[Renin Angiotensin Axis, Angiotensin Converting Enzyme 2 and Coronavirus]. / Eje Renina Angiotensina, Enzima Convertidora de Angiotensina 2 y Coronavirus.

The renin-angiotensin-aldosterone system (RAAS) is the main plasma volume regulator, which maintains cardiovascular and hydrosaline homeostasis. In the classical pathway, the angiotensin converting enzyme (ACE) generates Angiotensin II (AngII), which is powerfully inflammatory and vasoconstrictive. This classical pathway is also regulated by ACE2, which converts AngI to Ang 1-9, and degrades AngII to Ang 1-7, whose vasodilatory and anti-inflammatory functions balance out the effects of AngII. ACE2 has been associated with the pathogenesis of respiratory infections such as RSV and severe acute respiratory syndrome coronavirus (SARS-CoV and SARS-CoV-2). Recent studies have shown that ACE2 corresponds to the main SARS-CoV-2 receptor, which together with other receptors such as the TMPRSS2, allows the virus to attach, fuse, and enter the host cell. These studies have shown that in animals infected with coronavirus there is a drop in tissue concentration of ACE2 and Ang 1-7, leading to overexpression of AngII and its vasoconstrictive and inflammatory effects. Experiments with recombinant ACE2 have shown a protective effect against overexpression of RAAS in coronavirus-infected animals, which is similar to that demonstrated with the use of AngII receptor blockers (AT1). Evidence on the protective role of ACE2 seems to support the recommendations re garding not discontinuing these drugs in COVID-19 infection. In this article, we present the current knowledge about the role of RAAS in coronavirus infection, based on physiopathological concepts, molecular bases, and experimental and clinical evidence.

Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome.

BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines. METHODS: The guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations. RESULTS: A total of seven ARDS interventions were assessed. We suggest fluid restriction in patients with ARDS (weak recommendation, moderate quality evidence). Also, we suggest early use of neuromuscular blocking agents (NMBAs) in patients with severe ARDS (weak recommendation, moderate quality evidence). We recommend against the routine use of other drugs, including corticosteroids, beta2 agonists, statins, and inhaled nitric oxide (iNO) or prostanoids in adults with ARDS (strong recommendations: low- to high-quality evidence). These recommendations do not preclude the use of any drug or combination of drugs targeting underlying or co-existing disorders. CONCLUSION: This guideline emphasizes the paucity of evidence of benefit - and potential for harm - of common interventions in adults with ARDS and highlights the need for prudence when considering use of non-licensed interventions in this patient population.

Scandinavian clinical practice guideline on mechanical ventilation in adults with the acute respiratory distress syndrome.

BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on mechanical ventilation in adults with the acute respiratory distress syndrome (ARDS) is to formulate treatment recommendations based on available evidence from systematic reviews and randomised trials. METHODS: This guideline was developed according to standards for trustworthy guidelines through a systematic review of the literature and the use of the Grading of Recommendations Assessment, Development and Evaluation system for assessment of the quality of evidence and for moving from evidence to recommendations in a systematic and transparent process. RESULTS: We found evidence of moderately high quality to support a strong recommendation for pressure limitation and small tidal volumes in patients with ARDS. Also, we suggest positive end-expiratory pressure (PEEP) > 5 cm H2O in moderate to severe ARDS and prone ventilation 16/24 h for the first week in moderate to severe ARDS (weak recommendation, low quality evidence). Volume controlled ventilation or pressure control may be equally beneficial or harmful and partial modes of ventilatory support may be used if clinically feasible (weak recommendation, very low quality evidence). We suggest utilising recruitment manoeuvres as a rescue measure in catastrophic hypoxaemia only (weak recommendation, low quality evidence). Based on high-quality evidence, we strongly recommend not to use high-frequency oscillatory ventilation. We could find no relevant data from randomised trials to guide decisions on choice of FiO2 or utilisation of non-invasive ventilation. CONCLUSION: We strongly recommend pressure- and volume limitation and suggest using higher PEEP and prone ventilation in patients with severe respiratory failure.

Valyl-Transfer RNA: Role in Repression of the Isoleucine-Valine Enzymes in Escherichia coli.

alpha-Aminobutyric acid is activated but not transferred to valine-specific transfer RNA and is unable to repress the isoleucine-valine enzymes in Escherichia coli strain W. alpha-Amino-beta-chlorobutyric acid is activated and transferred to valine-specific transfer RNA and completely replaces valine in repression.

The nucleotide sequence of the Escherichia coli crp divergent RNA and an overlapping ORF.

