Activation and Inactivation of Nicotinic Receptnors in the Dorsal Hippocampal Region Restored Negative Effects of Total (TSD) and REM Sleep Deprivation (RSD) on Memory Acquisition, Locomotor Activity and Pain Perception.

Sleep deprivation (SD) is a common issue in today's society. Sleep is essential for proper cognitive functions, including learning and memory. Furthermore, sleep disorders can alter pain information processing. Meanwhile, hippocampal nicotinic receptors have a role in modulating pain and memory. The goal of this study is to investigate the effect of dorsal hippocampal (CA1) nicotinic receptors on behavioral changes induced by Total (TSD) and REM Sleep Deprivation (RSD). A modified water box and multi-platform apparatus were used to induce TSD and RSD, respectively. To investigate the interaction between nicotinic receptors and hippocampus-dependent memory, nicotinic receptor agonist (nicotine) or antagonist (mecamylamine) was injected into the CA1 region. The results showed, nicotine at the doses of 0.001 and 0.1 µg/rat and mecamylamine at the doses of 0.01 and 0.1 µg/rat decreased memory acquisition, while both at the doses of 0.01 and 0.1 µg/rat enhanced locomotor activity. Additionally, all doses used for both drugs did not alter pain perception. Also, 24 h TSD or RSD attenuated memory acquisition with no effect on locomotor activity and only TSD induced an analgesic effect. Intra-CA1 administration of subthreshold dose of nicotine (0.0001 µg/rat) and mecamylamine (0.001 µg/rat) did not alter memory acquisition, pain perception and locomotor activity in sham of TSD/RSD rats. Both drugs reversed all behavioral changes induced by TSD. Furthermore, both drugs reversed the effect of RSD on memory acquisition, while only mecamylamine reversed the effect of RSD on locomotor activity. In conclusion, CA1 nicotinic receptors play a significant role in TSD/RSD-induced behavioral changes.

Genetic Polymorphism of Mismatch Repair Genes and Susceptibility to Prostate Cancer.

PURPOSE: Mismatch repair (MMR) is one of the DNA repair systems that correct mispaired bases during DNA replication errors. Polymorphisms in genes can increase susceptibility to the development of prostate cancer (PCa). In this study, we investigated mutL homolog 1 (MLH1) -93G>A (rs1800734) and mutS homolog 3 (MSH3) (rs26279) polymorphisms with the risk of PCa. MATERIALS AND METHODS: In this study of Iranian population, 175 histopathologically confirmed (PCa) patients and 230 benign prostate hyperplasia (BPH) as the controls were recruited. The genotypes of MLH1 and MSH3 were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: There was no significant difference of MLH1 (P = 0.4) and MSH3 (P?=?0.5) genotype distributions among PCa cases and controls. And also patients with PCa were not significant differences compared to those without in stage of cancer, grade of tumor, perineural invasion, and vascular invasion. CONCLUSION: Our results did not show adequate evidence for any significant association of MLH1 and MSH3 polymorphisms and PCa .

Genetic Polymorphism of MMP2 Gene and Susceptibility to Prostate Cancer.

BACKGROUND AND AIMS: The polymorphic genetic variants of matrix metalloproteinase (MMPs) can play critical roles in development and progression of cancer. The purpose of this study was to investigate if any association exists between MMP2 -1306/T and risk of prostate cancer (PCa). METHODS: This case-control study comprised a total number of 241 subjects, including 102 patients with PCa and 139 controls with benign prostatic hyperplasia (BPH). MMP2 genotypes were detected by RFLP. RESULTS: There is no significant difference between different genotypes of MMP2 polymorphism and risk of developing PCa (p = 0.08). Although these genotypes increased the risk of developing PCa 79% (CT vs. CC) and 54% (TT vs. CC), none had a significant effect (p = 0.09 and p = 1 respectively). There were no significant differences in genotype frequencies between patients with low and high degrees of PCa (p = 0.4). Therefore, this polymorphism cannot be considered as a protective factor for PCa metastasis. It seems that MMP2 polymorphism has no protective effect on the grading of the tumor (p = 0.8). Our results indicated that MMP2 polymorphism had no role in the vascular invasion of PCa. CONCLUSION: We found no association between MMP2 polymorphism and cancer risk, overall or by grade, stage or age of diagnosis. Finally, there was no association between the different genotypes and PSA plasma levels among cases or controls. Further evaluations with larger samples from our population may illuminate the effects of polymorphisms on PCa risk and thus help early diagnosis, follow-up and prognostic determinations for PCa patients.

