Sex differences in basal and cocaine-induced alterations in PKA and CREB proteins in the nucleus accumbens

Introduction  Alterations in protein kinase (PKA) protein levels have been implicated in the regulation of responses to and development of cocaine addiction. However, the contribution of differences in PKA intracellular cascade to the known sex differences in responses to cocaine is not well understood. This study examined whether there are intrinsic or cocaine-induced alterations in PKA-mediated responses, such as phosphorylation of cyclic AMP response element binding protein, in male and female rats. Materials and methods  To this end, protein levels of PKA and phosphorylated CREB (pCREB) in the caudate putamen (CPu) and nucleus accumbens (NAc) of male and female rats were measured basally or after acute (one 30-mg/kg intraperitoneal injection) or chronic (twice-daily 15-mg/kg injections for 14 days) cocaine administration. Behavioral responses to both cocaine administration paradigms were also studied. Results  Similar to previous findings, ambulatory, rearing, and stereotypic activities were higher in female rats after acute cocaine administration. Sex differences in cocaine-induced responses were also observed after chronic cocaine administration: While males developed a robust sensitization in ambulatory activities to cocaine, females developed tolerance in cocaine-induced rearing and stereotypic activities. In the basal group, females had significantly higher PKA protein levels in the NAc. Regardless of the cocaine administration paradigm, PKA protein levels in the NAc were higher overall in females than in males. Furthermore, after cocaine administration, while pCREB protein levels in male rats were induced for a longer amount of time than in female rats, the magnitude of change on pCREB levels were higher in female than male rats. However, in the CPu, no sex differences in PKA or pCREB protein levels were observed either in the basal group or after acute or chronic cocaine administration. Discussion  Taken together, these findings suggest that sex differences in basal and cocaine-induced alterations in the PKA signaling regulation in the NAc may contribute to sex differences in the psychomotor responses to cocaine.     

Giant Unruptured Noncoronary Sinus of Valsalva Aneurysm

Abstract   Huge unruptured sinus of Valsalva aneurysms is rarely observed. We report a 32-year-old woman presenting with exertional dyspnea in which a giant unruptured noncoronary sinus of Valsalva aneurysm was detected after echocardiography. The aneurysm was surgically repaired and the aortic and mitral valves were replaced.     

Up-regulated CCL18, CCL28 and CXCL13 Expression is Associated with the Risk of Gastritis and Peptic Ulcer Disease in Helicobacter Pylori infection

BackgroundHelicobacter pylori (H. pylori) infection causes inflammation and increases the risk of developing peptic ulcer disease (PUD); however, the exact molecular mechanisms of PUD development remain unclear. The aim of this study was to investigate the expression of CCL18, CCL28, and CXCL13 in H. pylori-positive subjects in comparison with H. pylori-negative subjects, and to determine its association with different clinical outcomes and virulence factors.MethodsIn total, 55 H. pylori-positive subjects with gastritis, 47 H. pylori-positive subjects with PUD, and 48 H. pylori-negative subjects were enrolled in this study. CCL18, CCL28, and CXCL13 expression were determined using real time polymerase chain reaction (PCR). The virulence factors of H. pylori such as cytotoxin-associated gene A (cagA), outer inflammatory protein A (oipA), blood group antigen-binding adhesin (babA), and vacuolating cytotoxin A (VacA) genes were evaluated using PCR.ResultsCCL18, CCL28, and CXCL13 expression in H. pylori-positive subjects were significantly higher than H. pylori-negative subjects. CCL18 and CXCL13 expression in H. pylori-positive subjects with oipA⁺ and babA2⁺were significantly higher than H. pylori-positive subjects with oipA¯ and babA2¯. CCL18 and CXCL13 expression were found to be significantly elevated in H. pylori-positive subjects with gastritis compared with H. pylori-positive subjects with PUD. CCL28 expression was significantly higher in H. pylori-positive subjects with PUD compared with H. pylori-positive subjects with gastritis.ConclusionsThe increased of CCL18 and CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis, while the increased of CCL28 may be involved in the pathogenesis of H. pylori-associated PUD.     

Comparison of loop-mediated isothermal amplification (LAMP) and nested-PCR assay targeting the RE and B1 gene for detection of Toxoplasma gondii in blood samples of children with leukaemia

Toxoplasmosis diagnosis constitutes an important measure for disease prevention and control. In this paper, a newly described DNA amplification technique, loop-mediated isothermal amplification (LAMP), and nested-PCR targeting the repeated element (RE) and B1 gene, were compared to each other for the detection of Toxoplasma gondii DNA in blood samples of children with leukaemia. One hundred ten blood samples from these patients were analyzed by LAMP and nested-PCR. Out of 50 seropositive samples (IgM+, IgG+), positive results were obtained with 92% and 86% on RE, B1-LAMP and 82% and 68% on RE, B1-nested PCR analyses, respectively. Of the 50 seronegative samples, three, two and one samples were detected positive by RE-LAMP, B1-LAMP and RE-nested PCR assays, respectively, while none were detected positive by B1-nested PCR. None of the 10 IgM−, IgG+ samples was detected positive after testing LAMP and nested-PCR assays in duplicate. This is the first report of a study in which the LAMP method was applied with high sensitivity and efficacy for the diagnosis of T. gonii in blood samples of children with leukaemia.     

Oxidative stress in normal hematopoietic stem cells and leukemia

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000–2017) of English‐language literature using the terms ‘oxidative stress,’ ‘reactive oxygen species,’ ‘hematopoietic stem cell,’ and ‘leukemia.’ The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long‐term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject.