Preparations,solution conformations and molecular structures of N,N′-ethylene-bridged dipeptides and their derivatives

The solution conformations of novel dipeptides, methyl (2S, 3′S)-3-methyl-2-(2′-oxo-3′-isopropyl-1′-piperazinyl)-butanoate (EVV-OCH₃), methyl (2S, 3′S)-3-phenyl-2-(2′-oxo-3′-benzyl-1′-piperazinyl) propionate (EFF-OCH₃), and their derivatives (Boc-Gly-EW-OH, Boc-Gly-EVV-Gly-OH, and Boc-Gly-EFF-OH), were studied by ‘H NMR measurements and molecular mechanics calculations (1). The molecular structures of Boc-Gly-EVV-OH, Boc-Gly-EFF-OH, and the hydrochloride of EVV-OCH₃ were determined by X-ray analyses. The conformations of the piperazinone rings and the side chains of these oligopeptides were clarified.     

Herpes simplex on nipples inoculated from herpetic gingivostomatitis of a baby

Herpes simplex on the nipples of a 31-year-old woman inoculated from herpetic gingivostomatitis of her baby is described. It is proposed that this condition is another special form of cutaneous inoculation herpes simplex.     

Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

PURPOSE: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. MATERIALS AND METHODS: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n=6-8). RESULTS: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 micromol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 micromol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%]=growth of TAK-165 treated tumor/average growth of control tumorx100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. CONCLUSIONS: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer.     

Conserved and novel structural characteristics of enantiomorphic Leu-enkephalin

The crystal of the Leu-enkephalin raceinate (L-Tyr-Gly-Gly-L-Phe-L-Leu and d -Tyr-Gly-Gly-D-Phe-D-Leu) was obtained as a centrosymmetric space group. Crystal data: C₂₈H₃₇N₅O₇· 1.5H₂O, M_w, = 582.6, triclinic, space group PI, a = 11.176(3), b = 16.115(3), c = 10.204(4) Å, α= 92.41(3), β= 104.86(2), γ= 85.35(2) °, V= 1770(1) ų, Z= 2; F(000) = 640, μ(CuKα) = 6.50 cm^?1, D_x= 1.081 g cm^?3. The structure was determined by X-ray diffraction. The conformation of the Leu-enkephalin racemate was classified into the extended form which has been often observed in natural enkephalin. The symmetry-related molecules were connected by hydrogen bonds and arranged in an antiparallel fashion. The molecular packing showed a sheet structure similar to that of natural enkephalin.     

Periodicity and prediction of mania onsets in biopolar I affective disorders

Abstract In studying the periodicity of mania onsets, cycle-oriented diagrams were made of the clinical course from 257 manic episodes analyzed retrospectively in 34 bipolar I manic-depressive patients for a period of about 5 years. Using these diagrams, the frequent period of mania onsets located in one-quarter of the follow-up period was pre-estimated, and the accordance ratio during a 25 month follow-up period was analyzed. The accordance ratio in all subjects was 39% (11/28) for the first episode and 35% (7/20) for the second episode. These ratios were not significantly different from the expected level (25%). The number of subjects was limited to 11 patients (10 rapid and 1 non-rapid cyclers) whose number of episodes used for the determination of the index cycle was eight or more. The accordance ratio was 64% (7/11) and 60% (6/10) for the first and second episodes, respectively. Their levels were significantly higher than those expected. Periodicity of mania onsets existed at least in rapid cyclers with abundant past data.     

Juvenile Secretory Carcinoma and Juvenile Papillomatosis

Two cases of juvenile secretory carcinoma associated with juvenilepapillomatosis are reported. One patient's disease was initiallydiagnosed at the age of 13 and she died 12 years later withextensive metastases. The contralateral breast at autopsy showedfindings indicative of juvenile papillomatosis. The second caseis that of an 18-year-old girl who had multiple juvenile secretorycarcinomas in the left breast associated with juvenile papillomatosis.     

High Efficacy of Disopyramide in the Management of Ventricular Fibrillation Storms in a Patient with Brugada Syndrome

The patient was a 57‐year‐old man with Brugada syndrome, who had been implanted with a implantable cardioverter defibrillator (ICD). The frequency of ventricular fibrillation (VF) started to increase about 4 years after ICD implantation, occurring, at worst, six times in one night. Immediately after starting oral administration of disopyramide, VF stopped occurring. He then discontinued taking disopyramide, but immediately after the discontinuation VF started occurring again, so he restarted taking disopyramide. Thereafter, VF completely stopped occurring. Findings observed in our case suggest that disopyramide could be added in our arsenal of medications for treating arrhythmic storms in patient with Brugada syndrome. (PACE 2010; 33:e53–e56)