19,259 research outputs found
Regioselective anionic [3+2] cyclizations of isoxazole, pyrazole and 1,2,4-triazole dinucleophiles - Efficient synthesis of 2,4-dihydroimidazo-[4,5-b]quinoxalines, 3H-imidazo[1,2-b]pyrazoles and 5H-imidazo[2,1-c][1,2,4]triazoles
No full textRegioselective cyclization reactions between oxaldiimidoyl dichlorides and 3-aminopyrazole and 3-amino-1,2,4-triazole provide convenient access to biologically relevant 3H-imidazo[1,2-b]pyrazoles and a 5H-imidazo[2,1-c][1,2,4]triazole. In contrast, treatment of 3-aminoisoxazoles with diimidoyl dichlorides results in a new and efficient anionic domino process for the synthesis of biologically relevant 2,4-dihydro-1H-imidazo[4,5-b]quinoxalines. All cyclizations proceed with high regioselectivities, which are explained with the aid of semiempirical computations
Regioselective anionic [3+2] cyclizations of isoxazole, pyrazole and 1,2,4-triazole dinucleophiles - Efficient synthesis of 2,4-dihydroimidazo-[4,5-b]quinoxalines, 3H-imidazo[1,2-b]pyrazoles and 5H-imidazo[2,1-c][1,2,4]triazoles
No full textRegioselective cyclization reactions between oxaldiimidoyl dichlorides and 3-aminopyrazole and 3-amino-1,2,4-triazole provide convenient access to biologically relevant 3H-imidazo[1,2-b]pyrazoles and a 5H-imidazo[2,1-c][1,2,4]triazole. In contrast, treatment of 3-aminoisoxazoles with diimidoyl dichlorides results in a new and efficient anionic domino process for the synthesis of biologically relevant 2,4-dihydro-1H-imidazo[4,5-b]quinoxalines. All cyclizations proceed with high regioselectivities, which are explained with the aid of semiempirical computations
Decoy oligodeoxynucleotide againstactivator protein-1 reducesneointimal proliferation after coronaryangioplasty in hypercholesterolemic minipigs
No full textAbstractObjectivesWe sought to demonstrate, in an appropriate animal model, that co-medication with a transcription factor-blocking agent limits restenosis after percutaneous transluminal coronary angioplasty (PTCA).BackgroundEnhanced synthesis in the vessel wall of endothelin-1 (ET-1), a powerful co-mitogen for vascular smooth muscle cells, appears to be one mechanism that promotes restenosis after PTCA. Deformation-induced expression of prepro-ET-1 is governed by the transcription factor, activator protein-1 (AP-1).MethodsAn anti-AP-1 decoy oligodeoxynucleotide (dODN) strategy was devised in which the dODN-containing solution (20 nmol) was administered locally through a Dispatch catheter into the coronary arteries of hypercholesterolemic minipigs at the time of PTCA (AVE-GFX stent).ResultsTreatment with an AP-1 dODN, mimicking the consensus binding site of the transcription factor, significantly reduced neointimal formation in the coronary arteries of hypercholesterolemic minipigs (n = 10 to 12), compared with vehicle-treated coronary arteries, after four weeks of follow-up (neointimal area 2.64 ± 0.33 vs. 4.81 ± 1.04 mm2[mean ± SEM]; p < 0.05). This effect was maintained after eight weeks (neointimal area 2.04 ± 0.22 mm2; n = 3) and correlated with a reduction in both nuclear translocation of AP-1 and ET-1 synthesis in the vessel wall 48 h after PTCA (n = 4). In contrast, an AP-1 mutant dODN, to which the transcription factor does not bind, showed no effect on neointimal formation at either time point (n = 3 to 7). Moreover, a consensus dODN directed against CCAAT/enhancer binding protein (C/EBP), another deformation-sensitive transcription factor, did not significantly affect neointimal formation after four weeks (n = 3).ConclusionsThese findings demonstrate the feasibility, efficacy and specificity of the anti-AP-1 dODN approach to the treatment of restenosis, which principally but not exclusively targets deformation-induced ET-1 synthesis in the vessel wall. Provided that these findings can be extrapolated to the situation of patients with coronary artery disease, the observed extent of the inhibitory effect of the AP-1 dODN treatment suggests that this co-medication may greatly reduce the incidence of in-stent restenosis
Strategi Pelayanan Lintas Budaya Berdasarkan Markus 4:1-34
