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Biomedical subjects

M Centofanti

Publications and source records attributed to M Centofanti.

At least 19 recordsLinked to original sources
PubMed2006

Progesterone and progestins: effects on brain, allopregnanolone and beta-endorphin.

The increased use of hormonal therapies over the last years has led to improve the knowledge of pharmacological, biochemical and metabolic properties of several progestins and their effects in target tissues, such as the central nervous system. Progesterone and synthetic progestational agents are able to modulate the synthesis and release of several neurotransmitters and neuropeptides in response to specific physiological and pathological stimuli. While these actions may relay on differential activation of progesterone receptor or recruitment of intracellular pathways, some of the differences found between synthetic progestins may depend on the specific conversion to neuroactive steroids, such as the 3-alpha, 5-alpha reduced metabolite, allopregnanolone. This is a potent endogenous steroid that rapidly affects the excitability of neurons and glia cells through direct modulation of the GABA-A receptors activity exerting hypnotic/sedative, anxiolytic, anaesthetic and anticonvulsive properties. Estrogens increase the CNS and serum levels of allopregnanolone and the addition of certain but not all synthetic progestins determines a further increase in allopregnanolone levels, suggesting that the metabolism into this reduced product is related to the chemical structure of progestin molecule used. In addition, depending on specific progestin molecule used, different interaction are found with the estradiol-induced beta-endorphin synthesis and release, showing that diverse progestins have specific and divergent actions on the opiatergic system. These results highlight the concept that natural and synthetic progesterone receptor agonists may systematically induce different biological actions in CNS. This may have far-reaching implications for the clinical effects and related indications of each compound.

Animals↗
PubMed2005

Corneal birefringence changes after laser assisted in situ keratomileusis and their influence on retinal nerve fibre layer thickness measurement by means of scanning laser polarimetry.

AIM: To evaluate changes in corneal polarisation properties and their influence on peripapillary retinal nerve fibre layer (RNFL) thickness measurements after laser assisted in situ keratomileusis (LASIK) by means of scanning laser polarimetry (SLP) with variable corneal polarisation compensator (VCC) in normal white subjects. METHODS: SLP was performed by means of GDx VCC on 32 eyes of 32 normal subjects who underwent LASIK for ametropia correction. Corneal polarisation axis and magnitude and RNFL thickness were measured before and 8 days after LASIK. RNFL thickness data and corneal polarimetric data of one randomly selected eye per subject were analysed by the Wilcoxon signed ranks test. Correlations between corneal ablation depth, corneal polarimetric changes, and RNFL thickness changes were investigated using Spearman's rho test. RESULTS: The corneal polarisation axis significantly shifted from 15.1 degrees (17.0 degrees ) to 6.9 degrees (12.9 degrees ) (p = 0.00006) after LASIK and this change showed a strong correlation with corneal ablation depth (rho = -0.7, p = 0.00002). Among GDx parameters, TSNIT, SUP, and SD showed significant changes after LASIK and for SUP and SD these changes were well correlated with the shift in corneal polarisation axis (rho = 0.54, p = 0.03 and rho = 0.45, p = 0.01, respectively). SUP and SD changes were neutralised after compensating for corneal polarimetric changes but not TSNIT changes. NFI, a discriminating parameter, was found to be affected after LASIK only after compensating for corneal polarimetric changes. CONCLUSIONS: LASIK induces a shift in corneal polarisation axis which is responsible for inaccuracies in RNFL thickness measurements. A customised compensation for corneal polarimetric changes after LASIK allows normalisation of some of the thickness parameters except for TSNIT and NFI.

Adult↗
PubMed2001

Correlation between optical coherence tomography, pattern electroretinogram, and visual evoked potentials in open-angle glaucoma patients.

