118 research outputs found
Corticosteroid-Sparing Effect of Chromoglycate Sodium and Nedocromil
The most appropiate management for bronchial asthma is the control
of airway inflammation. Corticosteroids are the most effective
anti-inflammatory drugs available, but they have a number of side
effects; most of these are dose-dependent. In children, asthma
control should be accomplished with low steroid doses possibly given
by inhalation. In a double-bind placebo-controlled crossover study a
group of children with mild to moderate asthma received NED 16
mg/day or BDP 400 ÎĽg/day. Values for FEV1, PEF, symptoms use
ofbronchodilators overlapped, whereas bronchial hyper-responsiveness
assessed by histamine bronchoprovocation challenge was better with
BDP than NED. In another case, one boy with high bronchial
hyper-reactivity assessed by provocation test with hypertonic
solution, experienced a significant improvement only after 2 weeks
of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on
combined treatment with NED (16 mg/day) and BDP (300 ÎĽ/day). Authors
conclude that NED could have a steroidsparing effect over long-term use
L'esilio nella storia del Novecento: modelli interpretativi, spazi e comunitĂ di saperi
Il volume descrive gli anni dell'esilio americano di Bruno Zevi e il suo successivo impegno nella guerra fredda culturale in Italia
ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy
Objective: Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, with a prevalence of 1:12,000 to 1:25,000. OPA1 mutations are found in 70% of DOA patients, with a significant number remaining undiagnosed. Methods: We screened 286 index cases presenting optic atrophy, negative for OPA1 mutations, by targeted next generation sequencing or whole exome sequencing. Pathogenicity and molecular mechanisms of the identified variants were studied in yeast and patient-derived fibroblasts. Results: Twelve cases (4%) were found to carry novel variants in AFG3L2, a gene that has been associated with autosomal dominant spinocerebellar ataxia 28 (SCA28). Half of cases were familial with a dominant inheritance, whereas the others were sporadic, including de novo mutations. Biallelic mutations were found in 3 probands with severe syndromic optic neuropathy, acting as recessive or phenotype-modifier variants. All the DOA-associated AFG3L2 mutations were clustered in the ATPase domain, whereas SCA28-associated mutations mostly affect the proteolytic domain. The pathogenic role of DOA-associated AFG3L2 mutations was confirmed in yeast, unraveling a mechanism distinct from that of SCA28-associated AFG3L2 mutations. Patients' fibroblasts showed abnormal OPA1 processing, with accumulation of the fission-inducing short forms leading to mitochondrial network fragmentation, not observed in SCA28 patients' cells. Interpretation: This study demonstrates that mutations in AFG3L2 are a relevant cause of optic neuropathy, broadening the spectrum of clinical manifestations and genetic mechanisms associated with AFG3L2 mutations, and underscores the pivotal role of OPA1 and its processing in the pathogenesis of DOA. ANN NEUROL 2020
Calcium mishandling in absence of primary mitochondrial dysfunction drives cellular pathology in Wolfram Syndrome
Wolfram syndrome (WS) is a recessive multisystem disorder defined by the association of diabetes mellitus and optic atrophy, reminiscent of mitochondrial diseases. The role played by mitochondria remains elusive, with contradictory results on the occurrence of mitochondrial dysfunction. We evaluated 13 recessive WS patients by deep clinical phenotyping, including optical coherence tomography (OCT), serum lactic acid at rest and after standardized exercise, brain Magnetic Resonance Imaging, and brain and muscle Magnetic Resonance Spectroscopy (MRS). Finally, we investigated mitochondrial bioenergetics, network morphology, and calcium handling in patient-derived fibroblasts. Our results do not support a primary mitochondrial dysfunction in WS patients, as suggested by MRS studies, OCT pattern of retinal nerve fiber layer loss, and, in fibroblasts, by mitochondrial bioenergetics and network morphology results. However, we clearly found calcium mishandling between endoplasmic reticulum (ER) and mitochondria, which, under specific metabolic conditions of increased energy requirements and in selected tissue or cell types, may turn into a secondary mitochondrial dysfunction. Critically, we showed that Wolframin (WFS1) protein is enriched at mitochondrial-associated ER membranes and that in patient-derived fibroblasts WFS1 protein is completely absent. These findings support a loss-of-function pathogenic mechanism for missense mutations in WFS1, ultimately leading to defective calcium influx within mitochondria
Guideline on management of the acute asthma attack in children by Italian Society of Pediatrics
Background: Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. Methods: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted. A literature search was performed using the Cochrane Library and Medline/PubMed databases, retrieving studies in English or Italian and including children over age 2 year. Results: Inhaled
f2 agonists are the first line drugs for acute asthma attack in children. Ipratropium bromide should be added in moderate/severe attacks. Early use of systemic steroids is associated with reduced risk of ED visits and hospitalization. High doses of inhaled steroids should not replace systemic steroids. Aminophylline use should be avoided in mild/moderate attacks. Weak evidence supports its use in life-threatening attacks. Epinephrine should not be used in the treatment of acute asthma for its lower cost / benefit ratio, compared to \u3b22 agonists. Intravenous magnesium solphate could be used in children with severe attacks and/or forced expiratory volume1 (FEV1) lower than 60% predicted, unresponsive to initial inhaled therapy. Heliox could be administered in life-threatening attacks. Leukotriene receptor antagonists are not recommended. Conclusions: This Guideline is expected to be a useful resource in managing acute asthma attacks in children over age 2
Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases
Background: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. Methods: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. Results: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. Conclusions: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research
Impaired complex I repair causes recessive Leber's hereditary optic neuropathy
Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit-encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits
Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic
The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases
Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide.
Background: It has been proposed that asthma control may be achieved in part by minimizing
airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting β-
agonists and leukotriene antagonists on pulmonary function and airway inflammation are still
largely unexplored in children with moderate persistent asthma.
Objectives: The aim of this study was to investigate the effects of add-on therapy with long-acting
β-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels (FENO) in
children.
Methods: Forty-eight steroid-naĂŻve atopic asthmatic children, 7 to 11 years of age, were randomly treated in four groups fortwo consecutive one-month periods, as follows: 1) first month: budesonide 200 ÎĽg twice daily;second month: budesonide 400 ÎĽg twice daily; 2) first month: budesonide 200 ÎĽg twice daily +formoterol 9 ÎĽg twice daily; second month: budesonide 200 ÎĽg twice daily + montelukast 5 mg once daily; 3) first month: budesonide 200 ÎĽg twice daily + montelukast 5 mg once daily; second
month budesonide 200 ÎĽg + formoterol 9 ÎĽg twice daily; 4) first and second month: budesonide
400 ÎĽg twice daily.
Results: All treatments resulted in a significant increase in lung function and a decrease in FENO
compared with values at baseline. Budesonide + montelukast in combinationwas the most
effective treatment for reducing FENO levels.
Conclusion: This study demonstrates that add-on therapy with montelukast plus low-dose
budesonide is more effective than the addition of long-acting β-agonists or doubling the dose of
budesonide for controlling FENO in asthmatic children
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