Évaluer les propriétés d'une nouvelle larme artificiellepar administration directe en collyre et par lentille de contact. Nous avons employé un polysaccharide extrait du mélèze, l'arabinogalactan (AG). En solution à 5 %, l'AG présente des propriétés newtoniennes et non visqueuses. Des cultures cellulaires, en présence de l'AG, ont été évaluées. À l'aide de la résonance magnétique nucléaire (RMN-Bruker Minispec MQ), on a vérifié les interactions avec le polymère des lentilles de contact. La stratification et l'épaisseur tissulaire montrent les mêmes caractéristiques de l'épithélium natif. La RNM démontre que les coefficients d'autodiffusion de H2O d'une solution 5 % de AG sont moins élevés, dans les polymères, en comparaison avec une solution physiologique. Le poids d'une lentille incubée dans une solution à 5 % d'AG est moindre en comparaison avec une lentille incubée dans une solution physiologique ; le même est valable pour la vitesse d'évaporation. La propriété de « epithelium turnover promoter » de l'AG est très utile dans les kératopathies, surtout dans l'oeil sec. Les coefficients d'autodiffusion montrent une mobilité réduite des molécules de H2O à cause des intéractions (liaisons) entre la larme artificielle (AG) et le polymère. Cette meilleure pénétrance est due aux caractéristiques non-visqueuses de l'AG, et permet un usage thérapeutique par les lentilles de contact.

Évaluer les propriétés de l'arabinogalactan comme promoteur de la réépithélisation cornéenne. Nous avons testé un polysaccharide naturel, extrait du mélèze, l'arabinogalactan. Les épreuves rhéologiques et de muco-adhésion ont été effectuées par les suivantes techniques : Rheostress RS 150 et Hydraulic Press à 3.000 kg/cm2. En outre, on a évalué, par les méthodologies indiquées, ferning test, Schirmer test, épaisseur et vitesse de croissance de cultures cellulaires, histologie comparative. Bien que l'arabinogalactan ait des caractéristiques newtoniennes et non visqueuses (η = 1.6 mP.s solution 10 %ww), le temps de permanence sur la cornée du lapin a dépassé 60 minutes. L'épaisseur et la vitesse de réépithelisation furent très améliorées par rapport aux contrôles. Le « ferning test » de l'arabinogalactan fut très similaire à celui de la mucine naturelle des larmes. Les résultats expérimentaux de ce nouveau polysaccharide naturel, conceptuellement contraire aux autres substituts lacrymaux du commerce, sont liés à sa propriété élevée de muco-adhésion (Δη/η 17.21), en comparaison, par exemple, à l'HA (Δη/η 3.02), et à sa structure chimique ramifiée, comme la MUC1. Ces résultats, « in vitro » et « in vivo » chez le lapin, suggèrent l'emploi de l'arabinogalactan (en solution au 5 %) également chez l'homme, tant comme larmes artificielles que comme stimulant de la réépithélisation dans les kératopathies.

Évaluer les propriétés d'un polysaccharide naturel, l'arabinogalactan (AG), comme larme artificielle et comme re-épithélisateur de la cornée. L'arabinogalactan, polysaccharide naturel extrait du mélèze, a été évalué par plusieurs techniques : Rheostress RS 150 Viscosimeter, Hydraulic Press Perkin-Elmer et Shimadzu Fluorimeter En outre, ferning test, vitalité cellulaire, Schirmer test, histologie, interaction avec le polymère des lentilles de contact, ont été évalués par des méthodologies spécifiques dans différentes situations expérimentales. Bien que l'arabinogalactan ait les newton et les caractéristiques non visqueuses (n = 1.6 mPa ̇ s pour 10 % w/w solution), le temps de permanence sur la cornée du lapin dépassa 60 minutes. L'AG en solution à 5 % a montré une propriété élevée de muco-adhésion (Δ n/n17.21) en comparaison au HA (Δ n/n 3.02). La vitesse de re-épithélisation des ulcères cornéens standardisés chez le lapin a été plus rapide (44 heures) avec le traitement AG à 5 %, en comparaison aux contrôles (plus de 60 heures). Les techniques spectro-photométriques n'ont montré aucune interaction négative avec le polymère des lentilles souples. Aucun des soi-disant substituts lacrymaux mucomimétiques ne reproduit la structure chimique de la mucine naturelle, et par conséquent leur propriété d'adhésion sur l'oeil sec est très réduite. Pour cette raison nous avons employé un « muco-adhésif » non viscoélastique et non mucomimétique : l'arabinogalactan. Les propriétés muco-adhésives élevées de l'arabinogalactan expliquent sa longue rémanence sur la cornée, et son pouvoir de re-épithélisation. En particulier, l'emploi de l'arabinogalactan est conseillé quand la couche muqueuse du film lacrymal est réduite et altérée. L'instillation de l'arabinogalactan 5 % solution est indiquée également lors du port de lentilles de contact. En effet, à l'opposé des substituts viscoélastiques, il améliore l'hydratation des lentilles souples.

We screened 228 women with diabetes for bacteriuria during the period of January 1997 through December 2000 at Pisa General Hospital (Pisa, Italy). A control group of 146 women without diabetes was also evaluated. The frequency of significant bacteriuria was 17.5% (40 of 228) among women with diabetes and 18.5% (27 of 146) among women in the control group. Seven (13.5%) of 52 and 33 (18.8%) of 176 women with type 1 and in type 2 diabetes, respectively, had significant bacteriuria. The presence of higher glycated hemoglobin levels was the only significant risk factor for significant bacteriuria in women with type 2 diabetes. A similar frequency of bacteriuria in women with and women without diabetes was found. Severe impairment of metabolic control of type 2 diabetes increases the risk of acquiring asymptomatic bacteriuria.