OBJECTIVE: [corrected] To correlate the nerve fiber layer (NFL) thickness and the visual function evaluated by electrophysiologic retinal and cortical responses assessed in open-angle glaucoma (OAG) eyes. DESIGN: Prospective case-control study. PARTICIPANTS: Thirty glaucoma patients (mean age, 47.1 +/- 7.15 years; refractive error range, +/- 2 spherical equivalent) with a mean deviation of computerized static perimetry (24/2 Humphrey, Dublin, CA) from -5 to -28 dB and intraocular pressure less than 21 mmHg on pharmacologic treatment and 14 age-matched control participants. METHODS: Nerve fiber layer thickness was measured by optical coherence tomography. Retinal and visual pathway function was assessed by simultaneously recording pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) using high-contrast (80%) checkerboard stimuli (the single check edges subtend 15 minutes of the visual arc) reversed at the rate of two reversals per second. Linear regression analyses were adopted to establish the correlation between NFL thickness and PERG and VEP parameters. MAIN OUTCOME MEASURES: Nerve fiber layer thickness measurements in each quadrant (superior, inferior, nasal, and temporal) were taken and then averaged (12 values averaged) and identified as NFL overall, whereas the data obtained in the temporal quadrant only (three values averaged) were identified as NFL temporal. PERG P50 implicit time and P50-N95 amplitude and VEP P100 implicit time and N75-P100 amplitude were also measured. RESULTS: In OAG eyes, we found a significant (P < 0.01) reduction in NFL thickness in both NFL overall and NFL temporal evaluations with respect to the values observed in control eyes. PERG and VEP parameters showed a significant (P < 0.01) delay in implicit time and a reduction in peak-to-peak amplitude. In OAG eyes, the NFL overall and NFL temporal values were significantly correlated (P < 0.01) with the PERG P50 implicit time and P50-95 peak-to-peak amplitude. No correlations (P > 0.01) between NFL values and VEP parameters were found. CONCLUSIONS: There is a correlation between PERG changes and NFL thickness, but there is no correlation between VEP changes and NFL thickness in patients affected by OAG.

Adult↗
PubMed2000

Comparative acute effects of brimonidine 0.2% versus dorzolamide 2% combined with beta-blockers in glaucoma.

PURPOSE: To assess the acute intraocular hypotensive efficacy of brimonidine tartrate 0.2% (a highly selective alpha2-adrenergic agonist) compared with dorzolamide 2% (a topical carbonic anhydrase inhibitor) as adjunct therapy to topical beta-blockers in patients with primary open-angle glaucoma. METHODS: A randomized cross-over masked study was performed. We enrolled one eye of each of 28 patients who were on different beta-blocker therapy. We measured the intraocular pressure (IOP) 2 h after the beta-blocker instillation; we then randomly administered one of the two drugs and we compiled an IOP diurnal curve. One month later we repeated the same procedures with the second drug. Unpaired Mann-Whitney U-test was used to compare decreases in IOP between the two drugs (P<0.05). RESULTS: Both brimonidine 0.2% and dorzolamide 2% have good ocular hypotensive efficacy, significantly lowering IOP when compared to beta-blocker therapy alone, for the whole diurnal curve. Maximum mean percent IOP decrease from baseline was 22.0+/-15.7% (4.0+/-2.9 mmHg) for dorzolamide 2% 6 h after instillation and 35.5+/-16.4% (7.0+/-4.1 mmHg) for brimonidine 0.2% 8 h after administration of the drug. When we compared the two treatments, brimonidine 0.2% showed a higher hypotensive effect than 2% dorzolamide after 4 h (28.4+/-16.8% vs 17.6 +/-9.3%; P=0.04) and 8 h (35.5+/-16.4% vs 21.6 +/-10.8%; P=0.04). CONCLUSION: This study indicates that 0.2% brimonidine acutely associated with beta-blockers is an interesting new combination treatment useful in the management of glaucoma.

Adrenergic alpha-Agonists↗
PubMed2000

Do sex and hormonal status influence choroidal circulation?

