Organization of the respiratory supercomplexes in cells with defective complex III: Structural features and metabolic consequences

The mitochondrial respiratory chain encompasses four oligomeric enzymatic complexes (complex I, II, III and IV) which, together with the redox carrier ubiquinone and cytochrome c, catalyze electron transport coupled to proton extrusion from the inner membrane. The protonmotive force is utilized by complex V for ATP synthesis in the process of oxidative phosphorylation. Respiratory complexes are known to coexist in the membrane as single functional entities and as supramolecular aggregates or supercomplexes (SCs). Understanding the assembly features of SCs has relevant biomedical implications because defects in a single protein can derange the overall SC organization and compromise the energetic function, causing severe mitochondrial disorders. Here we describe in detail the main types of SCs, all characterized by the presence of complex III. We show that the genetic alterations that hinder the assembly of Complex III, not just the activity, cause a rearrangement of the architecture of the SC that can help to preserve a minimal energetic function. Finally, the major metabolic disturbances associated with severe SCs perturbation due to defective complex III are discussed along with interventions that may circumvent these deficiencies

Evaluación de residuos lignocelulósicos de la Patagonia argentina para el cultivo del hongo comestible Lentinula edodes (Basidiomycota)

Este trabajo evaluó la tasa de crecimiento micelial (Kr) y la producción de basidiomas de dos cepas comerciales del hongo shiitake Lentinula edodes (B05 y M3790) en formulaciones compuestas de residuos lignocelulósicos procedentes de actividades agrícolas y agroindustriales de la región andina de Patagonia Norte y de materiales leñosos de plantas invasoras. Las formulaciones consistieron de un sustrato base, como chips de madera de sauce (ChS), chips de madera de rosa mosqueta (ChRM), pelusa de rosa mosqueta (PRM) o virutas de lenga (VL), mezclado con un suplemento, como salvado de trigo (ST) o bagazo de cebada cervecera (BC). Las dos cepas evaluadas mostraron mayores Kr con ChRM-ST. La producción de basidiomas tuvo lugar lo largo de 1 a 4 oleadas, durante un máximo de 124 días. Las máximas eficiencias biológicas (EB) se obtuvieron con la cepa M3790, destacándose ChS (118,86%) y VL (88,73%), ambos suplementados con ST. La cepa B05 alcanzó las máximas EB con ChS-ST (54,72%) y con ChRM-BC (50,43%). Los resultados obtenidos especialmente con ChRM y ChS, sumado a su abundancia en Patagonia argentina, sugieren que estos materiales pueden ser aprovechados como sustratos para la producción comercial de shiitake, actividad aún no desarrollada a gran escala en la región

Why mitochondria must fuse to maintain their genome integrity

SIGNIFICANCE: The maintenance of mitochondrial genome integrity is a major challenge for cells to sustain energy production by respiration. RECENT ADVANCES: Recently, mitochondrial membrane dynamics emerged as a key process contributing to prevent mitochondrial DNA (mtDNA) alterations. Indeed, both fundamental and clinical data suggest that disruption of mitochondrial fusion, related to mutations in the OPA1, MFN2, PINK1, and PARK2 genes, leads to the accumulation of mutations in the mitochondrial genome. CRITICAL ISSUES: We discuss here the possibility that mitochondrial fusion acts as a direct mechanism to prevent the generation of altered mtDNA and to eliminate mutated deleterious genomes either by trans-complementation or by mitophagy. FUTURE DIRECTIONS: Finally, we conclude this review with a short evolutionary comparison between the mechanisms involved in mitochondrial and bacterial modes of genome distribution and plasticity, highlighting possible common conserved processes required for the maintenance of their genome integrity, which should inspire our future investigations

The frequency of pharmacological pain relief in university neonatal intensive care units