In 215 diabetics (52 type 1, 163 type 2) patients and 60 healthy controls, tHcy was measured to check the relationships between renal status and metabolic parameters. While tHcy resulted significantly higher in micromacroalbuminuric diabetics, compared to normoalbuminurics (14.3 +/- 84.7 vs 11.1 +/- 20.3 mumol/l, p 0.002) and in low-GFR (less than or equal to 70 ml/min) versus normal -GFR patients (16.2 +/- 7.9 vs 10.3 +/- 4.2 ml/min, respectively p < 0.0001), serum creatinine and GFR proved to be the main determinants of tHcy levels in diabetics as just proved in non-diabetic people.

Long-term use of topical medications for glaucoma therapy is often associated with alterations of corneal and conjunctival epithelium. The origin of the damaging mechanism is not entirely known yet, but particular attention is given to benzalkonium chloride (BAC) that is the most frequently used preservative in ophthalmic preparations and is specially present in timolol-based eye drops. Ophthalmic preservatives interfere with the growth, metabolism and reproduction of microbial organisms but, on the other hand, they cause similar effects on eukaryotic cells and this justifies their toxicity (Olson & White 1990). Long-term treatments required for patients suffering from glaucoma can deliver to serious damages for the ocular surface whose epithelia have a fundamental role in the formation and stability of the lacrimal layer (Kuppens et al. 1995). Reactions induced by preservatives on epithelia are both toxic and immunological ones, and this aspect is also described for BAC on the ocular surface. The toxicity is aimed at epithelial apical cells, at goblet cells and also at the lacrimal film, due to the cleansing properties of the preservative altering its stability and yield (Feher et al. 1990; Kuppens et al. 1995). Recent studies showed that BAC produces cellular necrosis at the concentrations usually present in eye drops, while causing apoptosis at lower concentrations (Debbasch et al. 2000, 2001). The influence of antiglaucoma treatments on the success ratio in filtering surgery is an aspect adequately ascertained (Lavin et al. 1990). It has also been reported that topical long-term antihypertensive treatments in patients with open-angle glaucoma are not infrequently linked with the development, in the conjunctiva and trabecular tissue, of inflammatory infiltrates predisposing fibrosis and thus determining a certain rate of failures in filtering surgery (Baudouin et al. 1999). Authors are now asserting the convinction that preservatives can induce a local stimulation of the immunity system, with the development at the conjunctival level of inflammatory infiltrates in the subepithelial stroma. Moreover, there are reports of a remarkable expression by the epithelium of proteins dependent from cytokines, such as HLA-DR and ICAM-l (De Saint Jean et al. 2000). It is known that the human conjunctiva is commonly colonized by cells belonging to the immune system. T-lymphocytes, macrophages, Langerhans cells and, occasionally, β-lymphocytes have been identified in the epithelium and in the substance typical of conjunctival tissue (Chang et al. 2000). Experimental studies recently performed in animals confirm that preservatives are for the most part responsible for the tissue iatrogenic alterations described after topical long-term applications of β-blocking drugs (Becquet et al. 1998; Baudouin et al. 1999). In all the cases cited here, BAC seems to be able to provoke an increased expression of both inflammatory cells at the conjunctival level and in the trabeculum area, and of apoptotic markers such as Fas and APO 2.7, also in the absence of a noticeable inflammatory reaction (Debbasch et al. 2000). It is opportune to consider the role that eye drops devoid of preservatives can produce in a long-term therapy. A key step in this direction was obtained with the use of ophthalmic preparations in ‘monodose’ containers, such as in the case of timolol. In the monodose container, the preparation, preservative-free, is always sterile, as there is no possibility at all of any form of pollution, as the use of the dose is immediate and in its entirety. A monodose container is anyhow insufficient to cover a daily treatment and the cost of this type of treatment is rather higher than the one with the conventional formulation. A valid alternative to monodose containers is represented by the use of reclosable minicontainers useful for a daily therapy (Van Santvliet et al. 1996). These preparations are ophthalmic solutions, preservative-free, usable within 12 h from their first opening. As far as monodose sterile preparations are concerned, the validity after the first opening proposed by the European Agency for the Evaluation of Medicinal Products (EMEA) must be around 3 h. Such a limit was fixed considering a possible environmental pollution and the resulting development of potential pathogens. In the case of ophthalmic solutions usable during a 12-h period, such a risk can be regarded as higher, considering the possible contact of open containers with the ocular surfaces of patients. In order to verify all polluting possibilities, an experimental analysis was performed considering the spontaneous contamination of timolol-based solutions packaged in reclosable minicontainers (Table 1). The study also evaluated the fate of known amounts of different bacterial species added to the ophthalmic preparations aiming at simulating a contact pollution with the infected conjunctiva (Table 2). These results show that preservative-free eye drops in reclosable minicontainers can be used for a daily therapy without any risk of ocular infection, even beyond 12 h after the first opening of the sterile package. It seems clear that preservatives in the eye drops can damage the ocular structures, so probably aggravating the alterations caused by the disease. Published data confirm that long-term use of BAC-free timolol eye drops is a safe way to improve local tolerance and to reduce filtering surgery failure In comparison with preservative-free solutions packaged in monodose containers, the most remarkable advantage of 0.5-mL reclosable minicontainers is the possibility of more than one instillation of preservative-free medication during the same day.

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 A1c (HbA1c), 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 HbA1c levels. Fetal growth indices (femur length, biparietal diameter and abdominal circumference) were correlated with both HbA1c 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.

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.