OBJECTIVETo investigate changes in apoptosis-related ligands in serum in rats with severe scald and the effect of intensive insulin therapy on the changes.

METHODSOne hundred and fifty Wistar rats were randomly divided into 3 groups: sham burn (SB), scald (S) and treatment (T) groups. Rats in S and T groups were inflicted with 40% TBSA full-thickness burn, followed by intraperitoneal injection with 40 mL/kg of isotonic saline for resuscitation. Rats in T group were subcutaneously injected insulin in a dose of 0.25 U/100 g 24 hours after burn injury, and every 12 hours for 5 days (0.25, 0.50, 0.75, 1.00, 1.25 U/100 g each day, respectively) to control the level of blood glucose between 3 and 6 mmol/L. Rats in SB group were sham scalded at 37 degrees C without resuscitation. Blood was drawn from abdominal aorta on 1, 4, 7, 10, 14 post burn day (PBD) for determination of serum levels of TNF-alpha, soluble Fas ligand (sFasL) and soluble Fas receptor (sFas) by enzyme-linked immunosorbent assay (ELISA), and insulin by radioimmunity assay (RIA).

RESULTSThe serum level of TNF-alpha in S group peaked on 1 PBD (30.9 +/- 8.7) ng/L, which showed statistically significant difference when compared with that of SB and T groups (12.7 +/- 2.8) ng/L, (16.8 +/- 4.7) ng/L, respectively, P < 0.01), then lowered gradually to become similar to that of SB group on 7 PBD. The level of TNF-alpha in T group increased gradually, but was obviously lower than that of S group on 1, 4, 7 PBD (P < 0.01). The level of sFasL in S (on 7-14 PBD) and T (4-10 PBD) groups was significantly higher than that in SB group (P < 0.05), then lowered to normal level. The levels of sFas on 4-10 PBD in T group were obviously higher than that in S and SB group (P < 0.05). Ratio of sFasL to sFas in serum of S group was higher than that in SB group on 7, 10 PBD, which was higher than that in T group on 7 PBD (P < 0.05). There was significant decrease in serum level of insulin in S group compared with that of SB group on 4-10 PBD (P < 0.05). The level of insulin in T group increased on 1 PBD, peaked on 4 PBD (327 +/- 15 microU/mL), which was significantly higher than that in SB and S groups (42 +/- 15, 28 +/- 10 microU/mL, respectively, P < 0.01), then decreased gradually to normal level.

CONCLUSIONSInsulin may inhibit apoptosis after burn by down-regulating secretion of apoptotic ligands.

Animals ; Apoptosis ; Blood Glucose ; analysis ; Burns ; blood ; drug therapy ; Fas Ligand Protein ; blood ; Insulin ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood ; fas Receptor ; blood

BACKGROUND/AIMS: Apoptosis via Fas/FasL system is thought to be involved in the development of hepatocyte death in viral hepatitis B. In chronic hepatitis C, sFas/sFasL system was reported to control liver injury induced by Fas/FasL mediated apoptosis. To determine the role of sFas/sFasL system in chronic hepatitis B, we analyzed serum sFas/sFasL in 58 HBV patients and 29 healthy controls. METHODS: HBV patients were categorized into two groups; normal ALT (< or =40 IU/L) and elevated ALT (>40 IU/L). Serum sFas/sFasL levels in HBV patients were measured by ELISA and was compared with those in 29 healthy controls. Serum ALT levels, histological activity, and Fas/FasL expression of liver were compared. RESULTS: Chronic hepatitis B patients with elevated ALT had significantly higher serum sFas levels than those in healthy controls (P<0.01). Serum sFasL levels, however, were significantly lower than those in healthy controls (P<0.01). Patients with moderate to marked degree of inflammation and fibrosis had significantly higher serum sFas levels than those in healthy controls (P<0.05). Serum sFasL levels had no correlation with the hepatic histological activity. Serum sFas/sFasL levels also had no significant correlation with the Fas/FasL expression of liver. CONCLUSIONS: Serum sFas/sFasL levels play a possible role in the pathogenesis of chronic hepatitis B. These results suggest that serum sFas levels might serve as a marker for estimating the degree of hepatic histological activity.
Adult ; Antigens, CD95/analysis/*blood ; Fas Ligand Protein/analysis/*blood ; Female ; Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/*diagnosis ; Humans ; Male ; Middle Aged

Animals ; Apoptosis ; Blood Glucose ; analysis ; CD8 Antigens ; analysis ; Diabetes Mellitus, Type 1 ; pathology ; Fas Ligand Protein ; Female ; Insulin ; analysis ; Islets of Langerhans ; pathology ; Membrane Glycoproteins ; physiology ; Mice ; Mice, Inbred NOD ; fas Receptor ; physiology

OBJECTIVETo investigate the effect of Astragalus injection (AI) on plasma levels of apoptosis-related factors in aged patients with chronic heart failure (CHF).

METHODSSeventy-two CHF patients were randomly divided into the AI group (36 cases) treated with AI and the control group (36 cases) treated with conventional treatment. Plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays (ELISA) with monoclonal anti-human antibodies. Besides, New York Heart Association (NYHA) grading was assessed according to improved symptoms and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were assessed by echocardiogram after 4 weeks of treatment.

RESULTSAfter 4 weeks of treatment, NYHA grading was markedly improved in the two groups, but it was significantly better in AI group than that in the control group (P < 0.05). As compared with the control group, sFas, sFasL, TNF-alpha and IL-6 in the AI group were obviously lower, the difference between the two groups and between before and after treatment were significant (P < 0.05 or P < 0.01). Moreover, in AI group, LVESV and LVEDV decreased, LVEF increased, which was significantly different than that before treatment (P < 0.05), respectively.