The nucleotide sequence specifying the crp divergent RNA of Escherichia coli was determined. An open reading frame (ORF) is located at +135 to +536 relative to the initiation site of the divergent RNA. Potential factor independent transcription terminators were found at +257 to +294 and +544 to +576. These putative termination sites may account for the two RNAs of approximately 300 and 550 nucleotides previously identified as originating from the crp divergent promoter.

Partial derepression of the isoleucine-valine enzymes during methionine starvation is Salmonella typhimurium.

Methionine starvation of methionine auxotrophs in the presence of excess branched-chain amino acids results in a partial derepression of the isoleucine and valine enzymes. Reversed-phase chromatography indicated that isoleucine, valine and leucine tRNA were altered during methionine starvation. In addition, the total tRNA isolated from cells under these conditions were undermethylated. The observed derepression may be caused by the inability of methyl-deficient tRNA's to participate adequately in normal regulatory functions.

Integration host factor binds specifically to sites in the ilvGMEDA operon in Escherichia coli.

Integration host factor (IHF) of Escherichia coli is a histone-like protein that is involved both in site-specific recombination and in regulating the expression of a number of phage and bacterial genes. We have shown previously that transcription of the ilvGMEDA operon in E. coli is greatly reduced in IHF mutants. We report here that IHF specifically protects two sites within the ilvGMEDA promoter-regulatory region against DNase I digestion. These sites are located upstream from the promoter and in the leader region just prior to the sequence that specifies the attenuator. The footprinting experiments and gel retardation assays show that these sites have strong affinity for IHF. These data and results with ilvGMEDA-lac promoter fusions suggest a direct role for IHF in expression of the ilvGMEDA operon.

Reduced expression of the isoleucine and valine enzymes in integration host factor mutants of Escherichia coli.

The level of the isoleucine and valine (Ilv) enzymes specified by the ilvB and ilvGEDA operons is reduced in integration host factor mutants (himA and himD) of Escherichia coli K-12. Growth inhibition of these strains in minimal medium can be explained by the decreased amounts of one of the Ilv enzymes, acetohydroxy acid synthase I (AHASI). No growth inhibition, or reduction in AHASI activity, was found in a himA derivative of a mutant strain containing high constitutive levels of AHASI. A strong correlation was observed in himA strains between the reduced amount of the Ilv enzymes and of Ilv-specific messenger RNA. These data suggest that integration host factor may be a positive effector for transcription of the ilvB and ilvGEDA operons.

Eje Renina Angiotensina, Enzima Convertidora de Angiotensina 2 y Coronavirus / Renin Angiotensin Axis, Angiotensin Converting Enzyme 2 and Coronavirus

Resumen: El sistema renina angiotensina aldosterona (SRAA) es el principal regulador del volumen plasmático, manteniendo la homeostasis cardiovascular e hidrosalina. En la vía clásica, la enzima convertidora de angiotensina (ECA) genera Angiotensina II (AngII), de potente efecto inflamatorio y vasoconstrictor. Esta vía clásica es a su vez regulada por la ECA2, que convierte AngII a Ang 1-7, cuyas acciones vaso dilatadoras y antiinflamatorias dan balance a los efectos de AngII. La ECA2 se ha relacionado con la patogenia de infecciones respiratorias como el virus respiratorio sincicial y el síndrome respiratorio agudo grave por coronavirus (SARS-CoV y SARS-CoV-2). Estudios recientes han demostrado que la ECA2 corresponde al principal receptor del SARS-CoV-2, que en conjunto con otros receptores como la serin proteasa TMPRSS2, permiten la fijación, fusión y entrada del virus a la célula huésped. En animales infectados por SARS-CoV se produce una caída de la concentración tisular de ECA2 y Ang 1-7, con la consiguiente sobreexpresión de AngII, y sus efectos vasoconstrictores e inflamatorios. Experimentos con ECA2 recombinante han mostrado un efecto protector frente a la sobreexpresión del SRAA en animales infectados por SARS-CoV, efecto similar al demostrado con el uso de bloquea- dores del receptor de AngII, AT1. La evidencia sobre el rol protector de ECA2 parece respaldar las recomendaciones respecto a no suspender estos medicamentos en la infección SARS-CoV-2. En este artículo presentamos el conocimiento actual sobre el rol del SRAA en la infección por SARS-CoV, a partir de conceptos fisiopatológicos, bases moleculares, y evidencia experimental y clínica.

