Serum chitotriosidase levels in cancer patients undergoing high dose chemotherapy and stem cell transplantation.

OBJECTIVE: Human chitotriosidase (ChT) is an active chitinase expressed by activated phagocytes. Increased ChT activity has been reported in systemic Candida albicans infections and in Gram-negative and Gram-positive bacterial infections, indicating that an increase in ChT activity reflects phagocyte activation. The aim of this study was to determine the changes in serum ChT activity in patients who underwent high dose chemotherapy (HDC) and stem cell transplantation (SCT), who are at an increased risk for fungal and bacterial infections due to depression of the immune system during the neutropenic period. PATIENTS AND METHODS: A total of 55 SCT patients were included in the study. Serum ChT activity was determined before the initiation of HDC and during the neutropenic period after hematopoietic stem cell reinfusion on post-transplant first, fifth and tenth days. RESULTS: Chitotriosidase levels before transplantation were significantly lower than the results at first, fifth and tenth days post-hematopoietic stem cell reinfusion. CONCLUSIONS: Although the number of neutrophils was low, ChT enzyme activity was high in newly produced granules of neutrophils. Chitotriosidase may be supplemented as a drug for preventing and treating infections in the near future.

Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

OBJECTIVE: Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). PATIENTS AND METHODS: We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary ß2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. RESULTS: The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine ß2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for ß2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. CONCLUSIONS: NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.

Adrenomedullin worsens skin necrosis in rats subjected to vincristine-induced extravasation.

BACKGROUND: Extravasation of vesicant drugs such as vinca alkaloids causes severe injury, which may range from erythema to skin necrosis or ulceration. The skin necrosis may not be fully evident until several weeks or months after the initial damage, and may require surgical intervention. The main treatments for vincristine extravasation are hyaluronidase injection and topical warming, and the aim of treatment is to increase the clearance of the drug from the extravasation site. AIM: To investigate the effect of adrenomedullin, a potent vasodilatory peptide, in rats subjected to vincristine-induced extravasation. METHODS: In total, 36 Wistar albino rats were given intradermal injection of vincristine and saline. The rats were assigned to one of three treatment groups (adrenomedullin, adrenomedullin + hyaluronidase, or hyaluronidase), a control group given vincristine only, or a sham group (saline). Tissue superoxide dismutase (SOD), glutathione peroxidase, malondialdehyde (MDA) and protein content were evaluated in skin biopsies taken on day 22. The ulcer size and histopathological grading scores were also recorded. RESULTS: SOD levels were significantly increased by adrenomedullin and increased by hyaluronidase. Glutathione peroxidase levels were significantly decreased in all four vincristine groups. Tissue MDA levels were highest in the adrenomedullin group. In all four vincristine groups, MDA levels were reduced, indicating preservation from tissue injury. Protein carbonyl (PCO) content levels in the adrenomedullin group were significantly greater than in the other three study groups (P < 0.05). In contrast, PCO levels in the hyaluronidase group were significantly lower than in the other three groups. CONCLUSIONS: In this animal model of vincristine-induced extravasation, antioxidant status and histology were preserved by hyaluronidase but worsened by adrenomedullin.

Effect of proanthocyanidin, arginine and glutamine supplementation on methotrexate-induced gastrointestinal toxicity in rats.

Methotrexate is a folate antagonist that is commonly used as an antitumor and antiarthritic drug. The aim of this study was to investigate the possible roles of exogenous glutamine (Glu), arginine (Arg) and proanthocyanidin (PA) on gut protection from methotrexate-induced intestinal damage in rats. Experimental rats were separated into eight groups. The first (sham) group received a 0.9% NaCl solution alone. The second group received intraperitoneal injections of methotrexate (20 mg/kg/day) administered on day 4 of the experiment and continued for 5 days. Rats in the other six groups were administered PA, Glu, Arg, Glu+PA, Arg+PA or Glu+Arg orally by gavage together with methotrexate and animals were sacrificed on day 8 of the experiment. All animals were sacrificed 4 days after methotrexate injection for histopathological analysis, tissue glutathione peroxidase, malondialdehyde and superoxide dismutase assays. Proanthocyanidin and Glu decreased the severity of intestinal injury and oxidant injury as evident by histopathology and changes in malondialdehyde levels. Histological analysis confirmed that PA and to a lesser extent Glu supplementation were more favorable than Arg for the protection of the small intestine from methotrexate-induced injury.

Evaluation of pertussis immunity status in schoolchildren immunized with whole-cell vaccine.

It has recently been reported that the worldwide increase in the number of pertussis cases is a result of the waning of whole-cell vaccine-induced immunity. Thus, in this study, we aimed to investigate the pertussis immunity status of primary and secondary school students in a district of Ankara, Turkey. A total of 997 healthy students, aged 9-17 years, who had been immunized with four doses of whole-cell pertussis vaccine were included in the study. The subjects were divided into two age groups: 9-14 and 15-17 years. To determine the immune status, serum levels of IgG anti-pertussis toxin (aPT) antibody were tested by in-house ELISA and arbitrarily evaluated as non-immune [< 10 ELISA units (EU)/ml], immune (10-100 EU/ml), and recent infection (> 100 EU/ml). Serum samples of 997 students (559 females, 438 males) aged between 9 and 17 years (mean 13.02 +/- 2.25, median 13 years) were tested. Non-immune, immune and recent infection levels of aPT were found in 27.3%, 59.3% and 13.4% of individuals, respectively. The immune group did not have statistically significant differences between males and females (P = 0.68). In the 9-14 and 15-17 years age groups, serum aPT antibody levels 10 EU/ml were 73.1% and 72.2%, respectively, which did not represent any statistical difference (P = 0.81). Students aged 15-17 years had a higher immunity rate than the 9-14 years group, and the percentage of students with recent infection in the 9-14 years group was higher than the 15-17 years group (P < 0.001). The peak age of non-immunized subjects was 9 years (47.0%), and decreased to a minimum at age 12-13 years, and began to increase again from age 13-14 years. In contrast, the ratio of recent infection was least at age 9-10 years, began to increase, and reached a peak at 12 years, and then decreased. On the other hand, it was observed that household size and monthly income were not associated with the immunity status (P = 0.65, P = 0.37, respectively). The results of the present study show that levels of antibody against pertussis decreased in the younger age groups and, as a result, there is an increase in the number of pertussis cases. Thus, in order to decrease the incidence of pertussis and protect infants, we recommend the application of booster doses at regular intervals.