Comparison of inflammation biomarkers among chronic obstructive pulmonary disease groups: A cross sectional study.

BACKGROUND: The Global Initiative classification (GOLD) for chronic obstructive pulmonary disease (COPD), which relies on the practical issues of treatment of this complex and heterogeneous disease, may not be reliable in predicting disease severity and prognosis as the term of inflammation is excluded from the definition. AIM: The aim of this study was to determine systemic inflammatory markers in GOLD ABCD groups and to compare these parameters according to clinical and functional features. METHODS: The study included 60 COPD patients and 59 healthy subjects. Comparisons were made with the pulmonary function test, transthoracic echocardiography and the six-minute walk test (6MWT). The COPD assessment test (CAT), modified Medical Research Council (mMRC), and index scores of body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) were recorded. The systemic inflammatory state was assessed using C-reactive protein, fibrinogen, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-18. RESULTS: The levels of all serum inflammatory markers were higher in the COPD group than in the control group. TNF-α and IL-6 were significantly higher in the symptomatic groups (B and D) than in the less symptomatic groups (A and C) (P < 0.05). Spirometric parameters were more severe in Group D, followed by groups C, B and A, respectively. The 6MWT and the BODE scores were worst in Group D, followed by groups B, C and A. CONCLUSION: The results suggest that bronchodilator treatment alone might be insufficient in Group B patients, as the systemic inflammatory markers in addition to exercise capacity and mortality predictors were at the worst level in Groups D and B.

Exposure of embryos to cyclically cold incubation temperatures durably affects energy metabolism and antioxidant pathways in broiler chickens.

Cyclically cold incubation temperatures have been suggested as a means to improve resistance of broiler chickens to ascites; however, the underlying mechanisms are not known. Nine hundred eggs obtained from 48 wk Ross broiler breeders were randomly assigned to 2 incubation treatments: control I eggs were incubated at 37.6°C throughout, whereas for cold I eggs the incubation temperature was reduced by 1°C for 6 h daily from 10 to 18 d of incubation. Thereafter, chickens were reared at standard temperatures or under cold exposure that was associated or not with a postnatal cold acclimation at d 5 posthatch. At hatch, hepatic catalase activity and malondialdehyde content were measured. Serum thyroid hormone and triglyceride concentrations, and muscle expression of several genes involved in the regulation of energy metabolism and oxidative stress were also measured at hatch and 5 and 25 d posthatch. Cold incubation induced modifications in antioxidant pathways with higher catalase activity, but lower expression of avian uncoupling protein 3 at hatch. However, long-term enhancement in the expression of avian uncoupling protein 3 was observed, probably caused by an increase in the expression of the transcription factor peroxisome proliferator activated receptor-γ coactivator-1α. These effects were not systematically associated with an increase in serum triiodothyronine concentrations that were observed only in chickens exposed to both cold incubation and later acclimation at 5 d with cold rearing. Our results suggest that these conditions of cyclically cold incubation resulted in the long-term in changes in antioxidant pathways and energy metabolism, which could enhance the health of chickens reared under cold conditions.

Effect of manipulation of incubation temperature on fatty acid profiles and antioxidant enzyme activities in meat-type chicken embryos.

Eggs (n = 1,800) obtained from Ross broiler breeders at 32 and 48 wk of age were incubated at either a constant temperature of 37.6°C throughout (T1), or the temperature was reduced for 6 h to 36.6°C each day during embryonic age (EA) 10 to 18 (T2). Yolk sac, liver, and brain fatty acid profiles and oxidant and antioxidant status of liver and brain were measured at EA 14, 19, and day of hatch (DOH). Fatty acid profiles of yolk sac, liver, and brain were influenced by age of breeder with significant breeder hen age × incubation temperature interactions. At EA 14, higher levels of 20:4n-6 and 22:6n-3 had been transferred from the yolk sac to T2 embryos from younger than older breeders, whereas for T1 and T2 embryos, yolk sac 20:4n-6 and 22.6n-3 values were similar for older breeders. Accumulation of 20:4n-6 and 22:6n-3 fatty acids in the liver of T1 and T2 embryos from younger breeders was similar; however, T2 embryos from older breeders had higher liver levels of 20:4n-6 and 22:6n-3 than T1 embryos. At EA 19, liver nitric oxide levels were higher for T2 embryos from younger breeders than those from breeders incubated at T1. Brain catalase levels of T2 embryos from younger breeders were higher than those from older breeders at DOH. Thus, changes in fatty acid profiles and catalase and nitric oxide production of brain and liver tissues resulting from 1°C lower incubation temperature from EA 10 to 18 reflect adaptive changes.

