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1.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33658363

RESUMO

Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules.


Assuntos
Acidose/sangue , Proteína HMGB1/sangue , Sepse/sangue , Sialoglicoproteínas/sangue , Zinco/sangue , Acidose/imunologia , Acidose/metabolismo , Acidose/patologia , Proteínas de Transporte , Proteína HMGB1/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Imunidade Inata , Lipopolissacarídeos/farmacologia , Polissacarídeos/química , Sepse/imunologia , Sepse/patologia , Ácidos Siálicos/química , Sialoglicoproteínas/química , Zinco/metabolismo
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(2): 216-222, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33729143

RESUMO

OBJECTIVE: To develop a diagnostic analysis software for determining the type of acid-base balance disorder. METHODS: Mathematical models were built based on Henderson-Hasselbalch equations and compensation formulas, to determine the important parameters of acid-base balance disorder, and to develope acid-base balance disorder analysis process. The software was compiled using the Visual Basic.NET programming language, and the installation package was generated after debugging. Acid-base balance disorder cases were searched by PubMed, Wanfang and CNKI databases from 1980 to 2015, and the blood gas parameters [pH, arterial partial pressure of carbon dioxide (PaCO2), HCO3- and anion gap (AG)] and the types of acid-base imbalance (literature results) were recorded. All cases were reanalyzed by software and the type of acid-base balance disorder was determined (software diagnostic type). Kappa-test and McNemar-test were performed for the two diagnostic results. RESULTS: The "four parameters-four steps" analysis method was used as the analysis process to judge the types of acid-base balance disorder. "Four parameters" included pH, PaCO2, HCO3- and AG. "Four steps" were outlined by following aspects: (1) according to the pH, combined with PaCO2 and HCO3-, the primary types of acid-base balance disorder was determined; (2) according to the compensation situation, double mixed acid-base balance disorder (DABD) was determined; (3) according to AG value, three mixed acid-base disorders (TABD) were determined; (4) the ratio of ΔAG ↑ /ΔHCO3- ↓ was also calculated to determine whether there was normal AG metabolic acidosis or metabolic alkalosis. The software had the characteristics of simple interface, convenient operation, rapid judgment, and comprehensive analysis. It could judge all acid-base balance disorder types excepted "AG normal metabolic acidosis combined metabolic alkalosis". The software was used to reanalyze 112 cases of acid-base balance disorder reported in the literature, with a consistent rate of 87.50% and better consistency of the diagnostic results (Kappa test: κ = 0.84, P < 0.01; McNemar test: χ2 = 0.87, P = 0.65). CONCLUSIONS: The software can be used as an important tool to judge the type of acid-base balance disorder, and provide clinicians with diagnostic reference, which have practical value and application prospect.


Assuntos
Desequilíbrio Ácido-Base , Acidose , Alcalose , Equilíbrio Ácido-Base , Desequilíbrio Ácido-Base/diagnóstico , Humanos , Concentração de Íons de Hidrogênio , Software
3.
Allergol. immunopatol ; 49(1): 101-106, ene.-feb. 2021. graf, tab
Artigo em Inglês | IBECS | ID: ibc-199232

RESUMO

BACKGROUND: Propionate inborn errors of metabolism (PIEM), including propionic (PA) and methylmalonic (MMA) acidemias, are inherited metabolic diseases characterized by toxic accumulation of propionic, 3-hydroxypropionic, methylcitric, and methylmalonic organic acids in biological fluids, causing recurrent acute metabolic acidosis events and encephalopathy, which can lead to fatal outcomes if managed inadequately. PIEM patients can develop hemato­logical abnormalities and immunodeficiency, either as part of the initial clinical presentation or as chronic complications. The origin and characteristics of these abnormalities have been studied poorly. Thus, the aim of the present work was to evaluate and describe lymphoid, myeloid, and erythroid cell population profiles in a group of clinically stable PIEM patients. METHODS: This was a retrospective study of 11 nonrelated Mexican PIEM patients. Clinical, bio­chemical, nutritional, hematological, and lymphocyte subsets were analyzed. RESULTS: Despite being considered clinically stable, 91% of patients had hematological or immu­nological abnormalities. The absolute lymphocyte subset counts were low in all patients but one, with CD4+ T-cell lymphopenia, being the most common one. Furthermore, of the 11 stud­ied subjects, nine presented with a low CD4/CD8 ratio. Among the observed hematological alterations, bicytopenia was the most common (82%) one, followed by anemia (27%). CONCLUSION: Our results contribute to the landscape of immunological abnormalities observed previously in PIEM patients; these abnormalities can become a life-threatening chronic com­plications because of the increased risk of opportunistic diseases. These findings allow us to propose the inclusion of monitoring immune biomarkers, such as subsets of lymphocytes in the follow up of PIEM patients


