Stereoselectivity of a potent calcium antagonist, 1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism.     

Effects of Increasing Concentrations of Propofol on Jugular Venous Bulb Oxygen Saturation in Neurosurgical Patients under Normothermic and Mildly Hypothermic Conditions

Background: Recent evidence suggested that propofol can deteriorate the cerebral oxygen balance compared with inhalational anesthetics. However, dose-related influences of propofol on cerebral oxygen balances were not clearly investigated. In the current study, the authors investigated the effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation (Sjo2) in neurosurgical patients under normothermic and mildly hypothermic conditions.

Methods: After institutional approval and informed consent were obtained, 30 adult patients undergoing elective craniotomy were studied. Patients were randomly allocated to either normothermic or hypothermic group (n = 15 in each group). In the normothermic and hypothermic groups, tympanic membrane temperature was maintained at 36.5[degrees] and 34.5[degrees]C, respectively. Sjo2 was measured at predicted propofol concentrations of 3, 5, and 7 [mu]g/ml using a target-controlled infusion system in both groups.

Results: At a predicted propofol concentration of 3 [mu]g/ml, there were no significant differences in Sjo2 values between the normothermic and hypothermic groups, although the incidence of desaturation (Sjo2 < 50%) was significantly higher in the normothermic group than in the hypothermic group (30% vs. 13%; P < 0.05). Sjo2 values and the incidence of desaturation remained unchanged during the changes in predicted propofol concentration from 3 to 7 [mu]g/ml both in the normothermic and hypothermic groups.     

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.     

Hemangioma of the Prostatic Urethra: Hematospermia and Massive Postejaculation Hematuria with Clot Retention

The case of a 53-year-old man with hematospermia and massive postejaculation hematuria that caused urinary retention is described. This is the sixth case in the English and Japanese language literature. Cystourethroscopic examination revealed that a solitary raised tumor was present just distal to the vermontanum, and that bleeding was from its apex. Histologic examination of an excisional biopsy sample showed features compatible with hemangioma.     

Influence of Osteoarthritis on Serum Marker Levels of Bone Formation and Resorption in Patients with Benign Prostatic Hypertrophy

Background :
The aim of this study was to investigate the influence of osteoarthritis of lumbar vertebrae on serum bone formation and resorption marker levels of patients with benign prostatic hypertrophy (BPH).
Methods :
Serum levels of carboxyterminal propeptide of type I procollagen (PICP), alkaline phosphatase (ALP), carboxyterminaltelopeptide of type I collagen (ICTP), and prostate-specific antigen (PSA) were examined in 40 patients with BPH, and the presence of osteoarthritis at the lumbar vertebrae of the patients was evaluated by plain x-ray-p.
Results :
Findings of osteoarthritis were observed in 23 of the 40 patients (58%), and 10 of the patients had severe osteoarthritis (involving at least 2 lumbar vertebral bodies). The serum levels of PICP, ALP, ICTP, and PSA of the patients without osteoarthritis findings were not different from those of the patients with osteoarthritis or severe osteoarthritis.
Conclusion :
The influence of osteoarthritis on serum bone formation and resorption marker levels of patients with BPH appears to be rather slight, if there is any influence at all.     

Shoulder instability: impact of glenohumeral arthrotomography on treatment

We used arthrotomography to study the glenoid labrum in 114 patients. Sixty-nine of the patients had anatomic instability of the shoulder (including recurrent dislocation and subluxation of the shoulder), and 45 patients had functional instability of the shoulder (denoted by chronic pain, clicking of the joint, and the sensation that an unstable condition exists without the objective signs of it). Labral tears were revealed arthrotomographically in 86% of the patients with anatomic instability, while only 40% of the patients with functional instability had labral abnormalities, and these were primarily of minor severity. Fifty-six patients (44 of whom had anatomic instability; 12, functional instability) required surgery. The surgical findings were correlated with the arthrotomographic findings, and no false-positive results were revealed. However, arthrotomography demonstrated only part of the pathologic condition of two patients. These results confirm that there is a strong correlation between labral pathologic conditions and anatomic instability of the shoulder. Arthrotomographic studies have a great impact on the selection of therapy in cases of both anatomic and functional instability of the shoulder.