Deficiency of Testosterone Associates with the Substrate of Atrial Fibrillation in the Rat Model

Background: Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF.
Methods and Results: We examined the electrophysiological properties of the atria in isolated-perfused hearts of sham-operated male (SM), female (SF), orchiectomized male with and without administration of testosterone (ORCH-T and ORCH), and ovariectomized female (OVX) Sprague-Dawley rats. An electrophysiological study revealed that repetitive atrial responses induced by electrical stimuli significantly increased in ORCH rats without changes in other electrophysiological properties and were abolished by administration of testosterone. To investigate the underlying mechanisms, we evaluated the expression level of calcium-handling proteins. In ORCH rats, the immunoreactive protein level of ryanodine receptor type 2 (RyR2) and sodium–calcium exchanger significantly increased as compared with SM and ORCH-T rats without alterations in the level of FK506-binding protein (FKBP12.6), sarcoendoplasmic reticulum Ca-ATPase, and phospholamban. Immunoprecipitation analysis demonstrated decreased binding of FKBP12.6 to RyR2 in ORCH rats, which was prevented by testosterone. In contrast, the expression levels of these proteins showed no significant differences between SF and OVX rats.
Conclusion: Deficiency of testosterone was arrhythmogenic in rat atria possibly through less binding of FKBP12.6 to RyR2, which could induce feasible calcium leakage from the sarcoendoplasmic reticulum. These results would explain, at least in part, the increase in the prevalence of AF in accordance with the decline of testosterone particularly in elderly men.     

Acquired total immunoglobulin G deficiency in a patient with primary biliary cirrhosis

Abstract. A 38-year-old Japanese woman was hospitalized for susceptibility to respiratory tract infections. Clinical examinations revealed asymptomatic primary cholestasis, abnormally elevated immunoglobulin M (IgM) and antimitochondrial antibody, being consistent with asymptomatic primary biliary cirrhosis. Three years later her serum immunoglobulin G (IgG) decreased remarkably, whereas other immunoglobulins were unchanged. Immunological examinations on the peripheral blood lymphocytes demonstrated spontaneous over-synthesis of serum IgM and decreased synthesis of IgG due to abnormal function of both T and B cells. Our case suggests a new possible association between primary biliary cirrhosis and IgG deficiency.     

Prostaglandin E2 release from isolated bladder strips in rats with spinal cord injury

AIM: Recent studies have shown that various factors contribute to the increased excitability into the bladder afferent nerves in spinal cord injury (SCI) rats. It has been reported that prostaglandins (PG) act as local modulators of reflex micturition in pathological conditions. In the present study, we measured the amount of PGE2 release from the bladder of chronic SCI rats. METHODS: Spinal cord was transected at the level of T8-9 in adult female Sprague-Dawley rats. After 10 weeks, specimens of the urinary bladder were obtained from SCI rats and sham-injured control rats, and bladder strips were dissected from the bladder. Using an muscle-bath technique and a microdialysis procedure, the dialysate, containing substance released from bladder strips, was collected. Then the amount of PGE2 in the dialysate was measured by radioimmunoassay. RESULTS: Excretion of urinary PGE2 was significantly higher in SCI rats than in control rats. PGE2 release from bladder strips was significantly higher in SCI rats than in control rats. Removal of urothelium caused significant decreases in PGE2 release in both control and SCI rats. Stretches of the bladder strips caused significant resting tension-dependent increases in PGE2 release from the strips with urothelium. CONCLUSIONS: The present data suggest that bladder urothelium partly contributes to the increase in PGE2 release from the bladder, and that bladder distension may cause increases in PGE2 release in SCI rats.     

In-situ Ocular Absorption of Ophthalmic β-Blockers through Ocular Membranes in Albino Rabbits

Ocular membranes have been characterized by in-situ absorption of the ophthalmic β-blockers carteolol (hydrophilic) and timolol and befunolol (lipophilic) using a cylindrical cell. After introduction of drug solution into the cell on the cornea, sclera (bulbar conjunctival and scleral layer) or palpebral conjunctiva, the disappearance of the drug from the cell was determined as in-situ absorption. The ophthalmic drugs disappeared from the conjunctival and scleral membranes although disappearance from the cornea was hardly observed. The conjunctival membrane showed the highest permeability. Lipophilic drugs were more permeable than hydrophilic. In-situ apparent permeability coefficients of the ophthalmic drugs through the conjunctiva and sclera correlated with the lipophilicity of drugs. A high drug concentration in the aqueous humor was observed after corneal application. There is a relationship between concentrations of drugs in the aqueous humor and previously reported in-vitro apparent permeability coefficients of the drugs in the cornea. This in-situ method using a cylindrical cell is a useful method of investigating the ocular absorption of ophthalmic drugs.     

Accidental transmission of HCV and treatment with interferon

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunode?ciency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2–3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.     

Adenosquamous Cell Carcinoma of the Colon with Severe Hypercalcemia: --Report of Two Cases--

Two patients with adenosquamous cell carcinoma of the colon,who presented severe hypercalcemia, are reported. Adenosquamouscell carcinoma of the colon is relatively rare, and there wereonly two cases among 1,053 patients who were hospitalized withmalignancy in the large intestine at the National Cancer CenterHospital during the past 18 years. Both of these cases presentedlethal hypercalcemia in the absence of osseous metastasis, andthere were no other patients who had malignant tumors of thelarge intestine and presented hypercalcemia. These observationssuggest that there is a close relationship between the squamouscell component and the occurrence of hypercalcemia, as is observedin the case of lung cancer. Radioimmunoactive parathyroid hormonewas undetectable in the plasma and the tumor tissue in thesetwo cases.     

A CASE OF FOAMY MYOCARDIAL TRANSFORMATION OF INFANCY

A case of Infantile cardiomyopathy in a year and four months old girl, which was clinically characterized by tachycardia resistent to any drugs and marked hyperplasia of mitochondria in their cytoplasms on electron microscopic observation, was presented. In the present case light and electron microscopical proof of the diagnosis was obtained by right endomyocardial biopsy, while most of this condition has not been recognized prior to autopsy. In Japan this newly recognized infantile cardiomyopathy has not been reported, and we proposed that this condition could be designated as mitochondrial cardiomyopathy caused by unknown etiology. The literatures described previously in the world have been reviewed.