Effect of sodium bicarbonate in an experimental model of radiocontrast nephropathy.

AIM: The aim of this study is to investigate the efficacy and mechanism of action of intravenous (IV) bicarbonate in preventing radiocontrast nephropathy (RCN). MATERIALS AND METHODS: Twenty-eight Wistar rats were randomized into four groups including control (group 1), radiocontrast (group 2), bicarbonate (group 3), and radiocontrast plus bicarbonate (group 4). Once blood chemistry and arterial blood gases were examined and 24 h urine samples were collected, all rats were administered furosemide (2 mg/kg subcutaneous) and deprived of water for 24 h. Iothalamate sodium (6 mL/kg) was administered to group 2 and group 4. IV bicarbonate (8.4%) was administered to group 3 and group 4 (3 h before the administration of iothalamate). On the fourth day, 24 h urine was collected, and at the end of the day rats were sacrificed and blood chemistry and arterial blood gases were reexamined. Myeloperoxidase (MPO), nitric oxide (NO), total glutathione, and malondialdehyde were quantified on the renal tissue. H&E slides were examined. RESULTS: Basal creatinine and creatinine clearance were similar between groups. There was no significant difference between creatinine and creatinine clearance by the end of the experiment. Glutathione level in group 2 was lower than in group 4. Histopathologically, there was no injury in the control group (group 1) whereas there was an intermediate-severe injury (71.4%) in the radiocontrast group (group 2). The percentage of intermediate-severe injury was significantly lower (71.4% vs. 28.6%, p = 0.02) in the radiocontrast plus bicarbonate group (group 4). CONCLUSIONS: Sodium bicarbonate attenuates the development of radiocontrast-induced tubular necrosis.

Brooding temperatures for chicks acclimated to heat during incubation: effects on post-hatch intestinal development and body weight under heat stress.

1. The objective was to evaluate the effects of brooding temperature on intestinal development, oxidative organ damage, and performance of chicks acclimated to high temperature during incubation. The effects of acclimation and brooding temperatures on slaughter weights of broilers under heat stress were also investigated. 2. Eggs were incubated at either 378 degrees C (INC(Cont)) or heat-acclimated at 395 degrees C for 6 h daily from d 10 to d 18 of incubation (INC(H)). Brooding temperatures at floor level were set at 32, 335 and 35 degrees C (Bt(32), Bt(335), Bt(35), respectively) for the first 5 d. The temperature was reduced gradually to 30 degrees C from d 6 to d 10. From 21 to 42 d, broilers from INC(Cont) Bt(32) and INC(H) Bt(32) and Bt(35) were divided into two groups; half from each group was exposed to daily cyclic higher ambient temperatures, while the other half was reared at control temperature. 3. INC(H) chicks had lower jejunum, but greater liver and residual yolk sac weights than INC(Cont) chicks on the day of hatching. Although INC(H) chicks from Bt(335) and Bt(35) had lighter body weights than Bt(32) on d 5, no significant differences were observed in the body weight of broilers among treatments at 10 and 21 d. 4. Similar jejunum protein, alkaline phosphatase, maltase, glutathione, and malondialdehyde contents of chicks from INC(Cont) and INC(H) suggested that heat acclimation during incubation has no effect on jejunum enzyme activity or oxidative status of chicks. 5. Taking into account INC(H) Bt(35) chicks having lower T(3) levels on d 5, lower heterophil/lymphocyte (H/L) ratios and similar weights at 42 d under heat stress compared with control broilers, the results suggested that although higher brooding temperatures had no effect on body weights of INC(H) chicks during the brooding period, those broilers may able to cope better with heat stress.

