Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

Inhibition of type-5 phosphodiesterase by sildenafil decreases capacitative Ca2+ entry mediated by transient receptor potential proteins (TRPs) in the pulmonary artery. These families of channels, especially the canonical TRP (TRPC) subfamily, may be involved in the development of bronchial hyperresponsiveness, a hallmark of asthma. In the present study, we evaluated i) the effects of sildenafil on tracheal rings of rats subjected to antigen challenge, ii) whether the extent of TRPC gene expression may be modified by antigen challenge, and iii) whether inhibition of type-5 phosphodiesterase (PDE5) may alter TRPC gene expression after antigen challenge. Sildenafil (0.1 µM to 0.6 mM) fully relaxed carbachol-induced contractions in isolated tracheal rings prepared from naive male Wistar rats (250-300 g) by activating the NO-cGMP-K+ channel pathway. Rats sensitized to antigen by intraperitoneal injections of ovalbumin were subjected to antigen challenge by ovalbumin inhalation, and their tracheal rings were used to study the effects of sildenafil, which more effectively inhibited contractions induced by either carbachol (10 µM) or extracellular Ca2+ restoration after thapsigargin (1 µM) treatment. Antigen challenge increased the expression of the TRPC1 and TRPC4 genes but not the expression of the TRPC5 and TRPC6 genes. Applied before the antigen challenge, sildenafil increased the gene expression, which was evaluated by RT-PCR, of TRPC1 and TRPC6, decreased TRPC5 expression, and was inert against TRPC4. Thus, we conclude that PDE5 inhibition is involved in the development of an airway hyperresponsive phenotype in rats after antigen challenge by altering TRPC gene expression.

Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice

Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm²) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm²). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo

Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis

In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.

HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.

Rippi-lasten coetus kysymyxet, sittecuin he owat Jumalan kymmenen käskyin, ja mniden [sic] christin opin pääcappalitten selityxet läpitze käynet, lyhykäisten kysymysten ja wastausten canssa, toisesta uscon cappalesta, nijn myös, autuuden perustuxest, järjestyxest, ja wälicappaleista. Joihin myös muutamia muitakin kysymyxiä, synnin tundemisest ja oikiast catumuxest, sopiwaisesti sisälle temmatan, coetelda, jos he owat rippischoulusa jo opennet sen cuin heidän opeta tule; lasten opettamisesa edesmenneinä wuosina, ja erinomattain tänä wuonna rippischoulusa harjoteldut, caikille yxinkertaisille hywäxi neuwoxi, opetuxexi, ja muistutuxexi, mitä ennengin jo opetettu olis, yhteen wedetyt: jotca kysymyxet, ynnä rippilasten oman coetuxen canssa casten lijton rickomisest ja uudistuxest, Nousiaisten pappilasta on wuonna 1766 pränttijn andanut Abraham Achrenius

Arkit: A-B12.

Rippi-lasten coetus kysymyxet, sittecuin he owat Jumalan kymmenen käskyin, ja mniden [sic] christin opin pääcappalitten selityxet läpitze käynet, lyhykäisten kysymysten ja wastausten canssa, toisesta uscon cappalesta, nijn myös, autuuden perustuxest, järjestyxest, ja wälicappaleista. Joihin myös muutamia muitakin kysymyxiä, synnin tundemisest ja oikiast catumuxest, sopiwaisesti sisälle temmatan, coetelda, jos he owat rippischoulusa jo opennet sen cuin heidän opeta tule; lasten opettamisesa edesmenneinä wuosina, ja erinomattain tänä wuonna rippischoulusa harjoteldut, caikille yxinkertaisille hywäxi neuwoxi, opetuxexi, ja muistutuxexi, mitä ennengin jo opetettu olis, yhteen wedetyt: jotca kysymyxet, ynnä rippilasten oman coetuxen canssa casten lijton rickomisest ja uudistuxest, Nousiaisten pappilasta on wuonna 1766 pränttijn andanut Abraham Achrenius

Arkit: A-B12.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1938/11/12.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1939/01/14.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1938/12/10.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1938/12/17.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

Etat de collection : 1938-1939

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1938/11/19.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1939/01/21.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1938/12/03.

Y học tân thanh. ["puis" Tuần báo phổ thông khoa thuốc]

1938/12/24.