Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile.

OBJECTIVE: Osteopontin (OPN) is a sialoprotein implicated in different immunity and metabolic pathways. Capable of activating dendritic cells and inducing Th1-Th17-mediated tissue damage, OPN plays a significant role in the development/progression of several autoimmune diseases; interestingly, it was also shown that OPN participates in the acute pancreatic islets response to experimentally induced diabetes in non-obese diabetic (NOD) mice. Furthermore, OPN promotes adipose tissue dysfunction, systemic inflammation and insulin resistance. Our aims of this study were to evaluate circulating OPN levels in adult patients with type 1 diabetes mellitus (T1DM) compared to non-diabetic control participants and to unravel clinical and biochemical correlates of OPN concentration. DESIGN: Case-control study. METHODS: We enrolled 54 consecutive T1DM patients referred to our diabetes outpatient clinic at Sapienza University of Rome and 52 healthy sex and age-comparable controls. The study population underwent clinical evaluation, blood sampling for biochemistry and complete screening for diabetes complications. Serum OPN levels were measured by MILLIPLEX Multiplex Assays Luminex. RESULTS: T1DM patients had significantly higher serum OPN levels than controls (17.2±12.9 vs 10.5±11.6 mg/ml, P=0.009). OPN levels correlated with T1DM, higher blood pressure, BMI, creatinine, γ-GT, ALP and lower HDL; the association between high OPN levels and T1DM was independent from all confounders. No correlation was shown between OPN and HbA1c, C-peptide, insulin requirement, co-medications and diabetes duration. CONCLUSIONS: This study demonstrates for the first time in a case-control study that adults with T1DM have increased serum OPN levels, and that higher OPN concentrations are associated with an unfavorable metabolic profile in these patients.

High prevalence of capillary abnormalities in patients with diabetes and association with retinopathy.

AIMS: To investigate the presence of capillary abnormalities in patients with Type 1 and Type 2 diabetes using nailfold videocapillaroscopy and to evaluate the possible correlation with the typical diabetes mellitus microangiopathic lesions detectable in retinal blood vessels. METHODS: Forty-nine patients with diabetes mellitus (21 with Type 1 and 28 with Type 2 diabetes) and 39 subjects without diabetes were enrolled. Ophthalmoscopy was performed on all patients and was followed by retinal fluorangiography when indicated. Subjects underwent nailfold videocapillaroscopy to evaluate density, length, morphology and distribution of capillary loops, presence of ectasia, microbleedings and blood flow modifications. A score (0-3) was applied to quantify features of nailfold videocapillaroscopy. RESULTS: Subjects with diabetes showed a significantly increased (P = 0.0001) nailfold videocapillaroscopy score and significantly greater alterations of capillary length (P = 0.004), distribution (P = 0.02), morphology (P = 0.0001), density (P = 0.02) and flux (P = 0.004), as well as presence of ectasic loops (P = 0.009) and of oedema/exudates (P = 0.03) compared with control subjects. In addition, patients with Type 1 diabetes had a significantly higher score (P = 0.01) and greater morphologic alterations (P = 0.03) compared with subjects with Type 2 diabetes. Nailfold videocapillaroscopy score also showed a positive correlation with retinopathy, detected by both ophthalmoscopy (P = 0.0001) and fluorangiography (P = 0.02), independently from sex, age, type of diabetes and all potential confounders. Moreover, nailfold videocapillaroscopy was capable of identifying alterations in almost 50% of patients with diabetes without retinopathy. CONCLUSIONS: A high prevalence of nailfold capillary changes is detected in patients with diabetes using nailfold videocapillaroscopy. These abnormalities tightly correlate with retinal damage and may be expression of a generalized microvessel involvement in both Type 1 and Type 2 diabetes.

The effects of 2% ibopamine eye drops on the intraocular pressure and pupil motility of patients with open-angle glaucoma.

PURPOSE: Ibopamine is a prodrug of N-methyldopamine that has a non-cycloplegic mydriatic action due to its a-adrenergic properties and is able to induce, when topically given, a transient increase of intraocular pressure (IOP) in eyes with hydrodynamic disorders. METHODS: This is a randomized, crossover, open-labeled, two- center study. Forty patients (20 open-angle glaucoma patients and 20 healthy subjects) were treated with ibopamine 2% eye drops and phenylephrine 10% eye drops. RESULTS: Ibopamine induced a significant increase in IOP only in glaucomatous eyes (p<0.001) without a significant hypertensive effect in normal eyes. Ibopamine and phenylephrine showed a similar mydriatic activity but ibopamine was able to induce an hypertensive effect only in glaucomatous eyes. CONCLUSIONS: The results confirm the use of ibopamine as provocative test in detection of hydrodynamic disorders.(Eur J Ophthalmol 2004; 14: #-13).

The effects of 2% ibopamine eye drops on the intraocular pressure and pupil motility of patients with open-angle glaucoma.

PURPOSE: Ibopamine is a prodrug of N-methyldopamine that has a non-cycloplegic mydriatic action due to its alpha-adrenergic properties and is able to induce, when topically given, a transient increase of intraocular pressure (IOP) in eyes with hydrodynamic disorders. METHODS: This is a randomized, crossover, open-labeled, two- center study. Forty patients (20 open-angle glaucoma patients and 20 healthy subjects) were treated with ibopamine 2% eye drops and phenylephrine 10% eye drops. RESULTS: Ibopamine induced a significant increase in IOP only in glaucomatous eyes (p<0.001) without a significant hypertensive effect in normal eyes. Ibopamine and phenylephrine showed a similar mydriatic activity but ibopamine was able to induce an hypertensive effect only in glaucomatous eyes. CONCLUSIONS: The results confirm the use of ibopamine as provocative test in detection of hydrodynamic disorders.