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Erros Inatos do Metabolismo/terapia , Erros Inatos do Metabolismo/diagnóstico , Acidemia Propiônica/diagnóstico , Acidose/complicações , Acidemia Propiônica/terapia , México , Estudos Retrospectivos , Antígenos CD4/imunologia , Antígenos CD8/imunologia , Espectrometria de Massas/métodos , Citometria de Fluxo , Acidose/imunologia
4.
Lakartidningen ; 1182021 02 19.
Artigo em Sueco | MEDLINE | ID: mdl-33616194

RESUMO

A woman in her sixties presented at the Emergency department with nausea, flank pain and profuse vomiting. She had an anion-gap metabolic acidosis, elevated liver enzymes and a pronounced renal failure with creatinine 1997 µmol/L (22,6 mg/dl). She was admitted and treated with haemodialysis. On hospital day 5 a bilateral facial palsy, blindness and a moderate generalized weakness rapidly developed. The patient now revealed that she had consumed about 2 dl of brake fluid with a high content of diethylene glycol about a week before hospital admission. Diethylene glycol poisoning typically causes irreversible kidney failure and demyelinating nerve damage in severe cases. The early and debilitating metabolic acidosis seen in ethylene glycol poisoning seems to be absent in diethylene glycol poisoning and patients often present late. This is the first known Swedish case of symptomatic diethylene glycol poisoning. Internationally, during the last century, several mass poisonings have been caused by diethylene glycol contaminated pharmaceutical products.


Assuntos
Acidose , Envenenamento , Acidose/induzido quimicamente , Creatinina , Etilenoglicóis , Feminino , Humanos , Suécia
5.
Life Sci ; 270: 119153, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33539911

RESUMO

Cardiac tissue ischemia/hypoxia increases glycolysis and lactic acid accumulation in cardiomyocytes, leading to intracellular metabolic acidosis. Sodium bicarbonate cotransporters (NBCs) play a vital role in modulating intracellular pH and maintaining sodium ion concentrations in cardiomyocytes. Cardiomyocytes mainly express electrogenic sodium bicarbonate cotransporter (NBCe1), which has been demonstrated to participate in myocardial ischemia/reperfusion (I/R) injury. This review outlines the structural and functional properties of NBCe1, summarizes the signaling pathways and factors that may regulate the activity of NBCe1, and reviews the roles of NBCe1 in the pathogenesis of I/R-induced cardiac diseases. Further studies revealing the regulatory mechanisms of NBCe1 activity should provide novel therapeutic targets for preventing I/R-induced cardiac diseases.


Assuntos
Cardiopatias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismo , Acidose/metabolismo , Animais , Astrócitos/metabolismo , Bicarbonatos/metabolismo , Doença da Artéria Coronariana/metabolismo , Coração/fisiologia , Cardiopatias/fisiopatologia , Humanos , Isquemia/metabolismo , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica/métodos , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/metabolismo , Sódio/metabolismo
6.
Kidney Int ; 99(3): 542-545, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33637200

RESUMO

The osteoclast proton-sensing receptors may play a role in osteoclastogenesis or bone resorption. The current study by Kreiger et al. found that in female mice, osteoclast-specific deletion of the gene for OGR1 resulted in increased bone mass, which demonstrates that in some situations this receptor is playing a role. However, there are some inconsistencies because the bone resorption was not reduced in their global knockout mice, and the effects are not seen in both genders or by other investigators. More work should be done to better define the role of OGR1 because acidosis is an important cause of bone loss.


