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.     

Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX

VanX, one of the five proteins required for the vancomycin-resistant phenotype in clinically pathogenic Enterococci, is a zinc-containing d-Ala-d-Ala dipeptidase. To identify potential zinc ligands and begin defining the active site residues, we have mutated the 2 cysteine, 5 histidine, and 4 of the 28 aspartate and glutamate residues in the 202 residue VanX protein. Of 10 mutations, 3 cause inactivation and greater than 90% loss of zinc in purified enzyme samples, implicating His116, Asp123, and His184 as zinc-coordinating residues. Homology searches using the 10 amino acid sequence SxHxxGxAxD, in which histidine and aspartate residues are putative zinc ligands, identified the metal coordinating ligands in the N-terminal domain of the murine Sonic hedgehog protein, which also exhibits an architecture for metal coordination identical to that observed in thermolysin from Bacillus thermoproteolyticus. Furthermore, this 10 amino acid consensus sequence is found in the Streptomyces albus G zinc-dependent N-acyl-d-Ala-d-Ala carboxypeptidase, an enzyme catalyzing essentially the same d-Ala-d-Ala dipeptide bond cleavage as VanX, suggesting equivalent mechanisms and zinc catalytic site architectures. VanX residue Glu181 is analogous to the Glu143 catalytic base in B. thermoproteolyticus thermolysin, and the E181A VanX mutant has no detectable dipeptidase activity, yet maintains near-stoichiometric zinc content, a result consistent with the participation of the residue as a catalytic base.     

Lobular carcinoma of the breast: cytological features supporting the diagnosis of lobular cancer

Lobular carcinomas have a distinct natural history with a better response to endocrine therapy and a higher incidence of local recurrence and are more often bilateral. The cytological diagnosis of lobular carcinoma permits a discriminating therapeutic approach with pre-operative Tamoxifen, more generous resection margins, and assessment of the contralateral breast. The cytological features of lobular cancer however are not well defined and the low cell yield from such neoplasms can result in a high false negative rate. To determine whether we could improve the pre-operative diagnosis, we reviewed the cytological features of 112 lobular carcinomas. They had small uniform sized nuclei with irregular outlines and inconspicuous nucleoli. The degree of dissociation was similar to duct carcinomas and the incidence of inadequate aspirates was no higher. We found no features that confidently diagnosed lobular cancer or its sub-types. However, using a combination of features, typing of lobular cancer on aspirated material is possible and should be attempted.     

The age-related characteristics of feather formation in birds and the physiological role of sulfur as sodium sulfate in keratin synthesis in the plumage

There were studied formation's processes of feathering in chickens and goslings and role of sulphur sulphate in synthesis of keratin's feathers. It is established, that sulphur sulphate sodium is used for synthesis of precursors of keratin's feathers. The including of 35S-sulphate natrii regulates the intensity of feather's growth. The content of sulphur in amino acids containing sulphur in feathers of chickens for period from 1 till 60 days of age is increasing from 6.34 to 94.47 per cent. Fattening in composition of feed the sulphate natrii stimulates by chickens and goslings the intensity of feather's growth and metabolism of sulphur in skin.     

Crossover comparison of the pharmacokinetics of amlodipine and felodipine ER in hypertensive patients

The pharmacokinetics of amlodipine 5 mg and felodipine ER (extended release) 5 mg o.d. after single and 2 weeks of repeated oral doses, were compared in 28 essential hypertensive patients using a crossover design. As a secondary parameter the effects of the drugs on blood pressure were assessed. Significant differences were found between all principal pharmacokinetic variables, when comparing the 2 treatments after both single and repeated dosing. The coefficients of variation of maximal drug concentration and AUC after single dosing and at steady-state were significantly higher for felodipine ER than for amlodipine. After repeated dosing the peak-to-trough plasma concentration ratio were 1.58 and 4.43 (p < 0.001) for amlodipine and felodipine ER, respectively. Both drugs lowered systolic and diastolic blood pressure to the same extent after 2 weeks of repeated dosing. No significant differences between the blood pressure lowering vs time profile of the 2 drugs were encountered. In conclusion, the interpatient drug concentration variability and the peak-to-trough plasma concentration ratio were more favorable for amlodipine compared to felodipine ER. It remains to be established whether these characteristics are also reflected in a more smooth and consistent blood pressure control.     

Effect of familial hypophosphatemic rickets on dental development: a controlled, longitudinal study

Familial or X-linked hypophosphatemic rickets (XLHR) is the most common type of rickets in developed countries today. While the dental manifestations of rickets are well reported, there is little information regarding its relationship to dental development and other dental anomalies. This investigation studied the rate of dental development and associated dental anomalies in 19 XLHR subjects compared with 38 race-, age-, and sex-matched control children. The results showed that in both XLHR and control children, no significant differences existed in dental age compared with the respective chronological age, indicating that rickets did not affect the rate of dental development. Longitudinal growth curves of seven XLHR and matched control children substantiated that relationships of dental to chronological ages were comparable in both groups. Male XLHR subjects showed significantly increased tendency for dental taurodontism with mean Crown-Body (CB):Root (R) ratio of 1.1 compared with 1.0 in females and 0.8 in controls (P < 0.02). Male XLHR children also showed significantly increased prevalence (50%) of ectopic permanent canines compared with control children (8%, P < 0.01).