Hyaluronan metabolism in overloaded temporomandibular joint.

This study aimed to examine hyaluronan (HA) metabolism in relation to the onset and progression of temporomandibular joint osteoarthritis (TMJ-OA) induced by mechanical overloading. Two-month-old and 6-month-old C57BL/6N mice were divided into experimental and untreated control groups (n = 5/group). A sliding plate was attached to the maxillary incisors of the experimental mice for 10 days to overload the condylar cartilage in TMJ. In experimental group, profound cartilage degradation was detected in haematoxylin-eosin, Safranin-O-Fast Green-stained sections. It was also shown that the cartilage degradation was greater in older mice in both the control and the experimental groups. The number of HABP-positive cells was decreased by mechanical overloading and with age. The reduction of HA expression was correlated with the progression of cartilage degradation induced by mechanical overloading. The absolute quantification of the mRNA expression related to HA synthesis and HA degradation was also performed in each group. The mRNA expression levels of HA synthase (HAS) 2 and 3 were lower in the experimental group compared with the control group in the younger mice. In contrast, the mRNA expression levels of the HA degradation gene, HYAL2 and KIAA1199, were higher in the experimental group compared with the control group in the older mice. Thus, mechanical overload differently affected the balance of HA degradation and HA synthesis in the older and younger mice, respectively. In conclusion, mechanical overloading affects HA metabolism and it might initiate or amplify the condylar cartilage degradation.

Prevalence and epidemiological traits of HIV infections in populations with high-risk behaviours as revealed by genetic analysis of HBV.

The prevalence and epidemiological traits of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) infections in high-risk populations (HRPs) remained unclarified in Japan. We determined the prevalence of HIV, HBV and Treponema pallidum (TP) and the viral genotypes in HRPs who attended primary sexually transmitted infection (STI) clinics in Osaka province during 2006-2011. Of 7898 specimens, 133 (1·7%) were HIV positive, which was significantly higher than the figures reported by Japanese Red Cross (0·0019%) and public health centres (0·27%) in Japan. The frequency of HIV-1 subtype B was 88·7%, followed by CRF01_AE (2·3%) and C (0·8%), which were almost identical to the national trend. HBV seroprevalence was surprisingly high in the HIV-positive group (63·2%), which was significantly higher than that in the HIV-negative group (25·6%). By contrast, there was no statistical correlation between HIV and TP infection. Interestingly, the distinct HBV genotypes Ae and G were prevalent in the HIV-positive population (60·0% and 20·0%, respectively), although both were rarely detected during nationwide surveillance. The transmission of HIV and HBV appeared to occur largely within a closed community early in life. Of note, about one-quarter of HIV-positive cases would have remained untested if health professionals had not motivated individuals to undergo HIV testing. This is the first evidence-based assessment of HIV positivity and HIV/HBV co-infection in HRPs at primary STIs in Japan and the effect of the involvement of health professionals in the diagnosis of HIV infections in asymptomatic carriers. The genotyping of HBV provided valuable information for understanding HIV epidemical traits.

Significance of late diastolic potential preceding Purkinje potential in verapamil-sensitive idiopathic left ventricular tachycardia.

BACKGROUND: Verapamil-sensitive idiopathic left ventricular tachycardia (VT) is due to reentry with an excitable gap. A late diastolic potential (LDP) is recorded during endocardial mapping of this VT, but its relation to the reentry circuit and significance in radiofrequency (RF) ablation remain to be elucidated. METHODS AND RESULTS: Sixteen consecutive patients with this specific VT were studied (12 men and 4 women; mean age, 32 years). In all patients, sustained VT was induced and during left ventricular endocardial mapping, LDP preceding Purkinje potential (PP) was recorded at the basal (11 patients), middle (3 patients), or apical septum (2 patients). The area with LDP recording was confined to a small region (0.5 to 1.0 cm2) in each patient and was included in the area where PP was recorded (2 to 3 cm2). The relative activation times of LDP, PP, and local ventricular potential (V) at the LDP recording site to the onset of QRS complex were -50.4+/-18.9, -15.2+/-9.6, and 3.0+/-13.3 ms, respectively. The earliest ventricular activation site during VT was identified at the posteroapical septum and was more apical in the septum than the region with LDP in every patient. In 9 patients, VT entrainment was done by pacing from the right ventricular outflow tract while recording LDP. During entrainment, LDP was orthodromically captured, and as the pacing rate was increased, the LDP-to-PP interval was prolonged, whereas stimulus-to-LDP and PP-to-V interval were constant. In 3 patients, the pressure applied to the catheter tip at the LDP region resulted in conduction block between LDP and PP and in VT termination. RF energy application at the LDP recording site successfully eliminated VT. CONCLUSIONS: LDP was suggested to represent the excitation at the entrance to the specialized area with a conduction delay in response to the increase in the rate within the critical slow conduction zone participating in the reentry circuit of this VT. LDP can be a useful marker for successful RF ablation for this VT.

