Side-Selective Solid-Phase Metallaphotoredox N(in)-Arylation of Peptides.

Postsynthetic diversification of peptides through selective modification of endogenous amino acid side chains has enabled significant advances in peptide drug discovery while expanding the biological and medical chemistry space. However, current tools have been focused on the modification of reactive polar and ionizable side chains, whereas the decoration of aromatic systems (e.g., the N(in) of the tryptophan) has been a long-standing challenge. Here, we introduce metallaphotocatalysis in solid-phase peptide synthesis for the on-resin orthogonal N-arylation of relevant tryptophan-containing peptides. The protocol allows the chemoselective introduction of a new C(sp2)-N bond at the N(in) of tryptophan in biologically active protected peptide sequences in the presence of native redox-sensitive side chains. The fusion of metallaphotocatalysis with solid-phase peptide synthesis opens new perspectives in diversifying native amino acid side chains.

Epidemiology and outcomes of anal abscess in patients on chronic dialysis: a 14-year retrospective study.

OBJECTIVES: We conducted this retrospective study to elucidate the clinical presentation and outcomes of anal abscess in chronic dialysis patients. METHODS: We performed a chart review of patients who were hospitalized for anal abscess from Jan. 2002 to Dec. 2015. A total of 3,074 episodes of anal abscess were identified. Of these, 43 chronic dialysis patients with first-time anal abscess were enrolled. Patients were divided into a surgical group and a nonsurgical group according to the treatment received during hospitalization. The baseline characteristics, clinical findings, treatments and outcomes were obtained and analyzed. The endpoints of this study were in-hospital mortality, one-year mortality and one-year recurrence. RESULTS: Of the 43 patients, 27 (62.7%) received surgical treatment, and 16 (37.2%) received antibiotic treatment alone. There was no significant difference in age, sex, body mass index, smoking habits, comorbidities, or dialysis characteristics between the two groups. Perianal abscess was the most common type of anal abscess, and 39.5% of patients experienced fistula formation. Most patients had mixed aerobic and anaerobic flora. Our data demonstrate that there was no significant difference in hospital stay, one-year survival or recurrence rate between the surgical group and nonsurgical group. However, there was a trend toward better in-hospital survival in patients who received surgical treatment (p=0.082). CONCLUSION: In chronic dialysis patients with anal abscess, there was no statistically significant difference in clinical presentation and outcomes between the surgical and nonsurgical groups, although the surgical group had a trend of better in-hospital survival.

Epidemiology and outcomes of anal abscess in patients on chronic dialysis: a 14-year retrospective study

OBJECTIVES: We conducted this retrospective study to elucidate the clinical presentation and outcomes of anal abscess in chronic dialysis patients. METHODS: We performed a chart review of patients who were hospitalized for anal abscess from Jan. 2002 to Dec. 2015. A total of 3,074 episodes of anal abscess were identified. Of these, 43 chronic dialysis patients with first-time anal abscess were enrolled. Patients were divided into a surgical group and a nonsurgical group according to the treatment received during hospitalization. The baseline characteristics, clinical findings, treatments and outcomes were obtained and analyzed. The endpoints of this study were in-hospital mortality, one-year mortality and one-year recurrence. RESULTS: Of the 43 patients, 27 (62.7%) received surgical treatment, and 16 (37.2%) received antibiotic treatment alone. There was no significant difference in age, sex, body mass index, smoking habits, comorbidities, or dialysis characteristics between the two groups. Perianal abscess was the most common type of anal abscess, and 39.5% of patients experienced fistula formation. Most patients had mixed aerobic and anaerobic flora. Our data demonstrate that there was no significant difference in hospital stay, one-year survival or recurrence rate between the surgical group and nonsurgical group. However, there was a trend toward better in-hospital survival in patients who received surgical treatment (p=0.082). CONCLUSION: In chronic dialysis patients with anal abscess, there was no statistically significant difference in clinical presentation and outcomes between the surgical and nonsurgical groups, although the surgical group had a trend of better in-hospital survival.

