ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury.

The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50-60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4-/-, Adamts5-/-, and wt mice but not in the sham-operated group. By contrast Adamts4-/- and Adamts5-/- mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4-/- mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4-/- or Adamts5-/- mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.

Interaction of metabolic syndrome with asthma in postmenopausal women: role of adipokines.

The increasing prevalence of both asthma and obesity are major health problems. Recent studies established a possible link between obesity and asthma; however, the underlying mechanism is not clear. The aim of the study was to analyze the prevalence of metabolic syndrome in postmenopausal subjects with asthma and search the interactions between adipokines, metabolic syndrome, and asthma. A total of 45 female patients (57.5 ± 13.9 years) with asthma and 30 healthy subjects (59.6 ± 12.8 years) in postmenopausal status were enrolled in this study. For the diagnosis of metabolic syndrome, modified World Health Organization diagnostic criteria were used. Blood levels of glucose, lipid profile, HbA1c, insulin, CRP, leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8 and plasminogen activator inhibitor-1 (PAI-1) were measured. The mean body mass index was 29.6 ± 5.4 for asthma patients and 28.2 ± 5.3 for the control group. The incidence of metabolic syndrome was found as 26 % for both groups. Insulin resistance as calculated by homeostasis model assessment (HOMA-IR) and fasting insulin levels were significantly higher in asthma patients (p < 0.001 for both parameters). Leptin levels were significantly higher (p = 0.001) and adiponectin levels were lower (p = 0.029) in asthma patients compared to controls. We concluded that although incidence of obesity and metabolic syndrome was not higher in postmenopausal asthma patients than controls, there was an impairment of glucose metabolism and altered adipokine levels in asthma patients.

In vivo and in vitro antineoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives.

Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at µM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.

ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases are involved in a variety of biological processes such as angiogenesis, cancer and arthritis. ADAMTSs appears to be responsible for the cleavage of proteoglycans in several tissues including brain and cartilage. Chondroitin sulfate proteoglycans (CSPGs) maintains the integrity of the brain extracellular matrix and major inhibitory contributors for glial scar and neural plasticity. The activity of aggrecanases in the central nervous system (CNS) has been reported. ADAMTSs are an enzyme degrading CSPGs in the brain. However, there is a little knowledge regarding ADAMTSs in the CNS. We investigated the expression levels of ADAMTSs mRNAs by RT-PCR after spinal cord injury in mouse. Transcripts encoding 4 of the 19 known ADAMTSs were evaluated in the mouse spinal cord following injury. ADAMTS1, -5 and -9 expression levels were found to be upregulated. No change was observed in ADAMTS4 expression. By means of immunohistochemistry, ADAMTSs were detected in the astrocytes implying its cellular source in SCI. Western blot analyses indicated that aggrecanase-generated proteoglycan fragments are produced after SCI.

Augmentation of ADAMTS9 gene expression by IL-1ß is reversed by NFκB and MAPK inhibitors, but not PI3 kinase inhibitors.

The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor-κB (NF-κB), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3-kinase (PI3 kinase) in ADAMTS9 gene regulation, with special focus on the involvement of NF-κB in IL-1ß-induced ADAMTS9 expression. The OUMS-27 chondrosarcoma cells were exposed to IL-1ß. They were pretreated with 20 µM PD98059 (specific inhibitor of p44/42 kinase), 10 µM SB203580 (specific inhibitor of p38 kinase), 20 µM SB600125 (MAPK inhibitor), and 1 µM Wortmannin and 10 µM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL-1ß. For the effects of NF-κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL-1ß. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on ADAMTS9 gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real-time polymerase chain reaction (PCR) was performed on cDNA samples. There was a significant difference between control and stimulated cells in terms of ADAMTS9/ß-actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS-27 whereas SB203580 and SP600125 were found to decrease the expression of ADAMTS9 gene. BAY 117085 and curcumin, which are two NF-κB inhibitors, led to a decrease in the ratio of ADAMTS9/ß-actin. As a conclusion, the pathways MAPK and NF-κB were thought to be responsible pathways for the induction of ADAMTS9 gene.

