Infective Endocarditis Due to Treponema pallidum: A Case Diagnosed Using Polymerase Chain Reaction Analysis of Aortic Valve

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis.     

Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Patients With Influenza

Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid.     

An updated review on pathophysiology and management of burning mouth syndrome with endocrinological,psychological and neuropathic perspectives

Burning mouth syndrome (BMS) is a chronic oro‐facial pain disorder of unknown cause. It is more common in peri‐ and post‐menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line–derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network–related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first‐line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well‐designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands.     

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

CYP2E1 and ALDH2 Genotypes and Alcohol Dependence in Japanese

The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and nonalcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphism of CYP2E1 (C₁/C₂) and ALDH2 ( ALDH2*1/ALDH2*2 ), and the susceptibility to alcoholism. There was no significant difference in C₂ gene frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas there was a significant difference in ALDH2 allele frequency, suggesting that, in Japanese, the C₂ genotype of CYP2E1 may have nothing to do with the risk of developing alcohol dependence. However, the ALDH2*1 allele may influence drinking behavior and the development of alcohol dependence. Furthermore, racial interethnic differences in the frequency of the mutated allele of the CYP2E1 gene (CJ were found, like the ALDH2 gene. Japanese healthy controls showed a significantly higher frequency of the C₂ allele than did Swedish healthy controls (0.05; reported by Persson et al., FEBS Lett. 319:207-211,1993).     

A case of lung cancer with hypercalcemia which was incidentally complicated with primary hyperparathyroidism due to parathyroid adenoma.

In lung cancer patients, hypercalcemia is a fairly common metabolic problem associated with malignancy. However, the occurrence of hypercalcemia in lung cancer patients means an ominous prognostic sign. As hypercalcemia often causes early death, quick diagnosis and treatment for hypercalcemia are required. A 69-year-old woman was admitted to our hospital with anorexia caused by hypercalcemia. On admission, serum level of PTH was elevated and PTHrP was normal. From the results of CT findings and transbronchial lung biopsy, the cause of the hypercalcemia was determined as lung cancer incidentally complicated with primary hyperparathyroidism. First, serum calcium level was returned to normal through hydration with saline and bisphosphonates. Next, left hemithyroidectomy for primary hyperparathyroidism was performed. Histologically, the tumor was diagnosed as parathyroid adenoma. Fifteen days later, left lower lobectomy for primary lung cancer was performed under a video-assisted thoracoscopic approach. Histologically, the tumor was diagnosed as a moderately differentiated adenocarcinoma. Four years and three months after the operation, the patient is alive and well with no sign of recurrence. When a lung cancer patient is complicated with hypercalcemia, we need to consider that primary hyperparathyroidism is a possible cause of the hypercalcemia.     

Functional and immunohistochemical studies of cultured rat microglia

We studied functional and immunohistochemical characteristics of cultured rat microglia. Unstimulated microglia did not proliferate. Microglia stimulated with LCM (L929 conditioned medium: colony stimulating factor-1) had proliferative activity and increased acid phosphatase activity. LPS (lipopolysaccharide) and IFN gamma (interferon-gamma) but did not affect proliferative activity. Immunohistochemically, RCA-1 lectin and GS-1 lectin, which react to beta-D-galactose and alpha-D-galactose respectively, strongly reacted to the cytoplasm and membrane of unstimulated microglia. After stimulation with LCM, microglia elongated processes and decreased response to these lectins. On the other hand, microglia stimulated with LCM showed increased reactivity to monoclonal antibody of vimentin. Microglia stimulated with LPS had round shape and had response to these lectins and vimentin. Microglia stimulated with IFN gamma had adhesive activity and weakly stained with these lectins but not with vimentin. ED-1 (monoclonal antibody of rat monocytes/macrophages) reacted to unstimulated and stimulated microglia. In flow cytometry, unstimulated microglia expressed OX-18 (MHC class I) and W3/25 (CD4) antigen. After stimulation with IFN gamma, microglia were induced to express these antigens. CD4 antigen is a marker of helper/inducer T cells and thought to be a receptor of HIV. The results that microglia had CD4 antigen which was further induced with IFN gamma are important to investigate infection of the CNS with HIV. OX-6 (Ia) antigen was induced with IFN gamma. This indicates that the microglia plays a central role in the CNS immune reaction. These characteristics of cultured rat microglia provide useful informations to investigate the pathogenesis of the CNS disorders.