Giuseppe Trimarchi

Effects of Melatonin Treatment in Septic Newborns

Free radicals have been implicated in the pathogenesis of neonatal sepsis and its complications. This study was conducted to determine the changes in the clinical status and the serum levels of lipid peroxidation products [malondialdehyde (MDA) and 4-hydroxylalkenals (4-HDA)] in 10 septic newborns treated with the antioxidant melatonin given within the first 12 h after diagnosis. Ten other septic newborns in a comparable state were used as “septic” controls, while 10 healthy newborns served as normal controls. A total of 20 mg melatonin was administered orally in two doses of 10 mg each, with a 1-h interval. One blood sample was collected before melatonin administration and two additional blood samples (at 1 and 4 h) were collected after melatonin administration to assess serum levels of lipid peroxidation products. Serum MDA + 4-HDA concentrations in newborns with sepsis were significantly higher than those in healthy infants without sepsis; in contrast, in septic newborns treated with melatonin there was a significant reduction (p < 0.05) of MDA + 4-HDA to the levels in the normal controls at both 1 and 4 h (p < 0.05). Melatonin also improved the clinical outcome of the septic newborns as judged by measurement of sepsis-related serum parameters after 24 and 48 h. Three of 10 septic children who were not treated with melatonin died within 72 h after diagnosis of sepsis; none of the 10 septic newborns treated with melatonin died. To our knowledge, this is the first study where melatonin was given to human newborns.

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

Abstract:  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)‐1β, IL‐6, tumor necrosis factor (TNF)‐α 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‐α) 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‐α 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.

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

Abstract:  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)‐α] 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.

Acute gallstone cholecystitis in the elderly: treatment with emergency ultrasonographic percutaneous cholecystostomy and interval laparoscopic cholecystectomy.

BackgroundThe treatment of acute cholecystitis in the elderly is still a subject of debate, particularly with reference to the timing of surgery and the role of laparoscopy.PatientsFrom January 1994 to June 2002 we observed 27 patients aged over 70 years with acute calcolous cholecystitis. The patients were submitted to ultrasonographic percutaneous cholecystostomy within 12 h of the acute attack. For two patients (7.4%) at high operative risk, we chose a conservative treatment. Twenty-five patients (92.6%) were submitted, in 15 cases (60%) within 5 days and in 10 patients (40%) within 8 days, to a laparoscopic cholecystectomy. Statistical significance was accepted when the value of p was less than 0.05.ResultsUltrasonographic percutaneous cholecystostomy was performed successfully in all patients, without major morbidity or mortality, and complete resolution of clinical symptoms was obtained within 48 h. The conversion rate of laparoscopy was 20% (13.3% in patients submitted to surgery within 5 days and 30% in the group submitted within 8 days — p > 0.05). The postoperative morbidity rate was 24%; it was higher (40% versus 15%) in patients converted to laparotomy (p > 0.05); mortality was 4%. The period of hospitalization was 11 days in patients operated laparoscopically and 21 days in those converted to open cholecystectomy (p < 0.001).ConclusionsThe more rational treatment of acute calcolous cholecystitis in elderly patients is represented by ultrasonographic percutaneous cholecystostomy followed, within 5 days, by laparoscopic cholecystectomy using an abdominal insufflation maximum to 12 mmHg and a limited 10–15° head-up tilt.

Serum levels of interleukin 1β, interleukin 8 and tumour necrosis factor α as markers of gastric cancer

Abstract Despite the efforts made, a serum marker reliable for the screening and follow-up of patients with gastric cancer has not yet been identified. The aim of this preliminary study was to test the role of pro-inflammatory cytokines interleukin 1β, interleukin 8 and tumour necrosis factor α in patients with gastric cancer and in control groups. The statistical analysis of cytokines serum levels in the group with gastric cancer versus control groups has shown considerable differences (p<0.001) in their mean rates. The results indicate that the cytokines interleukin 1β, interleukin 8 and tumour necrosis factor α might perhaps act as diagnostic markers in patients with gastric cancer. Therefore, it is hypothesized that after more extended trials, their use in the screening and prognostic assessment of these patients could be a possibility.

