Claudia Rossi

Role of central serotonergic neurons in the effect of sertraline in rats in the forced swimming test

Sertraline, administered i.p. in single doses or as three injections in 24 h, significantly reduced the immobility of rats in the forced swimming test at 64 and 100 mumol/kg. The effect of three doses of 64 mumol/kg in 24 h was not modified in animals treated i.p. with metergoline (5 mg/kg) 3 h before testing. I.c.v. administration of 150 micrograms 5,7-dihydroxytryptamine, which depleted brain serotonin, or infusion of 6 micrograms 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, was also ineffective. The effect of 64 mumol/kg sertraline, once daily for 7 days, was not modified by i.c.v. 5,7-dihydroxytryptamine. The effect of three doses of 64 mumol/kg sertraline in 24 h was instead completely antagonized by 100 mg/kg sulpiride given 90 min before testing. The exact mechanism of this effect and its relevance for the favourable effects of sertraline in human depression remain to be clarified.

Clonidine-induced place preference is mediated by α2-adrenoceptors outside the locus coeruleus

Abstract Clonidine, administered intraperitoneally at doses of 0.05 and 0.5 mg/kg, produced a conditioned place preference when paired with the less preferred compartment. No preference for either compartment was found when a balanced conditioning place preference paradigm was used. Infusion of 6 μg/μ1 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, did not modify the effect of 0.05 and 0.5 mg clonidine on place preference. The effect of 0.5 mg/kg was prevented by 1 mg/kg idazoxan, an α2-adrenoceptor antagonist, but not by 3 mg/kg prazosin, which blocks α1-adrenoceptors. Idazoxan by itself (at doses from 0.3 to 3 mg/kg) induced a conditioned place preference when paired with the less preferred side. The results suggest that clonidine has motivational properties which serve to attenuate the aversiveness of the less preferred side in a conditioned place preference paradigm. Stimulation of α1-adrenoceptors postsynaptic to noradrenaline-containing neurons seems to be involved.

Role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-propylamino) tetralin in the rat

The role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was investigated by using the shock titration test in rats. A subcutaneous injection of 300 micrograms/kg 8-OH-DPAT significantly raised the threshold for flinching, jumping and vocalization whereas 100 micrograms/kg only inhibited the flinch response. l-Propranolol and (+)-[N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl propanamide dihydrochloride], (+)-WAY100135, two antagonists at 5-HT1A receptors at 10 mg/kg s.c. antagonized the effect of 300 micrograms/kg 8-OH-DPAT on all measures. The effect of 300 micrograms/kg 8-OH-DPAT on the three measures was unmodified in rats which had received 150 micrograms 5,7-dihydroxytryptamine intracerebroventricularly 10 days before testing. The results suggest that 8-OH-DPAT inhibits nociceptive responses by stimulating postsynaptic 5-HT1A receptors.

Daily Oxygen/O3 Treatment Reduces Muscular Fatigue and Improves Cardiac Performance in Rats Subjected to Prolonged High Intensity Physical Exercise

Rats receiving daily intraperitoneal administration of O2 and running on a treadmill covered an average distance of 482.8 ± 21.8 m/week as calculated during 5-week observation. This distance was increased in rats receiving daily intraperitoneal administration of an oxygen/O3 mixture at a dose of 100; 150; and 300 μg/kg with the maximum increase being +34.5% at 300 μg/kg and still present after stopping the administration of oxygen/O3. Oxygen/O3 decreased the mean arterial blood pressure (−13%), the heart rate (−6%), the gastrocnemius and cardiac hypertrophy, and fibrosis and reduced by 49% the left ventricular mass and relative wall thickness measurements. Systolic and diastolic functions were improved in exercised oxygen/O3 rats compared to O2 rats. Oxygen/O3 treatment led to higher MPI index starting from the dose of 150 μg/kg (p < 0.05) and more effective (+14%) at a dose of 300 μg/kg oxygen/O3. Oxygen/O3 dose-dependently increased the expression of the antioxidant enzymes Mn-SOD and GPx1 and of eNOS compared to the exercised O2 rats. The same doses resulted in decrease of LDH levels, CPK, TnI, and nitrotyrosine concentration in the heart and gastrocnemius tissues, arguing a beneficial effect of the ozone molecule against the fatigue induced by a prolonged high intensity exercise.

