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Biomedical subjects

Carmelo Romeo

Publications and source records attributed to Carmelo Romeo.

12 recordsLinked to original sources

Scintigraphic evaluation of colonic motility in patients with anorectal malformations and constipation.

BACKGROUND AND PURPOSE: Constipation is one of the major sequelae in patients after correction of anorectal anomalies (ARAs). The aim of the present work has been to assess the colonic transit time, using radioisotope scintigraphy, in patients operated for ARA and experiencing constipation in the follow-up. The results were compared with transit time from children with true functional constipation. METHODS: Twelve or 32 patients operated for ARA during the period 1994-2003 experienced mild or severe constipation (6 with high or intermediate form of ARA and 6 with low type) at follow-up. The mean age of this group was 5.8 years. Eighteen patients, mean age 6.7 years, with true functional constipation were studied as well. Colonic transit times were investigated using radioisotope scintigraphy. Normal values for colonic transit time were derived from historical controls. Radioisotope diethylenetriamine pentaacetic acid labelled with indium 111 was administered orally to determine a segmental colonic transit. Images of the abdomen have been taken at 6, 24, 48, and again at 72 hours, if radioactivity was not cleared from the colon. To quantify colonic transit, we calculated the geometric centre (GC) dividing the colon into anatomic regions. RESULTS: According to normal controls, 2 different type of delayed transit can be observed: (a) slow-transit constipation if GC at 48 hours is less than 4.1; (b) functional rectosigmoid obstruction (FRSO) if GC at 48 hours is 4.1 or more but less than 6.1 at 72 hours. Patients with functional constipation were divided into 2 groups: (a) slow-transit constipation in 12 patients with a GC at 48 hours of 3.7 +/- 0.5; (b) FRSO in 6 patients with a GC of 4.7 +/- 0.04 and 5.02 at 48 and 72 hours, respectively. Patients operated for high ARA had values characteristic of FRSO with GC at 48 hours of 5.1 +/- 0.8 and 4.75 +/- 0.5 at 72 hours. In low ARA, the transit times were similar to the ones observed in patients with high ARA at 48 hours with a GC of 4.9 +/- 0.5. CONCLUSIONS: Patients with ARA frequently have functional sequelae in the postoperative period such as constipation. According to our results, constipation seems to be secondary to segmental motility disorders limited to the rectosigmoid area, similar to constipated children with FRSO. No evidence of more generalised motility disturbance, as previously postulated, could be recorded.

Abnormalities, Multiple↗

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↗

Prenatal testicular torsion: ultrasonographic features, management and histopathological findings.

AIM: To highlight the ultrasonographic features of prenatal torsion of the testis in utero (IUTT) at presentation, the neonatal management and the histological findings postorchiectomy or biopsy. METHODS: Seven newborns underwent emergency exploration for IUTT. All patients underwent a sonography and real-time color Doppler ultrasound study of the scrotum before any surgical procedure. A histological examination was performed in the removed specimens. RESULTS: Sonography of the scrotum revealed enlarged, heterogeneous testes. In all cases the color and power Doppler did not reveal any flow signal on the affected side. Four newborn with unilateral testicular torsion underwent orchiectomy and contralateral orchidopexy. In one neonate after detorsion and with the absence of gangrenous changes and a reassuring biopsy, a twisted testis could be treated conservatively with orchidopexy. In another case, the parents, acknowledging the inviability of the affected testis, gave consent only for a biopsy of the testis. In the neonate with bilateral IUTT, bilateral testicular biopsies were performed. Histology of the removed testes variably showed interstitial red cell extravasion and coagulation or hemorrhagic necrosis. Light microscopy of the preserved testis highlighted surviving seminiferous tubules, with gonocytes, spermatogonia and fetal Sertoli cells. CONCLUSIONS: An early diagnosis and treatment in IUTT is essential. Surgical exploration should be always performed through the inguinal route. In bilateral IUTT testes should be left to try to assure, as long as possible, a residual Leydig cell function.

Female↗

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↗

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↗

Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment.