AIMS: To investigate the relation between pulse amplitude (PA), pulsatile ocular blood flow (POBF), and sex and hormonal status. METHODS: Measurements of POBF and PA were obtained by ocular blood flow tonography in 76 healthy subjects: 32 males and 44 females (age range 17-77 years). Females were divided into two age groups: group 1 (premenopausal) 17-42 years, and group 2 (post-menopausal) 55 years old and over. Two groups of age matched males served as controls. RESULTS: Premenopausal females demonstrated a significantly higher rate of POBF and PA than age matched males and post-menopausal females. CONCLUSION: Sex and hormonal status were shown to influence choroidal circulation.

Adolescent↗
PubMed1999

Visual function correlates with nerve fiber layer thickness in eyes affected by ocular hypertension.

PURPOSE: To test whether the high variability observed when measuring pattern electroretinogram (PERG), visual evoked potentials (VEP), and spatial contrast sensitivity (SCS) in eyes with ocular hypertension is associated with variation in nerve fiber layer thickness, as measured by optical coherence tomography (OCT). METHODS: The study involved 32 untreated eyes (32 patients; age range, 29-64 years) showing a normal whiteon-white 24/2 Humphrey (San Leandro, CA) perimetry, IOP between 23 and 28 mm Hg, best corrected acuity of 20/20 or better, and none of the following papillary signs on conventional color stereo slides: rim notch(es), peripapillary splinter hemorrhages, or increased vertical-to-horizontal cup-to-disc ratio. On recruitment, each eye underwent SCS testing, OCT, PERG, and VEP recordings. Linear regression (Pearson's test) or Spearman's rank regression was adopted for the analysis of the data. RESULTS: The 95% confidence limits of the electrophysiological data were: PERG P50 latency, 59.3 to 63 msec; PERG P50 to N95 amplitude, 0.74 to 1.15 cmV; VEP P100 latency, 113 to 118 msec; VEP N75 to P100 amplitude, 3.81 to 4.90 micromV. The 360 degrees nerve fiber layer thickness overall (NFLO) ranged between 113 and 169 microm (145+/-16 microm; mean+/-SD) and significantly correlated with PERG P50 to N95 amplitude (r: 0.518; P = 0.002), PERG P50 latency (r: -0.470; P = 0.007), VEP N75 to P100 amplitude (r: 0.460; P = 0.008), VEP P100 latency (r = -0.422; P = 0.016) and SCS at 3 cyc/deg (r: -0.358; P = 0.044). CONCLUSIONS: The variability of PERG, VEP, and SCS testing observed in eyes with ocular hypertension is associated with differences in NFL thickness (the thinner the layer, the worse the visual function).

Adult↗
PubMed1998

ENVIRONMENTAL AUDITING: The Fish Fauna of the Doubs River Prior to Completion of the Rhine-Rhone Connection

/ The part of the Doubs River between Montbeliard and Dole (France), i.e., downstream from the confluence with the Allan River, will be affected by the Rhine- Rhone connection project. In order to improve the understanding of the Doubs ichthyofauna, aquatic environments of the Doubs were sampled by electrofishing. Fish diversity and the presence of some rheophilic species demonstrated the good ecological quality of some stretches of the Doubs. This quality was due to alternating areas with very diversified aquatic environments (riffles, islands and side-arms, backwaters) and a considerable range of flow velocities. The differences in the structure of the fish communities of the different types of aquatic environments were more qualitative (fish species) than quantitative (number of species and number of fish). However, the mean number of fish was statistically lower in the canals (Freycinet canal and channelized part of the Allan River) than in the main course and in the backwaters. The natural parts of the Doubs (unnavigable reaches) showed the most diversified environmental structure and had the most rheophilic fish communities. Thus, the rheophilic species were well represented, but they proved also the most vulnerable to river regulation. However, the most abundant fishes throughout the Doubs River were generalists with no special requirements for food sources or spawning substrate.KEY WORDS: Fish communities; Regulation; Restoration; Floodplain; Large ship canal; Doubs River

Journal Article↗
PubMed1997

Comparative effects of intraocular pressure between systemic and topical carbonic anhydrase inhibitors: a clinical masked, cross-over study.