The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity.

Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens.

Some inflammatory cytokine levels, iron metabolism and oxidan stress markers in subjects with nonalcoholic steatohepatitis.

OBJECTIVES: The relation between nonalcoholic steatohepatitis and iron metabolism is still controversial. Free fatty acids, iron, and other sources of oxidative stress probably result in cell damage, and necroinflammation mediated by various cytokines. DESIGN AND METHODS: Sixty patients were diagnosed with NASH were included in the study, and the patient group was divided into three subgroups. Iron metabolism markers, inflammatory cytokines, including TNF-α, IL-6 and IL-8, MDA and nitric oxide levels were measured. RESULTS: Serum ferritin, inflammatory cytokines, and oxidative stress markers were significantly higher in the patient group. Among three patient groups, divided according to the results of ultrasonic examination, there were significant changes with regard to these parameters. CONCLUSION: The study results suggest that liver iron and fat accumulation, oxidant stres, and inflammatory cytokines are closely related. Therefore, levels of serum ferritin, MDA, IL-6, TNF-α and IL-8 could represent the indices of activity and progression of NASH.

Serum lipid and lipoprotein profile in children with iron deficiency anemia.

BACKGROUND: A close association has been found between serum lipoprotein abnormalities and the risk of atherosclerosis. In adults, high stored body iron, high serum iron concentrations and low iron binding capacity were found to be risk factors for coronary heart disease. Iron-deficient diets have caused contradictory lipid changes in rats. This report investigates the relationships between iron deficiency, macronutrient intake and the serum lipid and lipoprotein profiles in children with iron deficiency anemia (IDA). METHODS AND RESULTS: Fifty-six children with IDA, aged 3.0 +/- 1.3 years and 60 healthy age- and sex-matched controls were evaluated. The mean total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), lipoprotein (a) levels and LDL-C/high density lipoprotein cholesterol (HDL-C) and TC/HDL-C ratios of the IDA group were significantly lower than those of controls. While there were no differences in triglycerides and apolipoprotein B (apoB) values between patients and controls, apolipoprotein A-1 (apoA-1) and HDL-C levels were higher in the IDA group. Dietary energy, carbohydrates, total fat and protein intakes of the IDA group were lower than those of controls. After oral iron supplementation, the lipoprotein profile of patients with IDA became similar to controls. In the multivariate analysis, while energy was taken as a covariate, there was no difference in the lipid profile of patients and controls. CONCLUSIONS: Patients with IDA are also deficient in macronutrients. The low atherogenic serum lipid profile of IDA is not a direct result of iron deficiency itself, but related to decreased energy and protein intakes.

Low levels of high density lipoprotein cholesterol in Turkish children: an important risk factor.

In Turkish adults, the incidence of coronary artery disease (CAD) has been found to be high. However, no detailed lipid, or lipoprotein data of children are available from Turkey. The present study was designed to define the borderline lipid and lipoprotein levels of sera in 397 healthy children (aged 5-14 years; 206 boys and 191 girls). Mean levels of total cholesterol (TC), triglyceride (TG), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively) were found to be 150, 79, 46.7, and 87.6 mg/dL, respectively, for boys, and 152, 77.5, 46.3 and 90.5 mg/dL, respectively, for girls. Lipids and lipoproteins did not show any significant correlation with age and body mass index (BMI), except for TG in boys in whom TG levels were positively correlated with age and BMI. There were no significant differences in lipid and lipoprotein levels between boys and girls. As in the Turkish adult population, serum HDL-C levels of Turkish children were profoundly low on international comparison. Twenty-three (53%) of 43 children with low HDL-C level (< or = 35 mg/dL) had abnormal ratios of TC/HDL-C (> or = 5) and/or LDL-C/HDL-C (> or = 4.5), whereas only 13 (3.7%) of the remaining 354 children with a HDL-C level less than 35 mg/dL had abnormal ratios of TC/HDL-C (> or = 5) and/or LDL-C/HDL-C (> or = 4.5). The low levels of HDL-C in Turkish children may be associated with the high incidence of CAD in the Turkish adult population.