Effects of verapamil and lidocaine on two components of the re-entry circuit of verapamil-senstitive idiopathic left ventricular tachycardia.

OBJECTIVES: We characterized pharmacologically the slow conduction zone of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) with regard to the late diastolic potential (LDP). BACKGROUND: We showed that the slow conduction zone of ILVT could be divided into two components by LDP; that is, the distal component with a tachycardia-dependent conduction delay property and the proximal one without it. METHODS: Electrophysiologic studies were performed in eight consecutive patients. The LDP was recorded during left ventricular (LV) mapping during ILVT. Entrainment was performed from the right ventricular outflow tract while recording LDP. The effects of lidocaine (1 mg/kg body weight) and verapamil (0.5 or 1.0 mg) were examined during entrainment. RESULTS: The LDPs preceding the Purkinje potential (PP) were serially recorded from the upper third to the middle of the LV septum along the narrow longitudinal line. The ventricular tachycardia (VT) cycle length increased after lidocaine (p < 0.05), and further after verapamil (p < 0.05). The increments in the VT cycle length after administration of the drugs strongly correlated with those in LDP-PP (r > 0.9 for both drugs). The interval from the ventricular potential to LDP was unchanged after administration of the drugs. In one patient, verapamil terminated VT by local conduction block between LDP and PP. The LDP-PP measured during entrainment increased after lidocaine, and further after verapamil, whereas the interval from the stimulus to LDP remained unchanged. CONCLUSIONS: The component distal to LDP is mainly calcium channel-dependent and partly depressed sodium channel-dependent. The proximal component is considered to be sodium channel-dependent (normal).

Comparative study on evaluation methods for serum testosterone level for PADAM diagnosis.

The International Society for the Study of the Aging Male (ISSAM) recommends that a diagnosis be based on a patient's total testosterone (TT), calculated free testosterone (cFT), or calculated bioavailable testosterone (cBT) for partial androgen deficiency of the aging male (PADAM). The purpose of this study was to confirm whether hypogonadism of patients with PADAM is related to symptoms and clarify which criteria of testosterone recommended by ISSAM is suitable for Japanese patients. A total of 90 patients with PADAM symptoms were included in this study. Endocrinologic profiles were reviewed as appropriate, and PADAM symptoms were judged by means of several questionnaires. Laboratory values and symptoms were compared between patients with and without hypogonadism. Even when any criterion of testosterone was used for diagnosis of hypogonadism, AMS (total and subscales), IIEF-5, or SDS scores of PADAM symptoms did not differ significantly between patients classified as having and not having hypogonadism. No other endocrinologic variables than testosterone differed significantly between them, either. PADAM symptoms are not related to testosterone level and it is still obscure whether ISSAM's criterion can be adopted for Japanese patients with PADAM. Other pathology needs to be addressed for evaluation and diagnosis of PADAM in Japan.

Purification and characterization of factor VII inhibitor found in a patient with life threatening bleeding.