Assuntos
Acidose , Reabsorção Óssea , Animais , Reabsorção Óssea/genética , Feminino , Masculino , Camundongos , Camundongos Knockout , Osteoclastos , Prótons , Receptores Acoplados a Proteínas-G
8.
Am J Physiol Heart Circ Physiol ; 320(3): H1199-H1212, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33449853

RESUMO

CaMKII is needed for the recovery of Ca2+ transients during acidosis but also mediates postacidic arrhythmias. CaMKIIδ can sustain its activity following Met281/282 oxidation. Increasing cytosolic Na+ during acidosis as well as postacidic pH normalization should result in prooxidant conditions within the cell favoring oxidative CaMKIIδ activation. We tested whether CaMKIIδ activation through Met281/282 oxidation is involved in recovery of Ca2+ transients during acidosis and promotes cellular arrhythmias post-acidosis. Single cardiac myocytes were isolated from a well-established mouse model in which CaMKIIδ was made resistant to oxidative activation by knock-in replacement of two oxidant-sensitive methionines (Met281/282) with valines (MM-VV). MM-VV myocytes were exposed to extracellular acidosis (pHo 6.5) and compared to wild type (WT) control cells. Full recovery of Ca2+ transients was observed in both WT and MM-VV cardiac myocytes during late-phase acidosis. This was associated with comparably enhanced sarcoplasmic reticulum Ca2+ load and preserved CaMKII specific phosphorylation of phospholamban at Thr17 in MM-VV myocytes. CaMKII was phosphorylated at Thr287, but not Met281/282 oxidized. In line with this, postacidic cellular arrhythmias occurred to a similar extent in WT and MM-VV cells, whereas inhibition of CaMKII using AIP completely prevented recovery of Ca2+ transients during acidosis and attenuated postacidic arrhythmias in MM-VV cells. Using genetically altered cardiomyocytes with cytosolic expression of redox-sensitive green fluorescent protein-2 coupled to glutaredoxin 1, we found that acidosis has a reductive effect within the cytosol of cardiac myocytes despite a significant acidosis-related increase in cytosolic Na+. Our study shows that activation of CaMKIIδ through Met281/282 oxidation is neither required for recovery of Ca2+ transients during acidosis nor relevant for postacidic arrhythmogenesis in isolated cardiac myocytes. Acidosis reduces the cytosolic glutathione redox state of isolated cardiac myocytes despite a significant increase in cytosolic Na+. Pharmacological inhibition of global CaMKII activity completely prevents recovery of Ca2+ transients and protects from postacidic arrhythmias in MM-VV myocytes, which confirms the relevance of CaMKII in the context of acidosis.NEW & NOTEWORTHY The current study shows that activation of CaMKIIδ through Met281/282 oxidation is neither required for CaMKII-dependent recovery of Ca2+ transients during acidosis nor relevant for the occurrence of postacidic cellular arrhythmias. Despite a usually prooxidant increase in cytosolic Na+, acidosis reduces the cytosolic glutathione redox state within cardiac myocytes. This novel finding suggests that oxidation of cytosolic proteins is less likely to occur during acidosis.


Assuntos
Acidose/enzimologia , Arritmias Cardíacas/enzimologia , Sinalização do Cálcio , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Frequência Cardíaca , Miócitos Cardíacos/enzimologia , Acidose/complicações , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Técnicas Biossensoriais , Proteínas de Ligação ao Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Feminino , Glutationa/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Contração Miocárdica , Oxirredução , Fosforilação , Espécies Reativas de Oxigênio/metabolismo
9.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462013

RESUMO

SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host's cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.


Assuntos
Insuficiência Adrenal/fisiopatologia , Hiponatremia/fisiopatologia , Hipotensão/fisiopatologia , Acidose/sangue , Acidose/fisiopatologia , Acidose/terapia , Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Hidratação , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/sangue , Hiponatremia/sangue , Hiponatremia/terapia , Hipofosfatemia/sangue , Hipofosfatemia/fisiopatologia , Hipofosfatemia/terapia , Hipotensão/terapia , Masculino , Pessoa de Meia-Idade , Testes de Função Adreno-Hipofisária , Prednisolona/uso terapêutico , Vômito/fisiopatologia , Desequilíbrio Hidroeletrolítico/sangue , Desequilíbrio Hidroeletrolítico/fisiopatologia , Desequilíbrio Hidroeletrolítico/terapia
10.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462030

RESUMO

This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced by Bacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential of B. cereus It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.


