Serpin Induced Antiviral Activity of Prostaglandin Synthetase-2 against HIV-1 Replication

The serine protease inhibitors (serpins) are anti-inflammatory proteins that have various functions. By screening a diverse panel of viruses, we demonstrate that the serpin antithrombin III (ATIII) has a broad-spectrum anti-viral activity for HIV-1, HCV and HSV. To investigate the mechanism of action in more detail we investigated the HIV-1 inhibition. Using gene-expression arrays we found that multiple host cell signal transduction pathways were activated by ATIII in HIV-1 infected cells but not in uninfected controls. Moreover, the signal pathways initiated by ATIII treatment, were more than 200-fold increased by the use of heparin-activated ATIII. The most up-regulated transcript in HIV-1 infected cells was prostaglandin synthetase-2 (PTGS2). Furthermore, we found that over-expression of PTGS2 reduced levels of HIV-1 replication in human PBMC. These findings suggest a central role for serpins in the host innate anti-viral response. Host factors such as PTGS2 elicited by ATIII treatment could be exploited in the development of novel anti-viral interventions

Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

BACKGROUND:Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS:We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS:TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition

double injection technique

Long-term intravascular access catheters with reservoirs are a common requirement for cancer patients. Complications resulting from the use of these devices have been studied in several single-institution investigations, the consensus being that they are safe and have a low complication rate. However, extravasation may occur especially in obese patients due to accidental infusion of the subcutaneous tissue. To prevent this problem we describe an easy method that could be an alternative to the widely used ultrasonography-guided injection method

An alternative method for preventing extravasation complications in vascular access catheters with reservoirs for subcutaneous infusion: the double injection technique.

Long-term intravascular access catheters with reservoirs are a common requirement for cancer patients. Complications resulting from the use of these devices have been studied in several single-institution investigations, the consensus being that they are safe and have a low complication rate. However, extravasation may occur especially in obese patients due to accidental infusion of the subcutaneous tissue. To prevent this problem we describe an easy method that could be an alternative to the widely used ultrasonography-guided injection method

in rabbits

Background and Objective: Pleurodesis is a frequently preferred procedure in thoracic surgery, and many factors may affect the process. We aimed to determine whether the administration of systemic diclofenac sodium diminishes the effectiveness of the pleurodesis induced by intrapleural tetracycline in rabbits.Methods: Twelve male New Zealand rabbits that received tetracycline 35 mg/kg intrapleurally were allocated into two groups. The first group (diclofenac group, n=6) received 2 mg/kg diclofenac sodium intramuscularly for 10 days, and the second group (control group, n=6) received acetaminophen 30 mg/kg orally for 10 days after the pleurodesis procedure. The rabbits were sacrificed after 28 days, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis, inflammation, and collagenization.Results: The mean macroscopic pleurodesis score of the diclofenac group was 2.16 +/- 0.40 compared with 2.83 +/- 0.40 in the control group (p=.027). The mean microscopic pleurodesis score of the diclofenac group was 2.3 +/- 1.03, whereas it was 3.5 +/- 0.54 in the control group (p=.045).Conclusion: The administration of diclofenac sodium for 10 days following tetracycline pleurodesis reduces the effectiveness of pleurodesis in rabbits

model

Background: Despite its advantages, iatrogenic gallbladder perforation with resultant spillage of bile and gallstones is not uncommon during laparoscopic cholecystectomy. Although this is not generally considered a significant problem, spilled gallstones may cause problems even years after the operation. Hyaluronic acid has been introduced into clinical practice and successfully used to decrease postoperative adhesions after abdominopelvic surgery. In this study, we investigated the effectiveness of a hyaluronic-acid derivative in preventing complications related to spilled gallstones and bile leakage in an experimental study.Methods: In 60 Wistar-Albino rats, an upper-midline abdominal incision was made, and the rats were divided into 5 groups (n = 12 in each group) as follows: group I = laparotomy alone; group II = laparotomy and intraperitoneal instillation of sterile bile plus gallstones; group III = laparotomy and instillation of infected bile and gallstones; group IV = laparotomy and instillation of sterile bile and gallstones plus hyaluronic acid; and group V = laparotomy and instillation of infected bile and gallstones plus HA. A second-look laparotomy was performed on postoperative day 10 to assess intraperitoneal adhesions and abscesses. Intraperitoneal adhesions were scored, and breaking strengths of gallstones were measured.Results: Adhesion scores were significantly higher in groups II and III compared with groups I, IV, and V (P < 0.05). There was a statistically significant decrease in breaking strengths and adhesion scores in groups IV and V compared with groups II and III (P < 0.001).Conclusions: Whether infected or not, spilled gallstones and bile caused postoperative adhesions in this experimental model. An HA derivative significantly prevented postoperative adhesions and decreased breaking strengths. Further clinical studies are needed to validate these findings. (C) 2004 Excerpta Medica, Inc. All rights reserved.C1 Pamukkale Univ, Sch Med, Dept Gen Surg, Denizli, Turkey