Involvement of Proteasome and Macrophages M2 in the Protection Afforded by Telmisartan against the Acute Myocardial Infarction in Zucker Diabetic Fatty Rats with Metabolic Syndrome

This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF) rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R). At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg) reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7%) and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R.

Transpupillary thermotherapy as a primary treatment for circumscribed choroidal haemangioma

range: 245–684), respectively. No other significant retinal diseases were present prior to treatment in the analysed patients of either group. Despite ocriplasmin approval for the treatment of FTMHs <400 lm with VMT, subgroup analyses suggest a greater efficacy in phakic patients without an ERM (Stalmans et al. 2012). Our results demonstrate a high closure rate and good median visual acuity with surgical repair of this FTMH subset. The initial closure rate in the ocriplasmin group is significantly lower, and median final visual acuity falls slightly below the vitrectomy group. Final visual acuity in the ocriplasmin group may suffer due to an initial decrease in visual acuity and an increase in both MLD and BD in unclosed FTMHs (Gupta et al. 2009; Wakely et al. 2012). Thus, it is important to establish whether ocriplasmin treatment results in non-inferior final visual acuity. Even if visual acuity after ocriplasmin only trails slightly behind primary vitrectomy, non-inferiority becomes substantially harder to achieve. With equal visual acuity, 54 patients are required in each study arm, whereas sample size increases to 214 patients in each arm if the mean visual acuity is 2.5 ETDRS letters poorer with ocriplasmin. Calculations are based on a 5-letter non-inferiority limit, standard deviation of 10.4 letters, 80% power and significance level of 5% (Chow et al. 2008). In conclusion, our results of both primary surgical and ocriplasmin FTMH treatment demonstrate similar, but not equal, final visual acuity. We therefore wish to highlight the need for studies to rule out visual inferiority of ocriplasmin treatment in small FTMHs with VMT.

Antiarrhythmic effect of acute oxygen-ozone administration to rats.

The antiarrhythmic effects of 100; 150; and 300microg/kg i.p. oxygen/ozone mixture were tested on arrhythmias induced by i) ischemia; ii) ischemia/reperfusion; iii) aconitine (15microg/kg/i.v.); potassium chloride (1.5% i.v.) in rats. 25min of cardiac left descending coronary artery ischemia caused severe incidence of ventricular tachycardia, ventricular fibrillation and mortality. These were significantly reduced by pre-treatment of rats with oxygen/ozone mixture at doses of 150 and 300microg/kg. In separate experiments using a protocol of 5min ischemia followed by 8min reperfusion this caused arrhythmias starting within 6+/-1s. The incidence of ventricular tachycardia was 100%, while ventricular fibrillation occurred in 75% of the animals and lasted 85+/-14s. The mortality was 62.5%. These figures were significantly (P<0.01) reduced in animals treated with 150microg/kg oxygen/ozone and a substantial increase observed with 300microg/kg, whilst not affected by the lower dose of 100microg/kg. 150 and 300microg/kg oxygen/ozone prolonged the onset time for the appearance of arrhythmias induced by aconitine (300microg/kg oxygen/ozone, approximately 81% longer). Oxygen/ozone also reduced the ventricular tachycardia duration, ventricular fibrillation incidence, arrhythmia score, and increased the rats survival rate. As for example, this latter was increased from 25% (aconitine) to 50% (aconitine+oxygen/ozone 150microg/kg). 100microg/kg oxygen/ozone was without effect. None of the oxygen/ozone doses affected the arrhythmias caused by potassium chloride 1.5% i.v. All the oxygen/ozone antiarrhythmic effects were similar to those observed with lidocaine (1.5mg/kg i.v.). In conclusion, oxygen/ozone has antiarrhythmic effects against arrhythmias caused by aconitine, myocardial ischemia and ischemia/reperfusion.