The role of allopurinol on oxidative stress in experimental hyperthyroidism.

AIM: During hyperthyroidism, production of free oxygen radicals derives, where xanthine oxidase may also play an important role. Allopurinol, a xanthine oxidase inhibitor, has a significant effect on thyrotoxicosis-related oxidative stress. However, the relationship between thyroid hormones, oxidative stress parameters and allopurinol remains to be explored. METHODS: Forty-two Wistar albino rats were divided into three groups. Rats in group A served as negative controls, while group B had untreated thyrotoxicosis and group C received allopurinol. Hyperthyroidism was induced by daily 0.2 mg/kg L-thyroxine intraperitoneally in groups B and C; 40 mg/kg allopurinol were given daily intraperitoneally. Efficacy of the treatment was assessed after 72 h and 21 days, by measuring serum xanthine oxidase (XO), malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and nitric oxide derivates (NO*x). RESULTS: In both time periods, serum XO, MDA, GSH and NO*x levels were significantly increased after thyroid hormone induction (p<0.05). Levels of XO, MDA and NO*x decreased with allopurinol treatment (p<0.05). There was a remarkable decrease in triiodothyronine levels in group C after 72 h (p<0.05), and in both triiodothyronine and thyroxine levels in group C after 21 days (p<0.05). There was no difference between groups B and C in means of serum GSH, GR and GPx levels (p>0.05). CONCLUSIONS: This study suggests an association between allopurinol and the biosynthesis of thyroid hormones. Allopurinol prevents the hyperthyroid state, which is mediated predominantly by triiodothyronine and not by XO. This issue has to be questioned in further studies where allopurinol is administered in control subjects.

Infliximab in experimental alkali burns of the oesophagus in the rat.

BACKGROUND: We aimed to investigate the efficacy of infliximab, a chimeric TNF-alpha antibody, in the prevention of fibrosis in an experimental alkaline burn of the oesophagus in the rat. METHODS: Thirty-two Wistar albino rats divided into four experimental groups. Caustic oesophageal burn was induced by applying 37.5% NaOH to the distal oesophagus. Infliximab was given at a dose of 5 mg/kg via the intraperitoneal route. Group A (sham) animals were uninjured, group B had untreated oesophageal burns, group C had oesophageal burns treated with a single dose of infliximab on the first day, and Group D had oesophageal burns treated with infliximab on the first and 14th days. Efficacy of the treatment was assessed on the 28th-day by measuring stenosis index of the oesophagus and histopathological damage score, and biochemically by determining tissue hydroxyproline content. RESULTS: There was no significant difference between the Group B and the infliximab treated Groups C and D in means of tissue hydroxyproline content and histopathological damage scores. Stenosis index was not significantly different between the Group B, Group C, and Group D. CONCLUSION: Anti-TNF-alpha treatment with infliximab does not ameliorate the degree of fibrosis in alkali burns of the oesophagus in the rat. Further evaluation of inflammatory and immunological events leading to stricture in alkaline oesophageal burns may provide new perspectives for the treatment of alkaline oesophageal burns.

The right method for midline laparotomy: what is the best choice for wound healing?

