Thioredoxin, an antioxidant redox protein, in ovarian follicles of women undergoing in vitro fertilization.

Oxidative stress has a bidirectional role in the development and maturation of zygotes and embryos. Reduction-oxidation reactions and regulatory proteins, such as thioredoxin (TRX) and thioredoxin reductase (TRXR), are intimately involved in the regulation of oxidative stress. The aim of this study was to determine the levels of TRX mRNA and protein in ovarian follicles collected from women undergoing in vitro fertilization (IVF) and to assess these levels relative to follicle size, presence of oocytes, and responsiveness to superovulation. Follicular fluid (FF) and/or granulosa cells (GCs) from large and small follicles were collected at the time of ovum pick-up from 42 IVF patients enrolled in this study. We divided the patients into normal and poor responders (NR and PR, respectively) based on the serum estradiol levels on the day of human chorionic gonadotropin (hCG) administration. We also compared the TRX concentration in FF (FF-TRX) between oocyte-containing follicles (Oc+) and empty follicles (Oc-). The transcript levels of TRX, but not TRXR, were significantly higher in GCs derived from follicles collected from NR than PR, as determined by semi-quantitative RT-PCR analysis. In NR, the FF-TRX was significantly higher in Oc+ follicles than in Oc- follicles and also in large Oc+ follicles than in large Oc- follicles. Unlike NR, PR exhibited no positive association with elevated FF-TRX and presence of oocytes. Based on its collective anti-oxidative, cytoprotective, and cytokine-like properties of TRX, TRX is likely to be involved in the optimal growth and maturation of ovarian follicles and responsiveness to hyperstimulation.

Two patients with acute rotavirus encephalitis associated with cerebellar signs and symptoms.

Rotavirus, one of the major causes of severe gastroenteritis in children, occasionally causes central nervous system complications. Recently several patients with acute encephalitis/encephalopathy due to rotavirus associated with cerebellar signs and symptoms have been reported. The condition is characterized by disturbances of consciousness at onset and cerebellar signs and symptoms such as hypotonia, ataxia, dysmetria, and speech disorders, including mutism, slow speech, and dysarthria at convalescence. We report two patients (3-year-old girl, 2-year-old boy) who developed acute encephalitis due to rotavirus and showed cerebellar signs and symptoms. Both patients had characteristic history of consciousness disturbances subsequent to several days of diarrhea, vomiting and fever, and cerebellar symptoms such as hypotonia, ataxia, dysmetria, and speech disorders during the recovery period. Electroencephalography showed diffuse high-voltage delta wave activity in each patient. Brain magnetic resonance imaging showed cerebellar edema in the acute phase followed by cerebellar atrophy on follow-up images in both patients. In the first patient, diffusion-weighted images (DWI) revealed high signals at the left cerebellar peduncle region and apparent diffusion coefficient (ADC) maps showed decreased ADC values of the lesion in the acute phase. The first patient had dysmetria at 1-year follow-up. However, she had normal motor and cognitive functions and could lead her daily life without impairment. In the second patient, no further symptoms were apparent at 1-year follow-up. Acute encephalitis/encephalopathy due to rotavirus with cerebellar signs and symptoms might be diagnosed on DWI, by demonstrating decreased ADC values in acute phase.

Pharmacokinetics and tissue penetration of a new carbapenem, doripenem, intravenously administered to laboratory animals.

The pharmacokinetic properties of doripenem following 20 mg/kg i.v. infusion were studied in various laboratory animals. The concentrations of doripenem in plasma, urine and tissue samples were determined by bioassay. Mean AUC0(0-infinityS) (microg x h/ml) and urinary recoveries (UR, %, 0-24 h) were 14.1 and 36.3 in mice, 9.3 and 42.1 in rats, 47.9 and 47.6 in rabbits, 78.6 and 83.1 in dogs and 44.1 and 51.0 in monkeys, respectively. In monkeys, with co-administration of probenecid, the mean AUC(0-infinity) of doripenem increased about 2.2 times and urinary excretion was delayed slightly. In mice, the doripenem level was highest in the blood plasma, followed by the kidney, liver, lung, heart and spleen. These doripenem levels in various tissues rapidly decreased and no accumulation was observed. Serum protein binding rates (%) of doripenem were 25.2 in mice, 35.2 in rats, 11.8 in rabbits, 10.2 in dogs, 6.1 in monkeys and 8.1 in humans, respectively.

Lobectomy of pulmonary metastasis of endometrial stromal sarcoma.

Pulmonary metastasis of low-grade endometrial stromal sarcoma is rare. A 61-year-old woman visited our hospital due to an abnormal chest shadow. Computed tomograhy showed a mass that was composed of a cystic and solid lesion, in the right lower lobe. She had undergone a combination of a hysterectomy and adnexectomy for a low-grade endometrial stromal sarcoma 57 months previously, and undergone adjuvant radiation therapy at the local site. To obtain a definitive diagnosis of the lung tumor, we performed lobectomy of the right lower lobe and lymph node dissection. To avoid possible dissemination, the tumor was resected not using video-assisted thoracic surgery but using thoracotomy. The pathologic diagnosis was pulmonary metastasis of the low-grade endometrial stromal sarcoma. Now, medroxyprogesterone acetate is being administered, and no signs of recurrence have been detected in the 24 months since the lung resection.

A nonsense mutation in the Arg345 of the insulin receptor gene in a Japanese type A insulin-resistant patient.

Defects in insulin receptor function have been associated with insulin resistant states such as obesity and type 2 diabetes mellitus. Several types of mutations in the insulin receptor gene have been identified in patients with genetic syndromes of extreme insulin resistance. We have studied a 10-year-old Japanese girl with type A insulin resistance with hirsutism and hyperinsulinemia but without the dysmorphic features characteristic of leprechaunism or Rabson-Mendenhall syndrome. Despite the presence of severe insulin resistance, the patient did not develop overt diabetes mellitus at the time of investigation. Using direct sequencing, we identified a nonsense mutation causing premature termination after amino acid 345 in the alpha subunit of the insulin receptor.