Study of the Radial Peripapillary Capillary Network in Congenital Optic Disc Anomalies With Optical Coherence Tomography Angiography

PURPOSE To evaluate the radial peripapillary capillary network with optical coherence tomography angiography (angio-OCT) in morning glory syndrome (MGS), optic disc colobomas, and optic disc pits, and to explore possible correlations between the neural vascular structure and the pathogenesis of congenital optic disc anomalies. DESIGN Prospective observational comparative case series. METHODS Fifteen eyes of 15 patients with congenital optic disc anomalies were enrolled in this study. All patients underwent angio-OCT. The scans were centered on optic discs. RESULTS The mean age at presentation was 33 years (range: 19-50 years). Congenital optic disc anomalies were identified in all 15 eyes. Three eyes had the characteristic funduscopic signs of MGS, and angio-OCT scans of the peripapillary retina revealed a dense microvascular network. Optic disc colobomas were found in 5 eyes, and the characteristic funduscopic signs of optic pits were found in 7 eyes. Angio-OCT showed the absence of a radial peripapillary microvascular network in these 12 eyes. CONCLUSION The finding that angio-OCT scans confirmed the presence of a peripapillary microvascular network only in MGS cases supports the hypothesis that a primary neuroectodermal abnormality and a secondary mesenchymal abnormality leads to MGS. Angio-OCT is a safe, rapid imaging technique that could shed light on the pathogenesis of rare diseases of the optic disc.

Ranibizumab in the treatment of choroidal neovascularization associated with morning glory syndrome.

trations in patients with diabetes (Zehetner et al. 2013). Yet, it remains unclear whether HbA1c correlates also with the concentrations of vasoactive proteins in the ocular tissues. Here, we report data of 39 diabetic eyes that were vitrectomized either due to persisting vitreous haemorrhage (VH), diabetic macular oedema (DME) with vitreomacular traction or due to proliferative diabetic retinopathy (PDR) with or without tractional retinal detachment (TRD). Intravitreal total protein concentrations were measured using a bicinchoninic acid protein assay kit (Pierce, Thermo Scientific, Rockford, IL, USA). Ang-2 and VEGF were measured by enzymelinked immunoassay kits (R&D Systems, Minneapolis, MN, USA). Using linear regression models, we demonstrate an association between the HbA1c and intravitreal levels of Ang2. We adjusted univariate model with sex and age and then added the following variables one at a time into the model: type of diabetes, duration of diabetes, body mass index, VH, DME, PDR, fibrosis formation and TRD. We found positive association between HbA1c and Ang-2 (p = 0.001), but not with VEGF (p = 0.327) in the patients with diabetes undergoing primary vitrectomy due to DR complications. Intravitreal Ang-2 levels were independent of duration of diabetes (p = 0.686) and the corresponding Ang-2 concentrations in the plasma (p = 0.680). The association between HbA1c and intravitreal Ang-2 levels remained significant in multivariate linear regression analysis including the confounding factors. Only TRD associated significantly with intravitreal Ang-2, but even after adjusting for it, the association with HbA1c remained significant (p = 0.015, Fig. 1). High intravitreal Ang-2 levels in patients vitrectomized due to TRD could be explained by the response to the tissue trauma, hypoxia and inflammation. Overall, these results reveal a relationship between poor glycemic control and high intravitreal Ang-2 levels, emphasizing that Ang-2 may play a role in the DR progression in patients with diabetes with high HbA1c. Conflict of interest: no conflicting relationship exists for any author. References

Evaluation of vascular changes with optical coherence tomography angiography after ruthenium-106 brachytherapy of circumscribed choroidal hemangioma

PurposeTo describe the vascular changes of circumscribed choroidal hemangioma (CCH) after ruthenium-106 brachytherapy using optical coherence tomography angiography (angio-OCT).MethodsSeven eyes of 7 patients diagnosed with symptomatic CCH who underwent ruthenium-106 plaque radiotherapy were included in the study. Patients underwent complete ophthalmic examination, bulbar echography and angio-OCT. The same protocol was applied 1 year after ruthenium-106 brachytherapy.ResultsAt baseline, the mean best-corrected visual acuity (BCVA) in affected eyes was 0.67 ± 0.14 logMAR, and the mean tumor thickness was 4.46 ± 0.91 mm measured by standardized A-scan echography. After ruthenium-106 plaque treatment, the mean BCVA increased to 0.17 ± 0.10 logMAR (p = 0.001) and the mean tumor thickness to 2.29 ± 0.71 mm (p = 0.003). Moreover, there was a significant reduction of the tumor basal diameter (p= 0.009). Intra-tumor angio-OCT measurements revealed a statistically significant reduction of the vessel and flow areas (p = 0.006 and p = 0.002, respectively) 1 year after brachytherapy.ConclusionsAngio-OCT is a non-invasive reliable method with which to evaluate the vascular features of CCH and consequently to monitor changes after conservative treatment.