Abstract: The renin-angiotensin-aldosterone system (RAAS) is the main plasma volume regulator, which maintains cardiovascular and hydrosaline homeostasis. In the classical pathway, the angiotensin converting enzyme (ACE) generates Angiotensin II (AngII), which is powerfully inflammatory and vasoconstrictive. This classical pathway is also regulated by ACE2, which converts AngI to Ang 1-9, and degrades AngII to Ang 1-7, whose vasodilatory and anti-inflammatory functions balance out the effects of AngII. ACE2 has been associated with the pathogenesis of respiratory infections such as RSV and severe acute respiratory syndrome coronavirus (SARS-CoV and SARS-CoV-2). Recent studies have shown that ACE2 corresponds to the main SARS-CoV-2 receptor, which together with other receptors such as the TMPRSS2, allows the virus to attach, fuse, and enter the host cell. These studies have shown that in animals infected with coronavirus there is a drop in tissue concentration of ACE2 and Ang 1-7, leading to overexpression of AngII and its vasoconstrictive and inflammatory effects. Experiments with recombinant ACE2 have shown a protective effect against overexpression of RAAS in coronavirus-infected animals, which is similar to that demonstrated with the use of AnglI receptor blockers (AT1). Evidence on the protective role of ACE2 seems to support the recommendations re garding not discontinuing these drugs in COVID-19 infection. In this article, we present the current knowledge about the role of RAAS in coronavirus infection, based on physiopathological concepts, molecular bases, and experimental and clinical evidence.

Bone modulating factors in nephrotic children with normal glomerular filtration rate.

Factors influencing bone and mineral metabolism were evaluated in 16 children with active nephrotic syndrome and normal glomerular filtration rate. All patients were proteinuric and/or hypoalbuminemic and had elevated serum triglyceride and cholesterol levels. Seven patients had never received or had discontinued glucocorticoid treatment at least 6 months before the study; six patients were receiving prednisone at the time of study. Although all patients were hypocalcemic (serum total or ionized calcium), none was hypomagnesemic. Despite the low serum calcium levels, circulating immunoreactive parathyroid hormone was elevated in only nine of 16. Plasma 25-hydroxyvitamin D was low in all 16 patients, averaging 7.6 +/- 1.2 ng/mL for the group. In contrast, levels of 1,25-dihydroxyvitamin D were normal in 12 of 14 patients. Bone mineral content measured by photon absorptiometry averaged 83% and was less than 90% of normal in six of nine patients tested. The findings were not influenced by the recent or concurrent administration of glucocorticoid. The data demonstrate abnormalities of mineral and bone modulation in nephrotic children even in the absence of impaired glomerular filtration rate and irrespective of glucocorticoid therapy. The decrease in serum ionized calcium may be related to an absolute deficiency in 25-hydroxyvitamin D and/or a relative deficiency in 1,25-dihydroxyvitamin D. Undermineralization of bone may result from the low levels of vitamin D metabolites and, in some patients, from an increase in immunoreactive parathyroid hormone. Whether treatment with vitamin D metabolites and/or calcium supplementation will prevent the abnormalities remains to be demonstrated.

Less commonly recognized features of childhood nephrotic syndrome.

This article reviews aspects in the clinical presentation of nephrotic syndrome that are not generally considered characteristics of the syndrome's definition. The importance of various general clinical aspects such as hematuria, hypertension, and other laboratory or histologic findings are discussed. The clinical relevance and management of other specific aspects such as lipid alterations, coagulation abnormalities, calcium and vitamin D metabolism, and nutritional complications derived from the nephrotic syndrome also are included in this review.

Acquisition planning for nuclear medicine imaging equipment.

The acquisition of imaging equipment is sometimes accomplished with less than optimal planning which leads less than satisfactory results. The purpose of this article is to outline a plan for acquisition designed to reduce some of the problems.

The case against preadoption genetic testing.

Adoption professionals and prospective adoptive families have become increasingly interested in obtaining genetic information on children prior to adoption. Predictive genetic testing of apparently healthy children has been urged as a way of generating information about children's future health and assisting families in deciding whether to adopt. Such genetic testing of children, however, raises a host of ethical issues with important implications for adoption policy and practice. The medical and psychosocial benefits and risks of predictive testing provide the context for analyzing the ethics of such testing. Ethical considerations strongly counsel against predictive genetic testing solely for purposes of evaluating a child for adoption.

Delivering health and mental health care services to children in family foster care after welfare and health care reform.

As the 20th century draws to a close, fundamental changes in the organization, financing, and delivery of health care and welfare services, principally directed at poor families, are likely to result in an increased number of children entering out-of-home care. These children typically have significant physical, mental health, and developmental problems. Whether the quality of health care services they receive will improve as a result of health care reform efforts and new approaches to service delivery remains to be seen. This article addresses some of the major changes wrought by welfare and health care reform and describes the essential features of a health care system that can meet the special needs of children in care.