BACKGROUND: The techniques used for midline laparotomy affect healing in surgical wounds, but the relationship between cold scalpel and haemostatic methods (harmonic scalpel, diathermy) regarding wound healing remains unclear. There are also limited studies concerning the effects of harmonic scalpel on abdominal fascia. This study was aimed at comparing myofascial wound healing following laparotomy incision on fascia by cold scalpel (CS), harmonic scalpel (HS), and diathermy in terms of hydroxyproline content, inflammatory changes and tensile strength. MATERIALS AND METHODS: Twenty-seven male Wistar albino rats underwent midline laparotomy either with cold scalpel (CS), harmonic scalpel (HS) or diathermy. Fascia incisions were closed with continuous 4/0 polypropylene and skin incisions were closed with interrupted 4/0 polypropylene stitches. On the 7th postoperative day, the abdominal walls of the rats were tested for tensile strength. In addition, each abdominal fascia was evaluated for inflammation scores and hydroxyproline levels. RESULTS: HS caused less inflammation and necrosis in abdominal fascia compared to the diathermy group (p < 0.01 and p < 0.05, respectively), whereas the CS group showed no difference in inflammation scores, but had significantly lower necrosis scores than the HS and diathermy groups (p < 0.05 and p < 0.001, respectively). Hydroxyproline content of the fascia did not differ among groups, while the tensile strength of the wound was obviously higher in the CS group (p < 0.001). CONCLUSION: HS causes less inflammatory reaction and necrosis than diathermy, but more necrosis than CS. Fascia incisions with CS gains tensile strength faster than in other groups. HS appears to cause less tissue injury than diathermy and also has comparable results for wound healing. Further clinical studies on the impact of HS in fascia incisions are needed.

Urinary calcium excretion in healthy Turkish children.

The aim of this study was to establish the age related reference percentile values for urinary calcium excretion in healthy Turkish children, and to determine the frequency of hypercalciuria and also the factors affecting urinary calcium excretion. A cross-sectional study was performed in Aydin, in western Turkey during winter. Study population was constituted from seventeen districts of this region (sample size was calculated from a formula using the results of the last population census) by stratified and random sampling methods. Urinary calcium excretion was measured as the calcium/creatinine concentration ratio in the second non-fasting urine samples. A total of 2252 children (1132 male) with a mean age of 8.57 +/- 4.44 years (ranged from 15 days to 15 years) were studied. The mean of urinary calcium/creatinine concentration ratio was calculated as 0.092 +/- 0.123. The percentile values between 3rd and 97th for urinary calcium/creatinine concentration ratio according to age were calculated and shown as multiple line graphs. Hypercalciuria prevalence was found as 9.6% when the upper limit of urinary calcium/creatinine concentration ratio was accepted as 0.21. Urinary calcium/creatinine concentration ratio of the children from different districts, altitudes, and ethnic origins were statistically different. Poor negative correlations were found between urinary calcium/creatinine concentration ratio and age and weight. No differences in urinary calcium/creatinine concentration ratios were observed in terms of sexes, diet, physical activity, urolithiasis in the family, symptoms related to hypercalciuria, amount of calcium in drinking water, and urine strip analysis. In conclusion, reference values for urinary calcium/creatinine concentration ratios should be established for children in each country and also in each geographic region.

Nitric oxide as an independent regulatory factor in regenerating rat liver.

Nitric oxide production and lipid peroxidation modulate the proliferating activity of liver cells, but the relationship between enhanced nitric oxide production, lipid peroxidation, and liver regeneration remains unclear. We examined the role of nitric oxide and lipid peroxidation on experimental liver regeneration. Thirty-five male Wistar albino rats underwent a sham operation (I), partial hepatectomy alone (II, IV), partial hepatectomy and daily N-nitro-L-arginine methyl ester (L-NAME) treatment for 24-hrs (III) or 48-hrs (V). Liver tissue concentrations of catalase, nitrite and nitrate, glutathione, and serum levels of alaninaminotransferase and bilirubin were measured. CD34, Ki-67 and proliferating cell nuclear antigen were evaluated in liver samples. Compared with other groups, both of the L-NAME groups had decreased tissue nitric oxide concentrations. Nitrate and nitrite (nitric oxide) concentrations were higher in partial hepatectomy-alone groups, as were CD34 counts and proliferation indexes. Partial hepatectomy elevated catalase, and glutathione levels in all groups compared to the sham-operated controls. In conclusion, nitric oxide inhibition impaired hepatic regeneration following partial hepatectomy. An obvious effect of nitric oxide on lipid peroxidation in the context of hepatocyte and endothelial cell proliferation could not be demonstrated. Thus, while lipid peroxidation could influence some steps in liver regeneration, nitric oxide poses as an independent regulatory factor in regenerating rat liver.