Assuntos
Bacillus cereus/genética , Exotoxinas/genética , Doenças Transmitidas por Alimentos/diagnóstico , Acetilcisteína/uso terapêutico , Acidose/fisiopatologia , Acidose/terapia , Adulto , Antiarrítmicos/uso terapêutico , Antibacterianos/uso terapêutico , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Bacillus cereus/isolamento & purificação , Transtornos da Coagulação Sanguínea/fisiopatologia , Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue , Encefalopatias , Terapia de Substituição Renal Contínua , Evolução Fatal , Feminino , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/fisiopatologia , Doenças Transmitidas por Alimentos/terapia , Depuradores de Radicais Livres/uso terapêutico , Humanos , Imunocompetência , Falência Hepática/fisiopatologia , Falência Hepática/terapia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Plasmaferese , Insuficiência Renal/fisiopatologia , Insuficiência Renal/terapia , Rabdomiólise/fisiopatologia , Rabdomiólise/terapia , Sepse/fisiopatologia , Sepse/terapia , Choque/fisiopatologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sequenciamento Completo do Genoma
11.
Kidney Int ; 99(1): 28-31, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33390237

RESUMO

Metabolic acidosis is an early and deleterious complication of chronic kidney disease. Because it is frequently eubicarbonatemic, diagnosis may be difficult. In this issue, Gianella et al. suggest that lower urinary citrate excretion, considered as an homeostatic response to metabolic acidosis, may be helpful for early diagnosis and monitoring of alkali treatment. This study should be an incentive for further assessment of the tubular handling of urinary citrate in CKD patients and determination of the performance of urinary citrate for the diagnosis of eubicarbonatemic metabolic acidosis and monitoring of alkali therapy.


Assuntos
Acidose , Insuficiência Renal Crônica , Acidose/diagnóstico , Acidose/etiologia , Citratos , Ácido Cítrico , Creatinina , Humanos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia
12.
BMJ Case Rep ; 14(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419747

RESUMO

A 75-year-old woman was admitted to a regional hospital with an acute kidney injury (AKI) and nausea on a background of recent treatment for Staphylococcus aureus bacteraemia secondary to pneumonia. The treatment thereof resulted in a high anion gap metabolic acidosis (HAGMA). The pneumonia was initially treated with intravenous piperacillin and tazobactam and the patient transferred to a tertiary hospital. There, the diagnosis of S. aureus bacteraemia secondary to a pulmonary source was confirmed and treatment was changed to intravenous flucloxacillin and the patient was discharged to hospital in the home (HITH is a service that allows short-term healthcare at home to be provided to people who would otherwise need to be in hospital) to complete the antibiotic course. Five weeks after commencing flucloxacillin, the patient was referred back to hospital with nausea and worsening kidney function with an associated significant HAGMA. The patient has a background of chronic kidney disease and chronic back pain for which she was taking long-term paracetamol. The HAGMA was determined to be due to a pyroglutamic acidosis (PGA), deemed secondary to the combined use of paracetamol and flucloxacillin. This was subsequently confirmed with a plasma pyroglutamic acid concentration level of 7467 µmol/L (reference range 20-50 µmol/L) and a urinary level of 1700 mmol/mol creatinine (<110 mmol/mol creatinine). To our knowledge, this is the highest plasma and urinary levels published to date. Furthermore, considering the common use of paracetamol and penicillins, it is important to recognise HAGMA as a potential complication of co-administration of paracetamol and iso-oxylopenicillin. The HAGMA resolved after cessation of flucloxacillin despite the continuation of paracetamol and without administration of N-acetylcysteine. PGA-related HAGMA appears to be a unique potential side effect of iso-oxylopenicillin rather than other beta-lactams.


