Oxidative stress in resuscitation and in ventilation of newborns.

The lungs of newborns are especially prone to oxidative damage induced by both reactive oxygen and reactive nitrogen species. Yet, these infants are often 1) exposed to high oxygen concentrations, 2) have infections or inflammation, 3) have reduced antioxidant defense, and 4) have high free iron levels which enhance toxic radical generation. Oxidative stress has been postulated to be implicated in several newborn conditions with the phrase "oxygen radical diseases of neonatology" having been coined. There is, however, reason to believe that oxidative stress is increased more when resuscitation is performed with pure oxygen compared with ambient air and that the most effective ventilatory strategy is the avoidance of mechanical ventilation with the use of nasopharyngeal continuous positive airway pressure whenever possible. Multiple ventilation strategies have been attempted to reduce injury and improve outcomes in newborn infants. In this review, the authors summarise the scientific evidence concerning oxidative stress as it relates to resuscitation in the delivery room and to the various modalities of ventilation.

Universal varicella vaccination in the Sicilian paediatric population: rapid uptake of the vaccination programme and morbidity trends over five years.

Following the licensure of the Oka/Merck varicella vaccine in Italy in January 2003, the Sicilian health authorities launched a universal vaccination programme in all nine Local Health Units. A two-cohort vaccination strategy was adopted to minimise the shift of the mean age of varicella occurrence to older age groups, with the goal of vaccinating with one dose at least 80% of children in their second year of life and 50% of susceptible adolescents in their 12th year of life. Two studies were implemented in parallel to closely monitor vaccination coverage as well as varicella incidence.

Double-blind evaluation of nimesulide vs lysine-aspirin in the treatment of paediatric acute respiratory tract infections.

70 children aged 4 to 12 years with acute infection and inflammation of the respiratory tract (laryngitis, tracheitis, bronchitis, pneumonia) were enrolled in a double-blind investigation and randomised to treatment with nimesulide (50mg granules twice daily) or lysine-aspirin (360mg granules twice daily) for 5 days. The drugs were similarly effective in reducing cough, asthenia and dyspnoea, although nimesulide-treated patients experienced fewer gastrointestinal adverse events. These results confirm the efficacy of nimesulide in the treatment of respiratory inflammation and provide preliminary evidence of its value in children.

The fragile X in Sicily: an epidemiological survey.

We have studied a group of 349 institutionalized propositi with mental retardation, and found 12 fra(X)-positive cases among 155 males (7.7%) and 8 fra(X)-positive cases among 194 females (4.1%). The males had characteristic manifestations of the Martin-Bell syndrome. Another 7 males, who were initially considered "borderline", having expression of fra(X) less than 4% and a non-characteristic phenotype, were eventually considered negative. Among 5,624 patients (2,764 males and 2,860 females) that were admitted to the Pediatric Department of the University of Catania during the period July 1986 - June 1987, 210 (120 males and 90 females) had mental retardation. Of these, 75 were analyzed for the presence of fra(X) (q27.3); 5 males (0.18% of all males) and 2 females (0.07% of all females) were fra(X)-positive. The males had the Martin Bell syndrome phenotype. The presence of fra(X) (q27) was confirmed in another 4 male propositi that were referred to our outpatient services with a clinical diagnosis of Martin-Bell syndrome.

Respiratory distress syndrome in the newborn: role of oxidative stress.

Reactive oxygen and nitrogen species are generated by several inflammatory and structural cells of the airways. These oxidant species have important effects on a variety of lung cells as regulators of signal transduction, activators of key transcription factors and modulators of gene expression and apoptosis. Thus, increased oxidative stress accompanied by reduced endogenous antioxidant defenses may play a role in the pathogenesis of a number of inflammatory pulmonary diseases, including respiratory distress syndrome (RDS) in the newborn. There obviously are conflicting reports on the effect of oxygen, ventilation and nitric oxide (NO) on RDS and, thus, the question arises as what the neonatologist should do when confronted with a newborn with RDS. Clearly, utilizing lung protective strategies requires compromises between gas exchange goals and potential toxicities associated with over-distension, derecruitment of lung units and high oxygen concentrations. The results discussed in this brief review suggest rigorous clinical tests with antioxidants which may help to define the mechanisms associated with RDS and which could lead to new treatment strategies.

Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury.

