A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics

Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL‐17A compared to control mice that resulted in an IL‐17/IFN‐γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL‐10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL‐10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL‐10/IFN‐γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.     

An acute abdominal syndrome reveals a postoperative ilio-iliac arteriovenous fistula: about one case

Introduction

Postoperative ilio-iliac arteriovenous fistula is an unusual but known complication after lumbar surgery.

Case report

We report the case of a 74-year-old patient consulted at the emergency department for intense acute abdominal syndrome revealing a post-operative common ilio-iliac arteriovenous fistula 5 years after a lumbosacral arthrodesis L3–S1. The patient was treated with an endovascular arterial stent-graft with immediate vascular and clinical results.

Conclusion

Arteriovenous fistula is a possible etiology of acute abdominal syndrome in patients with lumbar or abdominopelvic surgery history.

     

Evidence for a limited role of NAD(P)H in the nutritional regulation of glucagon release: Studies with menadione and NH4Cl

Summary Menadione and NH₄Cl were reported to lower the islet content of reduced pyridine nucleotides. They were used to investigate the possible significance of NAD(P)H in the regulation of glucagon release by glucose and arginine. Menadione (10–25 μmol/l) enhanced arginine-stimulated glucagon release at a low glucose concentration (3.3 mmol/l), but failed both to affect glucagon secretion in the sole presence of glucose (3.3 mmol/l) and to suppress the inhibitory action of glucose 11.1 mmol/l upon glucagon output. In contrast to menadione, NH₄Cl inhibited arginine-stimulated glucagon release at the low glucose concentration. The inhibitory action of glucose in high concentration upon glucagon release was not suppressed by NH₄Cl. These findings do not permit to extrapolate to the A₂-cell the concept that reduced pyridine nucleotides represent a major coupling factor in the nutritional regulation of hormonal release.     

Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: Regulation of HSP90-binding activity of FKBP52

FKBP52 (HSP56, p59, HBI) is the 59-kDa immunosuppressant FK506-binding protein and has peptidyl prolyl isomerase as well as a chaperone-like activity in vitro. FKBP52 associates with the heat shock protein HSP90 and is included in the steroid hormone receptor complexes in vivo. FKBP52 possesses a well conserved phosphorylation site for casein kinase II (CK2) that was previously shown to be associated with HSP90. Here we examined whether FKBP52 is phosphorylated by CK2 both in vivo and in vitro. Recombinant rabbit FKBP52 was phosphorylated by purified CK2. We expressed and purified deletion mutants of FKBP52 to determine the site(s) phosphorylated by CK2. Thr-143 in the hinge I region was identified as the major phosphorylation site for CK2. A synthetic peptide corresponding to this region was phosphorylated by CK2, and the peptide competitively inhibited the phosphorylation of other substrates by CK2. The [³²P]phosphate labeling of FKBP52-expressing cells revealed that the same site is also phosphorylated in vivo. FK506 binding to FKBP52 did not affect the phosphorylation by CK2 and, conversely, the FK506-binding activity of FKBP52 was not affected by the phosphorylation. Most importantly, CK2-phosphorylated FKBP52 did not bind to HSP90. These results indicate that CK2 phosphorylates FKBP52 both in vitro and in vivo and thus may regulate the protein composition of chaperone-containing complexes such as those of steroid receptors and certain protein kinases.     

Disentangling the influence of neighborhood and individual characteristics on early residential mobility among newly diagnosed patients with schizophrenia: a multilevel analysis

Purpose

Early residential mobility of schizophrenic patients may relate to discontinuity of treatment and adverse outcome. However, factors influencing early residential mobility of these patients are still poorly examined. The aim of this study was to disentangle the influence of individual and neighborhood characteristics on early residential mobility of schizophrenic patients.

Methods

The study used administrative data of 13, 400 individuals newly diagnosed with schizophrenia in Quebec between 2001 and 2002. These individuals were nested in 163 different health territories. Multilevel analyses were used to assess the contribution of individual and neighborhood characteristics on early residential mobility.

Results

The final model indicates that at the individual level, being men, wonder patients and physical comorbidity increased the likelihood of early residential mobility whereas older patients were less likely to migrate earlier. The health territory level explains about 7 % of the variation of early residential mobility and variables influencing residential mobility at this level are the fourth and the third quartiles of the population density.

Conclusions

Factors influencing early residential mobility of schizophrenic patients are located at both individual and neighborhood levels. This suggests that policies targeting only one-level factors are unlikely to significantly delays early residential mobility.     

Distribution of preproenkephalin,preprotachykinin A,and preprodynorphin mRNAs in the rat nucleus accumbens: Effect of repeated administration of nicotine

The effects of a repeated treatment with nicotine on the expression of mRNAs encoding preproenkephalin (PPE), preprotachykinin-A (PPT-A), and preprodynorphin (PPDYN) were examined by in situ hybridization histochemistry in various subregions of the nucleus accumbens (Acb). In saline-treated rats, optical density measurements on autoradiographic films showed marked anteroposterior decreasing gradients for PPE and PPT-A mRNAs in the rostral pole and the core, in the cone, and in the ventral shell of the Acb, whereas a lower anteroposterior gradient was observed for PPDYN mRNA signals. The intensity of the three mRNA signals also varied according to Acb subregion. However, analysis of percentages of prepropeptide mRNA-containing neurons as compared to total neurons showed, in the rostral pole, the core, and the cone, a similar percentage of PPE mRNA (around 45%)- and PPT-A mRNA (around 40%)- expressing neurons. The ventral shell can be distinguished from the other subregions by a lower percentage of PPE mRNA (35.8%)- and PPT-A mRNA (30.6%)-expressing neurons. The percentage of PPDYN mRNA-containing neurons, by contrast, was similar (around 37%) in the core, the cone, and the ventral shell. Repeated nicotine administration increases the PPE mRNA level in the rostral pole and the anterior third of the core without any change in PPT-A and PPDYN mRNA levels in the various Acb subregions examined. The PPE mRNA increase does not support an effect mediated through an interaction of nicotine with DA neurons. The effect could be linked to a nicotine activation of other afferents to the anterior Acb and/or to a direct nicotine stimulation of PPE mRNA neurons. © 1996 Wiley-Liss, Inc.