Effect of Pentoxifylline on the Healing of Ischemic Colorectal Anastomoses

Purpose The aim of this study was to evaluate the effect of pentoxifylline on the healing of experimental ischemic colorectal anastomoses. Methods Ninety-three Wistar rats were randomized into three groups (n = 31) and underwent resection of a colonic segment at the colorectal junction. Group A rats received standard end-to-end anastomoses. Ischemic anastomoses were performed in Groups B and C rats by coagulating mesocolon vessels 2 cm along each anastomotic end. Group C rats were treated with intraperitoneal injection of pentoxifylline. Wound complications, intra-abdominal abscesses, intraperitoneal adhesions, and anastomotic leaks and stenosis were recorded. Bursting pressure and tension were calculated. Histologic examination of the anastomosis was also performed. Results Ischemia increased wound and intra-abdominal infections, adhesion formation, and anastomotic stenosis. Anastomotic leakage was significantly higher in Group B (45.2 percent) than in Group A (9.7 percent). Bursting pressure and tension were significantly lower in Group B (118.19 mmHg and 48.43 N/m) than in Group A (191.84 mmHg and 86.82 N/m). There was evidence for decreased perianastomotic fibrosis and neutrophils presence after induced ischemia and a strong tendency to reduced neovascularization. Pentoxifylline administration ameliorated the effects of ischemia, reducing wound and intra-abdominal infections, adhesion formation, and leaks (16.1 percent). Anastomotic strength increased (bursting pressure and tension of 205.55 mmHg and 87.68 N/m, respectively). Treated Group C had significantly higher neutrophils infiltration and fibrosis formation and a strong tendency to increased neovascularization compared with Group B. Conclusions Selective anastomotic devascularization induces ischemia and impairs experimental anastomotic healing, increasing leakage rate. These effects may be ameliorated by pentoxifylline administration. Supported by a grant from the “Servicio Andaluz de Salud,” Consejería de Salud, Junta de Andalucía.     

Pancreatic tuberculosis with duodenal fistula

Tuberculosis is a common infection worldwide. In developed countries, the incidence of this disease was low until a few years ago. However, due to the rise in immigration and HIV infection, the frequency of tuberculosis has recently shown a marked increase. Although the most frequent location of tuberculosis infection continues to be respiratory, infection in other sites, such as musculoskeletal, genitourinary, neurological and abdominal areas, has recently become more common. Abdominal infection, the most frequently described extrapulmonary localization, commonly affects the spleen, liver, ileocecal region, peritoneum, and regional lymph nodes. Tuberculosis of the pancreas is considered a rare entity.     

Is it time to rethink the expanded-access programs for HIV infection?

The purpose of expanded-access programs (EAPs) for antiretroviral therapy has been to allow patients without alternative treatment options to obtain drugs before formal Food and Drug Administration approval. Given the dramatic changes that have occurred in antiretroviral therapeutic approaches during the past 2 decades, we wish to review the history of antiretroviral EAPs and to propose an updated model for expanded access that would achieve maximal patient benefit and add useful knowledge that could guide treatment decisions in patients infected with multidrug-resistant human immunodeficiency virus.     

The Medecins Sans Frontieres intervention in the Marburg hemorrhagic fever epidemic, Uige, Angola, 2005. II. lessons learned in the community

From 27 March 2005 onwards, the independent humanitarian medical aid agency Medecins Sans Frontieres, together with the World Health Organization, the Angolan Ministry of Health, and others, responded to the Marburg hemorrhagic fever (MHF) outbreak in Uige, Angola, to contain the epidemic and care for those infected. This response included community epidemiological surveillance, clinical assessment and isolation of patients with MHF, safe burials and disinfection, home-based risk reduction, peripheral health facility support, psychosocial support, and information and education campaigns. Lessons were learned during the implementation of each outbreak control component, and the subsequent modifications of protocols and strategies are discussed. Similar to what was seen in previous filovirus hemorrhagic fever outbreaks, the containment of the MHF epidemic depended on the collaboration of the affected community. Actively involving all stakeholders from the start of the outbreak response is crucial.     

Cellular cofactors affecting hepatitis C virus infection and replication

Recently identified hepatitis C virus (HCV) isolates that are infectious in cell culture provide a genetic system to evaluate the significance of virus-host interactions for HCV replication. We have completed a systematic RNAi screen wherein siRNAs were designed that target 62 host genes encoding proteins that physically interact with HCV RNA or proteins or belong to cellular pathways thought to modulate HCV infection. This includes 10 host proteins that we identify in this study to bind HCV NS5A. siRNAs that target 26 of these host genes alter infectious HCV production >3-fold. Included in this set of 26 were siRNAs that target Dicer, a principal component of the RNAi silencing pathway. Contrary to the hypothesis that RNAi is an antiviral pathway in mammals, as has been reported for subgenomic HCV replicons, siRNAs that target Dicer inhibited HCV replication. Furthermore, siRNAs that target several other components of the RNAi pathway also inhibit HCV replication. MicroRNA profiling of human liver, human hepatoma Huh-7.5 cells, and Huh-7.5 cells that harbor replicating HCV demonstrated that miR-122 is the predominant microRNA in each environment. miR-122 has been previously implicated in positively regulating the replication of HCV genotype 1 replicons. We find that 2'-O-methyl antisense oligonucleotide depletion of miR-122 also inhibits HCV genotype 2a replication and infectious virus production. Our data define 26 host genes that modulate HCV infection and indicate that the requirement for functional RNAi for HCV replication is dominant over any antiviral activity this pathway may exert against HCV.