Effect of brimonidine on patients undergoing uncontrolled IOP with beta-blockers.

The authors evaluated the effect of the replacement of beta-blockers with brimonidine drops in patients taking beta-blockers only or with dorzolamide, having IOP > 20 mmHg. The study was divided into two sections: one group treated with brimonidine b.i.d. (23 patients) and the other group treated with brimonidine + dorzolamide b.i.d. (17 patients). The effect of the substitution showed after 90 days of treatment with a reduction of 8.59 +/- 1.2 mmHg (P < 0.001) in the first group and 6.1 +/- 1.7 mmHg (P < 0.001) in the second group. Three patients in the first group and four patients in the second group presented minor adverse effects which did not justify discontinuation of treatment. Brimonidine was effective treatment as a substitute for beta-blockers only when associated with dorzolamide.

Increase in aqueous humor production following D1 receptors activation by means of ibopamine.

BACKGROUND: Topically administered 2% ibopamine (a dopaminergic agonist) induces a transitory ocular hypertension in 92% of patients with primary open-angle glaucoma and in 52% of patients with normal tension glaucoma. In normal eyes, ibopamine has no effect on IOP. PURPOSE: The aim of the present study was to verify, by means of fluorophotometric techniques, which hydrodynamic changes could be induced in normal and glaucomatous eyes, stimulating the D1 receptor with 2% ibopamine administered topically. In addiction, we wanted to evaluate if ibopamine could modify IOP before and after an experimentally induced outflow system impairment in rabbits. METHODS: In study 1 we performed a measurement of aqueous humor flow in 6 healthy volunteers and in 6 glaucomatous patients, before and after 2% ibopamine administration. In study 2 the alteration of outflow pathways was induced by means of Laminaria Digitata in 10 rabbits. RESULTS: After 2% ibopamine administration we found a significant increase in aqueous humor production, both in glaucomatous (P = 0.035) and normal eyes (P = 0.004). In rabbits, we found no significant change in IOP at basal conditions. After experimentally induced outflow system impairment by laminaria, we observed a marked increase in IOP (+ 13.5 mmHg SD 7.2; P < = 0.001) following ibopamine administration. CONCLUSIONS: These experimental data have a diagnostic value in glaucoma, since they show how an intraocular hypertensive response due to ibopamine in normotensive eyes is a sign of initial outflow impairment. Moreover, the possibility to increase the aqueous humor production sets new trends in the treatment of post surgical ocular hypotony.

Dopamine, dopaminergic drugs and ocular hypertension.

The study refers to the clinical experiences performed with several D1 and D2 dopaminergic receptors agonists in 20 patients with high tension open angle glaucoma. The substances were administered topically as eye drops as well as an ocular eye bath. The parameter examined was intraocular pressure (IOP). The substances taken in consideration were: Dopamine, Ibopamine (dopamine analog), Fenoldopam and 3B90 (D1-receptor agonists) and Bromocriptine (dopaminergic agonist with higher affinity for D2 than for D1-receptors). It has been shown that all selective D1-receptors agonists induce a significant increase in IOP only in eyes with hydrodynamic disorders (p < 0.001). Such hypertensive effects could not be antagonized either by topically administered dopaminergic antagonists (Sulpiride, D2-receptors antagonist, and Haloperidol, non-selective dopaminergic antagonist) or by the pretreatment with the commonly used topical antiglaucomatous drugs. The only substance which proved able to inhibit the IOP increase induced by the D1-receptors agonists was the D1-selective antagonist SCH-23390, suggesting that IOP increase may be a result of a stimulation of the D1-receptors. The authors hypothesize that dopaminergic system may play a role in the regulation of aqueous humor hydrodynamics.

[Effect of acetazolamide on Menière's disease]. / Effetto dell'acetazolamide sulla malattia di Menière.

The effect of acetazolamide was assessed in 25 patients with Menière's disease. During the test session hearing threshold and plasmatic osmolality were monitored along with fluctuations in hearing loss, fullness, tinnitus and balance. A single, 250 mg dose of acetazolamide was administered to all patients via os early in the morning on an empty stomach. Hearing was tested prior to administration and every hour for five hours thereafter. Plasmatic osmolality was also assessed during the same session. In 52% of this group an improvement in the threshold was seen. The greatest shift was observed two hours after administration of acetazolamide at 250 Hz, whereas the smallest threshold shift corresponded to 2000 Hz. In all cases, plasmatic osmolality remained constant throughout. Of the patients 44% presented an improvement of all or one of the symptoms: hearing loss, tinnitus, fullness, balance. The data were compared with data obtained for a control group (9 patients) which received a placebo while following the same testing criteria. The results of this study suggest that acetazolamide can have a positive effect on endolymphatic hydrops. It should be stressed, therefore, that acetazolamide could be introduced in the diagnostic and therapeutic strategies applied in Menière's disease.

[Perception of light modulation]. / Studio della percezione della modulazione luminosa.

A simple method for testing visual sensitivity to flickering light sources is proposed. The method employs a triangular function generator, which modulates the luminance of a chromatic light source. Amplitude and frequency of the triangular pattern are adjusted until the subject perceives a periodic variation of luminance. In normal subjects the maximum sensitivity was found at a frequency modulation of 5-10 Hz. In multiple sclerosis patients the method proved to be more accurate than flicker fusion frequency in revealing subclinical damage of the visual pathway.