CONCLUSIONAI could lower plasma levels of apoptosis-related factors, and is one of the effective drugs in improving cardiac function in the aged patients with CHF.

Age Factors ; Aged ; Apoptosis ; immunology ; Astragalus Plant ; Fas Ligand Protein ; Female ; Heart Failure ; blood ; drug therapy ; immunology ; Humans ; Injections ; Interleukin-6 ; blood ; Male ; Membrane Glycoproteins ; blood ; Middle Aged ; Phytotherapy ; Plant Preparations ; administration & dosage ; Tumor Necrosis Factor-alpha ; analysis ; Tumor Necrosis Factors ; blood ; fas Receptor ; blood

OBJECTIVETo explore the synergistic protective effect of co-transplanted testicular cells expressing FasL and CsA on survival of islet allografts.

METHODSThe allogeneic islets and testicular cells were co-transplanted into the renal subcapsular space of the diabetic recipients with or without CsA after operation. Allografts survival period and the testicular cells or islets function were analyzed.

RESULTSThe mean survival period of control group was 4.6 +/- 1.1 days. When CsA was administered after transplantation, the mean survival period of islet allografts, (21.8 +/- 4.7) days, was significantly longer than that of control group (P < 0.01). When islets were co-transplanted together with 1 x 10(7) testicular cells (group A), a significant prolongation of graft survival was found (more than 57.5 +/- 4.0 days; P < 0.01 vs. control). But if 1 x 10(7) testicular cells expressing FasL were cultured with FasL-mAb for 30 minutes before co-transplantation (group B), the mean survival period of islet allografts (5.8 +/- 2.6 days), was similar to that in control group, but significantly shorter than that in group A (P < 0.01). When islets and 1 x 10(5) testicular cells were co-transplanted separately into the bilateral renal subcapsular space with CsA (group C), the survival of islet allografts was significantly prolonged in comparison with control group (more than 55.0 +/- 6.5 days; P < 0.01 vs. control), and similar to islets co-transplanted together with 1 x 10(7) testicular cells (group A). When islets were co-transplanted separately with 1 x 10(6) testicular cells without CsA (group D), the mean survival period (11.5 +/- 3.1 days) was shorter than that in group C, but prolonged in comparison to control group (P < 0.05).

CONCLUSIONThe co-transplanted testicular cells expressing FasL with administering CsA post-transplantation can jointly inhibit immune rejection of islet allografts by different mechanism and play a systemic and synergistic protective role to islet allografts.

Animals ; Cyclosporine ; therapeutic use ; Fas Ligand Protein ; Graft Survival ; Immunohistochemistry ; Insulin ; blood ; Islets of Langerhans ; pathology ; ultrastructure ; Islets of Langerhans Transplantation ; Male ; Membrane Glycoproteins ; analysis ; genetics ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sertoli Cells ; metabolism ; transplantation ; Transplantation, Homologous

In order to observe the expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34(+) cells in patients with myelodysplastic syndrome (MDS), and to explore the relation between the expression of these antigens and apoptosis, the expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34(+) cell were evaluated by flow cytometry in 26 patients with MDS including 9 cases of refactory anemia (RA), 1 case of RA with ringed sideroblasts (RAS), 9 cases of RA with excess blasts (RAEB) and 7 cases of RAEB in transformation (RAEB-t), 10 patients with acute myeloid leukemia (AML) and 6 control patients with normal bone marrow. The results showed that the expression of Fas and FasL of CD34(+) cells significantly increased in all types of MDS patients compared with control group (P < 0.01). The expression of Bcl-2 on CD34(+) cells in RAEB and RAEB-t patients was much higher as compared with that in control group (P < 0.01), but there was no significant difference between RA/RAS patients and control group (P > 0.05). The expression rates of Fas on CD34(+) cells were almost identical in all kinds of MDS, but there was significant difference on the expression of Bcl-2 (RA/RAS < RAEB < RAEB-t). Apoptosis of CD34(+) cells significantly increased in RA/RAS and RAEB patients compared with control group (P < 0.01), but there was no difference between RAEB-t and control group. Moreover, apoptosis of CD34(+) cells in control much higher than that in AML group (P < 0.01). There was no correlation between the expression of Fas or FasL and apoptosis on CD34(+) cell of MDS patients. Nevertheless, there was a negative correlation between the expression of Bcl-2 and apoptosis. It is concluded that apoptosis of CD34(+) cells was affected by a lot of factors in MDS, in which Bcl-2 is an important factor of depressing apoptosis. During the progress from MDS to AML, apoptosis changes from overgoing to deficiency in CD34(+) cell.
Acute Disease ; Adult ; Anemia, Refractory, with Excess of Blasts ; blood ; pathology ; Antigens, CD34 ; blood ; Apoptosis ; Biomarkers ; analysis ; Bone Marrow Cells ; immunology ; metabolism ; pathology ; Fas Ligand Protein ; Female ; Flow Cytometry ; Humans ; Leukemia, Myeloid ; blood ; pathology ; Male ; Membrane Glycoproteins ; biosynthesis ; Middle Aged ; Myelodysplastic Syndromes ; blood ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; fas Receptor ; biosynthesis

Adult ; Antibodies, Monoclonal ; pharmacology ; Bronchoalveolar Lavage Fluid ; cytology ; Cells, Cultured ; Cytokines ; biosynthesis ; blood ; secretion ; Fas Ligand Protein ; antagonists & inhibitors ; metabolism ; Humans ; Macrophages, Alveolar ; immunology ; metabolism ; Middle Aged ; Occupational Exposure ; analysis ; Signal Transduction ; Silicon Dioxide ; adverse effects ; Silicosis ; blood ; immunology ; fas Receptor ; antagonists & inhibitors ; metabolism