Treatment of NASH: nutritional counseling and physical exercise

Nonalcoholic fatty liver disease(NAFLD) is recognized as a cause of potentially progressive liver damage. NAFLD is often associated with metabolic syndrome that comprises central obesity, insulin resistance, and hyperlipidemia. Among these, severer forms with histopathological features of increasing ballooned hepatocytes and fibrosis are defined as nonalcoholic steatohepatitis (NASH). The natural history of NASH is only partly known, the disease is slowly progressive and therapeutic outcomes are difficult to define. Since central obesity and insulin resistance are most likely involved in the pathogenesis, justification of life style including physical exercise and nutritional counseling is essential for the treatment of NASH.     

Divided-dose administration of miglitol just before and 15 minutes after the start of a meal smoothes postprandial plasma glucose excursions and serum insulin responses in healthy men

We recently demonstrated that administration of miglitol at 15 min after the start of a meal decreased the area under the curve (AUC) of plasma glucose, similar to the observation following its administration just before a meal. This finding prompted us to examine whether a divided-dose regimen of miglitol might attenuate postprandial glucose excursions even more effectively. We, therefore, examined several schedules of miglitol administration in 15 healthy men. Miglitol was administered by four different schedules in each subject (control: no miglitol, intake 1: drug administered just before a meal (50 mg); intake 2: drug administered at 15 min after the start of a meal (50 mg); intake 3: drug administered in two divided doses: just before a meal (25 mg) and at 15 min after the start of a meal (25 mg). The AUC of glucose excursions, defined as increment above the fasting glucose level, (AUC(0-180 min) of glucose excursions) was significantly reduced as compared with that in the control condition after miglitol administration by intake schedule 3, while this parameter showed a tendency towards decrease after the drug administration by intake schedules 1 and 2. The AUC(0-180 min) of the serum insulin level was also significantly decreased for all the intake schedules of miglitol, as compared with that in the control condition. Thus, administration of miglitol in two divided doses appeared to be the most suitable for obtaining effective regulation of postprandial glucose excursions in healthy men. This result may suggest that the divided-dose administration regimen may also be effective in diabetic patients.     

Early relapse of Burkitt's lymphoma with t(8;14) and t(14;18) after rituximab-combined CODOX-M and IVAC therapy

A 43-year-old female was admitted with therapy-resistant pancreatitis and an abdominal tumor around the pancreatic head. Laboratory data revealed leukocytosis with a white blood cell count of 18200/microl, 25% atypical cells and an LDH of 13410 IU/l. The bone marrow was comprised of 78.4 percent lymphoblastoid cells which were positive for CD10, CD19 and CD20, and the cytogenetic study of which demonstrated the presence of t(8;14) (q24;q32) and t(14;18) (q32;q21) in the same clone. The patient was diagnosed as having Burkitt's lymphoma (BL) with t(8;14) and t(14;18). Although CODOX-M and IVAC therapy combined with rituximab achieved complete remission, she died of rapid progressive disease during whole brain irradiation before autologous peripheral blood stem cell transplantation. Even if the intensive chemotherapy with rituximab is given adequately, durable remission may not be achieved in BL with translocation of t(8;14) and t(14;18). A more effective therapy remains to be established for the treatment of this disease.     

The hotei mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development

We previously performed mutant screens in the medaka for defects in gonadal development and identified a mutant of interest in this regard, which was designated as hotei (hot). This mutant manifests a number of remarkable phenotypic abnormalities including: (i) excessive proliferation of germ cells that initiates at around the hatching stage regardless of the genetic sex of the fish; (ii) initiation of premature meiosis in phenotypically male hot homozygotes; (iii) one-half of the hot-homozygous XY fish undergo sex reversal, which accompanies the expression of the female-characteristic aromatase gene in the somatic cells of the gonad; and (iv) in phenotypically female homozygotes, follicular development is arrested at an early stage. We have also performed genetic mapping, chromosome walking, and candidate gene sequencing analysis of hot and demonstrate that the underlying mutation occurs in the recently identified medaka anti-Müllerian hormone (Amh) receptor type II (amhrII) gene. Moreover, this gene was found to be responsible for each of the hot phenotypes, as an amhrII transgene rescues these abnormalities. In addition, the amhrII gene is expressed in the somatic cells of the gonads of both sexes. The phenotypes of the hot homozygotes indicate that there are multiple regulatory functions of the AMH/AMHRII signaling system in the development of the gonad, including the sex-dependent regulation of germ cell proliferation and follicular development. These presumably represent the basic roles of Amh, which precede Müllerian duct evolution during phylogeny.     

DEPOSITION OF IGA-DOMINANT IMMUNE-COMPLEXES IN MUSCULAR VESSELS FROM PATIENTS WITH IGA NEPHROPATHY

The emergence of immunoglobulin depositions in muscular vessels from patients with IgA nephropathy was examined to determine whether the pathogenesis of IgA nephropathy was mediated by circulating IgA-dominant immune-complexes. Muscle biopsy specimens were obtained from the right flank at the same time of modified open renal biopsy. These biopsy samples were stained with fluorescein-conjugated anti human IgG, IgA, IgM, IgE, and C3 antisera It was demonstrated that the depositions of IgA and/or C3 were observed in muscular vessels from some patients with IgA nephropathy. It is indicated that IgA nephropathy might be mediated by circulating IgA-dominant immune-complexes.     

Estrogen receptor expression by peripheral blood mononuclear cells of patients with systemic lupus erythematosus

To investigate the influence of sex hormones on the development of systemic lupus erythematosus (SLE), we examined the estrogen receptor (ER) expression by peripheral blood mononuclear cells (PBMC) in patients with SLE using the real-time quantitative polymerase chain reaction (TaqMan) method. The expression of messenger RNA (mRNA) for ER alpha (ERa) was increased and expression of ER beta (ERb) mRNA was decreased in PBMC from SLE patients compared with PBMC from normal controls. These findings may be useful for elucidation of the pathophysiology of SLE.     

A case of tuberculous bronchial stenosis, diagnosed after 50 years of pulmonary and laryngeal tuberculosis]

A 82-year-old woman was referred to our department for further evaluation of her atelectasis in the left lower lobe of the lung which was found under preoperative examination for a renal pelvic tumor resection. Bronchoscopic examination was performed, and a pin-hole stenosis at the orifice of the left main bronchus was detected. Tuberculous bronchial stenosis was suspected because she had pulmonary and laryngeal tuberculosis 50 years ago. The dilatation of the stenosis was supposed to be necessary in order to prevent a pulmonary complication during the perioperative period. The stenotic area was dilated using argon plasma coagulation. Eight weeks after the procedure, a bronchoscope 6mm in external diameter could pass the dilated area. We reported a rare case with tuberculous bronchial stenosis in which the patient had never experienced a severe complication for 50 years despite the pin-hole stenosis in the left main bronchus.     

Appropriate Heart Rate in a Patient with Repaired Tetralogy of Fallot

Appropriate heart rate in a failing pulmonary ventricle remains unknown, particularly in congenital heart disease with unique hemodynamics. A 71-year-old male with repaired tetralogy of Fallot and a pacemaker for a sinus node dysfunction suffered from heart failure symptoms with preserved left ventricular function. Simply changing the pacemaker’s lower rate from 60 to 75 bpm, New York Heart Association classification improved from III to II, and hemodynamic parameters drastically improved. We regarded this case as informative. Appropriate heart rate could be higher in congenital patients with failing right and non-failing left ventricles than in adults with malfunctioning LV.