Enhanced cyclooxygenase-2 activity leads to intestinal dysmotility following hemorrhagic shock

PURPOSE: To test whether hemorrhagic shock (HS) increases the Cyclooxygenase-2 (COX-2) expression in the intestine and whether this enhanced COX-2 expression mediates the intestinal dysmotility after HS. METHODS: Male Wistar rats were randomly divided into HS sham group and HS group. At 180 min following HS establishment, the duodenum samples were harvested to assess the motility function, protein expression of COX-2 and the downstream products of COX-2, prostaglandins. RESULTS: Examination of motility function ex vivo showed that the contractile response to acetylcholine of smooth muscle strips of rats subjected to HS was significantly suppressed. A COX-2 inhibitor, NS-398, abolished this depressed contractile response after HS. Western blotting revealed an increased protein expression of COX-2 in intestinal tissues of HS rats. Immunohistochemical examination indicated that intestine tissues of HS rats were manifested by part of villous expansion and disruption, a large amount of COX-2 positive cells appearance in lamina propria and submucosa. Furthermore, the contents of prostaglandin E2 was significantly increased in intestinal tissues of HS rats. CONCLUSION: The enhanced COX-2/ prostaglandin E2 involves in the hemorrhagic shock induced intestinal dysmotility.(AU)

Enhanced cyclooxygenase-2 activity leads to intestinal dysmotility following hemorrhagic shock

ABSTRACT PURPOSE: To test whether hemorrhagic shock (HS) increases the Cyclooxygenase-2 (COX-2) expression in the intestine and whether this enhanced COX-2 expression mediates the intestinal dysmotility after HS. METHODS: Male Wistar rats were randomly divided into HS sham group and HS group. At 180 min following HS establishment, the duodenum samples were harvested to assess the motility function, protein expression of COX-2 and the downstream products of COX-2, prostaglandins. RESULTS: Examination of motility function ex vivo showed that the contractile response to acetylcholine of smooth muscle strips of rats subjected to HS was significantly suppressed. A COX-2 inhibitor, NS-398, abolished this depressed contractile response after HS. Western blotting revealed an increased protein expression of COX-2 in intestinal tissues of HS rats. Immunohistochemical examination indicated that intestine tissues of HS rats were manifested by part of villous expansion and disruption, a large amount of COX-2 positive cells appearance in lamina propria and submucosa. Furthermore, the contents of prostaglandin E2 was significantly increased in intestinal tissues of HS rats. CONCLUSION: The enhanced COX-2/ prostaglandin E2 involves in the hemorrhagic shock induced intestinal dysmotility.

Enhanced cyclooxygenase-2 activity leads to intestinal dysmotility following hemorrhagic shock.

PURPOSE: To test whether hemorrhagic shock (HS) increases the Cyclooxygenase-2 (COX-2) expression in the intestine and whether this enhanced COX-2 expression mediates the intestinal dysmotility after HS. METHODS: Male Wistar rats were randomly divided into HS sham group and HS group. At 180 min following HS establishment, the duodenum samples were harvested to assess the motility function, protein expression of COX-2 and the downstream products of COX-2, prostaglandins. RESULTS: Examination of motility function ex vivo showed that the contractile response to acetylcholine of smooth muscle strips of rats subjected to HS was significantly suppressed. A COX-2 inhibitor, NS-398, abolished this depressed contractile response after HS. Western blotting revealed an increased protein expression of COX-2 in intestinal tissues of HS rats. Immunohistochemical examination indicated that intestine tissues of HS rats were manifested by part of villous expansion and disruption, a large amount of COX-2 positive cells appearance in lamina propria and submucosa. Furthermore, the contents of prostaglandin E2 was significantly increased in intestinal tissues of HS rats. CONCLUSION: The enhanced COX-2/ prostaglandin E2 involves in the hemorrhagic shock induced intestinal dysmotility.