Improved survival because of advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease. Even though the etiology of lung injury is multifactorial, recent animal and clinical data indicate that pulmonary damage depends in large part on the ventilatory strategies used. Ventilator-associated lung injury was believed to result from the use of high pressure, thus, the term barotraumas. This trauma is believed to involve free-radical damage. Oxidant injury is a serious cause of lung injury. In the present study, 110 newborns with respiratory distress syndrome were studied; 55 were treated with melatonin and the other 55 with placebo. All the subjects were mechanically ventilated with or without guaranteed volume. Proinflammatory cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha] were measured in tracheobronchial aspirate and the clinical outcome was evaluated. Melatonin treatment reduced the proinflammatory cytokines and improved the clinical outcome. The beneficial action of melatonin presumably related to its antioxidative actions.

Bronchopulmonary Dysplasia↗

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↗

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↗

Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics.

BACKGROUND: Reactive oxygen species (ROS) have been reported to play a significant role in the pathogenesis of sepsis and liver dysfunction. In particular, neonates are at risk for sepsis and have less protection against oxidation. Melatonin has been reported to reduce the oxidative stress status in neonates with sepsis. Little is known about the effect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective effect of melatonin on hepatocyte oxidative energy metabolism against hydrogen peroxide (H2O2), a free radical mediator of septic damage. METHODS: Hepatocytes were isolated from neonatal suckling rats (11-15 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 micromol/l or 10 micromol/l, or H2O2 plus melatonin at each of the two concentrations. Oxygen consumption was measured polarographically. In subsequent experiments, melatonin was added after the hydrogen peroxide. RESULTS: Hydrogen peroxide significantly reduced hepatocyte oxygen consumption ( p<0.001), but melatonin added at the same time was able to prevent this effect ( p<0.001). However, melatonin at a low dose significantly inhibited hepatocyte oxygen consumption ( p<0.001), an effect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a beneficial effect was not observed, indicating that melatonin is not able to reverse the effects of hydrogen peroxide. CONCLUSION: Melatonin has a protective effect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.

Animals↗

Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin.

Improved survival from advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease (CLD). Recently, it was reported that inflammatory mediators such as interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha and IL-8 are present in higher concentrations in lung lavage from babies who develop CLD. Previously, we found that melatonin reduced the rises in proinflammatory cytokines (IL-6, IL-8 and TNF-alpha) and nitrite/nitrate levels in the serum of preterm newborns with respiratory distress syndrome (RDS). The values correlated with gestational age and iatrogenic trauma in the form of oxygen exposure and mechanical ventilation. Increased concentrations of proinflammatory cytokines may, therefore, be the most valuable early indicator of developing CLD and these measurements may assist in selecting infants for interventions such as melatonin treatment or more selective blockage of components of inflammation. In the current study, we extend the original observations and report results in which 120 newborns diagnosed with RDS were either treated with melatonin (60 children) or given placebo (60 children). The cytokine measures were consistent with the previously reported findings and showed that melatonin reduced these values and also lowered nitrite/nitrate levels in serum of newborns with respiratory distress. Furthermore, when nonmelatonin-treated newborns who developed CLD (eight infants) were examined separately, they had levels of IL-6, IL-8, TNF-alpha and nitrite/nitrate values much higher than those in children who did not develop CLD. Two of the nonmelatonin-treated newborns died while no children who received melatonin died. Melatonin was well tolerated by the newborns.

Antioxidants↗

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↗

[Prenatal diagnosis of pelvic floor malformations].

Pelvic floor malformations are congenital defects in the pelvic and perineal area, which are derived from a defective development of the cloaca membrane, the uro-rectal septum, the mesonephric and para-mesonephric ducts and the urogenital sinus. These are complex anomalies with a profound emotional impact on parents. The prenatal diagnosis is possible favoring the prenatal counseling for the parents and expediting the post-natal evaluation and management. Aim of the present paper is to review the current criteria for the prenatal diagnosis of the following malformations: anorectal anomalies, cloacal anomalies, persistence of the urogenital sinus, bladder and cloacal exstrophy and ambiguous genitalia.

Anal Canal↗