observed that upregulation of DNMT3B enzyme in some cancers, including colon cancer, could lead to silencing of tumor suppressor genes. MiR-339 and miR-766 have been predicted to target 3′UTR of DNMT3B gene. Luciferase reporter assay validated that individual and co-transfection of miR-766 and miR-339 into the HEK293T cell reduced luciferase activity to 26% ± 0.41%, 43% ± 0.42 and 64% ± 0.52%, respectively, compared to the control (P < 0.05). Furthermore, transduction of miR-339 and miR-766 expressing viruses into colon cancer cell lines (SW480 and HCT116) decreased DNMT3B expression (1.5, 3-fold) and (3, 4-fold), respectively. In addition, DNA methylation of some tumor suppressor genes decreased. Expression of these genes such as SFRP1 (2 and 1.6-fold), SFRP2 (0.07 and 4-fold), WIF1 (0.05 and 4-fold), and DKK2 (2 and 4-fold) increased in SW-339 and SW-766 cell lines; besides, expression increments for these genes in HCT-339 and HCT-766 cell lines were (2.8, 4-fold), (0.005, 1.5-fold), (1.7 and 3-fold) and (0.04, 1.7-fold), respectively. Also, while in SW-766, cell proliferation reduced to 2.8% and 21.7% after 24 and 48 hours, respectively, SW-339 showed no reduced proliferation. Meanwhile, HCT-766 and HCT-339 showed (3.5%, 12.8%) and (18.8%, 33.9%) reduced proliferation after 24 and 48 hours, respectively. Finally, targeting DNMT3B by these miRs, decreased methylation of tumor suppressor genes such as SFRP1, SFRP2, WIF1 and DKK2 in the mentioned cell lines, and returned the expression of these tumor suppressor genes which can contribute to lethal effect on colon cancer cells and reducing tumorigenicity of these cells.     

Pharmacokinetics of 11C-BCNU in experimental brain tumor

Wistar rats implanted intracerebrally with AA ascites tumor were injected seven or eight days later with ¹¹C-labelled BCNU. Radioactive compounds in samples of plasma, tumor, and contralateral brain were identified after injection at intervals by doing chloroform extraction and thin layer radiochromatography. At 60 min after injection radioactivity levels were 56% higher in the tumor than in contralateral brain. This increase was due mainly to 2-chloroethyl isocyanate, which binds to amino groups and/ or nucleic acid. The results demonstrated both a higher concentration and a faster decomposition of BCNU in the tumor.     

New synthesis of fluorine-18-labeled 6-fluoro-L-dopa by cleaving the carbon-silicon bond with fluorine

A new synthesis of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine using 6-trimethylsilyl-3,4-dimethoxy-L-dopa-ethylester as a fluorination substrate is described. The silane is prepared from the corresponding bromo compound by reacting the latter with magnesium and trimethylsilyl chloride. Reaction of the silane with [18F]F2 (0.5% F2 in neon) in a mixture of freon-11/CCl4 (1:1) kept in a dry ice bath, subsequent hydrolysis with concentrated HBr in a bath at 140 degrees C, and simple chromatographic purification yielded 18F-labeled 6-fluoro-L-dopa. A radiochemical yield of about 8% was achieved at the end of the 1-hr synthesis. The specific activity at the end of the synthesis was about 680 mCi/mmol after a 30-min irradiation.