The combined effect of iloprost and N-acetylcysteine in preventing spinal cord ischemia in rabbits.

OBJECTIVES: This study investigated the cytoprotective effects of N-acetylcysteine (NAC) and iloprost on spinal cord ischemia in an experimental model. MATERIALS AND METHODS: Thirty-five (male) New Zealand white rabbits were included in five study groups (n=7, each group). One group served as Sham. Rabbits in other groups had their abdominal aorta cross-clamped just above the iliac bifurcation for 40 min. During aortic cross clamping, iloprost, NAC, both iloprost and NAC or saline (control) were infused. RESULTS: In NAC, iloprost, and iloprost+NAC groups, neurological status of rabbits (Tarlov score) 24 and 48 h after the operation was better than the control group (p<0.01), but worse than the Sham group (p<0.01). There was minimal neuronal damage in the iloprost treated groups compared to the NAC group (p<0.05). Mean viability index values in NAC, iloprost and iloprost+NAC groups were higher than the control group (p<0.01). Viability index in the NAC group was lower than the iloprost and iloprost+NAC groups. CONCLUSIONS: The use of iloprost and NAC may provide better protection from spinal cord ischemia.

Is synchronous bowel anastomosis safe?

In this study, we investigated the effects of synchronous anastomosis on intestinal healing in experimental colonic resection. Sprague-Dawley rats were randomized into 3 groups; control (group I), single anastomosis (group II) and synchronous (double) anastomosis (group III). Single and proximal anastomoses were located 3 cm distal to caecum, and distal anastomoses were done 3 cm distal to them. On the 7th postoperative day, bursting pressure, hydroxyproline level and histology of the anastomotic site were assessed. Bursting pressures and hydroxyproline levels indicated that impaired healing of proximal anastomoses in group III was evident. Proximal anastomoses in group III had the lowest hydroxyproline value and bursting pressure level. Significant fibrosis was observed in the histological examination of distal anastomoses in group III. Double colonic anastomoses is not as safe as single anastomoses and involves additional risk. The healing of proximal anastomosis is significantly altered after experimental synchronous resection.

Pro-inflammatory cytokine response of the fluid contents of spermatoceles and epididymal cysts.

The aim of the study was to determine the cellular contents and concentrations of interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) in fluids of patients with spermatocele or epididymal cyst. Twenty-five symptomatic patients, 14 with epididymal cysts and 11 with spermatoceles, were included in the study. Fluids were obtained during surgical excision of the cysts and cytological smears were stained with May-Gruenwald-Giemsa to establish cell components. The concentrations of IL-6, IL-8 and TNF-alpha were measured by chemiluminescent immunometric assay. Cytological analysis of the fluids demonstrated various sperm forms ranging from immature germ cells to degenerated spermatozoa without inflammatory cells such as neutrophils and macrophages. The concentrations (mean+/- SEM, pg/mg protein) of IL-6, IL-8 and TNF-alpha were 13.52 +/- 1.40, 22.20 +/- 2.43, 3.51 +/- 1.43 in spermatocele fluids and 5.76 +/- 0.48, 11.57 +/- 1.89, 2.53 +/- 0.41 in epididymal cyst fluids. Both IL-6 and IL-8 concentrations in the spermatocele group were higher than in the epididymal cyst group (P < 0.0001). There were no differences in TNF-alpha concentrations between the groups (P > 0.05). These findings indicate that local production of pro-inflammatory cytokines is involved in cyst formation. The presence of immunologic activation in these fluids advocates a policy of selective surgical intervention in patients with spermatocele or epididymal cyst.

