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Biomedical subjects

E Boldrini

Publications and source records attributed to E Boldrini.

At least 19 recordsLinked to original sources
PubMed1999

A new approach against sugar cataract through aldose reductase inhibitors.

Aldose reductase inhibition is one of the therapeutic strategies that has been proposed to prevent or ameliorate long term diabetic complications including retinopathy and sugar cataract. Rats were fed with a galactose rich diet and the aldose reductase inhibitor Tolrestat was topically delivered by ocular instillation. The levels of lens aldose reductase activity, galactitol and the onset of cataract were evaluated during and after treatment with the inhibitor. Topical application of 1-3% Tolrestat (10 microl) four times daily resulted, after 9 days, in a significant decrease in the enzyme activity. Well after interrupting treatment with the drug, the enzyme activity remained impaired and galactose induced cataract was prevented. Our findings may represent the basis for therapeutic plans to prevent sugar cataract by long term cyclic treatments with aldose reductase inhibitors, with reduction in drug doses and side effects.

Aldehyde Reductase↗
PubMed1999

Relation of fetal growth to maternal responses to oral glucose tolerance test throughout gestation.

Fetal growth is dependent on transplacental supply of fuels. We aimed to assess the effect of serial changes in maternal glucose tolerance and insulin secretion with advancing pregnancy on maternal-fetal outcomes. Sixty-nine healthy pregnant women were studied over the course of gestation for glucose tolerance, by oral glucose tolerance test (OGTT), and hemoglobin A(1c) (HbA(1c)), fetal intrauterine growth (by ultrasound) and pregnancy outcome. Seven women had an abnormal OGTT in the third trimester developing gestational diabetes mellitus (GDM), but none of the 12 mothers of large babies (> 3.9 kg) had GDM: the former had the highest post-load glycemic increment, despite an apparently 'normal' insulin secretory response, the latter showed the lowest post-load glucose increase in the face of the lowest insulinemic response. Neonatal body weight correlated with maternal gestational weight gain, placental weight, third trimester ratio of incremental plasma insulin and glucose integrated areas under the curve and first and second trimester HbA(1c) levels. Fetal growth indices (femur length, biparietal diameter and abdominal circumference) were correlated with both HbA(1c) and 2h OGTT. Fetal growth rate is confirmed as being associated with maternal glycemic equilibrium, but one of the main determinants of high infant birthweight seems to be an enhanced maternal insulin sensitivity, accompanied by remarkable gestational weight gain.

Adult↗
PubMed1999

Can insulin action induce myocardial texture alterations in essential hypertension?

The prevalence of hyperinsulinemia/insulin resistance in hypertensive individuals, as well as the effects of insulin on myocytic and fibroblastic growth, are well known in both epidemiologic and animal models. To check whether there are any links between ultrasonic myocardial texture parameters and insulin level in essential hypertensives, we compared 18 essential hypertensive men (Group 1, H) with 18 age- and gender-matched healthy controls (Group 2, C) (age, 57 +/- 10 years). For all study subjects we performed ambulatory blood pressure monitoring (ABPM); conventional 2-D Doppler echocardiography for the assessment of the left ventricular mass index (LVMi) and function; quantitative analysis of digitized echocardiographic images for evaluation of cyclic variation (CVI) of mean gray level (MGL) at the septum and posterior wall levels; and 75-g 3-h oral glucose tolerance test (OGTT) for analysis of area under glycemic curve (AUGC, g/min/dL) and insulinemic curve (AUIC, mU/min/mL), as well as serum glucose and insulin peaks. Both the daily mean blood pressure (H: 109 +/- 4.6 v C: 94.6 +/- 4.6, P < .0001) and LVMi (adjusted for body surface) (H: 133 +/- 24 v C: 97 +/- 21 g/m2, P < .0001) were significantly higher in hypertensives. Values for AUIC were significantly higher in hypertensives (10.37 +/- 5.53 v 6.33 +/- 5.28), P < .032); CVI was also significantly higher in group C, for both septum (C: 40.2 +/- 16.9 v H: 15.9 +/- 18.1, P < .0001) and posterior wall (C: 44.5 +/- 19.6 v H: 20 +/- 17.5; P < .0001). There was a significant inverse correlation between AUIC and CVI for both septum (r: -0.57, P < .001) and posterior wall (r: -0.50, P < .002). The significantly higher impairment of myocardial ultrasonic texture and the higher level of the AUIC insulinemia in hypertensives, as well as the significant inverse relationship between CVI and hyperinsulinemia, are our major findings. Hyperinsulinemia/insulin resistance could cause an altered collagen/muscular ratio, which could potentially explain, at least in part, the CVI alterations detected in hypertensive patients.

