Effect of artificial cells on hepatic function after ischemia-reperfusion injury in liver

BACKGROUND: The liver suffers from ischemia/reperfusion injury during transplantation. Reactive oxygen species generated by xanthine oxidase during reperfusion of the ischemic liver may be partially responsible for the hepatic injury. Oxygen free radicals are removed by antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. Using glutaraldehyde and lysine we constructed crosslinked hemoglobin, containing SOD and catalase, and assessed its ability to protect against ischemia/reperfusion injury during transplantation. METHODS: In contrast to the sham-operated control groups, blood was exchanged using crosslinked hemoglobin (polyHb) a PolyHb-SOD-catalase (PSC) group. After ischemia/reperfusion injury, several parameters of hepatic damage and oxygen free radicals were measured as well as microscopic examination. RESULTS: Alanine aminotransferase, aspartate aminotransferase, superoxide production, hydrogen peroxide, and malondialdehyde levels were higher among the PolyHb group than sham-operated controls. The PolyHb group revealed a few apoptotic bodies, some acute inflammatory infiltrates in the sinusoids, nuclear fragmentations, cell shrinkage, and chromatin clumping with formation of apoptotic bodies in the apoptotic cells under microscopic examination. Alanine aminotransferase, aspartate aminotransferase, superoxide production, and hydrogen peroxide levels were lower in the PSC than the PolyHb group. Hepatic structures were well preserved in the PSC group. CONCLUSIONS: Reactive oxygen species contribute to hepatic dysfunction with morphologic changes. PSC is effective to reduce hepatic damage by lowering oxygen free radical-mediated injury after ischemia/reperfusion in the liver.     

Effect of epigallocatechin gallate on renal function in cyclosporine-induced nephrotoxicity

INTRODUCTION: Nephrotoxicity is a clinically important side effect of cyclosporine (CsA). CsA-induced nephrotoxicity results from increased production of free radical species in the kidney. Epigallocatechin gallate (EGCG) acts as an antioxidant, thus, EGCG may have a protective effect on the alteration of renal function resultant from oxygen free radicals. The purpose of the present study was to investigate the protective effect of EGCG in a rodent model. METHODS: Experiments were performed on 3 groups. The normal control group (group 1) received normal saline solution. The CsA-treated group (group 2; 15 mg/kg body weight/d for 14 days) received subcutaneous injections. The EGCG-treated group (group 3) in addition received 25 mg of EGCG/kg body weight by intraperitoneal injection. RESULTS: There were significant increases in levels of blood urea nitrogen (BUN)(42.8 +/- 8.2 mg/dL; P < .001), serum creatinine (1.18 +/- 0.60 mg/dL; P < .05), and serum malondialdehyde (3.09 +/- 0.20 nmol/mL; P < .001), and a significant decrease in CCr(0.07 +/- 0.02 mL/min; P < .001) in group 2 compared with group 1. Levels of BUN (30.2 +/- 0.7 mg/dL; P < .01)and CCr (0.12 +/- 0.08 mL/min) were lower in group 3 than in group 2. Serum creatinine (0.71 +/- 0.04 mg/dL) and serum malondialdehyde level (2.13 +/- 0.15; P < .001 nmol/mL) were lower in group 3 than in group 2. There was no significant difference in CsA levels between group 2 (6.86 +/- 1.48 mug/mL) and group 3 (6.69 +/- 0.62 mug/mL). CONCLUSIONS: EGCG treatment significantly protected renal function and free radical-mediated injury in the kidney from CsA-induced changes.     

Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma

Previous studies transferring an intact chromosome 11 into HONE1 cells demonstrated the functional significance of chromosome regions, 11q13 and 11q22-23, in nasopharyngeal carcinoma (NPC) development. In our study the 11q22-23 region was comprehensively re-investigated by detailed microsatellite and single nucleotide polymorphism genotyping and by fluorescence in situ hybridization to map precisely the regions containing tumor suppressive activity. We observed 3 chromosomal intervals within 11q22-23 that were commonly lost in the tumor segregants derived from HONE1/chromosome 11 hybrids. One critical region of 0.36 Mb was mapped near the marker D11S2000 and a second 0.44 Mb region was located around the markers D11S1300 and D11S1391. In a third region high allelic loss was also observed at marker D11S4484, where a newly cloned tumor suppressor gene, TSLC1 (tumor suppressor in lung cancer 1), is located. The gene expression analysis showed absence or low expression levels of TSLC1 mRNA in 4 highly tumorigenic NPC cell lines. In addition, the methylation study results show that the TSLC1 promoter region was hypermethylated in all 4 NPC cell lines and re-expression of the gene occurs in HONE1 cells after 5-aza-2'-deoxycytidine treatment. Hence, the mode of silencing of this candidate TSG in NPC may be attributed to promoter hypermethylation. We have obtained functional evidence for multiple critical tumor suppressive regions in 11q22-23 by fine deletion mapping and for inactivation of TSLC1 being one of these candidate TSGs in NPC development.     