Effect of long-term alcohol abuse on male sexual function and serum gonadal hormone levels.

PURPOSE: The relationship between chronic alcohol abuse and male sexual dysfunction and pituitary gonadal function abnormalities remains uncertain. The purpose of this study was to assess the effect of chronic alcoholism on sexual functions and serum hormone levels. MATERIALS AND METHODS: Forty-five chronically alcoholic men and a control group of thirty healthy non-alcoholic volunteers were enrolled in the study. Each of the men in the study and control group were interviewed according to a sexual dysfunction questionnaire by an urologist. Blood samples were collected for evaluation of hormone levels. Sera were stored at -70 degrees C for analysis. RESULTS: The sexual desire and erection scores of alcoholic men were not statistically different from those of the control group. Fourteen out of the 45 alcoholic men complained of loss of erection during sexual activity. No significant difference in hormone levels between groups was found except for FSH. CONCLUSION: In the absence of hepatic and gonadal failure in chronically alcoholic men, there is no significant difference in serum hormonal levels, sexual dysfunction form, and sexual functions between alcoholics and normal healthy non-alcoholic men.

The effect of cigarette smoking during pregnancy on cord blood lipid, lipoprotein and apolipoprotein levels.

We examined the relationship between maternal smoking during pregnancy and serum lipid, lipoprotein and apolipoprotein levels in newborns. Serum concentrations of total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B and lipoprotein (a) were assessed in blood samples from 38 mothers who were smokers and their newborns obtained at delivery and compared to blood sample from 42 nonsmokers and their newborns. As compared with newborns of nonsmoker mothers, newborns of smoker mothers showed a lower mean level of high density lipoprotein cholesterol (21 versus 26 mg/dl, p < 0.01), a higher total cholesterol to high density lipoprotein cholesterol (4.7 versus 3.7, p < 0.01), a higher low density lipoprotein cholesterol to high density lipoprotein cholesterol ratios (3.2 versus 2.3, p < 0.05), a lower mean level of apolipoprotein A-1 (105 versus 129 mg/dl, p < 0.01) and a higher apolipoprotein B to apolipoprotein A-1 ratio (0.44 versus 0.3, p < 0.01). These parameters were also different between smoker and nonsmoker mothers. There were no significant differences in TC, TG, LDL-C, Apo B and Lp (a) values between the two newborn groups. These data suggest that maternal smoking during pregnancy markedly affects lipid metabolism in the fetus.

Beneficial effects of testosterone undecanoate on the lipoprotein profiles in healthy elderly men. A placebo controlled study.

BACKGROUND AND METHODS: In order to assess the effects of testosterone undecanoate (TU; 120 mg/d orally for 2 months) on serum lipid, lipoprotein, and apolipoprotein levels in healthy elderly men, the placebo (PL) controlled study was performed on 37 elderly men, aged between 53 and 89 years. In all subjects venous blood samples were taken after an overnight (10 hours) fast and sera were stored -70 degrees C until analysis. RESULTS: In PL group, neither hormonal data nor lipid, lipoprotein, and apolipoprotein levels showed significant changes. After TU supplementation, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and estradiol (E2) levels decreased from 198 +/- 30.7 mg/dl to 174 +/- 41.9 mg/dl (p < 0.05), from 111 +/- 18.14 mg/dl to 87.9 +/- 29.4 mg/dl (p < 0.01), and from 86.2 +/- 16.9 pmol/l to 70.5 +/- 18 pmol/l (p < 0.01), respectively. Statistically significant differences were not observed in the serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein (apo) A-1 and apo B levels after TU treatment. The mean ratios TC/HDL-C and LDL-C/HDL-C as coronary risk factor criteria decreased significantly in the TU but not in the PL group. No obvious side effect was observed in those who took TU except for reported pyrosis in 2 of 17 elderly men. CONCLUSIONS: These data indicate that the increased serum levels of total testosterone (TT) produced by administration of TU, 120 mg/d orally for 2 months lead to suppressed levels of TC and LDL-C and E2 but not significantly changed levels of TC, HDL-C, apo A-1 and apo B. Thus, we conclude that TU may be an effective drug for protecting coronary heart disease in healthy elderly men with lowered TT and FT levels. It may also have beneficial effects for sexual function and behavior.