We recently observed a patient with acquired inhibitor-induced F.VII deficiency whose plasma level of F.VII was < 1.0%. However, the biochemical nature of the inhibitor has not yet been clarified. In the present study, we purified the F.VII inhibitor from the patient's plasma by using activated F.VII (F.VIIa)-conjugated gel and characterized the inhibitor. The results showed that the inhibitor comprised two kinds of antibodies: one was eluted with EDTA (antibody 1) and the other with glycine-HCl buffer (pH 2.3) (antibody 2) from the F.VIIa affinity gel. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis of these inhibitors demonstrated that both antibodies had features of immunoglobulin G1 (IgG1) with kappa and lambda-light chains. Antibody 1 bound to the immobilized F.VIIa with a high affinity in the presence of calcium ion, while antibody 2 bound to the F.VIIa very weakly and the binding was independent of calcium ion. Immunoblotting analysis demonstrated that antibody 1 bound to the light chain of F.VIIa after reduction with 2-mercaptoethanol, while it did not react with either the gamma-carboxyglutamic acid (Gla)-domainless light chain of F.VIIa or the heavy chain with the protease domain. Antibody 1 markedly inhibited the activity of tissue factor-F.VIIa complex. Based on these observations, it is suggested that F.VIIa autoantibody (antibody 1) recognizes the calcium-dependent conformation within or near the Gla domain and inhibits F.VIIa activity by interacting with the light chain.

The upper turnover site in the reentry circuit of common atrial flutter.

The upper turnover site of the reentry circuit of common atrial flutter was examined with the uses of atrial activation mapping and extrastimulus techniques during atrial flutter. The findings suggest that it is anterior to the orifice of the superior vena cava, i.e., between the superior vena cava and tricuspid annulus.

Characteristics of slow conduction zone demonstrated during entrainment of idiopathic ventricular tachycardia of left ventricular origin.

Idiopathic ventricular tachycardia (VT) with the right bundle branch block pattern and left-axis deviation has been shown to be due to reentry, but the property of the slow conduction zone within the reentry circuit is little understood. In 7 patients (mean VT cycle length [CL]: 361 +/- 49 ms), rapid pacing from the right ventricular outflow tract was performed during VT while recording electrograms at the early activation site in the left ventricle and at the right ventricular apex; also, conduction times from the pacing site to these recording sits (St-A and St-B intervals, respectively) were measured. Both constant fusion (except for the last paced beat) and progressive fusion were seen in all patients, indicating VT entrainment. The left ventricular site was captured orthodromically with an St-A of 394 +/- 57 ms at the pacing CL of 351 +/- 47 ms during entrainment, while the right ventricular apex was captured directly with an St-B interval of 63 +/- 19 ms. The St-A interval was gradually prolonged with the shortening of the pacing CL, whereas the St-B interval remained unchanged. VT was interrupted in all patients at the pacing CL of 279 +/- 39 ms. The effects of intravenous lidocaine (1 mg/kg) and verapamil (1 mg) were examined in 5 and 7 patients, respectively. Neither drug terminated VT but the VT-CL was increased to 369 +/- 57 ms after lidocaine (p <0.05) and to 413 +/- 69 ms after verapamil (p <0.05) (p <0.05 vs after lidocaine). The St-A interval was significantly increased after lidocaine (p <0.05) and after verapamil (p <0.05), while the St-B interval remained unchanged. A significant correlation between changes in St-A interval and VT-CL after verapamil was noted (p <0.001). In conclusion, the slow conduction zone of this VT shows tachycardia-dependent conduction delay, and the mechanism of this slow conduction involves mainly calcium channel-dependent conduction and partly depressed sodium channel-dependent conduction.

Rapid decrease in neuropeptide Y gene expression in rat adrenal gland induced by the alpha 2-adrenoceptor agonist, clonidine.

1 The mechanism of regulation of the neuropeptide Y (NPY) gene by pharmacological treatment with the alpha 2-adrenenoceptor agonist, clonidine, was investigated by quantitative Northern blot analysis of the effects of this drug on the NPY mRNA levels in rat adrenal gland and medulla oblongata/pons. 2 In the adrenal gland, clonidine-treatment (50 microgram kg-1, s.c., once daily) resulted in decrease in the amount of NPY mRNA to 44 +/- 10% of the control level in 24 h and then its increase to 162 +/- 16% of the control level after 5 days. Concomitant changes in putative NPY pre-mRNA species (7.0 and 3.3 kb) were observed, probably due to changes at the level of NPY gene transcription. 3 The short-term (24 h) effect of clonidine was blocked by yohimbine (5 mg kg-1, i.p., once daily). Yohimbine alone tended to increase the NPY mRNA level after 24h. 4 The recovery/increase in the NPY mRNA level in the adrenal gland after 5 days treatment with clonidine was similar to its increase after treatment with reserpine (0.5 mg kg-1, i.p., once daily). 5 NPY gene expression in the medulla oblongata/pons was not changed by short- or long-term treatment with clonidine. 6 These results suggest that clonidine suppresses NPY gene expression in the adrenal gland, probably at the level of transcription, by activation of the alpha 2-adrenoceptor.

