SYNTHESIS OF SUBSTRATES SPECIFIC FOR HUMAN SPLEEN FIBRINOLYTIC PROTEINASE (SFP)

Two peptide anilides, Suc-Tyr-Leu-Val-pNA (III) and Ac-Ser-His-I.eu-Val-pNA (V) were synthesized by the conventional method with the object of obtaining specific substrates for human spleen fibrinolytic proteinase (SFP). The K_cat/K_m values for hydrolysis of HI and V by SFP were 22 64 7 and 2 700, respectively. On the contrary, the K_cat/K_m values for hydrolysis of III and V by porcine pancreatic elastase were 21 and 9, respectively.     

Clinical effectiveness of steroid pulse therapy combined with tonsillectomy in patients with immunoglobulin A nephropathy presenting glomerular haematuria and minimal proteinuria

Aim: The effectiveness of steroid pulse therapy combined with tonsillectomy (ST) has been shown in immunoglobulin A nephropathy (IgAN) patients with moderate or severe urinary abnormalities. The present study aimed to clarify whether the effectiveness may be extrapolated to IgAN with minor urinary abnormalities, and whether the effectiveness may depend on the histological severity with minor urinary abnormalities. Methods: Data on 388 IgAN patients diagnosed by renal biopsies between 1987 and 2000 in Sendai Shakaihoken Hospital, who presented glomerular haematuria and minimal proteinuria (≤0.5 g/day) at baseline, were analyzed. Cox regression was used to examine associations between baseline use of ST and subsequent clinical remission (CR), defined as negative proteinuria by dipstick and urinary erythrocytes of less than 1/high‐power field. The instrumental variable method was also used to overcome confounding by treatment indication. Results: During a median follow up of 24 months, we observed 170 CR cases. Patients receiving ST were younger and showed a better case‐mix profile. Patients with ST had a significantly higher rate of CR than patients without tonsillectomy or steroid pulse in an unadjusted (hazard ratio (HR) = 5.51, 95% confidence interval (CI) = 3.33–9.12, P < 0.001) or adjusted Cox model (HR = 4.65, 95% CI = 2.43–8.88, P < 0.001). Less severe histological findings were substantially associated with higher CR rate in ST group. Adjusting for confounding by treatment indication showed an attenuated but still significant effect of ST (HR = 3.10, 95% CI = 2.02–4.77, P < 0.001). Conclusion: ST significantly increased the probability of CR in IgAN patients with glomerular haematuria and minimal proteinuria, and it was more effective in those with less severe histological findings.     

Impact of aging on penile hemodynamics in men responding normally to prostaglandin injection: A power Doppler study

AIM: Hemodynamic changes with aging in the penile arterial circulation, including the helicine arteries, were evaluated with power Doppler imaging in erectile dysfunction patients with a normal response to prostaglandin injection. METHODS: In 36 patients with erectile dysfunction and no definite vascular risk factors, 72 corpora were examined using power Doppler imaging. Patients were classified by age: younger than 40 years, from 40 to 49, or 50 and older. Hemodynamic variables in the cavernous arteries, helicine arteries and dorsal arteries were measured after intracavernous injection of prostaglandin E1 (20 microg). RESULTS: All cavernous arteries had a maximum peak systolic velocity of greater than 35 cm/s and a minimum end-diastolic velocity of less than 0 cm/s. Mean peak systolic velocity in the cavernous artery differed between groups (P = 0.016), especially between the younger than 40 age group and the 40-49 age group. Peak systolic velocity correlated negatively with age (P = 0.0048). In the helicine arteries and dorsal arteries, peak systolic velocity did not differ between groups and showed no correlation with age. End-diastolic velocity, resistance index and acceleration time did not differ between groups, or correlate with age for any artery. CONCLUSIONS: Hemodynamic change with aging occurs predominantly in the cavernous arteries, where peak systolic velocity decreases. The arterial circulation beyond the cavernous arteries, including the helicine arteries, as well as veno-occlusive mechanisms, may have an important role in maintaining erectile function in aging.     

Giant retroperitoneal liposarcoma

Liposarcomas are one of the most common soft tissue sarcomas of adulthood. Liposarcomas are remarkable because of their frequently large size. We report a case with an extremely large dedifferentiated liposarcoma that weighed 18 kg. Although it was capsulated and could be excised en bloc, the patient suffered a relapse 9 months later and died 1 year after the operation.     

