Neurites of period-expressing PDH cells in the fly's optic lobe exhibit circadian oscillations in morphology

Circadian rhythms have been shown both in the expression of the period (per) gene in 'lateral neurons' and in cells of the outermost neuropil, or lamina, of the fly's optic lobe. Some lateral neurons also exhibit PDH peptide-like immunoreactivity, arborizing widely throughout the optic lobe. Using confocal microscopy in the housefly, we analysed the size and spacing of PDH neurite varicosities, sites of possible peptide release exhibiting circadian rhythmicity. During the subjective day in constant darkness, there were fewer, larger varicosities than during subjective night. The endogenous rhythm was masked by the light exposure that occurred under a day-night cycle and continuous light conditions. Our findings indicate that PDH neurites convey circadian information out from the pacemaker, where they could regulate the circadian rhythms that have been described in the lamina, possibly via cyclical release of their peptide.     

Effect of mycophenolic acid on TNF alpha-induced expression of cell adhesion molecules in human venous endothelial cells in vitro

1. The characteristic features of the endothelium-mediated regulation of the electrical and mechanical activity of the smooth muscle cells of cerebral arteries were studied by measuring membrane potential and isometric force in endothelium-intact and -denuded strips taken from the rabbit middle cerebral artery (MCA). 2. In endothelium-intact strips, histamine (His, 3-10 microM) and high K+ (20-80 mM) concentration-dependently produced a transient contraction followed by a sustained contraction. Noradrenaline (10 microM), 5-hydroxytryptamine (10 microM) and 9,11-epithio-11, 12-methano-thromboxane A2 (10 nM) each produced only a small contraction (less than 5% of the maximum K+-induced contraction). 3. N(G)-nitro-L-arginine (L-NOARG, 100 microM), but not indomethacin (10 microM), greatly enhanced the phasic and the tonic contractions induced by His (1-10 microM) in endothelium-intact, but not in endothelium-denuded strips, suggesting that spontaneous or basal release of nitric oxide (NO) from endothelial cells potently attenuates the His-induced contractions. Acetylcholine (ACh, 0.3-3 microM) caused concentration-dependent relaxation (maximum relaxation by 89.7 +/- 7.5%, n=4, P<0.05) when applied to endothelium-intact strips precontracted with His. L-NOARG had little effect on this ACh-induced relaxation (n=4; P<0.05). Apamin (0.1 microM), but not glibenclamide (3 microM), abolished the relaxation induced by ACh (0.3-3 microM) in L-NOARG-treated strips (n=4, P<0.05). 4. In endothelium-intact tissues, His (3 microM) depolarized the smooth muscle membrane potential (by 4.4 +/- 1.8 mV, n = 12, P < 0.05) whereas ACh (3 microM) caused membrane hyperpolarization (-20.9 +/- 3.0 mV, n = 25, P< 0.05). The ACh-induced membrane hypepolarization persisted after application of L-NOARG (-23.5 +/- 5.9 mV, n=8, P<0.05) or glibenclamide (-20.6 +/- 5.4 mV, n=5, P<0.05) but was greatly diminished by apamin (reduced to - 5.8 +/- 3.2 mV, n = 3, P< 0.05). 5. Sodium nitroprusside (0.1-10 microM) did not hyperpolarize the smooth muscle cell membrane potential (0.2 +/- 0.3 mV, n=4, P>0.05) but it greatly attenuated the His-induced contraction in endothelium-denuded strips (n-4, P<0.05). 6. These results suggest that, under the present experimental conditions: (i) spontaneous or basal release of NO from endothelial cells exerts a significant negative effect on agonist-induced contractions in rabbit MCA, and (ii) ACh primarily activates the release of endothelium-derived hyperpolarizing factor (EDHF) in rabbit MCA.     

Differential nitric oxide and TNF-alpha production of murine Kupffer cell subfractions upon priming with IFN-gamma and TNF-alpha

The effects of a nitric oxide (NO) donor on microcirculation and contractile function of reperfused skeletal muscle were studied. Rat cremaster muscles underwent 5 hours of ischemia and 90 minutes of reperfusion and were divided into two groups systemically infused with S-nitroso-N-acetylcysteine (SNAC, 100 nmol/min) and phosphate-buffered saline (PBS), respectively. The results showed that the vessels in the SNAC group had more rapid and complete recovery than that in controls. A significant difference was found from 10 to 40 minutes and at 90 minutes in 10-20-microm arterioles, from 10 to 90 minutes in 20-40-microm arterioles, and at 10 and 90 minutes in 40-70-microm arteries. When compared to controls, SNAC-treated muscles showed larger fluorescein filling areas at 15, 30, 60, and 90 minutes and greater isometric tetanic contractile forces in response to stimulation frequencies of 40, 70, 100, and 120 Hz. The data indicate that supplementation of exogenous NO could effectively improve microcirculation and contractile function of skeletal muscle during early reperfusion.     

