Allopurinol inhibits uric acid accumulation in the rat brain following focal cerebral ischemia

Uric acid (UA) in the rat brain was measured by HPLC with an electrochemical detector following focal ischemia. At 24 h after the operation, the UA level in the ischemic center was 105.47 +/- 8.39 nmol/g tissue, whereas it was 8.36 +/- 1.86 in the sham-operated group. Allopurinol, xanthine oxidase inhibitor, almost completely inhibited this UA accumulation. These data demonstrate that the UA increase in the ischemic brain is due to the xanthine oxidase reaction.     

A comparative study on the convulsant activity of carbapenems and beta-lactams.

Beta-lactams are well known to have potent convulsant activity. Imipenem, the first carbapenem antibiotic introduced in the clinical field, has been reported to induce convulsions. The neurochemical mechanism of the convulsions induced by carbapenems and cephalosporins were studied. Intraventricular injection of cefazolin, cephaloridine and imipenem, and of panipenem (a new carbapenem), induced convulsions in a dose-dependent manner in mice. They inhibited the receptor binding of gamma-aminobutyric acid (GABA), an inhibitory transmitter in the mammalian central nervous system. These in-vitro and in-vivo results suggest that carbapenems and cephalosporins might induce convulsions through the inhibition of GABA receptor binding when they are accumulated in the central nervous system.     

Chemo-sensitivity of a human salivary adenocarcinoma cell line to several anti-cancer drugs and enhancement of the antitumor effects by combination with filipin or verapamil

A human salivary adenocarcinoma cell line, HSGc, was tested for the chemosensitivity and compared with a human squamous cell carcinoma cell line, KB. From IC50 values of anti-cancer drugs on the cells, it was found that HSGc was sensitive to CDDP, 5-FU and DTIC but resistant to ADM, MTX, VCR, PEP and MMC as compared to KB. The chemosensitivity of HSGc was in agreement with previously reported clinical data on the therapeutic results of salivary gland tumors. This suggests that HSGc may be an useful model for understanding the biological response of salivary adenocarcinoma cells to anti-cancer drugs. We further examined the combined effects of filipin and verapamil with these anti-cancer drugs. Filipin was found to enhance cell-killing effect of 5-FU and PEP on HSGc, while the combination of filipin with either DTIC or PEP was also effective on KB. Verapamil was effective in combination with 5-FU, VCR or PEP on HSGc and with DTIC, VCR or PEP on KB. Especially the most predominant enhancement on HSGc was observed in combination of filipin or verapamil with PEP. These findings suggest that even low-sensitive drug, PEP, is also useful when combined with either filipin or verapamil.     

Experimental and clinical evaluation of latamoxef in newborn and premature infants

Fundamental and clinical studies in infants including neonates on latamoxef (LMOX) were carried out, and following results were obtained. In fundamental studies, half-lives of LMOX were 5.79, 4.38 hours, at dose 10 mg/kg by intravenous injection and intravenous drip infusion in neonates, respectively. And urinary excretions were 6.8, 15.6% for 6 hours, respectively. In 28--50 day-old neonates, half-lives were 2.26--4.3 hours at dose 20 mg/kg, and urinary excretions were ranged from 14.3 to 37.0%. Clinical results were following. In 8 cases of bronchopneumonia and 2 cases of pertussis, the clinical efficacy rate was 100% at daily dose 38--100 mg/kg twice or third a day by intravenous injection or intravenous drip infusion for 6--9 days duration. All causative organisms (K. pneumoniae 1, S. aureus 1) were eliminated after LMOX 43 or 38 mg/kg/day dose administration. Side effect and laboratory abnormal value were not noticed in all cases. We finally have a conclusion that LMOX should be administered 40--70 mg/kg/day, and given twice or third a day by intravenous injection or intravenous drip infusion.     

A 42-month disease free survival case of combined hepatocellular-cholangiocarcinoma with lymph node metastases treated with multimodal therapy

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare type of liver cancer. We herein report a case of HCC-CC with lymph node metastases treated by multimodality therapy. The patient has been alive for more than 42 months. A 52-year-old man with a 9 cm diameter mass lesion in the liver was admitted to our hospital. The tumor was diagnosed as peripheral type of cholangiocarcinoma. Preoperative transhepatic arterial chemoenbolization (TACE) was performed. An accumulation pattern of lipiodol after TACE and an increase of serum alpha-fetoprotein led us to diagnosis of combined HCC-CC. A three segmentectomies of the liver and dissection of the local lymph nodes were performed. A histological examination of the resected specimen showed combined HCC-CC with lymph node metastases. Alpha fetoprotein, cytokeratins 7 and 19 were partially positive with immunohistochemical staining. The final diagnosis was a mixed type of combined HCC-CC. To improve a poor prognosis of combined HCC-CC, adjuvant chemotherapy with CDDP, 5 FU and radiation therapy were achieved. Fortunately, the patient is alive without any recurrence for 42 months after the operation.