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Biomedical subjects

A Zanni

Publications and source records attributed to A Zanni.

6 recordsLinked to original sources

Indirect evidence that estrogen replacement therapy stimulates nitric oxide synthase in postmenopausal women.

The aim of the study was to investigate the effects of estrogen replacement therapy (ERT) on nitric oxide (NO) activity in healthy postmenopausal women. The study group consisted of 22 postmenopausal women (last menses at least 12 months prior to study entry) who were randomized to receive treatment for 2 months with patches that delivered either 50 micrograms/day of 17 beta-estradiol or placebo in a cross-over design. Blood samples for measurements of serum citrulline and arginine were collected at the start of the study and at the end of each treatment course. Serum citrulline and arginine were measured using high-performance liquid chromatography with fluorometric detection. Arginine levels were significantly lower in the ERT group compared to the placebo group, while citrulline levels did not change. The percentage citrulline/arginine ratio was significantly higher in the ERT group (42.9 +/- 21.6) compared to the placebo group (33.9 +/- 18.5) (p < 0.01). The citrulline/arginine ratio, both at baseline and during either ERT or placebo administration demonstrated a positive linear correlation with body mass index (BMI). No correlations were found between follicle stimulating hormone, estradiol and insulin levels and BMI. No correlations were found between age, time since menopause and baseline arginine and citrulline levels or the citrulline/arginine ratio. These data indirectly demonstrate that transdermal estradiol replacement in postmenopausal women is able to stimulate NO production through the involvement of endogenous L-arginine. A positive linear correlation was found between BMI and the citrulline/arginine ratio, suggesting an additional protective cardiovascular effect in overweight women.

Arginine↗

Physiological doses of estradiol decrease nocturnal blood pressure in normotensive postmenopausal women.

The effect of a 2-mo treatment with transdermal estradiol (50 microgram/day) versus placebo on 24 h of blood pressure rhythm was investigated in 18 normotensive healthy postmenopausal women. Whereas daytime blood pressure was not modified, nighttime blood pressure was reduced by estradiol. Estradiol magnified the nocturnal decrement of systolic (14.3 +/- 7.2 vs. 9.8 +/- 6.7 mmHg, P = 0. 0033), diastolic (11.6 +/- 5.0 vs. 7.5 +/- 7.3 mmHg, P = 0.028), and mean (10.8 +/- 5.6 vs. 7.2 +/- 4.5 mmHg, P = 0.011) blood pressure. As a consequence, the 24-h rhythm of mean blood pressure was restored in 50% of the subjects (P = 0.045) in whom it was absent and was amplified in the remaining 50% of the subjects. Body mass index was an independent determinant of blood pressure values being directly related to the amplitude of the 24-h mean blood pressure rhythm (r2 = 0.38; P = 0.0067). In normotensive postmenopausal women, physiological doses of estradiol amplify the nocturnal decline of blood pressure.

Blood Pressure↗

Epitope mapping of the anti-urokinase monoclonal antibody 5B4 by isolated domains of urokinase.

The amino terminal fragment (ATF) of urokinase-type plasminogen activator (uPA) is a degradation product comprising the entire growth factor-like and kringle domains. It has been previously shown that ATF is able to bind to the u-PA receptor through the growth factor-like domain and that the anti u-PA monoclonal antibody 5B4 (Mab 5B4) binds to ATF preventing u-PA receptor binding. To localize more precisely the epitope recognized by Mab 5B4, ATF was subfragmented by controlled enzymatic proteolysis with V8 protease. Three subfragments of 4,000 Mr (F-4k), 11,000 Mr (F-11k) and 12,000 Mr (F-12k) were purified from the reaction mixture and characterized. SDS-PAGE under reducing and non-reducing conditions, N-terminal aminoacid sequence analysis and C-terminal aminoacid analysis of each fragment indicate that F-4k and F-11k correspond to intact growth factor-like domain and kringle domain (residues 4-43 and 44-135 respectively) while F-12k corresponds to the kringle domain cleaved in the first loop at the glu52-gly53 bond. By Western blot and competitive binding experiments we show that Mab 5B4 recognizes an epitope located on the kringle domain of u-PA and that the binding is strongly reduced when the kringle contains an additional cleavage in its first loop. Since the receptor binding site of u-PA has been previously shown to be located on the growth factor-like domain, Mab 5B4 inhibits the binding of uPA to its cellular receptor likely by steric hindrance. Besides the proven utility in epitope localization of anti u-PA monoclonal antibodies, these u-PA fragments may represent powerful tools for studies of structure-function relationship of u-PA.

Amino Acid Sequence↗

A double-blind controlled study to compare the efficacy of an antacid plus oxethazaine with that of an antacid alone in the treatment of pain due to gastric or duodenal ulceration.

A double-blind study was carried out in 40 patients with typical ulcer pain and suffering from gastric or duodenal ulcer to compare the pain-relieving efficacy of oxethazaine/magnesium and aluminium hydroxide mixture with that of the antacid combination alone. Patients took 8 ml doses of either treatment when necessary over a period of 4 weeks. Both treatment regimens were equally effective in reducing the painful symptoms of peptic ulceration, but the total volume of medication required to achieve adequate symptomatic relief was less in patients taking antacid plus oxethazaine than in patients taking antacid alone. It is suggested that the combination of oxethazaine plus antacids, therefore, is to be preferred, because, by allowing a reduction in the intake of antacid, the risk of side-effects due to antacid therapy is thereby reduced.

Adult↗