Pain in neonatal intensive care: role of melatonin as an analgesic antioxidant

Abstract:  Endotracheal intubation is a common painful procedure in newborn care. Neonates are more sensitive to pain than older infants, children, and adults, and this hypersensitivity is further exacerbated in preterm neonates. The aim of this study was to evaluate the analgesic activity of melatonin during endotracheal intubation of the newborn by using the Neonatal Infant Pain Scale (NIPS) and Premature Infant Pain Profile (PIPP) score. Secondary outcome was an evaluation of melatonin as inflammatory responses. This was performed by measuring the levels of pro‐ and anti‐inflammatory cytokines implicated in the pain. Sixty preterm infants were enrolled in the study and were randomly divided into two groups: 30 infants treated with melatonin plus common sedation and analgesia recommended by Italian Society of Neonatology (group 1) and 30 infants treated with only common sedation and analgesia. The sedative and analgesic drugs included atropine, fentanyl, and vecuronium. The reduction in pain score (NIPS) was similar in both groups at an early phase, while it (PIPP score) was lower in melatonin‐treated group infants than the other newborns at a late phase, during intubation and mechanical ventilation. The differences were statistically significant at 12, 24, 48, and 72 hr (P < 0.001). Pro‐inflammatory and anti‐inflammatory cytokines (IL‐6, IL‐8, IL‐10 and IL‐12) were higher in the common sedation and analgesia group than in melatonin‐treated infants at 24, 48, 72 hr and 7 days (P < 0.001). This study suggests the use of melatonin as an adjunct analgesic therapy during procedural pain, especially when an inflammatory component is involved.

Self-reported halitosis and emotional state: impact on oral conditions and treatments.

BackgroundHalitosis represents a common dental condition, although sufferers are often not conscious of it. The aim of this study was to examine behavior in a sample of Italian subjects with reference to self-reported halitosis and emotional state, and specifically the presence of dental anxiety.MethodsThe study was performed on Italian subjects (N = 1052; range 15-65 years). A self-report questionnaire was used to detect self-reported halitosis and other variables possibly linked to it (sociodemographic data, medical and dental history, oral hygiene, and others), and a dental anxiety scale (DAS) divided into two subscales that explore a patients dental anxiety and dental anxiety concerning dentist-patient relations. Associations between self-reported halitosis and the abovementioned variables were examined using multiple logistic regression analysis. Correlations between the two groups, with self-perceived halitosis and without, were also investigated with dental anxiety and with the importance attributed to ones own mouth and that of others.ResultsThe rate of self-reported halitosis was 19.39%. The factors linked with halitosis were: anxiety regarding dentist patient relations (relational dental anxiety) (OR = 1.04, CI = 1.01-1.07), alcohol consumption (OR = 0.47, CI = 0.34-0.66), gum diseases (OR = 0.39, CI = 0.27-0.55), age > 30 years (OR = 1.01, CI = 1.00-1.02), female gender (OR = 0.71, CI = 0.51-0.98), poor oral hygiene (OR = 0.65, CI = 0.43-0.98), general anxiety (OR = 0.66, CI = 0.49-0.90), and urinary system pathologies (OR = 0.46, CI = 0.30-0.70). Other findings emerged concerning average differences between subjects with or without self-perceived halitosis, dental anxiety and the importance attributed to ones own mouth and that of others.ConclusionsHalitosis requires professional care not only by dentists, but also psychological support as it is a problem that leads to avoidance behaviors and thereby limits relationships. It is also linked to poor self care. In the study population, poor oral health related to self-reported halitosis was associated with dental anxiety factors.

