Saccular Aneurysm of the Azygos Anterior Cerebral Artery: Three Case Reports

The azygos anterior cerebral artery, a rare anomaly in the circle of Willis in which only a single vessel supplies the medial aspects of both anterior cerebral hemispheres, is closely associated with saccular aneurysms. We present three cases of azygos anterior cerebral artery aneurysms among the 781 cerebral aneurysms surgically treated at our institution in an 11-year period. These three cases all involved elderly women who presented with subarachnoid hemorrhage. Conventional cerebral angiography and CT angiography revealed small saccular aneurysms at the distal ends of the azygos anterior cerebral arteries. These aneurysms were clipped successfully using a bifrontal interhemispheric approach. Hence, the pathogenesis of these particular aneurysms relating to hemodynamic change, associated anomalies, and surgical pitfalls is discussed with review of literature.     

Why Are Human Cells Resistant to Malignant Cell Transformation in vitro?1

Transformation of human cells, both induced and spontaneous, is an extremely rare event, whereas rodent cells are relatively easily transformed when treated with a single carcinogenic agent. The present review addresses the question of why human cells are resistant to malignant transformation in vitro. To facilitate understanding of the problem, the process of transformation is divided operationally into two phases, i.e. phase I, immortalization; and phase II, malignant transformation. In human cells, one-phase transformation, i.e., the consecutive occurrence of phases I and II due to the action of a single carcinogenic agent, is observed only rarely. Once human cells are immortalized, however, malignant transformation by chemical carcinogens or oncogenes proceeds, suggesting that for human cells, phase I immortalization is a prerequisite for such transformation to take place. To date, about 20 papers have been published describing protocols for the two-phase transformation of a variety of human epithelial cells and fibroblasts. In most experiments, SV40, human papilloma viruses and their transforming genes are utilized for induction of phase I (immortalization) followed by the use of chemical carcinogens or activated oncogenes for induction of phase II (malignant transformation). Possible mechanisms that would render human cells refractory to transformation are discussed below.     

PAF antagonistic activity of 2-hydroxy-3-methoxybenzoic acid glucose ester fromGentiana scabra

In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract ofGentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with CH₂Cl₂ and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound1 was isolated by recrystallization. On the basis of spectral data, compound1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 μg/mouse.     

Dynamic alteration of human β-defensin 2 localization from cytoplasm to intercellular space in psoriatic skin

Defensins are cationic antimicrobial peptides with a broad spectrum. Recently human beta-defensin 2 (hBD-2) has been isolated from psoriatic skin; however, its exact localization and fate have not been fully understood. We studied the distribution pattern of hBD-2 in skin tissues of psoriasis and other inflammatory skin diseases. In the upper spinous and granular layer of psoriasis vulgaris hBD-2 was present in the cytoplasm. In the horny layer the positive signals were in a basket-weave pattern, indicating possible accumulation of hBD-2 in the intercellular space. The similar pattern of hBD-2 distribution was observed in the lesions of nummular eczema and atopic dermatitis. hBD-2 was not detected in the section of normal elbow and knee skin. When isolated psoriatic scales were stained, hBD-2 was detected in a wrapping paper-like distribution pattern surrounding the corneocytes. In horny layer of psoriatic skin hBD-2 was closely associated or colocalized with elafin, which is known to be in extracellular space, as demonstrated by double staining. Western blot analysis using cultured human keratinocytes detected hBD-2 with an expected size in the conditioned medium and in the cell lysates when stimulated with 5% FCS or IL-alpha. These results indicate that hBD-2 was synthesized and remained in cytoplasm in the upper spinous and granular layer, and then secreted into intercellular space in the horny layer. This dynamic change in hBD-2 distribution in epidermis is certainly relevant to function as an innate host defense mechanism against invading micro-organisms.     

Clinical characteristics of renal transplant recipients that underwent urologic surgery for de novo disease before and after transplantation

The pre-transplantation goal of the urologist is the optimization of urinary tract condition. Therefore, urologic surgery may be needed before or after renal transplantation. We analyzed the results of urologic surgery performed because of de novo urologic diseases. Between January 1986 and January 2001, 281 patients underwent renal transplantation, and 23 urologic surgical procedures were performed on 21 transplant recipients before or after renal transplantation because of de novo urologic diseases. By review the major reasons for urologic surgery in recipients were polycystic kidney diseases, vesicoureteral reflux, and dysfunctional voiding disorders. Nineteen surgical corrective procedures were done average 2.9 months before transplantation. The mortality rate was 10.5%. Four patients underwent urologic surgery at an average 57.5 months after transplantation. We highlight the fact that patients with uremia are vulnerable to surgical complications, and conclude that more intensive longterm urologic follow-ups should be conducted on recipients.     

Pharmacokinetics of oestrogens and progestogens

There are large inter- and intra-individual variations in the serum concentrations of natural and synthetic sex steroids irrespective of the route of administration. Oral ingestion of steroids has a stronger effect on hepatic metabolism than parenteral administration, as the local concentration in liver sinusoids are 4-5 times higher during the first liver passage. Oestradiol and oestrone are interconvertible, dependent on the local concentrations in liver and target organs, and oestrone sulphate serves as a large reservoir. The oestrone/oestradiol ratio has no physiological significance, as oestrone is only a weak oestrogen. Oestrone is both a precursor and a metabolite of oestradiol. Oestriol is extensively conjugated after oral administration. Therefore, the oestriol serum levels are similar after oral intake of 10 mg and after vaginal application of 0.5 mg oestriol resulting in similar systemic effectiveness. Conjugated oestrogens can easily enter the hepatocytes but are hormonally active only after hydrolyzation into the parent steroids. Ethinylestradiol which exerts strong effects on hepatic metabolism and inhibits metabolizing enzymes, should not be used for hormone replacement therapy. Among the progestogens, the progesterone derivatives have less effects on liver metabolism than the norethisterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes). The highly potent 13-ethyl-gonanes are effective at very low doses, because of a slow inactivation and elimination rate due to the ethinyl group.     