Endothelial nitric oxide synthase Glu298Asp polymorphism as a risk factor for prostate cancer.

BACKGROUND: The endothelial form of nitric oxide synthases (eNOS) seems to have an important role in vascular development, maintenance of the vascular tone and tumor growth in human prostate cancer (PC). The purpose of this study was to investigate the association between grade and stage of disease, age of diagnosis, vascular or perineural invasion, pre-diagnostic plasma prostate-specific antigen (PSA) levels, prostate cancer risk and Glu298Asp polymorphism of the eNOS gene.
 METHODS: Ninety-five prostate cancer patients and 111 benign prostate hyperplasia subjects were included. The Glu298Asp polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism 
 RESULTS: The odds ratio (OR) between the GT and GG polymorphism was 0.76, indicating that the presence of the GT polymorphism decreased the risk of prostate cancer of more than 20% compared to the GG polymorphism. This difference, however, was not statistically significant. The GT polymorphism had an inverse association with cancer grade compared to the reference group (OR=0.47, p value=0.2).
 CONCLUSIONS: These results suggest that prostate cancer development is not associated with the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene in our population. Further studies in larger samples are needed to confirm our results and characterize the molecular mechanisms by which eNOS is involved in the susceptibility to prostate cancer.

Association of G/A polymorphism, rs266882, in AREI region of the prostate-specific antigen gene with prostate cancer risk and clinicopathological features.

PURPOSE: To determine the association of prostate-specific antigen (PSA) 158A/G polymorphism with clinicopathologic characteristics of the disease and prostate cancer (PCa) risk. MATERIALS AND METHODS: Two hundred and six subjects, including 95 patients with PCa and 111 subjects with benign prostatic hyperplasia (BPH), were recruited in this study. Genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. RESULTS: Presence of GG genotype significantly increased the risk of PCa more than 2-fold compared to AG genotype (adjusted odds ratio = 2.4; P = .03). The percentages of G alleles of polymorphisms in patients with PCa were more than that in ones with BPH (odds ratio = 1.2; P = .7). CONCLUSION: The GG genotype of PSA 158A/G polymorphism is a predisposing factor for PCa. But no association was observed between alleles and grade, stage, or age of diagnosis. Similarly, the rs266882 polymorphism was not associated with PSA plasma levels.

Association of angiotensin I converting enzyme polymorphism as genetic risk factor in benign prostatic hyperplasia and prostate cancer.

INTRODUCTION: Angiotensin I converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is one of the genetic factors found to be related with prostate cancer (PC). We investigated the association between grade and stage of disease, age of diagnosis, vascular or perineural invasion, prediagnostic plasma prostate specific antigen (PSA) levels, and PC risk with I/D polymorphism of the ACE gene. MATERIALS AND METHODS: We recruited 206 subjects in this study, including 95 patients with PC and 111 patients with benign prostatic hyperplasia. RESULTS: The odds ratio between II and DD polymorphisms (reference) was 1.38. It means that the presence of the II polymorphism increased the risk of cancer more than 38% compared with DD polymorphism although still it was not statistically significant. The mean of total PSA in the patients with the II genotype was 20 ng/L more than that in those who had DD polymorphism. The odds ratio (OR) between the D allele and PC development was 1.16, indicating that this allele increased the risk of cancer about 16%. CONCLUSION: We found no association between the ACE polymorphism and cancer risk, overall or by grade, stage, or age of diagnosis. The difference in results for ACE polymorphisms between studies may be minimized by using larger study groups.