Increased lipoprotein (a) and its relationships with other parameters of lipoprotein metabolism in chronic renal failure treated by hemodialysis.

BACKGROUND: Studies have shown that patients with chronic renal failure have a high frequency of cardiovascular atheromatous disease. METHODS: We examined serum lipoprotein (a) [Lp(a)], very-low density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apo A1) and B (apo B), triglyceride (TG) and total cholesterol (TC) levels as possible risk factors for atherosclerosis in 45 patients with chronic renal failure (CRF) treated by hemodialysis (HD) and in 15 CRF patients who were not on HD. A control group of 20 healthy subjects was also studied. RESULTS: The proportion of smokers and body mass indexes were similar between the groups. In both patient groups, higher TG, TC and Lp(a) and lower apo A1 and HDL-C levels in serum were found than in those of controls. Serum apo B and LDL-C were similar in the patients treated by HD and the controls. Serum VLDL-C and LDL-C were similar in the CRF patients who were not on HD and the controls. The highest ratios of apo B/apo A1 and LDL-C/HDL-C were found in HD patients. The highest ratio of TC/HDL-C was found in the other patient group. We found significant correlations between Lp(a) and other parameters of lipoprotein metabolism in CRF patients, both those who were and those who were not on HD. CONCLUSIONS: Our results indicate that CRF patients who both were and were not on HD show atherogenic changes in the lipoprotein pattern, and that the increase in Lp(a) during the CRF phase is basically related to the loss of renal function and may also depend on the resultant alterations which are produced in other lipoprotein variables.

Increased serum copper and decreased serum zinc levels in children with iron deficiency anemia.

In order to evaluate serum copper and zinc status in children with iron deficiency anemia (IDA), 60 children with IDA aged 1-14 yr and 64 healthy children as controls aged 1-14 yr were included the study. Serum copper levels were higher in children with IDA (189 +/- 49 micrograms/dL) than those of controls (163 +/- 37 micrograms/dL) (p = 0.001). Serum zinc levels were lower in the patient group (109 +/- 59 micrograms/dL) than those of control subjects (135 +/- 56 micrograms/dL) (p = 0.017). In addition, there were statistically significant negative correlations between hematological parameters and serum copper levels in the patient group, but not in controls. No correlation between hematological parameters and serum zinc levels were found in both patient and control groups, except positive correlation between mean corpuscular volume (MCV) and serum zinc level in patients. It was concluded that at the time of managing children with IDA, zinc deficiency must be borne in mind and if necessary treatment should be initiated with zinc.

Kinetic Study of Ligand Exchange Reaction of Anions as Ligands on DAE-Sporopollenin

The specific rate coefficients and ligand sorption isotherms of Br and I- as ligands on diaminoethyl-sporopollenin were determined as a function of pH and temperature between 20 and 60°C. The ligand exchange rates were measured just after the rapid mixing of the ligand solution with the resin suspension. The data have also been analyzed to obtain activation parameters DeltaG, DeltaH, and DeltaS for reaction in the corresponding mixture. A single ligand-exchange process was observed; the sorption of ligand increased with decreasing pH and hydrated radius of ligands and increasing temperature. A reaction mechanism which describe the ligand exchange reaction is proposed.

Effects of passive exposure to tobacco, socioeconomic status and a family history of essential hypertension on lipid profiles in children.