The aims of the following study were to compare the efficacy of Dorzolamide 1% eye drops with systemic Acetazolamide on the ocular pressure diurnal curve in patients with maximal medical therapy. Three ocular pressure curve were performed in glaucomatous patients, already receiving maximal medical therapy. After a baseline curve, patients were pretreated either with Dorzolamide 1% eye drops or 250 mg Acetazolamide tablets in a double-blind cross-over study. Dorzolamide 1% eye drops and 250 mg Acetazolamide tablets significantly reduced intraocular pressure (IOP) at 2 and 4 h after pretreatment. Both treatments caused a significantly additional decrease of IOP despite maximal medical therapy. Dorzolamide 1% eye drops is as effective as Acetazolamide tablets in reducing the IOP curve. Topical carbonic anhydrase inhibitors may represent an additional and safer treatment for those patients with uncontrolled medical glaucoma.

Acetazolamide↗
PubMed1997

Nerve growth factor (NGF) reduces and NGF antibody exacerbates retinal damage induced in rabbit by experimental ocular hypertension.

BACKGROUND: It has been shown that intravitreal injection of NGF inhibits ganglion cell degeneration after optic nerve transection and ischemic injury. The aim of our study was to investigate the presence of NGF in aqueous humor and its involvement in retinal damage during ocular hypertension. METHODS: We used an experimental model of ocular hypertension in rabbit. Before treatment and 4, 10 and 15 days after induction of hypertension, we evaluated histological retinal damage and NGF levels in aqueous humor using an immunoenzymatic assay. Polyclonal anti-NGF antibodies were injected intravitreally into one eye of each rabbit (n = 6), and the animals were killed after 4 days of hypertension. Another group of rabbits (n = 12) was injected retro-ocularly with NGF and killed after 10 or 15 days of treatment for histologic evaluation of the retina. RESULTS: Our data show that experimental ocular hypertension in adult rabbits induces retinal damage and enhances local NGF levels. The highest NGF value was found after 4 days of intraocular hypertension: high levels persisted, though to a lesser extent, for up to 15 days. Histological examination revealed that the number of retinal ganglion cells (RGC) remained unchanged during the first 4 days but decreased at 10 days. These studies also showed that retro-ocular administration of NGF reduced RGC loss, whereas intraocular injection of NGF antibodies, which inhibited the endogenous NGF, exacerbated the retinal insult. CONCLUSION: These findings demonstrate a protective effect of NGF on RGC damaged by ocular hypertension and prompt further investigations to evaluate a possible therapeutic use of NGF to retard RGC death in humans.

Animals↗
PubMed1996

Histopathological evaluation of retinal damage during intraocular hypertension in rabbit: involvement of ganglion cells and nerve fiber layer.

BACKGROUND: Current clinical tests do not detect glaucomatous signs until the onset of substantial retinal damage. Therefore animal models are required to investigate the very early histopathological alterations in glaucoma disease. We used an experimental model of intraocular hypertension to compare early changes in retinal ganglion cell (RGC) density with the thickness of the nerve fiber layer (NFL). METHODS: Methylcellulose 2% was injected into the anterior chamber of 18 eyes of 18 New Zealand albino rabbits. Intraocular pressure was measured 6 h after the injection and thenceforth once a day using a Shiötz tonometer. Histopathological analysis was performed on days 4, 10, and 15 following the induction of hypertension (six eyes for each group). Sections from the upper temporal retina were stained with hematoxylin-eosin and immunohistochemically using a polyclonal antibody PGP 9.5 to identify RGC. An image analysis system was used to evaluate the RGC and the thickness of the NFL. RESULTS: We observed a significant increase in intraocular pressure until the end of the experiment. Histological analysis showed, after 10 days of ocular hypertension, a significant decrease in RGC density (P < 0.05) and a significant increase (P < 0.05) in glial cell density. We found a significant correlation between RGC loss and cell area at 4 days (P < 0.01; Cc = 0.86) and at 10 days (P < 0.002; Cc = 0.91) of intraocular hypertension. We did not observe a significant decrease in the NFL thickness until 10 days of intraocular hypertension. CONCLUSIONS: Our study confirms the size-dependent RGC loss during intraocular hypertension and shows no early decrease in NFL thickness.