OBJECTIVE: To evaluate the use of drugs to relieve the pain of invasive procedures newborn infants cared for at a university hospital NICU. METHODS: A prospective cohort study of all newborn infants hospitalized in four NICU during October 2001. The following data were collected: demographic data of the hospitalized newborn infants; clinical morbidity; number of potentially painful procedures and frequency of analgesic administration. Factors associated with the use of analgesia in this cohort of patients were studied by multiple linear regression using SPSS 8.0. RESULTS: Ninety-one newborn infants were admitted to the NICU during the study period (1,025 patient-days). Only 25% of the 1,025 patient-days received systemic analgesia. No specific drugs were administered to relieve acute pain during any of the following painful events: arterial punctures, venous, capillary and lumbar punctures or intubations. For chest tube insertion, 100% of newborn infants received specific analgesia. For the insertion of central catheters 8% of the newborn infants received painkillers. Only nine of the 17 newborn infants that underwent surgical procedures received any analgesic dosage during the postoperative period. For 93% of patients under analgesia the drug of choice was fentanyl. The presence of mechanical ventilation increased the chance of newborn infants receiving painkillers by 6.9 times and the presence of chest tube increased this chance by five times. CONCLUSION: It is necessary to train health professionals in order to bridge the gap between scientific knowledge regarding newborn infant pain and clinical practice.OBJETIVO: Verificar a freqüência com que são empregados analgésicos para o alívio da dor desencadeada por procedimentos invasivos em recém-nascidos internados em UTI universitárias e verificar o perfil de uso de medicamentos para o alívio da dor. MÉTODOS: Coorte prospectiva, avaliada entre 1° e 31 de outubro de 2001, de todos os recém-nascidos internados em quatro UTI. Dados coletados: características gerais das unidades; dados demográficos dos recém-nascidos; morbidade clínica e freqüência do emprego de analgésicos. Realizaram-se a análise estatística descritiva e a regressão linear múltipla por meio do SPSS 8.0, para analisar os fatores associados ao uso de analgésicos nesta coorte. RESULTADOS: No período, foram internados 91 recém-nascidos (1.025 pacientes-dia). Apenas 25% dos 1.025 pacientes-dia receberam alguma dose de analgésico por via sistêmica. Não foi administrada nenhuma medicação específica para o alívio da dor aguda durante os seguintes eventos dolorosos: intubações traqueais, punções arteriais, venosas, capilares e lombares. Na inserção de dreno de tórax, 100% dos recém-nascidos receberam analgesia específica e, para a passagem de cateteres centrais, apenas 8%. De 17 recém-nascidos submetidos a procedimentos cirúrgicos, somente nove receberam analgésicos no pós-operatório. O medicamento mais utilizado foi o fentanil (93%). A presença de ventilação mecânica elevou em 6,9 vezes, e a de dreno de tórax em cinco vezes a chance do recém-nascido receber alguma dose de analgésico. CONCLUSÃO: Há necessidade de melhorar a formação dos profissionais de saúde para diminuir a distância entre os conhecimentos científicos existentes a respeito da dor no recém-nascido e a prática clínica.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina Pediatria NeonatalUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de PediatriaUNICAMP Centro de Atenção Integral à Saúde da MulherUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Medicina Departamento de PediatriaSanta Casa de São Paulo Faculdade de Ciências Médicas Departamento de PediatriaUNIFESP, EPM, Disciplina Pediatria NeonatalSciEL

Application Of Continuous Positive Airway Pressure In The Delivery Room: A Multicenter Randomized Clinical Trial.

This study evaluated whether the use of continuous positive airway pressure (CPAP) in the delivery room alters the need for mechanical ventilation and surfactant during the first 5 days of life and modifies the incidence of respiratory morbidity and mortality during the hospital stay. The study was a multicenter randomized clinical trial conducted in five public university hospitals in Brazil, from June 2008 to December 2009. Participants were 197 infants with birth weight of 1000-1500 g and without major birth defects. They were treated according to the guidelines of the American Academy of Pediatrics (APP). Infants not intubated or extubated less than 15 min after birth were randomized for two treatments, routine or CPAP, and were followed until hospital discharge. The routine (n=99) and CPAP (n=98) infants studied presented no statistically significant differences regarding birth characteristics, complications during the prenatal period, the need for mechanical ventilation during the first 5 days of life (19.2 vs 23.4%, P=0.50), use of surfactant (18.2 vs 17.3% P=0.92), or respiratory morbidity and mortality until discharge. The CPAP group required a greater number of doses of surfactant (1.5 vs 1.0, P=0.02). When CPAP was applied to the routine group, it was installed within a median time of 30 min. We found that CPAP applied less than 15 min after birth was not able to reduce the need for ventilator support and was associated with a higher number of doses of surfactant when compared to CPAP applied as clinically indicated within a median time of 30 min.47259-6

The frequency of pharmacological pain relief in university neonatal intensive care units