There is abundant evidence that the atherosclerotic process begins in childhood. Dyslipidemia is a major risk factor for atherosclerosis in adults and children. In the present study, we measured serum lipoprotein concentrations in 194 healthy children aged between 4 to 14 years. Children were grouped according to the socioeconomic status of the families, family history of essential hypertension and passive tobacco exposure. The values of total cholesterol, low density lipoprotein cholesterol and the ratio of total cholesterol/high density lipoprotein cholesterol in the low socioeconomic group were found to be significantly higher than the values obtained for the middle-high socioeconomic group. The values of total cholesterol, low density lipoprotein cholesterol, the ratio of total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol in the passive smoker group were found to be significantly higher than those of the nonsmoker group. But, the socioeconomic level in the passive smoker group was found to be significantly lower than that of the nonsmoker group, and therefore, the impact of passive smoking on the serum lipids in children was related to socioeconomic status. A significant difference in terms of blood lipid fractions between the groups with and that without a family history of essential hypertension was not found. These results suggest that passive smoking and lower socioeconomic status are important risk factors for cardiovascular heart disease, while a positive family history of essential hypertension is not an important risk factor.

Plasma atrial natriuretic peptide levels in rabbits with alloxan monohydrate-induced diabetes mellitus.

The effect of alloxan monohydrate-induced diabetes on the resting plasma atrial natriuretic peptide (ANP) level was investigated in 22 male New Zealand white rabbits. Alloxan monohydrate (100 mg/kg) dissolved in saline at a concentration of 50 mg/ml was administered by a single intravenous injection 3 months before the experimental analysis. The diabetic state was examined 72 h later by quantitative determination of blood glucose levels of >350 mg/dl. Beginning on day 3, 14 animals (Group 1) received a daily subcutaneous injection of 1 U insulin having moderate hyperglycemia (blood glucose concentration [BGC] between 300 and 400 mg/dl). Eight animals (Group 2; normoglycemic controls) received 3.2 U of insulin daily to maintain the BGC below 100 mg/dl. Eight healthy rabbits were included in the study as controls (Group 3). Blood samples for ANP analysis were obtained three months after administration of alloxan monohydrate. The plasma ANP levels in moderately diabetic rabbits (328 +/- 43 pg/ml) were significantly higher than those in normoglycemic (98.5 +/- 20 pg/ml) and healthy (76.6 +/- 18 pg/ml) controls (p < 0.001 for both). In addition, we found a significant correlation between plasma levels of glucose and levels of ANP (r = 0.665, p < 0.001). Our data indicate that further experiments need to be performed to investigate what is responsible for the elevation of plasma ANP levels in diabetic rabbits.

Bilateral parotid duct fistula. Case report.

Parotid duct fistulas (PDFs) are rare and have various causes such as gunshot wounds and human and animal bites; they may also be congenital. We have not found previous publications on bilateral PDF. Our patient, although young, also had generalized pigmentation characteristic of aging and thick, dry, wrinkled skin, as well as pyoderma. Biochemical analysis was performed on discharge from the patient's face, and histopathologic and immunologic studies were done. The fistulas were treated by intraoral fistulization. Cephalosporins were given to the patient for 5 days postoperatively to treat the pyoderma.

Pendred's syndrome.

Although 5% of all cases of congenital deafness are caused by Pendred's syndrome, there are few reports in the literature. Seven patients with Pendred's syndrome in three families living in the same village were detected. For that reason, the syndrome is reviewed in light of the literature. The sex distribution of the patients with Pendred's syndrome and their families was recorded. We tested for thyroxine, triiodothyronine, thyroid-stimulating hormone, triiodothyronine resin uptake, and perchlorate, and performed caloric testing. In one patient, subtotal thyroidectomy was performed. In the histopathologic study, a thyroid nodule filled with colloid was found. Chromosome studies showed no anomalies in any patient. Five of the patients were deaf-mutes. We observed that the parents were cousins in all three families. These families also had healthy children, and the existence of the syndrome in both sexes points to an autosomal recessive trait.