No full textHarming & Katarina, Cross-cultural Service Strategy based on Mark 4: 1-34. The author conducted a study of the text of Mark 4: 1-34 using qualitative research literature study using the biblical hermeneutic principle. Based on the analysis of the text of Mark 4: 1-34 the authors find there are four cross-cultural service strategies namely by understanding local culture, using media. Harming & Katarina, Strategi Pelayanan Lintas budaya Berdasarkan Markus 4:1-34. Penulis melakukan penelitian terhadap teks Markus 4:1-34 dengan menggunakan penelitian kualitatif studi pustaka dengan menggunakan prinsip hermeneutik Alkitab. Berdasarkan analisis terhadap teks Markus 4:1-34 penulis menemukan ada empat strategi pelayanan lintas budaya yaitu dengan memahami budaya lokal, menggunakan media yang ada dalam budaya, memberdayakan potensi yang ada, dan menciptakan terobosan
Computational characterization of dimerization and ligand binding in biological systems
No full textThe self-association of proteins to form dimers or higher-order oligomers is a very common phenomenon in biology. Protein dimerization or oligomerization acts as a control tool for the execution of functions in many biological systems. Three systems were studied by computational methods in this thesis. Cyclic diguanylic acid (CDG) is a ubiquitous messenger involved in bacterial signaling networks. CDG can form an intercalated dimer and bind at the inhibition site of PleD. MD simulations were carried out for the CDG dimer as well as the analogue of CDG (endo-S-CDG) in solution and binding to the PleD protein. It was demonstrated, that dimeric CDG is only marginally stabilized even in high concentration. The results help the fundamental understanding of c-di-GMP and preventing biofilm formation. Insulin is a small protein that plays an eminent role in controlling glucose uptake in cells. Insulin can associate as a dimer which leads to diabetes. The key role of the B24 residue for insulin dimerization was identified. Our work provided an insight for designing analogues of human insulin and thus a therapy for diabetes
Exposition gegenüber HIV, Hepatitis B und C in Praxis und Spital : Vorbeugung und Post-Expositionsprophylaxe
No full textExposure to HIV, hepatitis B and C in office practice
and hospital. Prevention and post-exposure prophylaxis. The risk of infection after an occupational needle stick injury with blood from an infected source patient is approximately 0.3% for HIV and 0.5% for hepatitis C virus (HCV). In Switzerland no cases of occupational HBV infection have been recorded in fully vaccinated persons with a documented adequate vaccine response (HBsantibody titer >100 mIU/mL). Most occupational HIV und HBV infections can be prevented by appropriate emergency measures and post-exposure prophylaxis (PEP). No HCV-PEP is currently available. Early therapy with peginterferon and ribavirin should be considered in cases of occupational HCV seroconversion. Every hospital and office practice should establish a system for 24 h/24 h emergency management of occupational needle stick injuries. In the setting of an HIV-seropositive source patient and in complex situations,
early consultation with a specialist in occupational medicine or infectious diseases should be considered
Mesh penetration of the sigmoid colon following a transabdominal preperitoneal hernia repair
No full textThe laparascopic transabdominal preperitoneal (TAPP) repair of an inguinal hernia is an established technique associated with notably low rates of recurrence and complication. Inguinal pain and anal bleeding following a TAPP procedure may result from the penetration of the repair mesh into the sigmoid colon. In this case report, we discuss this particular complication following the TAPP procedure. Subsequently, we describe the diagnostics as well as the surgical treatment necessary
Paralysis of the femoral nerve following totally extraperitoneal laparascopic inguinal hernia repair