OBJECTIVE: To evaluate the use of drugs to relieve the pain of invasive procedures newborn infants cared for at a university hospital NICU. METHODS: A prospective cohort study of all newborn infants hospitalized in four NICU during October 2001. The following data were collected: demographic data of the hospitalized newborn infants; clinical morbidity; number of potentially painful procedures and frequency of analgesic administration. Factors associated with the use of analgesia in this cohort of patients were studied by multiple linear regression using SPSS 8.0. RESULTS: Ninety-one newborn infants were admitted to the NICU during the study period (1,025 patient-days). Only 25% of the 1,025 patient-days received systemic analgesia. No specific drugs were administered to relieve acute pain during any of the following painful events: arterial punctures, venous, capillary and lumbar punctures or intubations. For chest tube insertion, 100% of newborn infants received specific analgesia. For the insertion of central catheters 8% of the newborn infants received painkillers. Only nine of the 17 newborn infants that underwent surgical procedures received any analgesic dosage during the postoperative period. For 93% of patients under analgesia the drug of choice was fentanyl. The presence of mechanical ventilation increased the chance of newborn infants receiving painkillers by 6.9 times and the presence of chest tube increased this chance by five times. CONCLUSION: It is necessary to train health professionals in order to bridge the gap between scientific knowledge regarding newborn infant pain and clinical practice.OBJETIVO: Verificar a freqüência com que são empregados analgésicos para o alívio da dor desencadeada por procedimentos invasivos em recém-nascidos internados em UTI universitárias e verificar o perfil de uso de medicamentos para o alívio da dor. MÉTODOS: Coorte prospectiva, avaliada entre 1° e 31 de outubro de 2001, de todos os recém-nascidos internados em quatro UTI. Dados coletados: características gerais das unidades; dados demográficos dos recém-nascidos; morbidade clínica e freqüência do emprego de analgésicos. Realizaram-se a análise estatística descritiva e a regressão linear múltipla por meio do SPSS 8.0, para analisar os fatores associados ao uso de analgésicos nesta coorte. RESULTADOS: No período, foram internados 91 recém-nascidos (1.025 pacientes-dia). Apenas 25% dos 1.025 pacientes-dia receberam alguma dose de analgésico por via sistêmica. Não foi administrada nenhuma medicação específica para o alívio da dor aguda durante os seguintes eventos dolorosos: intubações traqueais, punções arteriais, venosas, capilares e lombares. Na inserção de dreno de tórax, 100% dos recém-nascidos receberam analgesia específica e, para a passagem de cateteres centrais, apenas 8%. De 17 recém-nascidos submetidos a procedimentos cirúrgicos, somente nove receberam analgésicos no pós-operatório. O medicamento mais utilizado foi o fentanil (93%). A presença de ventilação mecânica elevou em 6,9 vezes, e a de dreno de tórax em cinco vezes a chance do recém-nascido receber alguma dose de analgésico. CONCLUSÃO: Há necessidade de melhorar a formação dos profissionais de saúde para diminuir a distância entre os conhecimentos científicos existentes a respeito da dor no recém-nascido e a prática clínica.40541

Poor birth weight recovery among low birth weight/preterm infants following hospital discharge in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>Healthy infants typically regain their birth weight by 21 days of age; however, failure to do so may be due to medical, nutritional or environmental factors. Globally, the incidence of low birth weight deliveries is high, but few studies have assessed the postnatal weight changes in this category of infants, especially in Africa. The aim was to determine what proportion of LBW infants had not regained their birth weight by 21 days of age after discharge from the Special Care Unit of Mulago hospital, Kampala.</p> <p>Methods</p> <p>A cross sectional study was conducted assessing weight recovery of 235 LBW infants attending the Kangaroo Clinic in the Special Care Unit of Mulago Hospital between January and April 2010. Infants aged 21 days with a documented birth weight and whose mothers gave consent to participate were included in the study. Baseline information was collected on demographic characteristics, history on pregnancy, delivery and postnatal outcome through interviews. Pertinent infant information like gestation age, diagnosis and management was obtained from the medical records and summarized in the case report forms.</p> <p>Results</p> <p>Of the 235 LBW infants, 113 (48.1%) had not regained their birth weight by 21 days. Duration of hospitalization for more than 7 days (AOR: 4.2; 95% CI: 2.3 - 7.6; p value < 0.001) and initiation of the first feed after 48 hours (AOR: 1.9; 95% CI 1.1 - 3.4 p value 0.034) were independently associated with failure to regain birth weight. Maternal factors and the infant's physical examination findings were not significantly associated with failure to regain birth weight by 21 days of age.</p> <p>Conclusion</p> <p>Failure to regain birth weight among LBW infants by 21 days of age is a common problem in Mulago Hospital occurring in almost half of the neonates attending the Kangaroo clinic. Currently, the burden of morbidity in this group of high-risk infants is undetected and unaddressed in many developing countries. Measures for consideration to improve care of these infants would include; discharge after regaining birth weight and use of total parenteral nutrition. However, due to the pressure of space, keeping the baby and mother is not feasible at the moment hence the need for a strong community system to boost care of the infant. Close networking with support groups within the child's environment could help alleviate this problem.</p

OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes

Mutations in OPA1, a dynamin-related GTPase involved in mitochondrial fusion, cristae organization and control of apoptosis, have been linked to non-syndromic optic neuropathy transmitted as an autosomal-dominant trait (DOA). We here report on eight patients from six independent families showing that mutations in the OPA1 gene can also be responsible for a syndromic form of DOA associated with sensorineural deafness, ataxia, axonal sensory-motor polyneuropathy, chronic progressive external ophthalmoplegia and mitochondrial myopathy with cytochrome c oxidase negative and Ragged Red Fibres. Most remarkably, we demonstrate that these patients all harboured multiple deletions of mitochondrial DNA (mtDNA) in their skeletal muscle, thus revealing an unrecognized role of the OPA1 protein in mtDNA stability. The five OPA1 mutations associated with these DOA ‘plus’ phenotypes were all mis-sense point mutations affecting highly conserved amino acid positions and the nuclear genes previously known to induce mtDNA multiple deletions such as POLG1, PEO1 (Twinkle) and SLC25A4 (ANT1) were ruled out. Our results show that certain OPA1 mutations exert a dominant negative effect responsible for multi-systemic disease, closely related to classical mitochondrial cytopathies, by a mechanism involving mtDNA instability