Effectiveness of topical zinc oxide application on hypertrophic scar development in rabbits.

BACKGROUND: The etiology, biology, prevention and effective treatment of hypertrophic scars have not exactly been defined. Topical zinc oxide application was shown to be effective in the treatment of proliferative scars. We studied the effectiveness of topical zinc oxide ointment in the prevention of hypertrophic scar development by using the rabbit ear hypertrophic scar model. METHODS: Circular full-thickness skin excisions were performed on both ears of 10 rabbits. The rabbits were divided into two groups and topical 40% zinc oxide ointment was applied daily to one ear and the ointment base was applied as placebo to the other ear. Scar samples were taken in the 3rd week in group 1 and in the 6th week in group 2. All of the specimens were divided into two halves: one half for histopathologic/histomorphometric examinations and the other half for biochemical studies. RESULTS: Application of topical zinc oxide ointment decreased clinical scar hypertrophy scores significantly (p=0.017) at 6th week in comparison with placebo. Topical zinc oxide also reduced nodule formation histopathologically at 6th week in comparison with placebo but this was not significant statistically (p>0.05). CONCLUSION: The findings of this study may have clinical implications on the management of human hypertrophic scars.

Protective role of 27bp repeat polymorphism in intron 4 of eNOS gene in lacunar infarction.

Association of the three potential endothelial nitric oxide synthase gene (eNOS) polymorphisms (T-786C in promoter region, G894T in exon 7 and tandem 27-bp repeats in intron 4) with an increased risk of lacunar infarction (LI) were investigated. Genotypes of 70 patients and 81 healthy controls were determined through PCR with or without RFLP. Flow-mediated dilatation (FMD) was performed to assess endothelial-dependent vasodilatation, whereas the endothelial-independent vasodilatation was assessed with nitroglycerin (NTG). Genotype distribution was significantly different between LI patients and controls for intron 4aa (alleles for four repeats), genotype frequency being 1.4% and 16.0%, respectively (odds ratio for additive effect, 0.47; 95% CI, 0.28-0.81; p=0.006). Haplotypes with the intron 4aa polymorphism were significantly higher in controls when compared with the LI group (p=0.001). Diminished FMD but normal NTG response confirmed that patients with LI have generalized endothelial dysfunction. Intron 4aa genotype of eNOS gene seems to be protective for isolated LI and the effect was potentiated by the absence of 786C polymorphism in any allele of the promoter region.

Identification of two novel arylsulfatase A mutations with a polymorphism as a cause of metachromatic leukodystrophy.

OBJECTIVE: Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A or saposin B. Enzyme deficiency leads to the accumulation of sulfatide, which results in severe demyelination. METHODS: In this study, clinically suspected patients were diagnosed as metachromatic leukodystrophy by enzyme analysis using p-nitrocathecol sulfate as substrate. Eight exons and flanking regions of arylsulfatase A gene of patients were amplified by polymerase chain reaction and then subjected to single stranded conformational polymorphism analysis. Polymerase chain reaction products of suspicious exons in single stranded conformational polymorphism were purified from agarose gel and sequenced. RESULTS: DNA sequencing revealed two novel disease-causing missense mutations: the first one is 1568G-->A, 307Glu-->Lys in exon 5 which is together with a 2161C-->T, 391Thr-->Ser polymorphism in exon 7; and the second one is 1603G-->T, 318Trp-->Cys in exon 5. DISCUSSION: These two mutations are in highly conserved structural elements region of the arylsulfatase A protein. Thus, missense mutations 307Glu-->Lys in exon 5 and 318Trp-->Lys in exon 5 probably change the active site conformation by disrupting the sixth alpha helix and the twelfth beta-sheet structure of the arylsulfatase A protein, respectively, and cause deficiency in enzyme activity. This study provides the molecular basis for understanding the mechanism underlying metachromatic leukodystrophy.

Increased hexosaminidase activity in antipsychotic-induced extrapyramidal side effects: possible association with higher occurrence in bipolar disorder patients.

Dystonic movements and Parkinsonism are frequently seen in gangliosidoses and these conditions have been reported to modify dopaminergic plasticity. We investigated whether the activity of hexosaminidase, a type-two ganglioside (GM2) degrading enzyme, correlates with drug-induced extrapyramidal system (EPS) side effects in psychiatric patients. We compared hexosaminidase activity in the lymphocytes of 29 EPS-positive patients, 13 EPS-negative patients, and 30 healthy volunteers. The activities of A and B isoforms of hexosaminidase were higher in EPS-positive patients than EPS-negative patients and healthy controls. Multivariate analysis suggested an interaction with increased B isoform activity and EPS side effects in female bipolar disorder patients. Higher levels of hexosaminidase enzyme activity may explain the frequent occurrence of antipsychotic-induced extrapyramidal side effects in mood disorder patients.

Serum ribonuclease activity in the diagnosis of prostate cancer in men with serum prostate-specific antigen levels between 2.5 and 20 ng/mL.

