The effect of region of interest selection on dual energy X-ray absorptiometry measurements of the calcaneus in 55 post-menopausal women

Bone mineral density (BMD) of the calcaneus was assessed by dual energy X-ray absorptiometry (DXA) in four different regions of the calcaneus in 20 pre-menopausal and 55 post-menopausal women, none of whom were on treatment or suffering from conditions affecting bone. The total body option in the small animal software package of a Lunar DPX-L bone densitometer was used. The precision of the technique (%CV) varied from 0.7 to 2.2% depending on the region scanned. For post-menopausal women, BMD results in the mid and posterior parts of the calcaneus varied by < 7% while BMD in the anterior region was about 20% lower. DXA of the calcaneus was compared with measurements at the spine (L2-L4) and hip (femoral neck) and changes with age were estimated from cross-sectional data. BMD of the calcaneus was significantly reduced in 28 post-menopausal women with low lumbar spine BMD (-2SD) compared with women with normal spine BMD. Calcaneal BMD was significantly correlated to axial BMD (r = 0.45-0.77) and to age (r = 0.45 to -0.63). For a subgroup of 33 post-menopausal women measured twice after approximately 1 year, calcaneus BMD decreased by between 1.2% and 2.5% while axial BMD showed no significant change. Unlike spine or femoral neck BMD, the decrease in calcaneus BMD was significantly greater in women with low spine BMD than in normal women, possibly indicating improved detection of skeletal changes. The optimum measurement sites for BMD in the calcaneus were within the mid or posterior part of the calcaneus or enclosing the whole posterior calcaneus. The calcaneus was shown to be a precise, sensitive and simple measurement site suitable for the assessment of osteoporosis, especially in the elderly where degenerative changes in the spine and hip can complicate BMD assessment.     

Trans-synaptically induced bursts in regular spiking non-pyramidal cells in deep layers of the cat motor cortex

In deep layers of the cat motor cortex, we have investigated the properties of neurons displaying trans-synaptically induced bursts. In in vivo experiments, extracellularly recorded burst neurons were separated into two subtypes based on their dependence on stimulation sites, the medullary pyramid or the ventrolateral (VL) thalamic nucleus, from which bursts of 10-20 spikes were triggered. The spike amplitude attenuation and frequency adaptation during a burst were more prominent in pyramid-dependent burst neurons than in VL-dependent burst neurons. Intracellular recordings in in vivo experiments revealed that pyramid-dependent bursts emerged from a long-lasting depolarization, while each spike during a VL-dependent burst was narrow in half-width and was followed by a fast AHP, similar to fast spiking neurons. In in vitro slice experiments, intracellular recordings were obtained from neurons that displayed a burst of attenuated spikes emerging from a long-lasting depolarization, and were also obtained from fast spiking neurons. They were morphologically recovered to be multipolar cells with sparsely spiny dendrites and local axonal networks, suggesting that they are inhibitory interneurons. The multipolar neurons displaying bursts of attenuated spikes may mediate the recurrent inhibition of pyramidal tract cells.     

D-amphetamine-induced depletion of energy and dopamine in the rat striatum is attenuated by nicotinamide pretreatment

The present study examined the effects of nicotinamide on the D-amphetamine (AMPH)-induced dopamine (DA) depletion and energy metabolism change in the rat striatum. In chronic studies, co-administration of AMPH with desipramine, a drug that retards the metabolism of AMPH, (10 mg/kg, intraperitoneal [i.p.], respectively) caused a significant decrease of striatal DA content measured 7 days later. Pretreatment with nicotinamide (500 mg/kg, i.p.), the precursor molecule for the electron carrier molecule nicotinamide adenine dinucleotide (NAD), attenuated this effect of AMPH, whereas itself exerted no long-term effect on striatal DA content. In acute studies, a decrease in striatal adenosine triphospate/adenosine diphosphate (ATP/ADP) ratio was found 3 h after co-injection of AMPH and desipramine. However, nicotinamide pretreatment blocked the reduced striatal ATP/ADP ratio and resulted in a striking increase in striatal NAD content in AMPH-treated rats. Furthermore, nicotinamide was noted to increase striatal ATP/ADP ratio and NAD content in saline-treated rats. These findings suggest that nicotinamide protects against AMPH-induced DAergic neurotoxicity in the striatum of rats via energy supplement.     

