Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects.

This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the ß-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 µmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.

Isoflavonoids from Belamcanda chinensis.

Four new isoflavonoids were isolated along with six known related compounds from a rhizome of Belamcanda chinensis (Iridaceae), and their structures were characterized as 6''-O-p-hydroxybenzoyliridin, 6''-O-vanilloyliridin, 5,6,7,3'-tetrahydroxy-4'-methoxyisoflavone and 2,3-dihydroirigenin, respectively, on the basis of spectroscopic methods and chemical evidence.

The neuromodulatory effects of VIP/PACAP on PC-12 cells are associated with their N-terminal structures.

ONOUE, S., WAKI, Y., NAGANO, Y., SATOH, S., KASHIMOTO, K. Neuromodulatory Effects of VIP/PACAP on PC-12 Cells Are Associated with Their N-terminal Structures. PEPTIDES xx(xx) 000-000, 200x.- The current study explored whether the differences in biological activities in PC-12 cells between vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are attributable to the sequence difference in their N-terminal portions and are correlated with the solution structures of the peptides. In the neurite outgrowth assay, N-terminal modification of VIP to PACAP-like sequences altered its effect, the activity was confirmed even at a low concentration (10(-10) M). On the contrary, N-terminal modification of PACAP 27 to VIP-like sequences reduced its activity. These relationships were also confirmed for the inhibitory effects of the peptide analogues on PC-12 cells growth at 10(-7) M. The present results combined with our previously reported data, including binding assay, support that the N-termini of VIP/PACAP plays an important role in their activities.

Synchronous multiple primary cancers of the stomach and duodenum in aged patients: report of two cases.

We describe herein the cases of two aged patients found to have synchronous multiple primary cancers of the stomach and duodenum. The first patient was an 82-year-old man who was preoperatively diagnosed as having gastric cancer after presenting with signs of pyloric stenosis. At laparotomy, duodenal cancer was incidentally found to have infiltrated the transverse colon. A pancreatoduodenectomy and right hemicolectomy with radical lymph node dissection was performed. Two early well-differentiated adenocarcinomas of the stomach and an advanced poorly differentiated adenocarcinoma of the duodenum were confirmed. This patient is now well without any evidence of recurrence more than 5 years after surgery. The second patient was a 77-year-old man who was also diagnosed as having gastric cancer after presenting with signs of pyloric stenosis. Preoperatively, duodenal cancer was detected by endoscopy. A pancreatoduodenectomy and partial colectomy with radical lymph node dissection was performed because the duodenal cancer was suspected of having infiltrated the transverse colon. An early moderately differentiated adenocarcinoma of the stomach and an advanced moderately differentiated adenocarcinoma of the duodenum were confirmed, but the duodenal cancer was not seen to invade the transverse colon microscopically. This patient died of cancer 7 months after surgery. Because multiple primary cancers commonly develop in elderly patients, a precise preoperative diagnosis must be made and optimal treatment applied.

Iridal-type triterpenoids with ichthyotoxic activity from belamcanda chinensis

Ichthyotoxic activity-guided fractionation of the hexane and ether extracts of Belamcanda chinensis (Iridaceae) has resulted in the isolation of eleven iridal-type triterpenoids including six new compounds, 3-O-tetradecanoyl-16-O-acetylisoiridogermanal (4), 3-O-decanoyl-16-O-acetylisoiridogermanal (5), belachinal (7), anhydrobelachinal (9), epianhydrobelachinal (10), and isoanhydrobelachinal (11). Structures of the new iridals were determined by spectral and chemical methods. The absolute configuration of isoiridogermanal (1) at C-16 was determined to be R by the modified Mosher's method. Of these compounds, 16-O-acetylisoiridogermanal (3), 7, and spiroiridal (12) exhibited potent ichthyotoxic activity against killie-fish (Oryzias latipes).

[A case of cranial osteomyelitis after head injury with exaggeration and remission for thirty years].

We report a case of cranial osteomyelitis after head injury with exaggeration and remission for 30 years. A 41-year-old man was referred to our hospital with redness, swelling and pain in the left frontal region. He had noted a hard mass in the same region after an injury at the age of 12 years, and local heat and redness again in the same region which had disappeared without definite treatment at the age of 20 years. Presently, skull roentogenogram showed an erosive lesion in the left frontal bone. Plain CT revealed bone defect, epidural mass lesion, calcification of the dura mater and thickness of the extracranial soft tissue in the left frontal region. T1-weighted MR images showed an isointense lesion and T2-weighted MR images showed a high intensity lesion in the inner table and a diploic layer in the left frontal bone. 99thTc MDP bone scinntigram showed abnormal uptake in the same region. Operation performed through a left frontotemporal craniotomy revealed a degeneration of temporal muscle and frontal bone, and granulation tissue and pus in the subcutaneous and epidural spaces. These were removed together with the calcified dura mater. The subdural space was intact. Dural plasty was performed using fascia lata, but the craniotomied bone was replaced. Histological examination revealed typical findings of osteomyelitis. Postoperative course was uneventful, and he was discharged without neurological deficit. Cranioplasty was performed 8 months after the first surgery. The mechanism by which osteomyelitis continued over a long course of time was suspected to be the formation of a focus of recurrent inflammation due to the head injury 30 years earlier.

A Case of Apocrine Carcinoma of the Breast Presenting as Two Cysts.

