Antonio Giacomo Rizzo

Neuroprotective effects of Ginkgo biloba extract in brain ischemia are mediated by inhibition of nitric oxide synthesis

We studied the effects of pre-treatment (15 days) with oral administration of Ginkgo biloba extract (Ph-Gb 37.5-150 mg/kg) on brain malonildialdehyde (MDA), brain edema, brain nitrite and nitrate and delayed neuronal death following transient cerebral ischemia in the Mongolian gerbil. Survival was not modified, however, pre-treatment with Ginkgo biloba significantly and in a dose-dependent way reduced post-ischemic brain MDA levels and post-ischemic brain edema. Delayed neuronal death in the CA1 of the hippocampus was attenuated by the highest dose of the extract. Increase of nitrite and nitrate was observed after cerebral ischemia in the hippocampus and it was dose-dependently reduced in animals pretreated with Ph-Gb, thus suggesting that neuroprotective effects of Ginkgo biloba may be due to an inhibitory action on nitric oxide formation.

Multiple organ failure following zymosan-induced peritonitis is mediated by nitric oxide.

In the present study we tested the hypothesis that nitric oxide may play a role in the pathogenesis of multiple organ failure induced by peritoneal injection of zymosan in the rat. A severe inflammatory response characterized by peritoneal exudation, high plasma and peritoneal levels of nitrate/ nitrite (breakdown products of nitric oxide), prostaglandin E2 and leukocyte infiltration into peritoneal exudate was induced by zymosan administration. This inflammatory process started within 3 h of administration and onset occurred at 18 h, coinciding with damage of lung, small intestine and liver, as assessed by histological examination and by increase of myeloperoxidase activity, indicative of neutrophil infiltration. Furthermore, at 18 h after zymosan-induced peritonitis, expression of inducible nitric oxide synthase enzyme was found mainly in the macrophages of inflamed lungs. Subcutaneouly administration of a nonisoform selective nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, reduced formation of peritoneal exudate fluid, blocked plasma and peritoneal nitrate/nitrite accumulation, and attenuated the elevated release of peritoneal prostaglandin E2. In addition, nitric oxide synthase inhibition was effective in preventing the development of organ failure since tissue injury and neutrophil infiltration, by myeloperoxidase evaluation, was reduced in lung, small intestine, and liver. In conclusion, major findings of our study are that nitric oxide exerts a proinflammatory role in the development of multiple organ failure and nitric oxide synthase inhibition is an effective antiinflammatory therapeutic tool, since inhibits not only nitric oxide but also prostaglandin production and cellular infiltration in inflamed organs.

MULTIPLE ACTIONS OF THE COUMARINE DERIVATIVE CLORICROMENE AND ITS PROTECTIVE EFFECTS ON ISCHEMIC BRAIN INJURY

The effects of different doses (0.25, 0.5, 1 and 2 mg/kg/i.p.) of cloricromene, a coumarine derivative, have been investigated on brain malondialdehyde levels, brain edema, myeloperoxidase activity, survival, locomotor hyperactivity and hippocampal neuronal loss following transient cerebral ischemia induced by temporary bilateral carotid occlusion in the Mongolian gerbil. Cloricromene reduced brain lipid peroxidation, measured through the evaluation of malondialdehyde (−82.9% with the highest dose), and the formation of postischemic brain edema, evaluated by water content. The increase in myeloperoxidase activity observed in the hippocampus of postischemic animals was also reduced: 0.7±0.3 U × 10−3 vs. 3.3±0.3 U × 10−3/g tissue. The same treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischemia and reperfusion. Histological observations of the pyramidal layer of CAI showed a reduction of neuronal loss in animals that received the drug before occlusion but not in those that were treated after the occlusion. These results show that cloricromene, a drug with multiple actions, improves brain injury induced by transient cerebral ischemia.

Protective Effects of IRFI-016, a New Antioxidant Agent, in Myocardial Damage, following Coronary Artery Occlusion and Reperfusion in the Rat

The new free radical scavenger IRFI-016 [2(2,3-dihydro-5-acetoxy 4,6,7-trimethyl-benzofuranyl) acetic acid] was assessed in a rat model of myocardial injury induced by 1 h of left coronary artery occlusion followed by 30 min of reperfusion. Myocardial ischaemia plus reperfusion (MI/R) produced severe cardiac necrosis, neutrophil infiltration in the jeopardized tissue, increased serum creatine kinase (CK) and ST segment of the electrocardiogram (ECG), lowered the pressure rate index (PRI), increased serum levels of tumour necrosis factor (TNF-alpha) and caused a decrease in the survival rate. Administration of IRFI-016 (100 and 200 mg/kg i.p.) 30 min before occlusion resulted in a significant protective effect in post-ischaemic reperfusion. Compared with untreated rats, IRFI-016, in particular the dose of 200 mg/kg, caused a reduction of the necrotic zone whether the necrotic area was expressed as a percentage of the area at risk (55 +/- 4% in the MI/R vehicle group and 24 +/- 2.5% in the MI/R treated group; p < 0.001) or as a percentage of the total left ventricle (23 +/- 3.4% in the MI/R vehicle group and 8 +/- 2.1% in the MI/R treated group; p < 0.005), reduced the myeloperoxidase activity, an index of neutrophil infiltration in the necrotic area (from 4.8 +/- 0.8 to 1.6 +/- 0.4 U/g tissue; p < 0.005), reduced the serum levels of TNF-alpha (from 216 +/- 13 to 45 +/- 7 U/ml; p < 0.001), blunted the rise of the ST segment of the ECG (from 0.47 +/- 0.13 mV in the vehicle group to 0.3 +/- 0.18 mV in the treated group; p < 0.001), reduced the loss of CK (from 220 +/- 15 to 88 +/- 13 IU/ml of blood; p < 0.001) and improved the depressed PRI (from 56 +/- 4% to 78 +/- 3% mm Hg/beats/min; p < 0.005). Finally, IRFI-016 significantly enhanced the survival rate evaluated at the end of the experiment. The results strongly indicate that IRFI-016 is a promising drug for cardiac ischaemia and reperfusion.

Pre- and post-operative patient care for transoral thyroidectomy

Endoscopic thyroidectomy (ET) allows surgeons to remove a thyroid tumor from a remote site, while providing excellent results from a cosmetic viewpoint. Minimally invasive surgery is widely employed for the treatment of thyroid diseases. Several minimal access approaches to the thyroid gland have been described. The commonly performed surgeries have been endoscopic lobectomies. We have performed ET trans orally by the inferior vestibular approach. Our preliminary results indicate that ET performed via transoral is a technically feasible and safe procedure with excellent cosmetic results for patients with benign thyroid tumors. In this report, we have summarized a focused on the pre- and post-operative patient care of this procedure.

Thyroidectomy in elderly patients aged ≥70 years

Worldwide, the indications for thyroid surgery have been continuously extended among elderly patients in the last 20 years. The balance between treatment indication and surgical risk is certainly an interesting topic for every thyroid surgeon. This paper is a review of recent literature from January 2005 up to April 2017. We analyzed three principal subjects: indications for surgical treatment, medical complications and surgical complications. We can summarize the conclusions of our analysis, stating that age could not be considered as an absolute factor, but in relation to the comorbidities and the general clinical condition of the patient. Special risk indices dedicated to geriatric patients could be very useful in order to facilitate the decision-making process; however, relying on the current knowledge, we could state that there is value in providing surgery to geriatric patients in highly specialized and high-volume centers, where access to technology and its systematic use, coupled with surgeons experience, could certainly avail the geriatric patient management.