[ occurrence and contribution of germline BRCA1/2 sequence alterations in Iranian patients with breast cancer]

Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families. One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls. In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83[-TT], IVS8-70[-CATT], IVS2+9[G>C], IVS1-20[G>A], IVS1-8[A>G], p.Met1Ile, IVS2+24[A>G], IVS5-8 [A>G], IVS2[35-39]TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70[T>G], 1994-1995 [InsA] in BRCA2. Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments [42], 80% related to BRCA1 and 20% to mutations in BRCA2 genes

[Influence of nicotine and nitric oxide on anxiety behavior in mice]

Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. Anxiety is considered to be a normal reaction to stress, however excessive anxiety results in anxiety disorder. In this study, we investigated the possible interaction between nicotine and nitric oxide system of the dorsal hippocampus on anxiety-like behavior in mice. This experimental study was performed on 230 male NMRI mice. Mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Two stainless-steel cannulae were placed in the CA1 region of hippocampus. Nicotine [0.5 mg/kg] was injected intraperitoneally; L-arginine [1 micro g/mouse] and L-NAME 50 ng/mouse was instilled in the cannulae; The elevated plus-maze test was used to test for anxiety-like behaviors. One-way analyses of variance [ANOVAs] followed by LSD test, were used for analysis of the data. Intraperitoneal injection of nicotine or bilateral intra-dorsal hippocampal injections of L-arginine and L-NAME induced anxiogenic effects, p<0.05, p<0.05, p<0.01, respectively. Intraperitoneal injection of lower dose of nicotine [0.1 mg/kg] before different doses of Larginine or L-NAME inhibited anxiogenic effects of L-arginine or L-NAME. It seems that both nitric oxide and nicotinic cholinergic systems play a part in the modulation of anxiety in the dorsal hippocampus of mouse; however the interaction between these two systems is complex