Tuft-to-capsule adhesions and their precursors: differences between the vascular and tubular poles of the human glomerulus

The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone (CRH). The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol, testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed in nine premenopausal women (44-48 years of age), before and after ovariectomy. The CRH test was performed before and 8 days after ovariectomy. A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy, whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity. The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production.     

Provision of taxoids in 1996: inequality of care

OBJECTIVE: To inventory the utilization of taxoids in 1996. METHODS: A survey was conducted in february 1997 among the medical heads of 130 Dutch hospitals. The questions about the use of taxoids (paclitaxel and docetaxel) in 1996 concerned indications, numbers of patients treated, the funding and possible financial restrictions on the treatment. Three weeks after the mailing of the questionnaire, a reminder was sent to hospitals that had not responded. The data from 120 hospitals where oncological care was administered were analysed. RESULTS: Of the 120 hospitals, 111 (92.5%) returned the questionnaire, from 114 locations. Twelve locations reported not having used taxoids, four of them partly for financial reasons. Taxoids had been used at 102 locations: at the expense of the hospital budget at 101 locations, and exclusively at the expense of sickness insurers at one location. At 27 locations, paclitaxel and docetaxel had also been issued in the context of trials, and at 7 locations also via special agreements with the insurers and (or) at the expense of the patient himself. Fifty-three of the 102 taxoid using hospitals had a financial upper limit or a maximum number of patients to be treated. Eighteen of the 102 locations where paclitaxel or docetaxel was issued reported that for financial reasons not all patients eligible for taxoids had been given these drugs. The indications varied from one hospital to another: 67 locations used them for first-phase treatment of patients with ovarian carcinoma, 96 locations for second-phase treatment of patients with ovarian carcinoma and at 91 locations, patients with mammary carcinoma were given taxoids when anthracyclines were no longer indicated. CONCLUSION: Hospitals in 1996 varied greatly with regard to issuing of taxoids. This diversity in part had financial causes. Restrictions on the issuing of taxoids for financial reasons lead to unequal access to care.     

RNA-binding proteins tamed

OBJECTIVES: Enhancement of the remineralisation of artificial enamel lesions has been observed in an intraoral model whether subjects chewed gum sweetened with a non-cariogenic sweetener such as sorbitol [1-3] or sucrose [4] after meals or snacks, and with use of a conventional (1500 ppm F) fluoride dentifrice. Since most of the clinical surveys which have shown the potential cariogenicity of sucrose chewing gum [5] were conducted before use of fluoridated dentifrices became widespread, the effect of fluoride dentifrice on de- and remineralisation of artificial lesions in enamel in response to chewing sucrose-sweetened gum has been examined with the aim of attempting to resolve this apparent discrepancy. METHODS: Subjects wore an intraoral device bearing an enamel lesion and chewed one piece of sucrose gum for 20 min after each of three meals and two snacks daily for two 3-week periods, during which they used a dentifrice containing either 0 or 1500 ppm F in a double-blind, cross-over design. Measurement of the mineral content of the lesions was determined by microradiography or polarised light microscopy. RESULTS: It was found that remineralisation tended to occur with 1500 ppm F dentifrice, but demineralisation with non-F dentifrice; the difference in enamel mineral content between the two periods was significant (P < 0.05). CONCLUSIONS: The results indicate that the potential cariogenicity of sucrose-containing chewing gum may indeed be negated by the use of a conventional fluoride dentifrice.     

Fibroblast-like cells from tendons differ from skin fibroblasts in their ability to form three-dimensional structures in vitro

Recent structural information suggests that the HC(X)5R active-site motif defines three distinct evolutionary families of phosphatases that employ a common catalytic mechanism. In two instances, regulation of phosphatase activity employs autoinhibitory mechanisms involving either intermolecular or intramolecular interactions, whereby inhibition is mediated by sterically blocking the active-site cleft.     

Upper limb thrombosis associated with assisted conception treatment

Three cases of upper limb deep venous thrombosis occurring in association with assisted conception treatment are presented. The accepted argument that lower limb thrombosis occurring in cases of complicated or severe hyperstimulation syndrome represents the likeliest thrombo-embolic disorder in this situation is questioned.