Laparoscopic prediction of hepatocellular carcinoma in cirrhosis patients

Previously, laparoscopic studies have not been successful in predicting the occurrence of small hepatocellular carcinoma because cirrhotic patients had not been separated into groups of those who developed small hepatocellular carcinoma under 3 cm in diameter, and those who did not. Retrospective examination with better separation of the two groups gave improved results. Of the 26 laparoscopic findings, only the presence of large complex regenerative nodules was closely associated with the occurrence of subclinical small hepatocellular carcinoma. The study of other cirrhotic patients with and without large complex regenerative nodules gave a cumulative hepatocellular carcinoma occurrence rate of 73% for patients who had these nodules by the third year after laparoscopy. In contrast, the rate for patients without such nodules was 6%, showing a significant difference (P < 0.05) between the two groups. We concluded that the laparoscopic finding of large complex regenerative nodules of liver cirrhosis can be used to predict the occurrence, or a complication, of subclinical small hepatocellular carcinoma.     

Optimized First Phase Tilt in "Parallel-Series" Biphasic Waveform

“Parallel-Series” Biphasic Waveform. Introduction: A biphasic defibrillation waveform can achieve a large second phase leading-edge voltage by a “parallel-series” switching system. Recently, such a system using two 30-μF capacitances demonstrated better defibrillation threshold than standard waveforms available in current implantable devices. However, the optimized tilt of such a “parallel-series” system had not been defined. Methods and Results: Defibrillation thresholds were evaluated for five different biphasic “parallel-series” waveforms (60/15 μF) and a biphasic “parallel-parallel” waveform (60/60 μF) in 12 anesthetized pigs. The five “parallel-series” waveforms had first phase tilts of 40%, 50%, 60%, 70%, and 80% with second phase pulse width of 3 msec. The “parallel-parallel” waveform had first phase tilt of 50% with second phase pulse width of 3 msec. The defibrillation lead system comprised a left pectoral “hot can” electrode (cathode) and a right ventricular lead (anode). The stored energy at defibrillation threshold of the “parallel-series” waveform with first phase tilts of 40%, 50%, 60%, 70%, and 80% was 7.0 ± 2.1, 6.1 ± 2.8, 6.8 ± 2.8, 7.2 ± 2.9. and 8.4 ± 3.1 J, respectively. The stored energy of the “parallel-series” waveform with a 50% first phase tilt was 16% less than the nonswitching “parallel-parallel” waveform (7.3 ± 2.8 J, P = 0.006). Conclusions: A first phase tilt of 50% maximized defibrillation efficacy of biphasic waveforms implemented with a “parallel-series” switching system. This optimized “parallel-series” waveform was more efficient than the comparable “parallel-parallel” biphasic waveform having the same first phase capacitance and tilt.     

Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel

Application of ultraviolet light irradiation to a photocrosslinkable chitosan aqueous solution resulted in an insoluble, flexible hydrogel like soft rubber within 60 seconds. In order to evaluate its accelerating effect on wound healing, full-thickness skin incisions were made on the backs of mice and subsequently a photocrosslinkable chitosan aqueous solution was added into the wound and irradiated with UV light for 90 seconds. Application of the chitosan hydrogel significantly induced wound contraction and accelerated wound closure and healing compared with the untreated controls. Histological examination also showed an advanced contraction rate on the first 2 days and tissue fill rate on days 2 to 4 in the chitosan hydrogel-treated wounds. Furthermore, in cell culture studies, chitosan hydrogel culture medium supplemented with 5% fetal-bovine serum was found to be chemoattractant for human dermal fibroblasts in an invasion chamber assay using filters coated with Matrigel and in a cell migration assay. Due to its ability to accelerate wound contraction and healing, chitosan hydrogel may become accepted as an occlusive dressing for wound management.     

Changes in serum and hepatic levels of immunoreactive prolyl hydroxylase in two models of hepatic fibrosis in rats

Changes in serum and hepatic levels of immunoreactive prolyl hydroxylase (IRPH) as well as cellular localization of the enzyme were studied in 2 models of hepatic fibrosis, which was induced in male rats either by subcutaneous administration of CCl4 (Group A) or by intraperitoneal injection of porcine serum (Group B). Hepatic fibrosis appeared at the 8th week in Group A and at the 12th week in Group B, and liver cirrhosis developed at the 16th week in both models. Although tissue contents of hydroxyproline (HP) and IRPH increased in both models, only HP levels correlated with the degree of fibrosis. Serum IRPH levels and serum asparate aminotransferase (AST) activities increased, showing a significant positive correlation, in group A, whereas both remained in a control range in Group B. Moreover, in another model which received a single intraperitoneal injection of CCl4, serum IRPH showed a marked increase and then a rapid decrease in parallel with the change in serum AST. Immunohistochemical analysis also showed a difference between the two fibrosis models: in group A, IRPH was positive mainly in parenchymal cells in the peripheral zone of the pseudolobulus, while in group B the staining was diffuse. These results indicate that the elevation of serum IRPH is, at least in part, due to the parenchymal cell damage, and that IRPH levels should be carefully evaluated when being used as a parameter to estimate the activity of fibrogenesis in the liver.