Assuntos
Acetaminofen/efeitos adversos , Acidose/induzido quimicamente , Antibacterianos/efeitos adversos , Antipiréticos/efeitos adversos , Floxacilina/efeitos adversos , Ácido Pirrolidonocarboxílico/metabolismo , Acidose/diagnóstico , Lesão Renal Aguda/complicações , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/terapia , Idoso , Bacteriemia/tratamento farmacológico , Feminino , Humanos , Infecções Estafilocócicas/tratamento farmacológico
13.
J Dairy Sci ; 104(2): 1660-1679, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33309345

RESUMO

The objective of this experiment was to determine the effects of altering the dietary cation-anion difference (DCAD) fed for the last 21 or 42 d of gestation on glucose metabolism and tissue insulin responsiveness. Ninety parous Holstein cows at 232 d of gestation were assigned randomly to dietary treatments with 2 levels of DCAD (-70 or -180 mEq/kg) fed for 2 durations (short: the last 21 d of gestation; long: the last 42 d of gestation). For the short treatments, a diet with +110 mEq/kg was fed from 232 to 254 d of gestation. Intravenous glucose tolerance tests (IVGTT) were performed at either 250 or 270 d of gestation by infusing 0.25 g of dextrose/kg of body weight within 1 min. The following day, cows underwent an insulin challenge (IC) and received 0.1 IU of insulin/kg of body weight intravenously. Blood was sampled at min -15, -5, and 0 to establish a baseline and from 5 to 180 min relative to infusions; plasma concentrations of glucose, insulin, and fatty acids were determined, and the respective areas under the curves (AUC) were calculated. Liver was sampled after the IVGTT, and adipose tissue was sampled after the IVGTT and IC for quantification of mRNA expression and protein abundance. Reducing the DCAD altered acid-base balance compatible with a compensated metabolic acidosis. At 250 d, reducing the DCAD increased the AUC for glucose and reduced that of insulin following the IVGTT, whereas during the IC, clearance rate decreased and time to half-life of insulin increased with reducing DCAD, resulting in a tendency to a larger AUC for fatty acids. At 270 d, quantitative insulin sensitivity check index and the revised quantitative insulin sensitivity check index were smaller in cows fed the acidogenic diets for the last 42 d of gestation compared with the last 21 d of gestation, thereby suggesting reduced insulin sensitivity. In addition, cows fed for the long duration tended to have greater AUC for glucose but smaller AUC for insulin following an IVGTT than those fed for the short duration, thereby suggesting reduced insulin release and glucose disposal. Treatments did not affect hepatic mRNA expression of G6PC, PCK1, PCK2, and PC or adipose tissue mRNA expression of ATGL, ACC, B2AR, HSL, and PLIN1. On the other hand, for proteins, reducing the DCAD linearly reduced abundance of rabbit anti-mouse protein kinase B (AKT) and tended to reduce rabbit anti-human phosphorylated (Ser-9) glycogen synthase kinase-3 ß (pGSK) and the pGSK:rabbit anti-human glycogen synthase kinase-3 ß (GSK) ratio in hepatic tissue, whereas a linear increase in rabbit anti-human hormone-sensitive lipase (HSL) and rabbit anti-mouse phosphorylated (Ser-660) hormone-sensitive lipase (pHSL) in adipose tissue was observed after the IVGTT at 250 d. Moreover, reducing the DCAD resulted in a linear reduction of AKT and tended to reduce rabbit anti-human acetyl-CoA carboxylase (ACC) but increased pHSL linearly in adipose tissue after an IC at 250 d. Cows fed acidogenic diets for a short duration tended to have less pHSL in adipose tissue than those fed for a long duration after an IVGTT at 270 d. Associations were observed between blood pH and mRNA and protein abundance in hepatic and adipose tissues. Diet-induced metabolic acidosis altered insulin release and insulin signaling, resulting in a shift in adipose tissue metabolism that would favor lipolysis over lipogenesis.


