Biomedical subjects

Pietro Antonuccio

Publications and source records attributed to Pietro Antonuccio.

6 recordsLinked to original sources

PubMed2006

Lipid peroxidation activates mitogen-activated protein kinases in testicular ischemia-reperfusion injury.

PURPOSE: Testicular damage after torsion has been attributed to many mechanisms, of which one is lipid peroxidation of the plasma membrane, which could cause the activation of the mitogen-activated protein kinase family. These proteins are of vital importance for signal transduction pathways and 2 of them, extracellular signal-regulated kinase and c-jun N-terminal kinase, participate in the pathogenesis of testicular ischemia. We investigated whether lipid peroxidation may trigger mitogen-activated protein kinase activation in testicular ischemia-reperfusion. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were subjected to 1-hour testicular ischemia, followed by 24 hours of reperfusion. Sham testicular ischemia-reperfusion rats served as controls. Animals were randomized to receive raxofelast, an inhibitor of lipid peroxidation (20 mg/kg intraperitoneally administered 15 minutes before detorsion and 15 minutes after detorsion) or vehicle (1 ml/kg 10% dimethyl sulfoxide/NaCl solution). A group of animals was sacrificed 0, 10, 15, 20, 25 and 30 minutes, and 1, 2 and 3 hours, respectively, after detorsion to evaluate testicular c-jun N-terminal kinase, extracellular signal-regulated kinase and tumor necrosis factor-alpha activation by Western blot analysis, and mRNA expression and conjugated dienes using a spectrophotometer technique. Another group was sacrificed 24 hours after detorsion to evaluate histological alterations. RESULTS: Testicular ischemia-reperfusion injury caused a significant increase in the conjugated diene levels, extracellular signal-regulated kinase c-jun N-terminal kinase activity and tumor necrosis factor-alpha expression in both testes. Furthermore, histological examination revealed marked damage. Raxofelast inhibited these parameters and decreased histological damage. CONCLUSIONS: These data suggest that lipid peroxidation triggers extracellular signal-regulated kinase and c-jun N-terminal kinase activation. Furthermore, mitogen-activated protein kinase blockade might represent a potential therapeutic approach to treatment in patients with unilateral testicular torsion.

Animals↗

PubMed2005

Evidence for a role of mitogen-activated protein kinase 3/mitogen-activated protein kinase in the development of testicular ischemia-reperfusion injury.

Mitogen-activated protein kinase (MAPK) 3/MAPK1 (also known as ERK1/ERK2) plays an important role in the signal transduction pathways. To our knowledge, however, its role in the development of testicular ischemia-reperfusion injury has not yet been investigated. Therefore, we studied the pattern of MAPK3/MAPK1 activation in a experimental model of testicular ischemia-reperfusion injury. We also investigated MAPK8 to understand whether an association exists between these two MAPKs. Adult male Sprague-Dawley rats were subjected to 1 h of testicular ischemia followed by 24 h of reperfusion or to a sham testicular ischemia-reperfusion. Animals were randomized to receive PD98059, which is an inhibitor of MAPK3/MAPK1 (10 mg/kg i.p. administered immediately after detorsion), or its vehicle. The time course of MAPK3/MAPK1, MAPK8, and tumor necrosis factor (TNF; also known as TNF alpha) expression and a histological examination in both the ischemic-reperfused testis and the contralateral one were performed. In both testes, MAPK3/MAPK1 and MAPK8 expression appeared following 10 min of reperfusion and reached their highest activation after 30 min. The MAPK levels slowly decreased, and no significant expression of either kinase was observed following 2 h of reperfusion. Expression of TNF was evident after 1 h of reperfusion and reached its maximum increase after 3 h. PD98059 blunted MAPK3/MAPK1 and MAPK8, reduced TNF expression, and improved the testicular damage caused by ischemia-reperfusion injury in both testes. These data emphasize that MAPK3/MAPK1 has a role in testicular damage and that its blockade might have a future therapeutic role for the management of patients with unilateral testicular torsion.

Animals↗

PubMed2005

Long-term functional evaluation of diaphragmatic motility after repair of congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: A few studies have taken into account the diaphragmatic function in patients successfully treated for congenital diaphragmatic hernia (CDH). Monodimensional sonography has been reported to be useful in assessing the diaphragmatic motility. Aim of the present study was to investigate, in a long-term follow-up, the diaphragmatic function after CDH repair. METHODS: Ten patients, with a mean age of 16 (5-26) years, were enrolled. All had had a left diaphragmatic hernia repaired, but no one received a patch. Ten subjects of matched age were used as controls. The diaphragmatic excursions appear, at M-mode sonography, as a sinusoid; the amplitude of the curve on the vertical axis measured the movement in centimeters. Chest x-ray and spirometry were also performed in CDH patients. RESULTS: A reduced diaphragmatic motility on the left (treated) side was recorded. The amplitude of the contraction was significantly reduced when compared with the contralateral side (1.19 +/- 0.2 vs 2.33 +/- 0.9 cm; P = .017) and was also significantly reduced in comparison with the motion of the left side of controls (1.19 +/- 0.2 vs 1.83 +/- 0.4 cm; P = .01). There was no difference in the amplitude of contraction between the left and right sides of control patients and between the right side of CDH patients and the controls. Spirometry was normal in all patients but one, who had a slight reduction of ventilation on the left side. CONCLUSION: M-mode sonography appears as a very useful tool in quantitative evaluation of diaphragmatic movements and should be extensively used during follow-up of patients after CDH repair. Motility of the repaired diaphragmatic is reduced, even after a long period, but this does not affect the respiratory function in patients who survived CDH repair.