Hyperfibrinogenemia is an independent risk factor for atherosclerotic renal artery stenosis

It is important to identify patients at risk for atherosclerotic renal artery stenosis because renal artery stenosis is a progressive disease and a potentially correctable problem. To determine the risk factors for atherosclerotic renal artery stenosis, we performed renal arteriography at the time of cardiac catheterization in 270 patients (M:F, 193:77, mean age: 59 years) with clinical ischemic heart disease. Before the procedure, demographic data, medical history, physical findings and laboratory data were obtained. The degree of coronary artery stenosis and renal artery stenosis was quantified with automatic edge detection technique. Significant renal artery stenosis, defined as a narrowing of the diameter by more than 50%, was identified in 28 (10%) patients. Three patients (1%) had bilateral disease. Significant coronary artery disease, defined as a narrowing of the diameter by more than 50%, was present in 231 patients (85%). By univariate logistic regression analysis, older age (68 +/- 8 vs. 58 +/- 10 years), the presence of hypertension (61% vs. 38%), the extent of coronary artery disease, a high fibrinogen level (391 +/- 93 mg/dl vs. 335 +/- 109 mg/dl), a low albumin level (3.9 +/- 0.4 g/dl vs. 4.1 +/- 0.4 g/dl), and a low hemoglobin level (12.5 +/- 1.6 g/dl vs. 13.5 +/- 1.6 g/dl) were associated with the presence of renal artery stenosis (p < 0.05). Serum lipids, lipoprotein(a), creatinine, sex, smoking, or diabetes were not associated. By multivariate logistic regression analysis, older age (OR: 2.43 analyzed by 10 years increment, p = 0.0001), the presence of hypertension (OR: 2.68, p = 0.039) and a higher fibrinogen level (OR: 1.63 analyzed by 100 mg/dl increment, p = 0. 038) were significant risk factors of renal artery stenosis. Fibrinogen level was negatively correlated with albumin level (r = -0.18, p = 0.004). These results suggest that hyperfibrinogenemia as well as old age and hypertension are independent risk factors for atherosclerotic renal artery stenosis. Copyright Copyright 1999 S. Karger AG, Basel     

(-)-Epiafzelechin: cyclooxygenase-1 inhibitor and anti-inflammatory agent from aerial parts of Celastrus orbiculatus.

An inhibitor of cyclooxygenase (COX)-1 activity of prostaglandin H2 synthase was isolated from aerial parts of Celastrus orbiculatus Thunb. (Celastraceae), an oriental folk medicine for rheumatoid arthritis by activity-guided column chromatographic methods. The COX inhibitor was identified as (-)-epiafzelechin, a member of flavan-3-ols by the structural analysis with HR-EI-mass, 1H-NMR and 13C-NMR spectral data. The compound exhibited a dose-dependent inhibition on the COX activity with an IC50 value of 15 microM. (-)-Epiafzelechin exhibited about 3-fold weaker inhibitory potency on the enzyme activity than indomethacin as a positive control. (-)-Epiafzelechin exhibited significant anti-inflammatory activity on carrageenin-induced mouse paw edema when the compound (100 mg/kg) was orally administrated at 1 h before carrageenin treatment.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Synthesis of benzo[c]phenanthridine derivatives and theirin vitro antitumor activities

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screenedin vitro antitumor activities against five different cell lines as well as12. Among them the representative cytotoxic results are shown as follows;p-quinone (11) [ED₅₀ (A549=0.22 μg/ml), (HCT15=0.21 μg/ml), fagaridine (1) (HCT 15=0.41 μg/ml), olefin (6) (HCT 15=0.06 μg/ml), acetal (7) (SKMEL-2=0.07 μg/ml), dihydrofagaridne (10) (A549=0. 38 μg/ml), 10-hydroxyfagaridine (12) (A 549=0.45 μg/ml). From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significantin vitro antitumor activity.     

Accuracy of college students' reports of parental handedness

College students' reports of their parents' handedness were compared with data provided by the parents themselves. The students' reports of their parents' writing hand were highly accurate, the reports of their parents' general handedness somewhat less so. For the latter measure, the students were asked, 'What is your mother's (father's) handedness?' and were given the choice 'left','either', 'right',and 'don't know'. Their answers were then compared with the investigators' classification based on the parents' answers to a 10-item hand-use questionnaire. For this measure, the accuracy of the students' reports was also found to be related to the students' own handedness.     

Developing an adverse drug reaction program in nursing homes

The study of 826 geriatric nursing home patients was undertaken by a pharmacist to determine the incidence of adverse reactions to drugs. A formalized adverse drug reaction reporting program was used as the basis for the detection of unwanted drug effects. Approximately 27% of patients experienced a moderate to severe adverse effect. Five groups of drugs accounted for three-quarters of the reactions detected. The majority of these reactions were predictable and preventable. Females over the age of 70 on large quantities of drugs were significantly more susceptible to experiencing an adverse reaction. Physicians implemented 76% of pharmacist initiated recommendations for the treatment of adverse effects and were appreciative of increased pharmacy involvement. The implementation of such recommendations was felt to have substantially reduced the incidence of drug-induced acute hospitalizations. Although the information was generated in nursing homes, it may be generalized to other geriatric specialty areas such as medical wards and extended care units. Several recommendations are provided on how other pharmacists can implement similar clinical services in their areas of professional practice.