No full textTotally extraperitoneal. preparation (TEP) of an inguinal hernia is an established method of treating inguinal hernias associated with an acceptable complication rate (2-12%) and low rate of recurrence (0-3%). This is the first reported case of sensorimotor paralysis of the femoral nerve following the complete endoscopic mesh treatment of a primary inguinal hernia to the left side. Following a discussion of the necessary diagnostic and therapeutic steps, traumatic postsurgical paralysis of the nerve as well as spontaneous paralysis of the femoral nerve are discussed. The prognosis is positive given the lack of macroscopic evidence of any direct damage to the nerve
Pylorus preservation has no impact on delayed gastric emptying after pancreatic head resection
No full textObjectives: Delayed gastric emptying (DGE) has been specifically attributed to pylorus-preserving pancreaticoduodenectomy (PPPD). As PPPD has been shown to be comparable with the classic Kausch-Whipple pancreaticoduodenectomy (KWPD) in terms of oncological radicality, DGE has advanced to be the leading argument for hemigastrectomy in PD. Methods: A prospective, nonrandomized comparison of patients undergoing PPPD (n=113), KWPD (n=19), and duodenum-preserving, pancreatic head resection (DPPHR, n=18) for various diseases was performed. First, groups were analyzed with regard to structural similarity; then, they were compared with special emphasis on DGE and other postoperative complications. Finally, further prognostic factors were sought that had an impact on DGE. Results: The PPPD group was comparable with the KWPD group, but not to the DPPHR population. The in-clinic course after DPPHR compared favorably with PPPD as well as KWPD, and, here, no DGE occurred. The overall morbidity rates of PPPD and KWPD were comparable; 1 patient died in hospital (mortality rate, 0.7%). The gastric tube after PPPD and KWPD could be withdrawn at a median of 2 and 3 days, respectively, a liquid diet was started after 4 and 5 days, respectively, and a full diet was tolerated after 10 days each (n.s.). DGE was distributed evenly among PPPD (12%) and KWPD patients (21%, n.s.), and it was noted almost exclusively when other postoperative complications were present (P<0.0001). No further prognostic factors influencing DGE could be identified. Conclusion: Pylorus preservation does not increase the frequency of DGE. DGE almost exclusively occurs as a consequence of other postoperative complications. Therefore, DGE should not be used as an argument to advocate hemigastrectomy in PPPD
Acute impairment of hepatic microcirculation and recruitment of nonparenchymal cells by intrasplenic hepatocyte transplantation
No full textBackground/Purpose: Over the last 20 years, hepatocyte transplantation (HcTx) has advanced from the experimental to the clinical stage. To date, HcTx has been performed in 30 patients in the United States. Regardless whether hepatocytes are transplanted into the spleen and migrate to the liver or are injected directly into the portal vein, transplanted liver cells will, to some extent, congest the recipient liver microcirculation. The potential negative consequences of intrasplenic HcTx were the subject of this study. Methods: By using intravital microscopy, the authors investigated whether intrasplenic HcTx of 20 X 10(6) allogenic hepatocytes would influence liver perfusion, excretory liver function, and nonparenchymal cells (Kupffer and Ito cells) in vivo. Results: The sinusoidal perfusion rate declined significantly from 94% (control) to 84% on day 1 and 76% on day 7. Bile acid excretion decreased in a similar fashion from 0.924 mg/h (control) to 0.669 mg/h on day 7. The authors observed a significant increase of Ito cells from 81.1 cells per microscopic field (control) to 97.1 (day 1) and an increase of Kupffer cells (KC; 6.1 cells per microscopic field on day 1 v3.8 on control). Conclusions: This study shows an acute impairment of hepatic microcirculation and hepatucellular function along with an recruitment and activation of nonparenchymal cells in the early posttransplantation period after intrasplenic HcTx. Kupffer cell recruitment indicates an activation of local host defense, and Ito cell activation implies the initiation of liver repair mechanisms owing to ischemia-related cell damage. (C) 2004 Elsevier Inc. All rights reserved
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