Evidence for a protective role of trimetazidine during cold ischemia: targeting inflammation and nephron mass

Ischemia-reperfusion injury (IRI) is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria plays a central role in this process. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in HEH after 24 hr and particularly 48- and 72-hr cold storage than in CEL and UW. TMZ improved the preservation quality when added to the different solutions tested, particularly after 48- and 72-hr cold storage. Interstitial fibrosis and tubular atrophy were reduced in HEH with TMZ. CD4(+) T-cell infiltration was also modulated by the preservation conditions. Peripheral-type benzodiazepine receptor (PBR) positive cells infiltration was also modulated by preservation conditions. TMZ was efficient to reduce IRI when added in the various preservation solutions. These results suggest that protection of the mitochondrial function should be a major target to limit IRI. In addition, this study outlines the role of CD4(+) T cells and PBR expression in inflammatory responses after IRI.     

Assessment of the PKU card as a retrospective index of neonatal blood lead status.

PKU cards were obtained for 50 one-year-old children whose cord blood lead, maternal blood lead and household water lead were known. These 3 values are known to correlate well. Lead values were measured from the blood on the cards, and correlated significantly with the other values. However, predictive validity was poor due to card contamination and it is felt that, for the individual patient, this is not a reliable retrospective index of blood lead at the time of birth.     

Preservation of pancreatic islets in cold UW solution before transplantation

Culture of islets prior to transplantation needs to be revisited for maintaining functional islet capacity. This study was conducted to compare cold UW (University of Wisconsin) preservation with conventional culture based on insulin secretory capacity in vitro and in vivo. Islets isolated from Wistar rats were either cultured for 24 h at 37°C in RPMI1640 medium or DMEM containing various concentrations of glucose or preserved for the same period in UW solution or in DMEM solution at 4°C. The islet yield in UW group, but not in other groups, was maintained as comparable with that of fresh islets. Insulin secretory capacity in response to glucose was maintained only in the islets of UW group, but not in other groups. SCID mice given 300 IEQ islets of UW group showed gradual restoration of normoglycemia as found in the mice given freshly isolated islets. Meanwhile, those mice given cultured islets for 24 h at 37°C in RPMI1640 medium showed rapid decrease of blood glucose levels on day 1 followed by relatively elevated levels on day 2, suggesting unstable insulin secretory capacity of islets.

Morphological staining with anti-HMGB1 (high mobility group B1) antibody revealed central damage of islets in all culture groups regardless of glucose concentration and in islets of cold DMEM group, whereas those in the UW group were quite intact. These results suggest that cold preservation in UW solution is simple and beneficial in protecting islets morphologically and functionally before transplantation.     

Clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of hepatocellular carcinoma: a systematic review and meta-analysis

Introduction and ObjectivesBoth external radiotherapy and sorafenib are promising treatments for hepatocellular carcinoma (HCC). Nevertheless, the combined treatment of external radiotherapy and sorafenib has not been widely applied clinically due to potentially adverse effects. This meta-analysis aimed to evaluate the clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of HCC.MethodsPubmed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched. The primary and secondary observation endpoints were the end of survival and incidence of adverse events, respectively. 11 studies involving 664 patients were included in this meta-analysis.ResultsThe results demonstrated that median overall survival (mOS) and median progression-free survival (mPFS) of the external radiotherapy combined with sorafenib (RS) group were 19.45 months and 8.20 months. The one- and two-year survival rates were 0.65 (95%CI: 0.55–0.76) and 0.40 (95%CI: 0.24–0.56). The incidence of adverse events was 0.34 (95%CI: 0.25–0.44).ConclusionsThe findings demonstrated that the survival of the RS group was significantly improved and few severe adverse events were observed. Hence, it can be concluded that external radiotherapy combined with sorafenib is a safe, effective, and promising therapeutic option for HCC.     

Development of the serological response in rabbits infected with Toxocara canis and Toxascaris leonina

The indirect fluorescent antibody test using frozen sections of infective Toxocara canis and Toxascaris leonina eggs, and the enzyme linked immunosorbent assay using homogenized Toxocara canis embryonated egg extract and T canis excretory-secretory products as adsorbed antigens were used to determine the specificity and development of circulating antibodies in rabbits. Frozen sections were subdivided into four morphologically distinct compartments for analysis of the development of the circulating antibody response. The fluid surrounding the larva was the most reactive up to 21 days after infection, and this material was found to be predominantly excretory-secretory in nature. As the infection progressed antibodies directed against ‘somatic’ tissue materials increased. Cross reactions between sera from rabbits infected with T. canis eggs and Toxascaris leonina frozen sections, and rabbits infected with T. leonina eggs and Toxocara canis frozen sections occurred between both the excretory-secretory fluid and somatic components of the infective eggs. These results were substantiated using the enzyme linked immunosorbent assay. When T. canis excretory-secretory antigen was used, an earlier response (peak day 21) was detected than when using T. canis embryonated egg extract (peak day 35). However, cross reactions between T. canis excretory-secretory antigen and sera from rabbits infected with Toxascaris leonina occurred, indicating that the serodiagnosis of visceral larva migrans using Toxocara canis excretory-secretory antigen may still prove unsatisfactory when considering the role of Toxascaris as a possible causative agent.     

A long-term study of the effects of norethisterone on lipoprotein metabolism in menopausal women

Long-term effects of the androgenic progestogen norethisterone on lipoprotein metabolism were studied by measuring lipoprotein concentrations in 21 women during one year on treatment for the relief of climacteric symptoms. There were significant reductions in total serum triglyceride (p less than 0.01), very low density lipoprotein (VLDL) cholesterol (p less than 0.01) and high density lipoprotein (HDL) cholesterol (p less than 0.001) after two months on treatment, all of which were still in evidence after one year. Low density lipoprotein (LDL) cholesterol levels climbed gradually becoming significantly higher than baseline after one year on treatment (p less than 0.01). Comparison of cholesterol concentrations in HDL subfractions in the one year treated subjects with those in a control group of untreated subjects suggests that the fall in HDL cholesterol is due to reductions in both the HDL2 and HDL3 fractions. We conclude that norethisterone adversely affects the important lipoprotein risk factors for coronary heart disease.     

31P-NMR study of cardiac preservation: St. Thomas' Hospital cardioplegic solution versus UW preservation solution

Abstract. Ex vivo cardiac preservation was evaluated by measuring the catabolism of high-energy phosphate (ATP and creatine phosphate, CrP) using ³¹P-NMR spectroscopy. After cardioplegic arrest St. Thomas' Hospital cardioplegic solution (group A), and University of Wisconsin (UW) preservation solution (group B) were tested. The hearts were mounted in the 4.7 T horizontal bore magnet of the NMR spectrometer and were continuously perfused with the test solution under 25 cm H₂O pressure for 6 h at 10°C. Peak heights of the β-phosphate of ATP and CrP were measured and expressed as percentages of the initial value. For both group A and group B, ATP declined less rapidly during preservation than CrP. In group A, ATP remained constant for 60 min while CrP decreased from the onset of preservation. After 6 h of preservation 28.3% of ATP and 24.5% of CrP remained (group A). On the other hand, in group B, levels of both ATP and CrP remained much more stable: CrP did not decrease during the first 3 h of preservation, while ATP started to decrease after 5 h. At the end of preservation 76.1% of ATP and 71.5% of CrP were still present. We conclude that UW solution is superior to St. Thomas' Hospital solution for the preservation of high-energy phosphates during 6 h cardiac preservation with continuous hypothermic low-flow perfusion.