Combination of pre-operative radiotherapy and surgery suppresses local accumulation of collagen and TGF-beta1 in rats

BACKGROUND: The systemic and local tissue repair responses of radiation in combination with surgery are still unclear. We have studied the effect of fractionated pre-operative radiotherapy with or without subsequent laparotomy on collagen accumulation using a rodent model. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats were divided into four groups (eight rats per group): 1) sham radiation and sham laparotomy (control); 2) sham radiation and laparotomy; 3) radiation and sham laparotomy; and 4) radiation followed by laparotomy. Expanded polytetrafluoroethylene (ePTFE) tubes were implanted subcutaneously in the abdominal wall in the radiotherapy field and on the back outside the radiotherapy field day 0. The abdomen (3 cm x 4 cm) was irradiated day 3 (10 Gy) and again day 7 (10 Gy). On day 10, implants were extirpated, laparotomy undertaken in groups 2 and 4 and new ePTFE tubes implanted subcutaneously. The second implants were extirpated on day 20. Implants were analyzed for hydroxyproline, total protein and transforming growth factor-beta1 (TGF-beta1) levels. RESULTS: On day 10, hydroxyproline (P < 0.05) and TGF-beta1 (P < 0.001) were lower in ePTFE tubes in irradiated compared with non-irradiated rats. On day 20, the abdominal ePTFE hydroxyproline remained low (P < 0.001) in animals subjected to laparotomy and pre-operative irradiation while hydroxyproline levels of rats subjected to irradiation only were similar to controls. The effects of radiation on hydroxyproline were confined to the irradiated abdominal area. There was a positive correlation between hydroxyproline and TGF-beta1 levels in the abdominal wall implant day 20 (r = 0.53, P < 0.005). CONCLUSION: A clinically relevant fractionated radiation scheme reduced subcutaneous collagen accumulation pre-operatively and profoundly within the radiation field post-operatively after laparotomy, possibly because of lowered TGF-beta1 levels.     

Circadian blood pressure variation in patients with type 2 diabetes--relationship to macro- and microvascular subclinical organ damage

Aims

To explore the association between nocturnal blood pressure (BP) dipper status and macro- and microvascular organ damage in type 2 diabetes.

Methods

Cross-sectional data from 663 patients with type 2 diabetes, aged 55–66 years, were analysed. Nurses measured office BP and ambulatory BP during 24 h. Individuals with ≥10% difference in nocturnal systolic blood pressure (SBP) relative to daytime values were defined as dippers. Non-dippers were defined as <10% nocturnal decrease in SBP. Estimated glomerular filtration rate (GFR) was calculated and microalbuminuria was measured by albumin:creatinine ratio (ACR). Aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries.

Results

We identified 433 dippers and 230 subjects with a nocturnal non-dipping pattern. Nocturnal SBP dipping was independently of office SBP associated with decreased PWV (p = 0.008), lower ACR (p = 0.001) and NT-proBNP (p = 0.001) and increased GFR (p < 0.001).

Conclusions

We conclude that diurnal BP variation provides further information about early macro- and microvascular subclinical organ damage that goes beyond standardized office BP measurements in patients with type 2 diabetes.     

P-selectin glycoprotein ligand-1-mediated leukocyte recruitment regulates hepatocellular damage in acute obstructive cholestasis in mice

Objective  

Leukocytes mediate hepatocellular injury in obstructive cholestasis. The aim of the present study was to define the role of P-selectin glycoprotein ligand-1 (PSGL-1) in cholestasis-induced leukocyte recruitment and liver damage.     

Protective effect of fasudil, a Rho-kinase inhibitor, on chemokine expression, leukocyte recruitment, and hepatocellular apoptosis in septic liver injury