There is evidence that the excessive generation of reactive-oxygen radicals contributes to the brain injury associated with transient, cerebral ischemia. This study investigates the effects of tempol, a small, water-soluble molecule, that crosses biological membranes, on the brain injury caused by bilateral occlusion and reperfusion of both common carotid arteries in the gerbil (BCO). Treatment of gerbils with tempol (30 mg/kg i.p. at 30 min prior to reperfusion and at 1 and 6 h after the onset of reperfusion) reduced the formation of post-ischemic brain oedema. Tempol also attenuated the increase in the cerebral levels of malondialdehyde (MDA) and the hippocampal levels of myeloperoxidase (MPO) caused by cerebral ischemia and reperfusion. The immunohistochemical analysis of the hippocampal region of brains subjected to ischemia-reperfusion exhibited positive staining for nitrotyrosine (an indicator of the generation of peroxynitrite) and poly(ADP-ribose) synthetase (PARS) (an indicator of the activation of this nuclear enzyme secondary to single strand breaks in DNA). In gerbils subjected to BCO, which were treated with tempol, the degree of staining for nitrotyrosine and PARS was markedly reduced. Tempol increased survival and reduced the hyperactivity (secondary to the ischemia-induced neurodegeneration) caused by cerebral ischemia and reperfusion. The loss of neurons from the pyramidal layer of the CA1 region caused by ischemia and reperfusion was also attenuated by treatment of gerbils with tempol. This is the first evidence that the membrane-permeable, radical scavenger tempol reduces the cerebral injury caused by transient, cerebral ischemia in vivo.

Mitochondrial DNA mutation at np 3243 in a family with maternally inherited diabetes mellitus.

Mitochondrial DNA (mtDNA) gene defects may play a role in the development of maternally inherited diabetes mellitus and deafness (MIDD). A family from Southern Italy who showed maternal transmission of type 2 diabetes mellitus with three individuals affected is described. A 10.4 kb deletion and mutations at nucleotide positions (np) 3243, 7445 and 11778 in the mtDNA of six relatives were sought. The mitochondrial np 3243 mutation of the tRNA Leu (UUR) gene was identified in a boy affected by optic atrophy and mental retardation, as well as in his diabetic mother. No other mutations or deletions were found. Our study points out the variable phenotypic expression of the np 3243 mtDNA mutation. This may suggest the presence of other mitochondrial or nuclear mutations required to modulate the phenotype. A clinical and metabolic follow-up of all family members was necessary to understand the role of the np 3243 mutation, especially in one child affected by optic atrophy and mental retardation. Further studies will be aimed at investigating the prevalence of mutations and deletions of mtDNA in type 2 diabetes mellitus.

Individual and synergistic antioxidative actions of melatonin: studies with vitamin E, vitamin C, glutathione and desferrioxamine (desferoxamine) in rat liver homogenates.

The pharmacological effects of melatonin, vitamin E, vitamin C, glutathione and desferrioxamine (desferoxamine) alone and in combination on iron-induced membrane lipid damage in rat liver homogenates were examined by estimating levels of malondialdehyde and 4-hydroxyalkenals (MDA+4-HDA). Individually, melatonin (2.5-1600 microM), vitamin E (0.5-50 microM), glutathione (100-7000 microM) and desferrioxamine (1-8 microM) inhibited lipid peroxidation in a concentration-dependent manner. Vitamin C had both a pro-oxidative (25-2000 microM) and an antioxidative (2600-5000 microM) effect. The IC50 (concentration that reduces damage by 50%) values were 4, 10, 426, 2290 and 4325 microM for vitamin E, desferrioxamine, melatonin, glutathione and vitamin C, respectively. The synergistic actions of melatonin with vitamin C, vitamin E, and glutathione were systematically investigated. When melatonin was combined with vitamin E, glutathione, or vitamin C, the protective effects against iron-induced lipid peroxidation were dramatically enhanced. Even though melatonin was added at very low concentrations, it still showed synergistic effects with other antioxidants at certain concentrations. Furthermore, melatonin not only reversed the pro-oxidative effects of vitamin C, but its efficacy in reducing lipid peroxidation was improved when it was combined with pro-oxidative concentrations of vitamin C. The results provide new information in terms of the possible pharmacological use of the combination of melatonin and classical antioxidants to treat free radical-related conditions.

Minor changes in the sodium dodecyl sulphate-gel electrophoresis periodic acid-Schiff-staining profiles of erythrocyte membranes in beta-thalassemia major.