postoperative adhesions in experimental secondary peritonitis

Background: The effect of relaparotomies and temporary abdominal closure on colonic anastomoses and postoperative adhesions is under debate.Methods: In the experiments reported here, colonic anastomosis was constructed 24 hours after cecal ligation and puncture in rats that were divided into three groups of eight animals each. The abdomen was closed primarily in groups I and II, and a Bogota bag was used for abdominal closure in group III. At 24 hours following anastomosis, relaparotomy was performed only in group II and III rats, and the abdomen was closed directly in group II; after removal of the Bogota bag in group III animals, the abdomen was closed directly. On the fifth day of anastomotic construction, bursting pressures and tissue hydroxyproline content of the anastomoses, along with peritoneal adhesions, were assessed and compared.Results: Mean anastomotic bursting pressures and hydroxyproline contents did not differ among the groups. Median adhesion scores were significantly higher in group III than the other two groups.Conclusions: Relaparotomy and the type of temporary closure have no negative effect on anastomotic healing in rats with peritonitis. Temporary abdominal closure with a Bogota bag caused a significantly high rate of adhesions

ischemia-reperfusion injury on healing of colonic anastomoses

Background: Antithrombin III is known as the most important natural inhibitor of thrombin activity and has been shown to attenuate local harmful effects of ischemia-reperfusion injury in many organs. In recent animal studies, delaying effect of remote organ ischemia-reperfusion injury on healing of intestinal anastomoses has been demonstrated. In this study, we investigated whether antithrombin III reduces deleterious systemic effects of ischemia-reperfusion injury on healing of colonic anastomoses in rats.Methods: Anastomosis of the left colon was performed in 24 rats that were divided into three groups: sham operated control (group 1, n = 8), 30 minutes of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group 11, n = 8), antithrombin III treated group (250 U/kg before and after the ischemia-reperfusion, group III, n = 8). On postoperative day 6, all animals were sacrificed, and bursting pressure and tissue hydroxyproline content of the anastomoses were assessed and compared.Results: On postoperative day 6 the mean bursting pressures were 149.6 +/- 4.8, 69.8 +/- 13.5, and 121.8 +/- 8.7 mm Hg for groups I, II, and III, respectively (P = 0.000). Mean tissue hydroxyproline concentration values were 389.5 +/- 29.6, 263.1 +/- 10.0, and 376.0 +/- 33.8 mug/mg for groups I, II, III respectively (P = 0.005).Conclusions: This study showed that, antithrombin III treatment significantly prevented the delaying effect of remote organ ischemia-reperfusion injury on anastomotic healing in the colon. Further clinical studies are needed to clarify whether antithrombin may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where remote organ ischemia-reperfusion injury takes place. (C) 2002 Excerpta Medica, Inc. All rights reserved

bleeding - Report of a case

PURPOSE: Ectopic prostatic tissue at various sites within and outside the genitourinary system has been reported previously. A case of ectopic prostatic tissue located in the anal canal causing rectal bleeding is presented. METHOD: The patient was referred to our clinic with rectal bleeding. At rectal examination a bleeding sessile polypoid mass 2.5 cm in size was found in anal canal and removed surgically. RESULTS: Histopathologic and immunohistochemical staining of the specimen confirmed the prostatic nature of the tissue. CONCLUSION: Prostatic heterotopia is significant in several respects. Either it may be an important cause of hematuria or unusually, as in our case, it may cause rectal bleeding. In addition, ectopic tissue may be endoscopically confused with malignancy in either urinary or lower gastrointestinal system. This and other reports may disclose the genesis and significance of this peculiar tissue remnant