Decrease in prepro-neuropeptide Y gene expression in the adrenal gland and cerebral cortex of spontaneously hypertensive rats.

Changes in the mRNA and peptide levels of neuropeptide Y (NPY) in the adrenal gland and brain areas of spontaneously hypertensive rats (SHR) and of age-matched normotensive rats were investigated. The level of adrenal NPY mRNA of SHR decreased during progression of hypertension and was lower than that of Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats in the early stage of hypertension, while the level of adrenal NPY was unchanged or even higher than that of control rats. These findings suggest that both the biosynthesis and release of vasoconstrictive NPY peptide in the adrenal glands of SHR might decrease during progression of hypertension. In contrast, the NPY mRNA level neither decreased remarkably until week 17 in the cerebral cortex of SHR, nor changed at all in the other brain areas. This late decrease in cerebral NPY gene expression might be related to the disturbance in behavior and memory of SHR.

Effects of pilsicainide and propafenone on vagally induced atrial fibrillation: role of suppressant effect in conductivity.

The effects of pilsicainide on vagally induced atrial fibrillation and on electrophysiological parameters were compared with those of propafenone in alpha-chloralose-anesthetized dogs. Conduction velocity, effective refractory period, wavelength, averaged atrial fibrillation cycle length and activation sequence in the right atrial free wall were determined before and after drug administration. Pilsicainide (2 mg/kg/5 min and 3 mg/kg/h)(n=10) or propafenone (2 mg/kg/15 min and 4 mg/kg/h)(n=10) was intravenously infused during stable atrial fibrillation sustaining > 30 min. Pilsicainide terminated atrial fibrillation in nine dogs, while propafenone did so in three (p < 0.01). After the drug, conduction velocity was suppressed more in the pilsicainide than in the propafenone group(p < 0.01). There was no difference in effective refractory period after drug between the two groups. Mean wavelength was prolonged from 46.0 to 70.4 mm in the pilsicainide group and from 45.0 to 110.8 mm in the propafenone (p < 0.01 vs. pilsicainide). Activation mapping during atrial fibrillation showed Type II or III atrial fibrillation as previously defined [Konings, K.T.S., Kirchhof, C.J.H.J., Smeets, J.R.L.M., Wellens, H.J.J., Penn, O.C., Allessie, M.A., 1994. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. Vol. 89, pp. 511-521.] before the drug, and changed to Type I before atrial fibrillation termination. Thus, pilsicainide was more effective to terminate vagally induced atrial fibrillation than was propafenone despite a greater effect of propafenone than of pilsicainide on wavelength. In this canine atrial fibrillation model, the suppression of conduction velocity may play an important role in changing the activation pattern of atrial fibrillation and thus, terminating atrial fibrillation.

Clinical experience with the ACS RX Lifestream coronary dilatation catheter: a new low profile perfusion balloon catheter.