A case of apocrine carcinoma of the breast presenting as two cysts is reported. A 60-year-old woman had two soft, mobile, well-defined masses measuring 4 x 2.5 cm and 1.5 x2.5 cm in diameter in the lower-inner quadrant of the right breast. Tumor markers such as CEA, CA15-3, BCA225 and NCC-ST-439 were within normal limits. Mammography showed two oval radioopaque masses with microcalcificatin in the smaller one. Ultrasonography disclosed two cysts and papillary projection in the larger one. Fine needle aspiration cytology revealed apocrine carcinoma of the breast. Excisional biopsy confirmed the diagnosis of apocrine carcinoma with focal invasion. Modified radical mastectomy was performed. Pathological study showed that the tumor mainly proliferated in the cysts and the two cysts communicated with each other through an involved duct. There was no apocrine metaplasia in adjacent mammary gland. There were no metastatic lymph nodes. This case may be regarded as intraductal apocrine carcinoma developing two cysts with focal invasion.

Increase of mtDNA-binding proteins and mitochondrial mRNAs in regenerating liver.

In order to elucidate the mechanism of energy supply for liver regeneration after partial hepatectomy, we investigated mtDNA replication and transcription in regenerating rat liver. Changes of mtDNA-binding proteins, mtDNA, and mitochondrial mRNAs were monitored at 0, 12, 24, 48, 96, and 168 hr after the operation by gel mobility shift assay and Southern and Northern blot analyses, respectively. We focused on mtDNA-binding proteins specific for four different sequence elements possibly involved in regulation of mtDNA replication and transcription. Amounts of all the proteins sharply increased to maximum (4- to 10-fold of the preoperative level) 12 hr after partial hepatectomy and then decreased for 24 hr. After 24 hr, the amount of the respective binding protein changed diversely. Mitochondrial mRNA levels per gram tissue weight were unchanged during the first 12 hr after partial hepatectomy, but dramatically increased to maximum (4-fold) at 24 hr. In contrast, mtDNA content, expressed as a ratio of the nuclear cytochrome c1 gene, was unchanged during the first 48 hr and then started to increase, reaching maximum (1.5-fold) at 4 days. These results suggest that the energy supply in the early stage of the liver regeneration following hepatectomy is achieved mainly through enhancement of mtDNA transcription in which the mtDNA-binding proteins probably play regulatory roles.

Extraction and characterization of the smooth-type lipopolysaccharide from Fusobacterium nucleatum JCM 8532 and its biological activities.

The lipopolysaccharide (LPS) of Fusobacterium nucleatum JCM 8532 was isolated by hot-phenol water extraction. Most of the LPS was extracted in the phenolic phase and shown to be the smooth-type, whereas the aqueous phase contained mainly rough-type LPS. The chemical composition of the LPS was similar to that reported in other studies, but D-quinovosamine, which may be a major component of O-antigenic polysaccharide, and 3-deoxy-D-manno-2-octulosonic acid (Kdoi) were detected for the first time by gas chromatography-mass spectrometry. The biological activities of smooth-type LPS, including limulus activity, lethal toxicity, pyrogenicity, and B lymphocyte mitogenicity, were comparable to those of entero-bacterial LPS. Smooth-type LPS inhibited the cell growth and DNA synthesis of adult and fetal human gingival fibroblasts in a dose-dependent manner, suggesting that LPS may play a role in the occurrence of human gingivitis.

Elevated mitochondrial gene expression during rat liver regeneration after portal vein ligation.

We explored the molecular basis of mitochondrial energy production during rat liver regeneration after portal vein ligation. Ligation of the left branch of the portal vein induces an increase in the weight of the nonligated lobe, counterbalancing the reduced weight of the ligated lobe. Using this model, we investigated changes in mitochondrial DNA-binding proteins, mitochondrial DNA, and mitochondrial messenger RNA (mRNA) in rat hepatocytes of the nonligated lobes. The amount of mitochondrial DNA-binding protein increased maximally (200% to 300% of the preoperative level) at 12 hours after the operation, before an increase (390%) in mitochondrial DNA content at 24 hours, and parallel to an increase (240%) in mitochondrial mRNA levels at 12 hours. These results suggest that the energy supply for liver regeneration is achieved through enhancement of mitochondrial DNA replication as well as transcription, in which the mitochondrial DNA-binding proteins probably play regulatory roles. We also found that in the nonligated lobes, mRNA levels of hepatocyte growth factor increased to a detectable level only 12 hours after the operation. These molecular biochemical data help explain why preoperative portal vein embolization, which is a modification of portal vein branch ligation, is an effective method to prevent posthepatectomy liver failure.

Rat mitochondrial mtDNA-binding proteins to inter-specifically conserved sequences in the displacement loop region of vertebrate mtDNAs.

We describe two new inter-specifically conserved sequences named Mt5 and Mt6 elements which are around the termination associated sequence (TAS) at the 3' end of the displacement loop (D-loop) region of vertebrate mtDNAs. We employed gel mobility shift assay to search for D-loop-binding proteins using partially purified rat mitochondrial mtDNA-binding proteins and 10 human DNA fragments covering the entire D-loop region as probe DNAs. Competition binding assays indicated the presence of four different rat mitochondrial D-loop-binding proteins. Each of the rat proteins bound, in a sequence-specific manner, to a probe DNA containing an inter-specifically conserved sequence; TAS, Mt5, B block, and a A+T-rich sequence overlapping the conserved sequence block I.