Sesquiterpenoid derivatives from Gonospermum elegans and their cytotoxic activity for HL-60 human promyelocytic cells

Four new compounds, a sesquiterpene, eleganodiol (1), and three sesquiterpene lactones, eleganolactone A (2), eleganolactone B (3), and elegain (4), were isolated from Gonospermum elegans along with 16 known compounds. The structures of 1, 2, and 4 were determined on the basis of MS and NMR studies of their acetate derivatives (1a, 2a, 4a). The structure of the acetate derivative (3a) of 3 was determined on the basis of spectroscopic data interpretation and by single-crystal X-ray diffraction. Compounds 2a and 3a were used to study their biological activities on the HL-60 human promyelocytic leukemia cell line. These compounds induced morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death.     

Functional outcome,rehabilitation use and length of hospital stay for stroke patients in south Madrid

BACKGROUND: Health status and use of resources by stroke patients in Spain are unknown. METHODS: A total of 103 acute stroke patients resident in south Madrid, population 665,168, were seen in 1996 at a general hospital and three primary care centres and evaluated at 5-10 days, 3 and 6 months after stroke. Health outcomes and patterns of rehabilitation and hospital use by patient groups were studied using multivariate logistic regression. RESULTS: The group receiving rehabilitation exhibited higher levels of impairment, disability and handicap at each time point, these differences decreasing with time, except in the distribution of walking ability which was unimodal in that group. Younger age, poor walking ability and motor capacity, pain on the paretic side and living with a spouse predicted use of rehabilitation; low level of education predicted a long hospital stay. CONCLUSION: Rehabilitation for stroke in south Madrid was sparse and used mainly by young, severely affected patients.     

Pyruvate protection against beta-amyloid-induced neuronal death: role of mitochondrial redox state

The mechanism by which beta-amyloid protein (A beta) causes degeneration in cultured neurons is not completely understood, but several lines of evidence suggest that A beta-mediated neuronal death is associated with an enhanced production of reactive oxygen species (ROS) and oxidative damage. In the present study, we address whether supplementation of glucose-containing culture media with energy substrates, pyruvate plus malate (P/M), protects rat primary neurons from A beta-induced degeneration and death. We found that P/M addition attenuated cell death evoked by beta-amyloid peptides (A beta(25-35) and A beta(1-40)) after 24 hr treatment and that this effect was blocked by alpha-ciano-3-hydroxycinnamate (CIN), suggesting that it requires mitochondrial pyruvate uptake. P/M supply to control and A beta-treated neuronal cultures increases cellular reducing power, as indicated by the ability to reduce the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The early increases in ROS levels, measured by dichlorofluorescein (DCF) fluorescence, and caspase-3 activity that follow exposure to A beta were notably reduced in the presence of P/M. These results place activation of caspase-3 most likely downstream of oxidative damage to the mitochondria and indicate that mitochondrial NAD(P) redox status plays a central role in the neuroprotective effect of pyruvate. Inhibition of respiratory chain complexes and mitochondrial uncoupling did not block the early increase in ROS levels, suggesting that A beta could initiate oxidative stress by activating a source of ROS that is not accesible to the antioxidant defenses fueled by mitochondrial substrates.     

Bietti's crystalline dystrophy. A 5-year progression

CASE REPORT: The case of a 54 year old male patient with Bietti's Crystalline Dystrophy is presented. Bietti's Crystalline Dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits, geographic areas of atrophy of the retinal pigment epithelium and choriocapillaris in the posterior pole as well as pigment clumps in the mid-periphery. The case of one patient with a 5 year follow-up is described. DISCUSSION: Minimal changes were observed by means of the ophthalmoscopic and fluorescein angiographic examinations. A slow progression of the pigmentary epithelium defects and of the choriocapillary atrophy was observed.     

The novel Na(+)/Ca(2+) exchange inhibitor KB-R7943 also blocks native and expressed neuronal nicotinic receptors

We studied the effects of the novel Na(+)/Ca(2+) exchange inhibitor KB-R7943, 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate, on the native nicotinic receptors present at the bovine adrenal chromaffin cells, as well as on rat brain alpha(3)beta(4) and alpha(7) nicotinic acetylcholine receptors (AChRs) expressed in XENOPUS: oocytes. As expected, KB-R7943 blocked the Na(+)-gradient dependent (45)Ca(2+) uptake into chromaffin cells (IC(50) of 5.5 microM); but in addition, the compound also inhibited the (45)Ca(2+) entry and the increase of cytosolic Ca(2+) concentration, [Ca(2+)](c), stimulated by 5 s pulses of ACh (IC(50) of 6.5 and 1.7 microM, respectively). In oocytes expressing alpha(3)beta(4) and alpha(7) nicotinic AChRs, voltage-clamped at -60 mV, inward currents elicited by 1 s pulses of 100 microM ACh (I(ACh)) were blocked by KB-R7943 with an IC(50) of 0.4 microM and a Hill coefficient of 0.9. Blockade of alpha(3)beta(4) currents by KB-R7943 was noncompetitive; moreover, the blocker (0.3 microM) became more active as the ACh concentration increased (34 versus 66% blockade at 30 microM and 1 mM ACh, respectively). Inhibition of alpha(3)beta(4) currents by 0.3 microM KB-R7943 was more pronounced at hyperpolarized potentials. If given within the ACh pulse (10 microM), the inhibition amounted to 33, 64 and 80% in oocytes voltage-clamped at -40, -60 and -100 mV, respectively. The onset of blockade was faster and the recovery slower at -100 mV; the reverse was true at -40 mV. In conclusion, KB-R7943 is a potent blocker of nicotinic AChRs; moreover, it displays many features of an open-channel blocker at the rat brain alpha(3)beta(4) AChR. These results should be considered when KB-R7943 is to be used to study Ca(2+) homeostasis in cells expressing nicotinic AChRs and the Na(+)/Ca(2+) exchanger.     

Association between androgen receptor gene CAG repeat polymorphism and breast cancer risk: a meta-analysis

Androgens have been hypothesized to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol and their binding to the estrogen receptor and/or androgen receptor (AR) in the breast. The CAG repeat polymorphism in AR exon 1 has been implicated in breast cancer risk; however, studies on the association between this polymorphism and breast cancer risk remain conflicting. In order to derive a more precise estimation of the relationship, a large population-based case–control study was performed. We found that a long CAG sequence has a protective effect on breast cancer using an a priori determined cutoff (<22 or ≥22) in a dominant model analysis [SL–LL vs. SS, odds ratio (OR) = 0.86, 95% confidence intervals (CI): 0.67–1.10]. A similar result was obtained by analyzing seven detailed genotyping case–control studies by allele comparison in dominant and recessive models. However, larger scale primary study is required to further evaluate the interaction of AR CAG polymorphism and breast cancer risk.     

Orthotopic heart transplantation in a patient with situs invs, transposition of the great arteries and Mustard operation.

Orthotopic heart transplantation has become standard treatment for end-stage cardiomyopathy, but experience with this technique for complex congenital heart diseases is limited. We report a patient with visceroatrial situs invs, transposition of the great arteries and previous Mustard correction, who successfully underwent orthotopic heart transplantation.