Animals↗
PubMed1996

Efficacy of mipragoside ophthalmic gel in vernal keratoconjunctivitis.

To evaluate the efficacy of Mipragoside, a ganglioside derivative, in vernal keratoconjunctivitis we performed a controlled randomised clinical trial involving 24 patients (mean age 10 +/- 3.4 years, range 5-20 years). Patients received either Mipragoside 0.5% aqueous ophthalmic gel or placebo four times a day for 2 weeks after a week of treatment with placebo. Ocular signs and symptoms were evaluated and considered for statistical analysis. Results show that Mipragoside significantly reduces all symptoms, being most effective on itching (p = 0.01; p = 0.0001) and hyperaemia (p = 0.01; p = 0.0006) after 1 and 2 weeks respectively when compared with placebo. Physician judgement of drug efficacy at the end of treatment was significantly in favour of Mipragoside (p = 0.0001) compared with placebo. We conclude that Mipragoside topical treatment improves symptoms of patients with vernal keratoconjunctivitis and we postulate a possible anti-inflammatory activity of this compound.

Administration, Topical↗
PubMed1996

Tear tryptase levels and allergic conjunctivitis.

We measured tryptase, a neutral protease stored in the secretory granules of mast cells, by solid-phase radioimmunoassay in tears of 12 subjects with vernal keratoconjunctivitis (VKC) during remission phases, nine subjects with seasonal or perennial allergic conjunctivitis, and eight healthy controls. Mean values of tear tryptase levels were significantly (P < 0.02) increased in VKC patients (14.5 +/- 13 micrograms/l) when compared to those measured in patients with seasonal or perennial allergic conjunctivitis (0.6 +/- 0.1 microgram/l) and in controls (3.3 +/- 3.2 micrograms/l). In subjects with allergic conjunctivitis, the levels of tryptase, almost undetectable before allergen conjunctival challenge, showed a significant increase in the challenged eye 20 min-but not 6 h-after provocation in 5/9 cases. Our results indicate that VKC a severe ocular disease characterized by an increased number and abnormal distribution of mast cells in the conjunctiva, also shows elevated levels of tryptase in tears even during remission phases. Evidence of mast-cell activation, as revealed by a significant increase of tryptase levels in tears, in documented during the early-phase reaction, but not during the late-phase reaction, of allergic conjunctivitis patients challenged topically by specific allergen.

Adolescent↗
PubMed1995

Estrogen and progesterone receptors in vernal keratoconjunctivitis.

PURPOSE: Sex-related influences have been implicated in the pathogenesis of vernal keratoconjunctivitis (VKC), an allergic eosinophilic disease. METHODS: The authors evaluated tarsal and bulbar conjunctival biopsies from seven patients with severe and symptomatic VKC for the presence of estrogen and progesterone receptors by using monoclonal antibodies with a peroxidase-antiperoxidase technique. RESULTS: Both the epithelium and subepithelium of the tarsal and bulbar conjunctiva of patients with VKC, but not those of four nonatopic control subjects, showed intense positive staining for estrogen and progesterone receptors. Immunofluorescence colocalization of both estrogen and progesterone receptors with eosinophil cationic protein showed that approximately 70% of positive cells were eosinophils. CONCLUSIONS: Sexual hormones, through their receptors, may influence the activity of eosinophils in patients with VKC.

Adolescent↗