The effect of beta adrenergic stimulation on QT and QTc interval in syncope children with or without coexisting ventricular arrhythmias

We investigated the effect of beta-adrenergic stimulation on the heart rate and QT interval in syncope children with or without coexisting ventricular arrhythmias (VA). Of the 24 children who presented with syncope or presyncope and showed negative tilt test, 13 were classified into a group with VA and the remaining 11 without VA. The provocative test was performed in bolus infusion and continuous infusion. RR, QT, and QTc intervals on routine 12-lead surface electrocardiogram were obtained during each stage of isoproterenol infusion. In all cases, malignant ventricular arrhythmia and syncope were not induced by isoproterenol provocative test. RR and QT intervals were shortened and QTc intervals were prolonged as the isoproterenol dose was increased in both groups and methods. The QTc interval reached its peak level after the bolus injection of 1.0 microgram and during the continuous infusion of 0.03 microgram/kg/min. The two groups showed no significant difference in the QTc interval change according to the infusion methods. This study indicates that changes in the heart rate and QT interval by beta-adrenergic stimulation were not different according to the coexisting ventricular arrhythmias in syncope children with negative head-up tilt test.     

Differential modulation by baclofen on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the formalin test

Our previous studies have demonstrated that supraspinal GABAergic receptors are differentially involved in the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) in the tail-flick and hot-plate tests. These two models employed a phasic, thermal nociceptive stimulus. The present study was designed to examine the possible involvement of supraspinal GABAergic receptors in opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed the almost complete inhibitory effects against the hyperalgesic response in both phases. Muscimol (75-100 ng) and baclofen (5-10 ng) injected i.c.v. produced the hypoalgesic response in the both phases. The hypoalgesic response induced by muscimol and baclofen observed during the second phase was more pronounced than that observed during the second phase. Baclofen (2.5 ng), at the dose which did not affect the hyperalgesic response, resulted in a significant reversal of the i.c.v. administered beta-endorphin-induced hypoalgesic response observed during the second, but not the first, phase. However, the hypoalgesic response induced by i.c.v. administered morphine was not changed by the same dose of muscimol or baclofen injected i.c.v. Our results indicate that, at the supraspinal level, GABA(B)receptors appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin test model.     

Purification and characterization of Moran 20K fromMorus alba

A new glycoprotein was purified from the aqueous methanolic extract of the root bark ofMorus alba which has been used as a component of antidiabetic remedy in Oriental Medicine. SDS-PAGE result shows that the molecular weight of the glycoprotein was approximately 20 kDa. This new glycoprotein was named as Moran 20K. The protein lowered blood glucose level in streptozotocin-induced hyperglycemic mice model and it also increased the glucose transport in cultured epididymis fat cells. The amino acid composition of the protein was analyzed, and the protein contained above 20% serine and cysteine such as insulin. The actual molecular weight of the protein was determined as 21,858 Da by MALDI-TOF mass spectroscopy.     

Stimulus properties of the L-type calcium channel agonist BAY k 8644 in rats

Calcium (Ca(2+)) channels appear to be involved in the regulation of ethanol (EtOH) intake, as indicated by the effectiveness of both L-type Ca(2+) channel antagonists and agonists in reducing EtOH intake in animals. The present study was aimed to investigate rewarding/aversive and discriminative stimulus effects of the Ca(2+) channel agonist BAY k 8644, a compound showing pronounced anti-alcohol effects in rats. Therefore, a series of conditioned taste aversion (CTA), conditioned place preference (CPP) and two-lever drug discrimination (DD) experiments were conducted in Wistar rats, with (+/-)-BAY k 8644 and its enantiomers. After i.p. application, (+/-)-BAY k 8644 (0.0625-1mg/kg), (-)-BAY k 8644 (0.125-1mg/kg) and (+)-BAY k 8644 (2.5-20mg/kg) all induced a dose-dependent CTA. The minimal effective doses (MED) for (+/-)-, (-)- and (+)-BAY k 8644 were 0.25, 0.25 and 10mg/kg, respectively. In a CPP study, however, (+/-)-BAY k 8644 (0.25-2mg/kg, i.p.) showed neither aversive nor rewarding stimulus properties. Rats were trained to discriminate (-)-BAY k 8644 (0.3mg/kg, i.p.), the enantiomer acting as a high potency Ca(2+) channel agonist, from vehicle, in a two-lever DD procedure (ED(50)) value: 0.05mg/kg); full generalisation: 0.1mg/kg). The (-)-BAY k 8644 cue dose-dependently generalized to (+/-)-BAY k 8644 and (+)-BAY k 8644, the enantiomer acting as a low potency Ca(2+) channel antagonist, with ED(50) values of 0.06 and 0.28mg/kg, respectively. Both (+/-)- and (+)-BAY k 8644 produced full generalization at 1mg/kg, the latter compound showing an inverted U-shaped curve (i.e., this was the only dose showing >80% drug lever selection). The stimulus patterns of BAY k 8644 and its enantiomers appear to resemble the anti-alcohol profiles of these compounds. Therefore, commonalities between the stimulus properties of the agonistic and antagonistic enantiomers might provide a clue for the mechanism underlying the anti-alcohol effects of L-type Ca(2+) channel antagonists and agonists.