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Biomedical subjects

E Boldrini

Publications and source records attributed to E Boldrini.

At least 19 recordsLinked to original sources
PubMed2003

The polysaccharide from Tamarindus indica (TS-polysaccharide) protects cultured corneal-derived cells (SIRC cells) from ultraviolet rays.

The aim of this work was to investigate the possible protective effect of a new viscosising agent, TS-polysaccharide, on corneal-derived cells (SIRC) exposed to ultraviolet-B rays. To verify this, SIRC cells were first exposed, in the absence or in the presence of TS-polysaccharide (1% w/v), for 9 s at the UV-B source and then post-incubated for 45 min at 37 degrees C. After this period the hydrogen peroxide (H(2)O(2)) accumulated in the medium and the concentration of 8-hydroxy-2'-deoxy-guanosine (8-OHdG) in cell DNA was measured. In addition, the amount of (3)H-methyl-thymidine incorporated in cellular DNA was evaluated after 18 h from irradiation. Our results show that cells exposed to UV-B rays accumulate H(2)O(2), and have higher levels of 8OHdG and a lower amount of (3)H-methyl-thymidine incorporated in DNA than control cells. In the presence of TS-polysaccharide, the H(2)O(2) and 8-OHdG accumulation, and the (3)H-methyl-thymidine incorporation were significantly reduced with respect to the values measured in cells exposed in the absence of the polysaccharide. We propose a protective role of the polysaccharide in reducing UV-B derived DNA damage to eye cells. This finding could be of some clinical importance when the polysaccharide is used as a delivery system for ophthalmic preparations.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Effect of different terpene-containing essential oils on permeation of estradiol through hairless mouse skin.

Purpose of the present investigation was to evaluate six terpene-containing essential oils for their capacity to promote permeation of estradiol (ES) through hairless mouse skin in vitro. Tests on cajuput, cardamom, melissa, myrtle, niaouli and orange oil, all used at the 10% w/w concentration in propylene glycol (PG), evidenced niaouli oil (NIA) as the best permeation promoter for ES. Tests on the main terpene components of NIA (1,8 cineole, alpha-pinene, alpha-terpineol and D-limonene), evaluated neat (10% w/w in PG) or in admixture, confirmed the better promoting activity of whole NIA. The present data point to the validity of complex terpene mixtures, such as that composing NIA, as transdermal penetration enhancers for moderately lipophilic drugs like ES.

Administration, Cutaneous↗
PubMed2001

[1,2,4]Triazino[4,3-a]benzimidazole acetic acid derivatives: a new class of selective aldose reductase inhibitors.

Acetic acid derivatives of [1,2,4]triazino[4,3-a]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as a novel class of aldose reductase (ALR2) inhibitors. Compound 3, (10-benzyl[1,2,4]triazino[4,3-a]benzimidazol-3,4(10H)-dion-2-yl)acetic acid, displayed the highest inhibitory activity (IC(50) = 0.36 microM) and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The activity of 3 was lowered by inserting various substituents on the pendant phenyl ring, by shifting the acetic acid moiety from the 2 to the 3 position of the TBI nucleus, or by cleaving the TBI system to yield benzimidazolylidenehydrazines as open-chain analogues. A three-dimensional model of human ALR2 was built, taking into account the conformational changes induced by the binding of inhibitors such as zopolrestat, to simulate the docking of 3 into the enzyme active site. The theoretical binding mode of 3 was fully consistent with the structure-activity relationships in the TBI series and will guide the design of novel ALR2 inhibitors.

Acetates↗
PubMed2000

Xyloglucan as a novel vehicle for timolol: pharmacokinetics and pressure lowering activity in rabbits.

This study was aimed at verifying the performances of a mucoadhesive polysaccharide from tamarind seed (xyloglucan or TSP, tamarind seed polysaccharide) as an adjuvant for ophthalmic vehicles containing timolol. Three formulations (one experimental vehicle based on TSP and two reference commercial eye drops) containing 5 mg/ml timolol base equivalents were administered to the eyes of pigmented rabbits. Drug concentrations in tear fluid, cornea, iris-ciliary body, aqueous humor and plasma were determined, as well as intraocular pressure. The polymer under investigation, in spite of a comparatively low viscosity, produced high timolol concentrations in the ocular tissues and a low systemic absorption. The performances of the TSP vehicle were comparable to those of a reference "in situ" gelling formulation (Timoptic XE). The results point to TSP as a potentially useful adjuvant for ophthalmic delivery systems.

Adrenergic beta-Antagonists↗
PubMed2000

Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits.

This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics. Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide. Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone. The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.

Administration, Topical↗
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↗