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1.
Cir Cir ; 89(5): 583-587, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665180

RESUMO

OBJECTIVE: We investigated the effect of carotid body ischemia-induced cerebrospinal fluid acidosis on spinal cord during subarachnoid hemorrhage (SAH). METHODS: Twenty-three hybrid rabbits were divided into three groups: control (n = 5), Sham (injected with 0.5 ml isotonic) (n = 6), and the SAH (n = 12) (injected with 0.5 ml autologous blood into the 4th ventricle) and then monitored for 3 weeks. Cerebrospinal fluid pH and degenerated ependymal cell density and volume of cervical central canal were analyzed. RESULTS: The mean cervical central canal volumes, degenerated ependymal cells densities, and cerebrospinal pH values were 1.056 ± 0.053 mm3-6 ± 2 per mm2-7.342 ± 0.034, 1.321 ± 0.12 mm3-35 ± 9 per mm2-7.314 ± 0.056, and 1.743 ± 0.245 mm3-159 ± 24 per mm2-7.257 ± 0.049 in the Control, Sham, and SAH groups, respectively. The more degenerated carotid body neuron density induced decreased cerebrospinal fluid pH values (p < 0.0001) could result in the more ependymal cells desquamation (p < 0.0005) and central canal dilatation (p < 0.00001). CONCLUSION: Increased neurodegeneration of carotid bodies can reduce cause cerebrospinal fluid pH-induced ependymal cell degeneration and central canal dilatation following SAH.


Assuntos
Acidose , Hemorragia Subaracnóidea , Animais , Modelos Animais de Doenças , Isquemia , Coelhos , Medula Espinal
2.
Clin J Am Soc Nephrol ; 16(9): 1306-1308, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34497106
3.
Adv Ther ; 38(10): 5238-5252, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34471991

RESUMO

INTRODUCTION: Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD and hyperkalemia is understudied. Therefore, we used medical record data from the Research Action for Health Network to estimate this prevalence. METHODS: Adult patients with CKD stage 3-5, ≥ 1 outpatient potassium value > 5.0 mEq/l, and ≥ 1 outpatient bicarbonate value available were identified. Patients with end stage kidney disease (ESKD) in the prior year were excluded. The prevalence of metabolic acidosis in each calendar year from 2014 to 2017 among patients with CKD and hyperkalemia was estimated using two definitions of hyperkalemia (potassium > 5.0 mEq/l and > 5.5 mEq/l) and metabolic acidosis (bicarbonate < 18 mEq/l and < 22 mEq/l). RESULTS: In the 2017 patient cohort and among patients with CKD and hyperkalemia, patients with metabolic acidosis were younger (69 versus 74 years), more likely to have advanced CKD (35% versus 13%), and use oral sodium bicarbonate (21% versus 4%) than patients without metabolic acidosis. The prevalence of metabolic acidosis (< 22 mEq/l) ranged from 25 to 29% when hyperkalemia was defined by potassium > 5.0 mEq/l and ranged from 33 to 39% when hyperkalemia was defined by potassium > 5.5 mEq/l. CONCLUSION: Results demonstrated that prevalence estimates of metabolic acidosis varied based on the definition of hyperkalemia and metabolic acidosis utilized.


Assuntos
Acidose , Hiperpotassemia , Insuficiência Renal Crônica , Acidose/epidemiologia , Humanos , Hiperpotassemia/epidemiologia , Potássio , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia
4.
Animal ; 15(10): 100370, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34583314

RESUMO

Ruminant animals are generally fed with starch-rich grain as the main energy source, and the incidence of metabolic diseases such as subacute ruminal acidosis (SARA) is high due to the intensive farming. Thiamin has been reported to alleviate SARA caused by high-concentrate diets, but the exact mechanism is not well understood. The goal of this study was to examine the role of thiamine in intestinal inflammation and microbiota caused by high-concentrate diets. The SARA model was induced by low neutral detergent fibre/starch ration to study the effects of thiamine on intestinal tissue structure and microbiota. 18 mid-lactation (148 ± 3 d in milk; milk yield = 0.71 ± 0.0300 kg/d) Saanen goats (BW = 36.5 ± 1.99 kg; body condition score = 2.73 ± 0.16, where 1 = emaciated and 6 = obese) in parities 1 or 2 were selected. The goats were randomly divided into three groups with six replicates: (1) control diet (C; concentrate:forage 30:70), (2) high-concentrate diet (H; concentrate:forage 70:30), and (3) high-concentrate diet with 200 mg of thiamine/kg of DM intake (H + T;concentrate:forage 70:30). The experimental period was lasted for 56 d. The small and large intestine, expression of inflammatory factor genes, tight junction protein genes, total antioxidant capacity, and intestinal microbiota were measured. The results showed that SARA was observed in treatment H, whereas rumen fluid pH was improved in treatment H + T. Treatment H + T also significantly repaired the intestinal tissue structure damaged by SARA, improved the total antioxidant capacity of the small intestinal mucosa, reduced mRNA expression of inflammatory factors in the small intestine tissue, and increased the mRNA expression of tight junction genes in small intestine tissue. The high-concentrate diet reduced the diversity of intestinal microbiota. When thiamine is added to the high-concentrate diet, the relative abundance of intestinal Firmicutes and beneficial bacteria represented by Lactobacilli were upregulated, and the relative abundance of Proteus, a marker of intestinal dysbacteriosis, returned to normal. In conclusion, thiamine supplementation could alleviate the damage to the intestinal tissue structure and microbial environment caused by SARA condition in dairy goats fed a high-concentrate diet.