Adolescent↗
PubMed1999

Development of a simple dry eye model in the albino rabbit and evaluation of some tear substitutes.

The present paper is concerned with the development of a simple dry eye model in the rabbit, induced by daily repeated instillations of 1.0% atropine sulphate. The evolution of the dry eye syndrome in the animals was assessed by the Schirmer I test and by examination of the cornea after fluorescein staining. The model produced rapidly some typical dry eye symptoms and could be satisfactorily used for a preliminary assessment of the protective activity of some polymeric tear substitutes. These were based on hydroxypropylmethylcellulose, sodium hyaluronate, sodium polyacrylate or tamarind gum. The latter polymer showed the best overall results. Ferning tests on the formulations were also performed: their validity as predictors of the efficacy of tear substitutes is discussed.

Animals↗
PubMed1999

Prevention of a first episode of variceal bleeding: role of duplex Doppler sonographic measurement of the acute response to beta-blockers.

The aim of our study was to assess whether acute variations in portal vein Doppler sonographic parameters induced by administration of a single beta-blocker agent are predictive of the long-term effects of these drugs in the prevention of a first episode of variceal bleeding. In 30 patients with liver cirrhosis at high risk for variceal bleeding, duplex Doppler sonographic parameters (maximal portal flow velocity, portal blood flow, and congestion index) were measured before and 4 h after the administration of 40 mg of propranolol. Twenty-three of these patients started chronic therapy with propanolol and were evaluated periodically (seven patients were excluded because they did not continue the therapy). The percentage of patients free from bleeding was 86.9% at the first year and 77.8% at the second year. Among a series of clinical, laboratory, and instrument-based parameters, the only one related to first bleeding, selected by the Cox regression model, was the percentage decrease in maximal portal flow velocity observed after initial administration of propranolol (P < 0.01). The best cutoff value for the percentage decrease in portal flow velocity (portal flow velocity test) was 12%. The prevalence of bleeding had been 25% (3 of 12) in patients with positive portal flow velocity test results (12% decrease or more), versus 64% (7 of 11) in patients with negative portal flow velocity test results. The actuarial probability of remaining free from bleeding (Kaplan-Meier analysis) was different in these two groups (log rank P < 0.01). The portal flow velocity test represents a safe and feasible method to predict the efficacy of beta-blockers in the prevention of a first bleeding episode in patients with cirrhosis. In patients with negative results on the portal flow velocity test, an alternative therapeutic approach should be considered.

Actuarial Analysis↗
PubMed1998

With regard to glycohemoglobin measurement: are we sure that high-performance liquid chromatography currently works in the clinical routine?

The clinical usefulness of glycated hemoglobin (HbA1C) depends crucially on the accuracy and precision of its assay. When we compared an immunological bench-top analyzer (DCA 2000, Bayer Diagnostici, Milan) to the high-performance liquid chromatography (HPLC) reference method used in a routine hospital laboratory (Diamat and Fast Diamat, Bio-Rad Lab., Milan) by assaying multiple control sera, we found so many sources of systematic analytical errors in the routine use of HPLC as to compromise between-assay precision. DCA 2000 showed intra- and interassay coefficients of variation (CV) of 1.1% and 2.3% with the normal standard serum, 1.0% and 4.2% with the pathological one; Diamat yielded CVs of 1.3% and 7.0%, 1.3% and 5.7%, respectively. Although the measurement of 161 blood samples showed that Diamat usually overestimated HbA1C (paired t-test, P<0.001), a great variability of Diamat performance became evident when the relationship Diamat vs DCA was evaluated day by day over 17 days of observation (analysis of variance, ANOVA, P<0.001). Intra- and interassay CVs of Fast Diamat initially (new instrument still on approval) were 0.6% and 2.5% (normal standard serum), 0.3% and 1.9% (high standard serum), yet after 6 months of routine laboratory use, they became 3.1% and 3.2%, 1% and 12.3%, respectively. Main sources of error were: inaccurate autodilution, unsuitable parameter settings, disregard of the maintenance schedule. We conclude that the tendency to overlook major critical aspects in the routine use of HPLC is detrimental to the quality of HbA1C determination and implies the loss of HbA1C value in clinical practice. Both carefully supervising laboratory quality and checking the likelihood of the analytical result with the clinical setting appear even more important.

Adolescent↗
PubMed1998

Urinary excretion rates of multiple renal indicators after kidney transplantation: clinical significance for early graft outcome.