Assuntos
Acidose/veterinária , Doenças dos Bovinos/etiologia , Dieta/veterinária , Insulina/administração & dosagem , Complicações na Gravidez/veterinária , Acidose/etiologia , Tecido Adiposo/química , Tecido Adiposo/efeitos dos fármacos , Ração Animal/análise , Animais , Glicemia/análise , Bovinos , Indústria de Laticínios/métodos , Dieta/efeitos adversos , Metabolismo Energético , Feminino , Idade Gestacional , Teste de Tolerância a Glucose/veterinária , Insulina/sangue , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Lipólise/efeitos dos fármacos , Lipólise/genética , Fígado/química , Fígado/efeitos dos fármacos , Gravidez , Complicações na Gravidez/etiologia
14.
J Dairy Sci ; 104(2): 2087-2105, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33358156

RESUMO

The high-grain diets fed to ruminants generally alters the structure and function of rumen microbiota, resulting in variations of rumen fermentation patterns and the occurrence of subacute rumen acidosis (SARA). To clarify the microbial mechanism for carbohydrate metabolism during SARA, 8 ruminally cannulated Holstein cows in mid lactation were selected for a 3-wk experiment. The cows were randomly divided into 2 groups, fed either a conventional diet (CON; 40% concentrate; dry matter basis) or a high-grain diet (HG; 60% concentrate; dry matter basis). Compared with the CON diet, the HG diet reduced average daily pH (5.71 vs. 6.13), acetate concentration (72.56 vs. 78.44 mM), acetate ratio (54.81 vs. 65.24%), and the ratio of the concentrations of acetate to propionate (1.87 vs. 3.21) but increased the concentrations of total volatile fatty acids (133.03 vs. 120.22 mM), propionate (41.32 vs. 24.71 mM), and valerate (2.46 vs. 1.68 mM) and the propionate ratio (30.51 vs. 20.47%). Taxonomic analysis indicated that the HG cows had a higher relative abundance of Ruminococcus, Eubacterium, Selenomonas, Ruminobacter, Succinimonas, Methanomicrobium, and Methanocaldococcus accompanied by a lower relative abundance of unclassified Firmicutes, unclassified Bacteroidetes, Bacteroides, Fibrobacter, Alistipes, Candidatus Methanoplasma, Methanomassiliicoccus, and Methanolobus. Carbohydrate-active enzyme annotation suggested that there was enriched abundance of glycosyltransferases (GT) 2, glycoside hydrolase (GH) 13, GH24, carbohydrate-binding module (CBM) 26, GH73, GH25, CBM12, GH23, GT8, CBM50, and GT9 and reduced abundance of GH78, GH31, S-layer homology, GH109, carbohydrate esterase 1, GH3, carbohydrate esterase 10, and GH43 in the HG group. Functional profiling revealed that the HG feeding mainly downregulated the pentose phosphate pathway of carbohydrate catabolism, acetate metabolism, propionate metabolism (succinate pathway), and methane metabolism, whereas it upregulated the Embden-Meyerhof-Parnas and Entner-Doudoroff pathways of glycolysis and the citrate cycle. Additionally, the HG feeding promoted the abundance of various antibiotic resistance genes and antimicrobial resistance gene families. These results elucidated the structure and function adjustment of rumen microbiota for carbohydrate metabolism and summarized the enrichment of rumen antibiotic resistance genes under the HG feeding, which expands our understanding of the mechanism underlying the response of rumen microbiota to SARA in dairy cattle.


Assuntos
Acidose/veterinária , Ração Animal , Metabolismo dos Carboidratos/genética , Doenças dos Bovinos/genética , Resistência Microbiana a Medicamentos/genética , Grão Comestível , Microbioma Gastrointestinal/genética , Rúmen/microbiologia , Acidose/dietoterapia , Acidose/etiologia , Animais , Antibacterianos/farmacologia , Bovinos , Doenças dos Bovinos/metabolismo , Dieta/veterinária , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Lactação , Leite , Rúmen/metabolismo
17.
Gan To Kagaku Ryoho ; 47(9): 1379-1381, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130705

RESUMO

The patient was an 81-year-old man. Laparoscopic sigmoidectomy was performed for a sigmoid colon cancer(S, type 2, pT3[SS], INF a, Ly0, V0, BD1, Pn0, pPM0, pDM0, RM0, pN0, pM0, pStage Ⅲa, R0, Cur A). One year after the surgery, a blood test showed CEA as high as 68.9 ng/mL, and an abdominal enhanced computed tomography revealed a hepatic tumor showing marginal contrast in the 4th liver segment. Positron emission tomography showed an accumulation of SUVmax 19.0 at the same site, and a metastatic liver tumor was diagnosed. A laparoscopic medial hepatectomy was performed. Bleeding from the hepatectomy site increased significantly after completion. Subcutaneous emphysema spreading from the face to the trunk and thigh was observed, and blood tests revealed a pH of 7.172, PaCO2 of 71.0 mmHg, lactate of 67 mg/dL, mixed acidosis, D-dimer of 118 µg/mL, and a disseminated intravascular coagulation(DIC)syndrome was diagnosed. Following the difficulty of hemostasis, the surgery was changed to laparotomy and terminated by gauze packing. We encountered a case of acidosis exacerbated by hypercapnia that progressed to DIC during laparoscopic medial hepatectomy.