Protective effect of vitamin E on gastric mucosal injury in rats with biliary obstruction.

Patients with liver disease display increased susceptibility to gastric mucosal damage. A role of free radicals has been suggested in the development of gastric mucosal damage in normal subjects. The effects of antioxidant vitamin E treatment on the liver and stomach in cirrhotic rats were examined. Fifty rats were divided into three groups. Cirrhosis was induced by bile duct ligation in 40 of 50 rats. Controls underwent a sham operation. Gastric mucosal lesions were produced by intragastric administration of 1 mL of 95% ethanol in all three groups. Twenty bile duct-ligated rats were injected intramuscularly with vitamin E (100 mg/kg/day). Liver and stomach histology, and stomach malondialdehyde and glutathione levels were determined. Portal hypertension was measured. Macroscopic and microscopic gastric mucosal injury were significantly greater in the control and common bile duct-ligated groups than in the vitamin E-pretreated group (P<0.05). The tissue malondialdehyde and glutathione levels were significantly decreased in the vitamin E-administrated group compared with the common bile duct-ligated group (P<0.001). Vitamin E administration may be cytoprotective for both the liver and gastric mucosa in bile duct-ligated rats.

Experimental cirrhosis of the liver and cytoprotective effects of alpha tocopherol.

OBJECTIVE: To investigate whether alpha tocopherol (alpha-T) treatment influences liver cirrhosis induced by carbon tetrachloride (CCl4) in the rat. DESIGN: Laboratory experiment. SETTING: Teaching hospital, Turkey. SUBJECTS: Fifty rats were divided into three groups. Group I consisted of ten controls; Group II: twenty CCl4 induced cirrhotic rats and Group III: twenty cirrhotic rats treated with Vitamin E. INTERVENTIONS: Experimental cirrhosis was induced in rats by subcutaneous administration of 0.4 ml CCl4 (diluted 1:4 with olive oil) per kilogram body weight twice a week for 12 weeks. MAIN OUTCOME MEASURES: Histopathologically evaluation of liver, liver malondialdehyde and glutathione peroxidase levels and aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT) and gamma-glutamyltranspeptidase (GGT) levels. RESULTS: Histopathologic evaluation of liver samples demonstrated cirrhotic changes in CCl4 treated groups. The enzyme levels in Group II were significantly increased (p < 0.05) but it was insignificantly lower in the alpha tocopherol treated group III. In Group II, statistically significant increase in liver malondialdehyde levels was determined (p < 0.001). CONCLUSION: Our results demonstrate that alpha-T administration may protect liver against CCl4 induced cirrhosis.

The protective effect of vitamin E on gastric mucosal injury in rats with cirrhosis of the liver.

OBJECTIVE: To evaluate the functional and morphologic features of stomach in liver cirrhosis model and the cytoprotective effects of Vitamin E. METHODS: Experimental cirrhosis was induced in rats by subcutaneous administration of 0.4 ml CCl4 (diluted 1:4 with olive oil) per kilogram of body weight twice a week for 12 weeks. Rats were divided into three groups. Group 1 was control. Group 2 consisted cirrhotic rats induced by CCl4 and Group 3 cirrhotic rats treated with Vitamin E (intramuscularly 100 mg/kg per day during study). At the end of 12 weeks, gastric mucosal injury was produced by instillation of absolute alcohol via an orogastric tube. After 3 hours, each animal was sacrificed. The stomachs were macroscopically, microscopically and biochemically analyzed. RESULTS: Macroscopic and microscopic area of gastric mucosal injury were significantly larger in cirrhotic rats (P < 0.05). Gastric mucosal injury was more serious in cirrhotic rats as compared with Group 1. With vitamin E treatment, tissue Malondialdehyde (MDA) and glutathione [GSH (X)] levels were significantly lower in group 3 as compared with group 2 (P < 0.001). CONCLUSION: Gastric mucosa in cirrhotic rats has distinctive histological and functional abnormalities. These abnormalities can be reversed by Vitamin E or other antioxidants.