Assuntos
Acidose , Doenças dos Bovinos , Doenças das Cabras , Microbiota , Acidose/veterinária , Animais , Bovinos , Dieta/veterinária , Feminino , Cabras , Concentração de Íons de Hidrogênio , Lactação , Leite , Rúmen , Tiamina
5.
JNMA J Nepal Med Assoc ; 59(239): 692-696, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34508499

RESUMO

INTRODUCTION: An acid-base disorder is a change in the normal value of extracellular pH that may result when renal or respiratory function is abnormal or when an acid or base load overwhelms their excretory capacity. Clinical acid-base disorders are conventionally defined from the vantage point of their impact on carbonic-acid-bicarbonate buffer system. The aim of the study is to find out the prevalence of acid-base disorder among patients visiting the emergency department of a tertiary care hospital. METHODS: This is a descriptive cross-sectional study conducted among 370 patients who underwent arterial gas analysis at the emergency department of a tertiary care hospital. The study was carried out from 15th July 2016 to 15th July 2017 after receiving ethical approval from Institutional Review Committee. Convenient sampling was done. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. Data were entered in Microsoft-Excel. Statistical Package for Social Sciences version 17 was used for analysis. RESULTS: Out of 370 patients analyzed, 329 (88.91%) (84.68-91.311 at 95% Confidence Interval) had acid-base disorder. The mixed disorder was the most common finding 80 (21.6%), followed by compensated Respiratory Acidosis 56 (17.8%). The mean age group of male patients studied was 50.72±20.586 and among females, it was 49.95±20.908 Among those most common symptoms were shortness of breath 151 (40.81%) followed by vomiting 91 (24.59%). CONCLUSIONS: Most common acid-base disorder was mixed disorder presenting with prominent symptoms of shortness of breathe in non-geriatric patients wherein the geriatric patient, the most common disorder was compensated respiratory acidosis with the prominent symptom of shortness of breath.


Assuntos
Acidose , Serviço Hospitalar de Emergência , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Centros de Atenção Terciária
6.
Am J Physiol Renal Physiol ; 321(4): F424-F430, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34396788

RESUMO

Chronic metabolic acidosis stimulates cell-mediated net Ca2+ efflux from bone mediated by increased osteoblastic cyclooxygenase 2, leading to prostaglandin E2-induced stimulation of receptor activator of NF-κB ligand-induced osteoclastic bone resorption. Ovarian cancer G protein-coupled receptor-1 (OGR1), an osteoblastic H+-sensing G protein-coupled receptor, is activated by acidosis and leads to increased bone resorption. As regulator of G protein signaling (RGS) proteins limit GPCR signaling, we tested whether RGS proteins themselves are regulated by metabolic acidosis. Primary osteoblasts were isolated from neonatal mouse calvariae and incubated in physiological neutral or acidic (MET) medium. Cells were collected, and RNA was extracted for real-time PCR analysis with mRNA levels normalized to ribosomal protein L13a. RGS1, RGS2, RGS3, RGS4, RGS10, RGS11, and RGS18 mRNA did not differ between MET and neutral medium; however, by 30 min, MET decreased RGS16, which persisted for 60 min and 3 h. Incubation of osteoblasts with the OGR1 inhibitor CuCl2 inhibited the MET-induced increase in RGS16 mRNA. Gallein, a specific inhibitor of Gßγ signaling, was used to determine if downstream signaling by the ßγ-subunit was critical for the response to acidosis. Gallein decreased net Ca2+ efflux from calvariae and cyclooxygenase 2 and receptor activator of NF-κB ligand gene expression from isolated osteoblasts. These results indicate that regulation of RGS16 plays an important role in modulating the response of the osteoblastic GPCR OGR1 to metabolic acidosis and subsequent stimulation of osteoclastic bone resorption.NEW & NOTEWORTHY The results presented in this study indicate that regulation of regulator of G protein signaling 16 and G protein signaling in the osteoblast plays an important role in modulating the response of osteoblastic ovarian cancer G protein-coupled receptor 1 (OGR1) to metabolic acidosis and the subsequent stimulation of osteoclastic bone resorption. Further characterization of the regulation of OGR1 in metabolic acidosis-induced bone resorption will help in understanding bone loss in acidotic patients with chronic kidney disease.