OBJECTIVES: To evaluate the diagnostic value of serum ribonuclease activity for prostate cancer detection and to compare its performance with serum PSA. DESIGN AND METHODS: 111 subjects with serum PSA levels between 2.5 and 20 ng/mL underwent prostate biopsy. The diagnostic performance of serum ribonuclease activity, PSA, free PSA, complex PSA and PSA derivatives was studied in regard to discriminating prostate cancer from BPH. RESULTS: Of 111 patients, 27 (24.3%) were positive for prostate cancer. Median serum ribonuclease level in patients with prostate cancer was significantly higher than the non-cancer patients (21.3 U/mL vs. 6.6 U/mL, P < 0.001). Area under curve (AUC) values for ribonuclease activity level, PSA, f/tPSA and cPSA were 0.696, 0.514, 0.617 and 0.662, respectively. Of 27 patients with prostate cancer, radical prostatectomy was performed in 15. Of these 15 cases, four (26.7%) had clinical insignificant tumors; all with undetectable serum ribonuclease activity. When median values of various diagnostic parameters were compared in regard to predicting clinically significant and insignificant cancers, only serum ribonuclease activity was found to be significant. CONCLUSIONS: Although serum ribonuclease activity had no additional benefit beyond serum PSA in the diagnosis of patients with PSA levels between 2.5 and 20 ng/mL, it may be helpful to discriminate the clinically significant prostate cancers and thus select the proper treatment accordingly.

Does serum hexosaminidase activity play a role in the diagnosis of strangulated bowel obstruction? An experimental study.

Strangulation is associated with an increased risk of mortality and morbidity in patients with mechanical bowel obstruction. The accurate and early recognition of the presence of strangulation is important to allow safe nonoperative treatment. A number of studies have shown that there was no single and reliable test to detect or exclude the presence of strangulation. The aim of this study was to evaluate the role of serum hexosaminidase (Hex) levels in recognition of strangulation in an experimental model of closed loop small bowel obstruction. Forty-two Wistar albino rats were divided into four groups: I, control (n = 5); II, sham laparotomy (n = 5); III, simple obstruction (n = 16); and IV, strangulation groups (n = 16). Activity levels of total Hex and its fractions (Hex A and B) were assayed in serum samples obtained from rats after 3 and 8 hr. Samples of small bowel were also evaluated histologically. Histological evaluation of bowel sections obtained from the strangulation group after 8 hr, revealed transmural hemorrhagic infarction in all animals with a mean +/- SD total Hex activity of 978.25 +/- 150 nmol/hr/ml, which was significantly higher than that in the other groups (P < 0.001). Although sections of bowel from the strangulation group after 3 hr showed severe ischemic injury, the activities of total Hex, Hex A, and Hex B were not different from those of the control, sham, and simple obstruction groups. Histological examination of these groups did not show any sign of ischemia. Total Hex, Hex A, and Hex B activities in the strangulation group were all significantly greater than the activities seen in the simple obstruction group (P < 0.001, for all). In conclusion, increased serum hex levels indicate irreversible transmural infarction only in the late period of strangulation in the closed loop small bowel obstruction model. It seems unuseful for detecting reversible and/or irreversible ischemia in the early period of strangulation.

Biochemical and molecular characterization of mutant hexosaminidase A in a Turkish family.

BACKGROUND: Tay-Sachs disease is a form of monosialoganglioside triaose (GM2) gangliosidosis that results from the mutations in the alpha-subunit gene of hexosaminidase A. In the B1 variant, the active site of the alpha-subunit of the enzyme is thought to be affected. In the present study, a patient who had previously been diagnosed as a B1 variant is further analyzed. The patient's parents and brother were also analyzed. METHODS: Single-stranded conformational polymorphism (SSCP) and DNA sequencing analysis were conducted in all cases. In addition, hexosaminidase A (Hex A) was isolated from leukocyte homogenates of the patient's parents and brother using DE 52 ion-exchange chromatography, and thermostability analyses of the isolated enzymes were performed. RESULTS: Hexosaminidase A of the parents was found to be more thermostable than normal Hex A. DNA sequencing analysis revealed a 12-bp deletion mutation in exon 10 of the Hex A gene. The patient was a homozygote and the parents were heterozygotes for the mutation, which could also be observed at the DNA double strands by SSCP analysis. These deleted bases are located within the catalytic domain of the alpha-subunit. CONCLUSIONS: The 12-bp deletion mutation in exon 10 of Hex A is responsible for the increased thermostability of the enzyme. Considering this mutation has previously been found in a Turkish Tay-Sachs patient, the patient in the present study may have another mutation on the Hex B gene that causes decreased thermostability of the enzyme. Thermal inactivation assay may not be sufficient for a correct diagnosis in such unusual cases.

Propofol anaesthesia and metabolic acidosis in children.

BACKGROUND: We aimed to investigate the effect of propofol infusion anaesthesia on acid-base status and liver and myocardial enzyme levels of children during short-term anaesthesia. METHODS: Thirty-six children, aged 3-12 years, were randomized into two groups. In group P (n = 18), induction and maintenance were performed with propofol, 3 mg x kg-1 and 20, 15 and 10 mg x kg-1 x h-1, respectively. In group H (n = 18) following induction with 5 mg x kg-1 thiopenthal, anaesthesia was maintained with 2-3% halothane. Blood samples were obtained following anaesthesia induction and 30, 60 and 120 min after discontinuation of anaesthesia. RESULTS: There was no difference in lactate dehydrogenase, myocardial creatininephosphokinase, aspartate aminotransferase, alanine aminotransferase and cholesterol levels between and within the groups. All postoperative triglyceride levels were higher and pH levels were lower in group P than group H (P < 0.05) and there was no difference within the groups. CONCLUSIONS: In these healthy patients, short-term use of propofol did not result in significant acidaemia, nor alterations in hepatic or myocardial enzyme levels.