The effects of prostaglandin E2 indomethacin & Ginkgo biloba extract on resistance to experimental sepsis.

We investigated the effect of 16,16-dimethyl prostaglandin E2 indomethacin and Ginkgo biloba extract on the survival in two experimental sepsis models in rats due to administration of 1 x 10(7) cfu and 1 x 10(9) cfu Escherichia coli. Animals in each model were then randomly divided (10/group) into four groups, administered saline, indomethacin, G. biloba extract and prostaglandin E2 respectively. When compared, there was no significant difference in the survival period between the two sepsis models (P > 0.05). The best survival rate was observed in the PGE2-administered animals in the first major model (P < 0.05). Indomethacin appeared not to decrease the mortality rates. There was no significant difference in PGE2 levels between two sepsis models (P > 0.05). Our results suggest that elevated prostaglandin E2 levels following major trauma are not responsible for the postinjury increased susceptibility to infectious complications. Our observations should also discourage aggressive use of cyclo-oxygenase inhibitors for protection against infectious complications after major trauma.

Cytoprotective effects of alpha tocopherol against liver injury induced by extrahepatic biliary obstruction.

There are several important aetiologies of extrahepatic biliary obstruction (EBO). If EBO is surgically reconstructed in the critical time period, liver damage can be halted or reversed. In this golden period, lipid peroxidations significantly intensify liver defects. We hypothesised that alpha tocopherol (alpha-T) could protect the liver from the damage caused by response to EBO. In standard conditions, albino rats of Wistar strain were divided into two groups. All rats underwent double ligations and divisions of common bile ducts (CBD). One of these groups received alpha-T (CBDL-alpha-T). The other CBDL animals received intramuscular injections of normal saline (CBDL-NS). Serum samples were taken for biochemical analyses by light microscopy. The data showed a decrease in plasma bilirubin and liver enzyme levels in CBDL-alpha-T group, when compared with CBDL-NS (p < 0.05). Morphologic analyses showed better results for CBD-alpha-T. Serum levels of Malonyldialdehyd (MDA) in the CBDL-alpha-T group was 9.2 +/- 3.4 nmol/g compared to that in CBDL-NS, 12.3 +/- 4.4 nmol/g (p < 0.05). In conclusion, a dramatic protective effect of alpha-T on functional and structural features of the liver in rats with EBO was demonstrated. The data suggest that EBO may cause liver damage by stimulation of lipid peroxidation and that alpha-T may slow down liver damage in this setting.

A role for perlecan in the suppression of growth and invasion in fibrosarcoma cells.

Perlecan is a major heparan sulfate proteoglycan of basement membranes and cell surfaces. Because of its strategic location and ability to store and protect growth factors, perlecan has been implicated in the control of tumor cell growth and metastatic behavior. To test the role of perlecan in malignancy, we generated several stably transfected clones of HT-1080, a human fibrosarcoma cell line, harboring a perlecan cDNA in the antisense orientation. Surprisingly, clones with a reduced synthesis of perlecan mRNA and protein core grew faster, formed larger colonies in semisolid agar, and induced faster formation of s.c. tumors in nude mice than the wild-type cells. Their growth properties in vitro were independent of exogenous basic fibroblast growth factor. Reduction of perlecan expression was associated with three distinct properties typical of tumor cells with a more aggressive phenotype: enhanced migration through 8-microm-pore filter, increased invasion in Matrigel-coated filters, and heightened adhesiveness to type IV collagen substrata. These results thus provide the first evidence that perlecan may inhibit the growth and invasiveness of fibrosarcoma cells in a basic fibroblast growth factor-independent pathway and raise the possibility that perlecan may prevent the infiltration of host tissues in mesenchymal neoplasms.