Post-reperfusion inflammation as well as anti-allograft response occur following kidney transplantation. We evaluated tissue damage by multiple renal indicators and searched for rejection predictors forewarning serum creatinine upturns. Twenty recipients (43 +/- 9 y; donors' age 35 +/- 16 y) of first renal grafts were studied. All through their hospital stay (35 +/- 18 d, range 17-75 d) we measured serum levels of urea, creatinine and electrolytes along with urinary excretion rates of total protein, albumin, enzymes (GGT, NAG, AAP) and electrolytes. During the period of observation, peaks were seen on the 1st day for serum creatinine, serum K+ and urine albumin output; on the 2nd day for urine Na+, GGT, AAP and protein excretion rates; on the 4th day for urea and creatinine outputs; on the 5th day for NAG output. On the 14th day, serum urea and creatinine as well as urine GGT, NAG, AAP, albumin and total protein were still elevated compared to 20 healthy control subjects. Delayed/slow graft function was observed in six recipients with higher pre-transplantation plasma lipids and lower donor HDL cholesterol. Hospital stay time was correlated with need for post-transplantation dialysis (p = 0.01) and recipient proteinuria by time 0 (TO) to day 3 (p = 0.02). Cold ischemia time was positively associated with 0-3 d serum creatinine, 0-3 d urinary urea and protein outputs (multiple r 0.9, p < 0.001). Multivariate analysis of longitudinal data showed that recipients' serum creatinine was positively correlated (p < 0.001) with urine AAP and negatively correlated with urine albumin, with diuresis volume and urine creatinine (p < 0.01). Serum creatinine elevations were preceded (previous 1-7 d) by increases in urinary indicators, the probability being higher in the presence of multiple simultaneous abnormalities. Useful parameters predictive of favorable graft outcome prior to transplantation included a brief cold ischemia time and a normal donor/recipient serum lipoprotein profile. Following transplantation, useful parameters were a high diuresis volume at time zero along with low urine NAG and high albumin outputs; early (first opst-graft 3 d) polyuria, low urea and GGT, high K, NAG and total protein excretions.

Adult↗
PubMed1998

Bioavailability of timolol and aceclidine after ocular instillation in the rabbit.

The bioavailability of timolol and aceclidine after the ocular instillation of each drug (timolol 0.5% or aceclidine 2%) or both combined (timolol 0.5% + aceclidine 2%) has been evaluated in rabbits. 15 male albino rabbits were treated by the instillation of timolol and aceclidine alone or combined in the conjunctival sac of the right eye. Timolol concentrations in humor aqueous were assayed at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 6 hr after instillation by high-performance liquid chromatography (HPLC). Aceclidine was assayed by a pharmacodynamic method: pupillary diameter at the following time intervals 0 (basal value), 1 min, 5 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr after treatment. Our results demonstrated that no differences in timolol and aceclidine bioavailability were found between simple-drug preparations and their combination.

Administration, Topical↗
PubMed1997

Erythrocyte Na+/H+ exchange and preclinical abnormalities of the left ventricular diastolic function in normotensive type 1 (insulin-dependent) diabetic patients.

We assessed the relationship between erythrocyte Na+/H+ antiport activity and myocardial anatomical-functional parameters (by Doppler echocardiography) in normotensive IDDM patients, with and without microalbuminuria. We studied 33 normotensive IDDM subjects and 14 matched healthy controls (group 4). Based on urinary albumin excretion rate (UAER), 23 diabetics were normoalbuminuric, 10 microalbuminuric (group 3). Normoalbuminurics were divided up for normal (group 1, n = 13) or high (group 2, n = 10) antiport activity. We evaluated fasting glycaemia and 24-h urine glucose output, HbA1c, plasma lipids, urea, creatinine and electrolyte clearances, UAER, erythrocyte Na+/H+ countertransport, M-Mode and 2D echocardiograms with Doppler analysis. Antiport, which was higher in diabetics than controls, was significantly overactive in groups 2 and 3 vs group 4, independently from UAER. Diabetics showed left ventricular volume, cardiac mass and systolic function within the control range. In left ventricular diastolic filling, while peak E was similar in diabetic and healthy people, the late peak transmitral flow velocity (peak A) was significantly higher in diabetics than controls, and this was also true in groups 2 and 3 vs group 4. Antiport activity was positively related to peak A (p < 0.03). These observations suggest that (a) the Na+/H+ antiport may be overactive in diabetes, apart from microalbuminuria; (b) increased Na+/H+ antiport activity, in normotensive IDDM people, may be associated with preclinical diastolic myocardial dysfunction ("incipient diabetic cardiomyopathy"?).

Adult↗
PubMed1997

Benzisothiazole-1,1-dioxide alkanoic acid derivatives as inhibitors of rat lens aldose reductase.