Effect of 2,6-Diisopropylphenol on the delayed hippocampal cell loss following transient forebrain ischemia in the gerbil

We examined the protective activity of 2,6-diisopropylphenol on mortality and delayed hippocampal cell death induced by transient cerebral ischemia in the gerbil. Forebrain ischemia was produced by bilaterally occluding the common carotid arteries for 10 minutes; then the blood supply to the brain was restored. The number of survivors was counted for 8 days, and the histopathological damage in the CA1 region of the hippocampus was scored according to the semiquantitative scale of Rudolphi and Colleagues. When intraperitoneally injected immediately after the ischemic attack, 2,6-diisopropylphenol (25, 50, 100 mg kg-1) produced no significant reduction in the rate of mortality in comparison with its vehicle. However, the survivors that had received the compound at the dose of 50 and 100 mg kg-1 elicited a significant increase in the number of viable pyramidal cells in the CA1 hippocampal region. Moreover, we obtained similar results by injecting the compound 30 minutes after the release of the carotid artery occlusion. These results suggest that 2,6-diisopropylphenol, although it does not show any capability of improving the rate of survival, it elicits protective properties against the transient forebrain ischemia-induced delayed hippocampal neuronal death.

Antioxidant effect of atorvastatin is independent of PON1 gene T(-107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients.

ABSTRACT Background: Serum paraoxonase (PON1), a high density lipoprotein (HDL)-bound antioxidant enzyme, plays a role in atherosclerosis. An increase in PON1 activity has been reported following statin treatment. Objective: In the present study the following factors were evaluated: the influence of PON1 gene Q192R, L55M and T(–107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment. Research design and methods: 205 Sicilian subjects with primary hypercholesterolaemia (HCh) and 69 healthy subjects as controls were concurrently enrolled. Hypercholesterolaemic patients were randomly divided into two groups: an atorvastatin group (10 mg/day atorvastatin) and a placebo group. Lipid profile, markers of LDL resistance to in vitro oxidation (lag-phase, oxidation rate and thiobarbituric acid-reactive substances), vitamin E content in LDL, PON1 activity and genotypes in both HCh and control subjects were determined at baseline. The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups. Results: HCh subjects showed significantly lower LDL resistance to oxidation, vitamin E content and PON1 activity levels than controls. A strong association was found among PON1 T(–107)C genotypes, LDL susceptibility to oxidation, vitamin E content and PON1 activity. After treatment, the atorvastatin group displayed a significant decrease in total cholesterol, LDL-cholesterol levels, and LDL susceptibility to oxidation, and an increase in vitamin E content and PON1 activity, compared with baseline values. Unlike PON1 activity levels, no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed. Conclusions: These results show, for the first time, that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism.

Anticonvulsant effects of U-54494A and U-50488H in genetically epilepsy-prone rats and DBA/2 mice: A possible involvement of glycine/NMDA receptor complex

1. The effects of U-54494A and U-50488H on convulsions produced by sound have been studied in genetically epilepsy-prone DBA/2 mice and genetically epilepsy-prone rats. 2. Both compounds showed a dose-dependent anticonvulsant activity. U-54494A was less potent as an anticonvulsant than U-50488H in genetically epilepsy-prone rats and elicited a similar potency to that of U-50488H in DBA/2 mice when administered intracerebroventricularly or intraperitoneally. 3. Similar sedative and hypothermic effects were observed after the highest dose of U-54494A and U-50488H in DBA/2 mice. U-50488H seems to exhibit a greater sedative effect and to affect the rotarod test in rats much more than U-54494A. U-54494A elicited a better therapeutic index than U-50488H. 4. The anticonvulsant properties of both compounds are antagonized by high doses of naloxone and nor-binaltorphimine, a selective kappa-opioid antagonist. 5. The effects of U-50488H and U-54494A in DBA/2 mice were also antagonized by the glycine/NMDA receptor antagonist D-serine. 6. The present results suggest a possible interaction between kappa-opioid and the glycine/NMDA receptors during epileptic phenomena.