Rho-kinase signaling regulates important features of inflammatory reactions. Herein, we investigated the effect and mechanisms of action of the Rho-kinase inhibitor fasudil in endotoxemic liver injury. C57/BL/6 mice were challenged with lipopolysaccharide (LPS) and D-galactosamine, with or without pretreatment with the Rho-kinase inhibitor fasudil. Six hours after endotoxin challenge, leukocyte-endothelium interactions in the hepatic microvasculature were studied by use of intravital fluorescence microscopy and tumor necrosis factor alpha (TNF-alpha); CXC chemokines as well as liver enzymes and apoptosis were determined. Administration of fasudil reduced LPS-induced leukocyte adhesion in postsinusoidal venules and sequestration in sinusoids. Moreover, we found that fasudil abolished extravascular infiltration of leukocytes as well as production of TNF-alpha and CXC chemokines in the liver of endotoxemic mice. Liver enzymes and hepatocellular apoptosis were markedly reduced, and sinusoidal perfusion was improved significantly in endotoxemic mice pretreated with fasudil. Our novel data document that fasudil is a potent inhibitor of endotoxin-induced expression of TNF-alpha and CXC chemokines as well as leukocyte infiltration and hepatocellular apoptosis in the liver. Based on the present findings, it is suggested that inhibition of the Rho-kinase signaling pathway may be a useful target in the treatment of septic liver injury.     

In-hospital cardiac arrest--an Utstein style report of seven years experience from the Sahlgrenska University Hospital

BACKGROUND: In-hospital cardiac arrest is one of the most stressful situations in modern medicine. Since 1997, there has been a uniform way of reporting - the Utstein guidelines for in-hospital cardiac arrest reporting. MATERIAL AND METHODS: We have studied all consecutive cardiac arrest in the Sahlgrenska University Hospital (SU) between 1994 and 2001 for who the rescue team was alerted in all 833 patients. The primary endpoint for this study was survival to discharge. RESULTS: Thirty-seven percent survived to hospital discharge. Among patients who were discharged alive, 86% were alive 1 year later. The survivors have a good cerebral outcome (94% among those who were discharged alive had cerebral performance category (CPC) score 1 or 2). The organization at SU is efficient; 80% of the cardiac arrest had CPR within 1 min. Time from cardiac arrest to first defibrillation is a median of 2 min. Almost two-thirds of the patients were admitted for cardiac related diagnoses. CONCLUSION: The current study is the largest single-centre study of in hospital cardiac arrest reported according to the Utstein guidelines. We report a high survival for in-hospital cardiac arrest. We have pointed out that a functional chain of survival, short intervals before the start of CPR and defibrillation are probably contributing factors for this.     

Characteristics and outcome of false cardiac arrests in hospital

BACKGROUND: Not all hospitalised patients with symptoms of a presumed or threatened cardiac arrest, for whom the rescue team is alerted, eventually suffer a cardiac arrest. This article aims to describe the characteristics and outcome of "false cardiac arrests". METHODS: All patients hospitalised at Sahlgrenska University Hospital for whom the rescue team was alerted between 1 November 1994 and 15 October 2002 were included. RESULTS: In all, there were 1538 calls for the rescue team, of which 70% were caused by cardiac arrest, 9% by respiratory arrest and 21% by "other causes". Survival to discharge was 36% among patients with cardiac arrest, 64% among patients with respiratory arrest and 77% among patients with "other reasons for calling" (p<0.0001 for trend). Among survivors, a cerebral performance categories (CPC) score of 1 at hospital discharge was found in 83% of those with a cardiac arrest, 59% with respiratory arrest and 82% with other reasons for calling (NS for trend). CONCLUSION: Among patients at a Swedish university hospital for whom the rescue team was alerted, about one-third have a "false cardiac arrest". These patients had a survival rate which was about twice that of patients with a "true cardiac arrest". However, among survivors, cerebral function at discharge was similar, regardless of "false" or "true" cardiac arrest.     

Rose Hip and Lactobacillus plantarum DSM 9843 Reduce Ischemia/Reperfusion Injury in the Mouse Colon

Ischaemia/reperfusion (I/R) of the colon is an inflammatory condition that leads to tissue injury where reactive oxygen species play a central role. Rose hip is rich in biologically active polyphenols with antioxidative properties, which may be important in prevention of lipid peroxidation. L. plantarum DSM 9843 possesses enzymatic activity towards polyphenols. The objective of this study was to define the effect of oral administration of L. plantarum and rose hip in I/R injury. Administration of rose hip and L. plantarum significantly decreased MDA levels in caecum tissue and Enterobacteriaceae counts in caecum stool. A positive correlation between MDA levels and Enterobacteriaceae counts was found. The results support a synergistic/additive role of rose hip and L. plantarum in reducing lipid peroxidation. Therefore rose hip and L. plantarum may be used as a pretreatment to tissue injuries, e.g. colonic surgery, organ transplantation and vascular surgery.