Oligodendrocyte maturation is inhibited by bone morphogenetic protein

Mature oligodendrocytes myelinate axons in the CNS. The development of the myelin sheath is dependent on the proper maturation of oligodendrocytes from precursors cells, a spatially restricted process that is regulated by inductive and repressive cues. Several members of the bone morphogenetic protein family (BMP2 and 4) have been implicated as repressors of oligodendrocyte development in vitro by shifting oligodendrocyte precursors into the astrocyte lineage. We now report on a second role of BMPs in oligodendrocyte development, regulation of myelin protein expression in immature oligodendrocytes. Purified immature rodent oligodendrocytes treated with BMP4 maintained galactocerebroside (GalC) expression, whereas the expression of three key myelin proteins, proteolipid protein (PLP), myelin basic protein (MBP), and 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP), was severely decreased. Paradoxically, BMP-treated oligodendrocytes show increased process extension and complexity, normally a feature of oligodendrocyte maturation. We also investigated whether BMP4 could inhibit myelin protein expression in an E 12.5 mouse explant culture of cervical spinal cord and hindbrain that maintains the in vivo cellular relationships and architecture. Beads soaked in BMP protein implanted into these explants inhibited the expression of myelin proteins, proteolipid protein, and myelin-associated glycoprotein (MAG), in the local area surrounding the bead. Since these explants also contained precursors cells, expression of galactocerebroside and O4, an oligodendrocyte marker, were also decreased by BMP treatment but to a much lesser degree than the myelin markers. Together, these data indicate that BMPs have multiple roles in oligodendrocyte development. At earlier stages, they affect cell lineage decisions and at later stages, they inhibit cell specialization.     

Polymeric complexes of lidocaine hydrochloride with poly(acrylic acid) and poly(2-hydroxyethyl vinyl ether)

The specific interactions of local anesthetic lidocaine hydrochloride with poly(acrylic acid) and poly(2-hydroxyethyl vinyl ether), as well as in a triple system composed of the drug and both polymers, have been studied in aqueous solutions by viscometric, turbidimetric, potentiometric, and FTIR spectroscopic methods. The mechanism of the drug binding to the polymers and the structures of the polycomplexes formed are clarified.     

Vulnerable atherosclerotic plaque: clinical implications

Coronary Artery Disease (CAD) remains globally the leading cause of death and long-term morbidity. Among the many manifestations of CAD, acute coronary syndrome (ACS), ranging from unstable angina to acute myocardial infarction, is the most catastrophic event due to our inability to predict its occurrence. Despite improved treatments of CAD, ACS results in sudden death or permanent disability in a substantial percentage of patients. If we could predict the timing of ACS or better yet prevent its occurrence, we could alter the otherwise unfavorable course of CAD. Several studies have convincingly demonstrated that majority of all ACS develops from previously mild to moderate stenoses. Thus, based on these and autopsy studies, sudden disruption or rupture of the non-obstructive "vulnerable" atherosclerotic lesion is currently considered the cause of ACS. Recent clinical studies have substantiated earlier autopsy observations that plaque vulnerability is a systemic process, involving multiple locations concurrently. Although the exact inciting factors of the vulnerable plaque rupture are unknown, inflammation is accepted to be a pivotal event. The possibility of stabilizing the vulnerable plaques has strongly been supported by the lipid lowering trials, in which dramatic reduction of the acute coronary events was noted despite subtle improvements in luminal diameter. Furthermore, antiplatelet therapies have become an important preventative therapy due to the essential role of platelets in the aftermath of plaque rupture. Finally, various imaging modalities to diagnose the plaque vulnerability could help prevent the acute coronary events in the future.     

Mucosa-associated lymphoid tissue lymphoma of the thymus resected using combined thoracoscopic and transcervical approaches

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade variant of B cell lymphoma that arises in extranodal tissue of the gastrointestinal tract, lung, salivary gland, thyroid, or other organ derived from the foregut. However, MALT lymphoma in the thymus is extremely rare. We report a case of thymic MALT lymphoma, extending to the neck, resected using combined thoracoscopic and transcervical approaches. To the best of our knowledge, thoracoscopic management of MALT lymphoma in the thymus has not previous been reported.