Increased expression of serum matrix metalloproteinase-9 in patients with moyamoya disease

Background

Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology characterized by an abnormal vascular network at the base of the brain, which can manifest both as ischemic stroke and as cerebral hemorrhage. It was also reported that the patients with moyamoya disease are more vulnerable to cerebral hyperperfusion such as postoperative hemorrhagic complication after extracranial-intracranial bypass surgery despite its low flow revascularization. However, the underlying mechanisms of its pathologic angiogenesis and the occurrence of hemorrhage are undetermined. Excessive degradation of the vascular matrix by MMPs, proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. The MMPs also play an important role in tissue remodeling including angiogenesis in both physiologic and pathologic condition.

Methods

We examined the serum levels of MMP-2 and MMP-9 in 16 cases with definitive moyamoya disease by enzyme-linked immunosorbent assay and compared them with those from healthy controls.

Results

The serum MMP-9 level was significantly higher in moyamoya disease (40.18 ng/mL) than in healthy controls (13.75 ng/mL, P = .0372). There was no difference in serum MMP-2 level between moyamoya disease (646.65 ng/mL) and healthy control (677.60 ng/mL). Immunohistochemistry on the surgical specimens showed significant increase in MMP-9 expression within the arachnoid membrane of moyamoya disease.

Conclusion

The increased expression of MMP-9 may contribute to pathologic angiogenesis and/or to the instability of the vascular structure and could thereby cause hemorrhage in moyamoya disease.     

Does CT-Based Navigation Improve the Long-Term Survival in Ceramic-on-Ceramic THA?

Background  

Although navigated THA provides improved precision in implant positioning and alignment, it is unclear whether these translate into long-term implant survival.     

Urinary lead as a possible surrogate of blood lead among workers occupationally exposed to lead

Objectives: The aim of the present study is to investigate whether lead (Pb) in urine (Pb-U) can be a valid surrogate of lead in blood (Pb-B), the traditional biomarker of exposure to lead in occupational health. Methods: Blood and spot urine samples were collected from 258 workers of both sexes occupationally exposed to lead. The samples were analyzed for lead by graphite furnace atomic absorption spectrometry, and the correlation between Pb-B and Pb-U was examined by linear regression analysis before and after logarithmic conversion. Results: The correlation coefficient (0.824; P < 0.01) was largest when the relationship between Pb-B and Pb-U was examined with 214 cases of one sex (i.e., men) after Pb-U was corrected for a specific gravity (1.016) of urine (Pb-Usg) and both Pb-B and Pb-Usg were converted to logarithms. The geometric means (GMs) of Pb-B and Pb-Usg for the 214 men were 489 μg/l and 81 μg/l, respectively. When Pb-Usg was assumed to be 100 μg/l in this set of correlations, the 95% confidence range of Pb-B for the group mean was narrow, i.e., 543–575 μg/l (with GM of 559 μg/l), whereas that for individual Pb-B values was as wide as 355–881 μg/l. Conclusions: The correlation of Pb-U with Pb-B among workers occupationally exposed to Pb was close enough to suggest that Pb-U may be a good alternative to Pb-B on a group basis, but not close enough to allow Pb-U to predict Pb-B on an individual basis. Received: 6 April 1999 / Accepted: 17 July 1999     

Prevention of Neonatal HBV Infection with the Combination of HBIG and HBV Vaccine and Its Long-Term Efficacy in Infants Born to HBeAg Positive HBV Carrier Mothers

Seventy-three infants born to HBeAg positive HBV carrier mothers were protected from neonatal HBV infection with our standard prevention schedule consisting of two doses of HBIC (0, 2 mo) and three doses of HBV vaccine (2, 3, 5 mo). In 62 infants who successfully responded to HBV vaccine with a titer of anti-HBs greater than 2³, anti-HBs titer was monitored for as long as 48 months (25.6 ±11.0 mo) and found to decrease as follows: 5.1 ± 1.7 at 12 mo., 4.5 ± 1.8 at 18 mo., 4.2 ± 1.8 at 24 mo., 4.0± 1.6 at 30 mo., 3.7 ± 1.7 at 36 mo., 32 ± 2.0 at 48 mo. During the follow-up period, eight HBV events (11.9%) were demonstrated: one case showed an increase of anti-HBs, three showed a reappearance of anti-HBc alone, three showed a reappearance of anti-HBc with increase of anti-HBs, and one became a chronic HBV carrier. All infants were further divided into three groups by their maximal response of anti-HBs to HBV vaccine: Group I (2⁶), Group II (2³-2⁵), and Group III (2²). Group I sustained a higher titer from 12 to 30 months of age and had less HBV events than (3-II and G-III. Our study suggests that acquisition of a high titer of anti-HBs is important in long-term prevention of HBV infection as well as in the neonatal period in infants born to HBeAg positive HBV carrier mothers.     

Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

Mass Protection Program of Perinatal Hepatitis B Virus Infection in Japan and Impact of an Optional Booster Vaccination on Its Efficacy

We assessed the efficacy of a government-sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow-up procedures in such infants, including an evaluation of anti-HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti-HBs was higher in the standard group than in the follow-up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti-HBs response. In conclusion, we recommend that a follow-up blood test to confirm a response of anti-HBs to HBV vaccine should be performed at 4–8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy.     

AU-1 from Agavaceae plants causes transient increase in p21/Cip1 expression in renal adenocarcinoma ACHN cells in an miR-34-dependent manner

Here, we show that AU-1, spirostanol saponin isolated from Agavaceae plants, causes a transient increase in cyclin-dependent kinase inhibitor (CDKI) p21/Cip1 through the upregulation of miRNAs, miR-34 and miR-21. AU-1 stimulated p21/Cip1 expression without exerting cytotoxicity against different types of carcinoma cell lines. In renal adenocarcinoma ACHN cells, AU-1 transiently elevated the expression level of p21/Cip1 protein without marked increases in p21/Cip1 mRNA levels. Rapid and transient increases in miR-34 and miR-21, both of which are known to upregulate p21/Cip1, were observed in AU-1-treated cells. Inhibitor for miR-34 and for miR-21 significantly blocked the AU-1-caused increase in p21/Cip1, indicating that elevation of p21/Cip1 protein by AU-1 is dependent on these microRNAs. We further clarified that NAD-dependent deacetylase SIRT1, a direct target of miR-34, is decreased by the treatment with AU-1. Furthermore, we found that SIRT1-knockdown increases p21/Cip1 protein levels in an miR-21-dependent manner. On the other hand, ectopic expression of p21/Cip1 resulted in the lowered expression of miR-34 and miR-21, suggesting that reciprocal regulation exists between p21/Cip1 and these miRNAs. We propose that the following feedback network composed of miR-34/SIRT1/miR-21/p21 is triggered by the treatment with AU-1: in cells treated with AU-1, transient elevation of miR-34 leads to the downregulation of SIRT1, thereby miR-21 is freed from SIRT1-dependent suppression. Then, elevated miR-21 upregulates p21/Cip1 protein, followed by the suppression of miR-34 expression.     

Adverse effects of longterm, continual administration of high doses of albendazole in the treatment of echinococcal disease

BACKGROUND/AIM: Modern treatment of cystic echinococcosis, except for surgical treatment and percutaneous drainage of cyst considers also administration of albendazole as a type of individual therapy. However, clinicians fear of the serious adverse effects of high doses of albendazole, first of all the elevation of serum transaminases activity, very frequently results in subdosing of albendazole and wrong conclusions its efficacy and safety. The aim of this study was to investigate adverse effects of a longterm, continual administration of high doses of albendazole in the treatment of patients with echinococcal disease. METHODS: A total of 42 patients (mean age 40.4 +/- 18.3 years) with echinococcal disease were included in the study. They were treated with continual administration of high doses of albendazole within the period of 4 to 6 months. The subgroups of 27 and 15 patients were treated with 15-20 mg/kg/day and with 21-25 mg/kg/day albendazole, respectively. The patients in the control group (18 with surgical treatment, 6 with percutaneous drainage of cyst) were treated with 800 mg albendazole per day (< 15 mg/kg body weight) in the cycles of 28 days (1-3 cycles) and a two-week pause between them. RESULTS: In the study group adverse effects of albendazole were registered in 20 (47.6%), whereas in the control group in 6 (30.0%) of the patients. In both subgroups elevated activity of serum transaminases were found more frequently in the study group compared to the control one (35.7% vs 25%, p < 0.05), especially in the patients who were treated with higher doses of albendazole. The patients in the study group, compared to the patients in the control group had significantly higher mean activity of serum alanin aminotransferase in the course of the second and third month of the therapy (p < 0.05). Administration of albendazole due to adverse effects was stopped in 3 (7.1%) of the patients in the study group. Two (4.8%) of them had a very high activity of serum transaminases and one had a muscle pains and high activity of serum creatine kinase. After the interruption of the therapy we documented a nonnalization of serum enzyme levels in all the patients. CONCLUSION: Longterm, continual administration of high doses of albendazole in the patients with echinococcal disease results in significant elevation of serum transaminases activity, compared to the patients treated with albendazole in the cycles, but in the majority of the patients serum transaminases activity was normalizated by the end of a 6-month period.