BACKGROUND: Although the use of the perfusion balloon catheter (PBC) has been widely accepted, there are some indicational limitations in percutaneous transluminal coronary angioplasty (PTCA). A new low profile perfusion balloon catheter, the ACS RX Lifestream Coronary Dilatation Catheter, was developed by Advanced Cardiovascular Systems, Inc. in which material and structures were improved to reduce previous limitations. PURPOSE AND STUDY DESIGN: In order to evaluate the ACS RX Lifestream Catheter's performance not only in PTCA but also in stent implantation, we used the catheter in 45 consecutive patients (male = 35, mean age 66 years) with combined use of 6F guiding catheter. Exclusions included total occlusions, long diffuse and acute MI lesions. There were 4 with Left Main Trunk Disease (LMTD), 15 with single vessel disease, 26 with multi-vessel disease, 20 with prior MI, 4 with prior CABG, and 10 with unstable angina. In bare stent procedures, a Johnson & Johnson metal stent was mounted on an ACS RX Lifestream Catheter previously used for predilation. Stent delivery and post-dilatation were performed using the same balloon. RESULTS: Forty-nine lesions in 45 cases (de novo lesion-31) including 7 of Type A, 15 of Type B1, 19 of Type B2, and 8 of Type C lesions were successfully dilated without any complications. Primary guiding catheter use was 6F in 40, 7F in 2 and 8F in 3 cases. The perfusion balloon was used alone in 30 cases and combined with stent placement in 15 cases. In 40 cases of 6F use, the ACS RX Lifestream Catheter could not cross the lesion in 3 cases at first attempt, of which 2 cases were successfully dilated with the balloon after predilatation with standard low-profile balloon catheters. Two cases with 7F use were bail-out cases after PTCA for long diffuse lesions. In one case of 8F guide use, flow patterns of ACS RX Lifestream Catheters and ACS RX Flowtrack Coronary Dilatation Catheters were examined with a flow-wire in the same lesion for comparison. All 15 stent cases performed using bare technique (10 with 6F, 2 with 7F and 3 with 8F guiding catheters) including 7 primary and 8 secondary use, were successful. Percent diameter stenosis pre-dilatation was 81% and 12.8% post-procedure. CONCLUSION: ACS RX Lifestream Catheter is a useful device in both PTCA and bare stent procedures. Consequently, it is possible to expand its indications to more difficult types of lesions.

[Determination of scopolia extract in commercial gastrointestinal drugs by high-performance liquid chromatography].

Tropane alkaloids, contained in gastrointestinal drugs including Scopolia Extract, were determined using high-performance liquid chromatographic method. Tropane alkaloids in commercial drugs were extracted with 0.5 N hydrochloric acid test solution. This solution was adjusted to pH 10.0 with a strong ammonia solution, extracted with ethyl ether, and separated on TSKgel ODS-120T (4.6 mm i.d. x 15 cm; temperature, 30 degrees C; flow rate, 1.5 ml/min; detector, UV 210 nm) with a mixture of 1/15 M sodium phosphate buffer (pH 2.5) and acetonitrile (68:32) containing 12 mM sodium dodecyl sulfate. The contents of atropine in the gastrointestinal drugs were 0.25-0.34 mg (coefficient of variation = 0.20-2.61%) a day.

[Therapeutic efficacies of neticonazole (SS717) cream and solution in experimental cutaneous Candida albicans infection of guinea pigs].

The therapeutic efficacies of 1% neticonazole (SS717) cream and solution on experimental cutaneous Candida albicans infection produced in prednisolone-treated guinea pigs were compared with those of 1% bifonazole (BFZ). Active preparations or blank vehicles were applied once daily for 3 consecutive days starting 5 days postinfection. Therapeutic effects were assessed on the basis of viable counts recovered from the infected loci 9 days postinfection. In animals treated with SS 717 or BFZ cream, a significant mycological improvement was observed when compared to untreated controls. A significant therapeutic efficacy of a SS717 cream compared to cream vehicle was also noted, while there was no significant difference in the recovery of Candida between the untreated control group and the cream vehicle-treated groups. The mycological result of the SS717 solution treated group was significantly superior to those of the untreated control group, the solution vehicle-treated group and the BFZ solution-treated group. The treatment with a solution vehicle or a BFZ solution appeared to lower, though not to a significant level, viable counts at the infected loci. These results led us to the conclusion that both SS717 cream and solution preparations exhibited significantly superior activity to that of BFZ in experimental cutaneous candidasis of guinea pigs.

[Congenital vesical diverticulum in a child].

A case of congenital vesical diverticulum in childhood is reported and 28 other cases in children from the Japanese literature are reviewed. A 9-year-old boy presented with hematuria and two-phase micturition. Excretory urogram and voiding cystourethrogram showed a diverticulum of the bladder on the left side and left vesico-ureteral reflex. Diverticulectomy and left ureteroneocystostomy (by Paquin's method) were performed. Post-surgical recovery was very good. All 28 cases we reviewed were in males whose average age was 6 years and 2 months. Their chief complaints consisted of dysuria, urinary infection and hematuria. The two-phase micturition appeared to be rather rare.