Adolescent↗

PubMed2004

Raxofelast, a hydrophilic vitamin E-like antioxidant, reduces testicular ischemia-reperfusion injury.

Testis torsion is a surgical emergency that lead to permanent gonad damage. The damage has been ascribed to mechanisms of ischemia-reperfusion similar to other tissues. The mechanisms involved are different, but the lipid peroxidation of plasma membrane, caused by reactive oxygen species (ROS), generated particularly during reperfusion, is one of the most accredited. In the present study, we aimed to evaluate the effects of raxofelast, a vitamin E-like antioxidant with potent action and no systemic toxicity, on lipid peroxidation and histopathology in both testes after unilateral testicular torsion and detorsion. Adult male Wistar rats were subjected to total occlusion (3 h) of the left testis followed by 4 hours of reperfusion (TI/R). Sham testicular ischemia-reperfusion rats (SHAM TI/R) were used as controls. The animals were then randomized to receive either vehicle (1 ml/kg/i.p. of a dimetylsulphoxide/NaCl 0.9% 1:10 v/v solution, injected either 15 min before detorsion and 15 min after detorsion) or raxofelast (20 mg/kg i.p. 15 min before detorsion and 15 min after detorsion). Conjugated dienes (CD) levels, an index of lipid peroxidation, and testis histopathology were evaluated. Testicular ischemia reperfusion (TI/R) in untreated rats produced high testicular levels of CD (3.6+/-0.3 DeltaABS/g protein on the left side and 2.5+/-0.2 DeltaABS/g protein on the right side). Furthermore, histological examination revealed marked damage to the testis interstitium with severe haemorrhage and edema. The administration of raxofelast lowered CD levels (2.8+/-0.2 DeltaABS/g protein on the left side and 1.9+/-0.1 DeltaABS/g protein in the right side) and significantly reduced histological damage. These data suggest that the hydrophilic vitamin E-like antioxidants are good candidates for designing a novel therapeutic strategy to halt the oxidative stress that follows acute testis torsion.

Animals↗

PubMed2004

Immunohistology of aquaporin-1 and stem cell factor-receptor in human undescended testes.

OBJECTIVES: Both aquaporin (AQP) 1 and the stem-cell factor/C-kit system seem to have a definite role in testis function, but very few studies have been reported in humans, especially in the paediatric age group. With the present study we wanted to investigate the expression of these proteins to better delineate their role in normal and pathologic testes. METHODS: Immunohistology using AQP 1 and C-kit antibodies was performed on paraffin sections of open-testicular biopsies from 32 undescended testes. The testes of cryptorchid patients, with ages ranging from 2 to 15 years, were biopsied during an orchidopexy operation, after obtaining informed consent. Control biopsies, from 8 patients of matched age, were obtained during operations for inguinal hernia or hydrocele, always after obtaining informed consent. Positive results were recorded as diffuse or focal patterns and scored as weak, moderate or strong immunostaining. RESULTS: AQP 1 antibody strongly depicted microvessel endothelial cells, but was unlabeled in endotubular and interstitial cell lines, in both control and undescended testes. The C-kit immunostaining in normal testes revealed a diffuse, strong staining in the cytoplasm of spermatogonia and primary spermatocytes. However, in the undescended testes a focal C-kit immunolabelling was weakly recognized in both spermatogonial and immature Sertoli cells. CONCLUSIONS: These results indicate a direct involvement of AQP 1 in the regulation of fluid transport across the endothelial cell membranes of testicular microvessels. A role of the C-kit receptor protein is also substantiated by its strong expression in the maturing spermatogonia of the normal testes, but was minimally or not recognizable in undescended prepubertal testes.

Adolescent↗

PubMed2003

Peritoneal macrophage activity after laparoscopy or laparotomy.

BACKGROUND/PURPOSE: The beneficial effect of laparoscopy on the immune system seems not to be present at the peritoneal level at which the local immunity appears to be impaired by CO2. The aim of this study was to investigate the peritoneal macrophages (MPhis) activity after laparoscopy and laparotomy. METHODS: Thirty rats (300 to 350 g) were used and divided into 3 groups. In the laparotomy group, the peritoneum was opened and the abdominal wall exposed to air for 60'. In the laparoscopy group, pneumoperitoneum was created and maintained at 4 to 6 mm Hg for 60'. In the control group, anaesthesia was maintained for 60' without any other manipulations. Twenty-four hours after operation, peritoneal MPhis were harvested and cultured. The authors investigated nitrite/nitrate (NOx) production as well as the message for the inducible nitric oxide (iNOS), with the reverse transcriptase polymerase chain reaction under basal condition and after Lipopolysaccharide (LPS) stimulation. RESULTS: Basal MPhi NOx release was significantly higher after laparoscopy than either after laparotomy or control. LPS stimulation produced a strong increase in NOx production in laparotomy MPhis and control MPhis. In contrast, the increase in NOx production was markedly reduced in MPhi harvested after laparoscopy. Similar results were obtained for macrophage mRNA for iNOS; indeed, the increase in iNOS mRNA after LPS stimulation was blunted severely in MPhi from laparoscopy group. CONCLUSIONS: MPhis after laparoscopy display an higher basal immune performance. After a second insult (LPS), they display a state of tolerance or desensitisation (blunted NOx production and reduced mRNA expression). This observation could have important implications in considering laparoscopy in patients with malignancy or sepsis.

Animals↗