The sialic acid content of the human erythrocyte membrane is higher in homozygous beta-thalassemia than in heterozygous and healthy donors. Analysis of the difference by means of polyacrylamide gel electrophoresis in 1% sodium dodecyl sulphate and PAS staining failed to reveal significant variations in mobility and relative staining intensity of the main glycoprotein components, PAS-1, PAS-2 and PAS-3. The minor, although highly significant, changes which were recognized in the PAS pattern of beta-thalassemia patients compared with normal controls concerned the PAS-4 region and a shoulder trailing band PAS-2, which both increased in staining intensity relatively to the main sialocomponent PAS-1. Moreover, the shoulder was found to be more prominent in profiles from erythrocytes of blood group 0, in both normal and thalassemic subjects. The experimental data are discussed in the light of the presence of blood group ABH specific macroglycolipids in human erythrocytes (Dejter-Juszynski et al. 1978).

Altered sialic acid contents of red blood cell membrane preparations in homozygous beta-thalassemia.

In the present work the sialic acid content of the red blood cell ghost membranes was measured in blood specimens obtained from 18 patients with beta-thalassemia major and 10 controls. The sialic acid-protein weight ratio was reduced in comparison with normal mean value only in four patients who had undergone splenectomy several years ago. The remaining 14 unsplenectomized patients showed a sialic acid/protein ratio that was 50% higher than normal (P less than 0.001). The titratable sulphydryl groups were also measured in red blood cell membrane preparations. SH groups content was reduced in patients with beta-thalassemia major, and a dramatic decrease (-60%) was observed in patients after splenectomy.

Methionine activating enzyme in various human platelet populations.

Human platelets have been separated into four populations by a discontinuous sucrose gradient. MAE activity has been determined in the various platelet populations and significant differences were obtained with respect to platelet size, the large-heavy platelets showing a higher enzymatic activity than the small-light ones. These data suggest that higher MAE activity in the younger and large-heavy platelets may be responsible for a much higher biochemical and functional efficiency.

Cathechol-O-methyl transferase activity in the individual human platelet populations.

COMT activity is present in many animal tissues, but there is no evidence on the presence or the functional role of COMT activity in platelets. The present work reports the results obtained on COMT activity in the individual platelet populations separated by a discontinuous sucrose density gradient. In the young platelet populations the activity is remarkable higher than in the old and light populations. Low values of COMT activity in the old platelets may reflect platelet senescence.

[Chlamydia trachomatis conjunctivitis in the newborn]. / La conjonctivite à Chlamydia trachomatis du nouveau-né.

Infections of the conjunctiva are frequent in the neonatal period. While Neisseria gonorrhoea and chemical agents were considered as the main etiologies of ophtalmiae neonatorum in the past, Chlamydia trachomatis is today a major cause of neonatal conjunctivitis. Thus in a study of 180 uni-or bilateral neonatal conjunctivitis the authors found a prevalence of Chlamydia trachomatis infection of 41%. The importance of the etiological diagnosis of neonatal conjunctivitis is emphasized, in order to define a specific treatment. Etiological diagnosis of Chlamydia trachomatis infection is based upon immunofluorescence and molecular diagnosis techniques (PCR, LCR). Prevention of neonatal Chlamydia trachomatis conjunctivitis relies upon screening and treatment of Chlamydia trachomatis infections in pregnant women and their partners. Treatment requires oral macrolides, the topical treatment being ineffective.

Potential association of specific Candida parapsilosis genotypes, bloodstream infections and colonization of health workers' hands.

Fungal nosocomial infections continue to be a serious problem among hospitalized patients, decreasing quality of life and adding millions of euros to healthcare costs. The aim of this study was to describe the pattern of fungi associated with the hands of healthcare workers and to genotype Candida parapsilosis isolates in order to understand whether their high clinical prevalence stems from endemic nosocomial genotypes or from the real emergence of epidemiologically-unrelated strains. Approximately 39% (50/129) of healthcare workers were positive for yeasts and among 77 different fungal isolates recovered, C. parapsilosis was the most frequent (44/77; 57%). Twenty-seven diverse genotypes were obtained by microsatellite analysis of 42 selected blood and hand isolates. Most of the isolates from hands showed a new, unrelated, genotype, whereas a particular group of closely related genotypes prevailed in blood samples. Some of the latter genotypes were also found on the hands of healthcare workers, indicating a persistence of these clones within our hospital. C. parapsilosis genotypes from the hands were much more heterogeneous than clinical ones, thus reflecting a high genetic diversity among isolates, which is notably unusual and unexpected for this species.

Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.