[Retroperitoneal ganglioneuroma: report of 3 cases].

We have experienced 3 cases of retroperitoneal ganglioneuroma. One case was in a 5-year-old boy with the chief complaint of abdominal mass. The preoperative diagnosis was neuroblastoma due to excessive urinary excretion of vanillylmandelic acid. The other two cases were in adults, 40 and 28 years old, and were found incidentally. All three cases were doing well without any clinical signs of recurrence almost 10 years, 5 years, and 6 months, postoperatively. The literature is reviewed briefly concerning some cases in children under 5 years of age whose ganglioneuromas were sometimes confused with neuroblastoma because of excessive catecholamines.

[A case of signet ring cell carcinoma of the urinary bladder].

A case of primary signet ring cell carcinoma of the urinary bladder is reported. A 52-year-old man was admitted with the complaint of gross hematuria. Cystoscopy showed non-papillary tumor on the right lateral wall. Abdominal CT, Ga scintigraphy, upper gastrointestinal series and barium enema, revealed no signs of a tumor other than the bladder carcinoma. The routine hematologic and chemistry profiles showed no abnormalities except for the serum level of carcinoembryonic antigen elevated to 210 ng/ml. Total cystectomy and right nephroureterectomy with left cutaneous ureterostomy was performed and the surgical specimen showed adenocarcinoma of the bladder. The patient died 5 months after the operation, and autopsy was performed. No tumors were found on the mucosa of the whole digestive tracts or pancreas. This case might be of primary adenocarcinoma originated from the bladder. The literature on the differential diagnosis of the cases reported as bladder adenocarcinoma are reviewed briefly.

[Metastasis of cancer of the renal pelvis and ureter to the adrenal gland].

A 67-year-old man was found to have a metastatic tumor of left adrenal gland originating from the left renal pelvic and ureteral cancer. Histopathological findings of the renal pelvic and ureteral cancer indicated transitional cell carcinoma, which was the diagnosis for the adrenal tumor. Diagnosis of cancer of the renal pelvis and ureter with metastasis to the adrenal gland before operation is very rare. A review of the literature on the metastasis from cancer of renal pelvis and ureter was made.

[Solitary ureteral metastasis from cervical cancer: a case report].

A case of solitary ureteral metastasis from cervical cancer in a 36-year-old female is reported. On April 4, 1988, the patient visited the gynecological department of our hospital with abnormal genital bleeding. Colposcopy and cervical biopsy revealed invasive cervical cancer, and computerized tomography (CT) indicated right hydronephrosis. She was referred to the urological department for further examinations. Right retrograde pyelography (RP) however could not be performed. On April 13, 1988, the patient underwent laparotomy due to acute abdomen, which was proved to be caused by subileus. On exploration, a tumor was found in the lower one third section of the right ureter, whereupon a right nephroureterectomy was performed because primary ureteral tumor was suspected. The histology of the ureteral tumor revealed it to be a metastatic squamous cell carcinoma identical to that obtained from punch biopsy of the cervix. At that time, a hysterectomy could not be done because of invasive cervical cancer. Following the operation, radiation therapy was conducted for primary cervical cancer. At present, 7 months after the operation, the patient is alive with good performance status.

[Distribution of neuropeptide Y (NPY) and its binding sites in human lower urinary tract. Histological analysis].

Neuropeptide Y (NPY), consisting of 36 amino acids, has been reported to coexist usually with noradrenaline in peripheral sympathetic neurons. For the purpose of clarifying the physiological role of NPY in lower urinary tract, I studied the existence of NPY and its binding sites around human bladder neck. The distribution of NPY in bladder neck was identified by means of immunohistochemistry. Abundant NPY fibers run parallel to muscle fibers, and NPY positive neuron plexus was recognized just beneath the serosa. Binding assay and autoradiographic study indicated the abundant NPY specificities in the epithelial and muscle layers from bladder neck to prostatic urethra. Present study revealed that NPY might be a possible neuromodulator in lower urinary tract, cooperating with noradrenaline.