Derivatives of 4-substituted 1,2-benzisothiazole-1,1-dioxide alkanoic acids were prepared and their in vitro aldose reductase inhibitory activity was tested in rat lens enzyme. The acetic derivatives 10, 12, and 16a-d proved to be much more potent inhibitors than the propionic derivatives 11, 13, and 17a-d. The presence of an acyl moiety on the amino group in position 4 of the acetic derivatives 16a-d led to a significant increase in activity with respect to the parent compound 14. One of the most active compounds in vitro, 10, was also evaluated in vivo as an inhibitor of glutathione lens depletion in galactosemic rats, but it did not show any activity in maintaining the rat lens glutathione level, probably due to problems of ocular bioavailability or metabolism.

Aldehyde Reductase↗
PubMed1997

[Blood doping].

Explore the source record for details and available documents.

Doping in Sports↗
PubMed1996

In vitro activity of metronidazole alone and in combination with clotrimazole against clinical isolates of Trichomonas vaginalis.

Trichomonas vaginalis vaginitis is generally treated with oral metronidazole. Widespread use of this drug has led, however, to selection of resistant strains. Topical therapy seems appropriate whenever systemic high dosage schedule cannot be adopted in order to overcome resistance. This study was designed to assess the activity of metronidazole alone and in combination with clotrimazole, an imidazole derivative for topical use, against T. vaginalis. Tests were performed employing the antitrichomonas activity of a fixed ratio of metronidazole with clotrimazole (5:1) which has been recently suggested for topical therapy and the checkerboard technique. All tests were carried out under aerobic conditions to maximize T. vaginalis resistance traits. Minimum inhibitory concentrations (MICs) of metronidazole for the 12 strains studied were in the range reported in the literature (0.5-32 micrograms/ml). The interaction of metronidazole with clotrimazole as assessed by the checkerboard technique gave an indifferent outcome with all the strains assayed (FIC = 1-2). The fixed concentration of drugs, however, produced synergism (FIC = 0.5) in 5 of 12 isolates. Spontaneous resistant strains were not selected from T. vaginalis exposed to sub-lethal levels of the drugs or by culturing a large inoculum in the presence of 1, 2, 4 and 8 times the MICs of metronidazole alone or in combination with clotrimazole. These results confirm and extend previous reports highlighting the good in vitro efficacy of the association of metronidazole plus clotrimazole against T. vaginalis.

Animals↗
PubMed1996

[Spontaneous bacterial peritonitis in liver cirrhosis. What tests to perform on the ascitic fluid?].

Spontaneous bacterial perionitis (SBP) is a relatively frequent complication of liver cirrhosis and is associated with a high mortality if not early recognized and immediately treated. The text-books of Medicine available in Italy suggest the use of traditional laboratory tests (gravity, total protein concentration, Rivalta's test) to whom add white blood cell count for the assessment of the nature transudative (not infected) or exudative (infected) of ascitic fluid; nevertheless, in every day clinical practice, the association between total protein concentration and type of ascitic fluid may be misleading with respect to the diagnosis of SPB. The aim of this retrospective study, undertaken on 86 patients with liver cirrhosis consecutively admitted and separated in two groups, one without and the other with PSB (white blood cell count > 500/mm3), was to identify criteria for diagnosis of PSB. The traditional laboratory tests were significantly different in the two groups but Rivalta's test. Yet, none of them showed a diagnostic measurement sufficient for the use in the diagnosis of PSB (positive predittive value: gravity 41%, Rivalta's test 36%, total protein concentration 40%). The results of this work show the traditional laboratory tests unable to define the nature of the ascitic fluid. For the diagnosis of PSB the only reliable parameter is the white blood cell count.

Aged↗
PubMed1996

Acid derivatives of benzisothiazole-1,1-dioxide as inhibitors of rat lens aldose reductase.

A number of 6-substituted 1, 2-benzisothiazole-1, 1-dioxide alkanoic acids were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. The inhibitory potency of the acetic (6a, 10a), propionic (6b, 10b, 11b), and isopropionic (6c, 10c, 11c) derivatives was very similar and generally lower than that of the reference compound, Sorbinil. The presence of an acyl moiety on the amino group in position 6, as in the acetic and propionic derivatives 14a-f and 15a, b, respectively, resulted in a significant increase in activity. A good potency was shown by compounds 14g and 15g, in which a second carboxylic function is present on the 6-acylamino group. Also the open products 16, which contain the phenylsulfonyl fragment found in several known inhibitors of aldose reductase, were obtained and tested in the rat lens assay.

Aldehyde Reductase↗