Assuntos
Acidose , Laparoscopia , Neoplasias Hepáticas , Neoplasias do Colo Sigmoide , Idoso de 80 Anos ou mais , Dacarbazina , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Neoplasias do Colo Sigmoide/complicações , Neoplasias do Colo Sigmoide/cirurgia
18.
Praxis (Bern 1994) ; 109(12): 979-983, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32933388

RESUMO

Lactic Acidosis and Other Misunderstandings Abstract. Lactic acidosis is a frequently encountered clinical problem in intensive care medicine. Nevertheless, many of the underlying biochemical processes are insufficiently understood, which leads to various misconceptions. Physiologically, lactate is an important, continuously produced carrier of energy and by no means a metabolic 'waste product'. Lactate is the corresponding base to lactic acid and is produced directly from pyruvate. In this reaction H+ is consumed and therefore lactate production itself cannot be directly responsible for the simultaneously arising acidosis. An elevated lactate level allows no conclusions about the underlying pathophysiological process, and, more importantly, it is not an appropriate marker for tissue oxygenation.


Assuntos
Acidose Láctica , Acidose , Acidose Láctica/diagnóstico , Acidose Láctica/terapia , Biomarcadores , Cuidados Críticos , Humanos , Ácido Láctico
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(7): 972-980, 2020 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895149

RESUMO

OBJECTIVE: To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition. METHODS: We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K + concentration or the application of an antagonist of GABAA receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs. RESULTS: Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K +]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K+]o and disinhibition models. CONCLUSIONS: ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.


Assuntos
Acidose , Canais Iônicos Sensíveis a Ácido , Animais , Hipocampo , Concentração de Íons de Hidrogênio , Camundongos , Células Piramidais
20.
Crit Care Resusc ; 22(3): 275-280, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900336

RESUMO

OBJECTIVE: To help shape the design of a future double blind placebo-controlled randomised clinical trial of bicarbonate therapy for metabolic acidosis, based on opinions of intensive care clinicians in Australia and New Zealand. DESIGN: An online survey was designed, piloted and distributed electronically to members of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) mailing list. The survey sought to collect information about choice of placebo, method of bicarbonate administration, and acid-base monitoring. MAIN OUTCOME MEASURES: Responses to six questions in the following domains were sought: 1) solution to be used as placebo; 2) method of administration; 3) target of the intervention; 4) timing of arterial blood gases to monitor the intervention; 5) duration of therapy; and 6) rate of bolus therapy (if selected as the best option). RESULTS: One in every eight ANZICS CTG members completed the survey (118/880, 13.4%). Compound sodium lactate was the preferred solution for placebo (54/118, 45.8%), and continuous infusion of bicarbonate (80/118, 67.8%) was the most frequently selected method of administration. A pH > 7.30 was the preferred target (50/118, 42.4%), while monitoring with arterial blood gas analysis every 2 hours until the target is reached and then every 4 hours was the most favoured option (40/118, 33.9%). The preferred duration of therapy was until the target is achieved (53/118, 44.9%). CONCLUSIONS: This survey offers important insights into the preferences of Australian and New Zealand clinicians in regards to any future randomised controlled trial of bicarbonate therapy for metabolic acidosis in the critically ill.


Assuntos
Acidose/tratamento farmacológico , Bicarbonato de Sódio/uso terapêutico , Acidose/sangue , Austrália , Cálcio/sangue , Cuidados Críticos , Estado Terminal , Método Duplo-Cego , Humanos , Nova Zelândia , Bicarbonato de Sódio/efeitos adversos , Inquéritos e Questionários , Resultado do Tratamento
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