Assuntos
Acidose/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoblastos/metabolismo , Proteínas RGS/metabolismo , Animais , Bicarbonatos/administração & dosagem , Bicarbonatos/farmacologia , Dióxido de Carbono , Células Cultivadas , Proteínas de Ligação ao GTP/genética , Concentração de Íons de Hidrogênio , Camundongos , Proteínas RGS/genética , RNA/genética , RNA/metabolismo , Xantenos/farmacologia
7.
Am J Kidney Dis ; 78(4): 590-600, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34400023

RESUMO

The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It is a helpful calculation that divides the metabolic acidoses into 2 categories: high AG metabolic acidosis (HAGMA) and hyperchloremic metabolic acidosis-and thereby delimits the potential etiologies of the disorder. When the [AG] is compared with changes in the bicarbonate concentration, other occult acid-base disorders can be identified. Furthermore, finding that the AG is very small or negative can suggest several occult clinical disorders or raise the possibility of electrolyte measurement artifacts. In this installment of AJKD's Core Curriculum in Nephrology, we discuss cases that represent several very common and several rare causes of HAGMA. These case scenarios highlight how the AG can provide vital clues that direct the clinician toward the correct diagnosis. We also show how to calculate and, if necessary, correct the AG for hypoalbuminemia and severe hyperglycemia. Plasma osmolality and osmolal gap calculations are described and when used together with the AG guide appropriate clinical decision making.


Assuntos
Equilíbrio Ácido-Base/fisiologia , Desequilíbrio Ácido-Base/metabolismo , Desequilíbrio Ácido-Base/terapia , Acidose/metabolismo , Acidose/terapia , Currículo , Desequilíbrio Ácido-Base/diagnóstico , Acidose/diagnóstico , Adulto , Idoso , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/metabolismo , Cetoacidose Diabética/terapia , Feminino , Hidratação/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Adulto Jovem
8.
Crit Care ; 25(1): 314, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461963

RESUMO

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .


Assuntos
Acidose/terapia , Terapia de Substituição Renal/normas , Bicarbonato de Sódio/uso terapêutico , Acidose/epidemiologia , Tampões (Química) , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Terapia de Substituição Renal/instrumentação , Terapia de Substituição Renal/métodos
9.
Rev Med Liege ; 76(7-8): 620-624, 2021 Jul.
Artigo em Francês | MEDLINE | ID: mdl-34357715

RESUMO

The occurrence of metabolic acidosis with increased anion gap in the context of chronic paracetamol intoxication is an easily treatable clinical situation. Its rapid recognition is essential given its complete reversibility in the event of adequate management by eviction of the toxic agent, in this case paracetamol. It has an unknown cause and therefore potentially under-diagnosed, to be considered in the same way as the other more frequent etiologies. Because of this lack of knowledge, its frequency is probably underestimated considering the widespread consumption of paracetamol in the population.


Assuntos
Acetaminofen , Acidose , Equilíbrio Ácido-Base , Acidose/induzido quimicamente , Humanos , Doença Iatrogênica , Ácido Pirrolidonocarboxílico/metabolismo
10.
Obstet Gynecol ; 138(3): 366-373, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34352847

RESUMO

OBJECTIVE: To evaluate the relationship between umbilical artery cord gas values and fetal tolerance of labor, as reflected by Apgar score. We hypothesized the existence of wide biological variability in fetal tolerance of metabolic acidemia, which, if present, would weaken one fundamental assumption underlying the use of electronic fetal heart rate (FHR) monitoring. METHODS: We conducted a retrospective cohort study of term, singleton, nonanomalous fetuses delivered in our institution between March 2012 and July 2020. Universally obtained umbilical cord gas values and Apgar scores were extracted. We calculated Spearman correlation coefficients and receiver operating characteristic curves for various levels of umbilical artery pH, base excess, and Apgar scores. RESULTS: We analyzed data from 29,787 deliveries. The statistical correlation between umbilical artery pH and base excess and both 1- and 5-minute Apgar scores was weak or nonexistent in all pH range subgroups (range 0.064-0.213). Receiver operating characteristic curve analysis suggested umbilical artery pH value of 7.22 yields the best discrimination for prediction of a severely depressed newborn (5-minute Apgar score less than 4), but sensitivity and specificity for this predictive value remains poor to moderate. CONCLUSION: The use of electronic FHR monitoring is predicated on a documented relationship between FHR patterns and umbilical artery pH, and an assumed correlation between pH and fetal outcomes, reflecting fetal tolerance of labor and delivery. Our data demonstrate a weak-to-absent correlation between metabolic acidemia and even short-term fetal condition, thus significantly weakening this latter assumption. No amount of future modification of FHR pattern interpretation to better predict newborn pH is likely to lead to improved newborn outcomes, given this weakness in a fundamental assumption on which FHR monitoring is based.


Assuntos
Índice de Apgar , Frequência Cardíaca Fetal , Trabalho de Parto , Artérias Umbilicais/fisiopatologia , Acidose/sangue , Adulto , Gasometria , Cardiotocografia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Sensibilidade e Especificidade
11.
Nutrients ; 13(8)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34444694

RESUMO

Metabolic acidosis is a severe complication of chronic kidney disease (CKD) which is associated with nefarious impairments such as bone demineralization, muscle wasting, and hormonal alterations, for example, insulin resistance. Whilst it is possible to control this condition with alkali treatment, consisting in the oral administration of sodium citrate or sodium bicarbonate, this type of intervention is not free from side effects. On the contrary, opting for the implementation of a targeted dietetic-nutritional treatment for the control of CKD metabolic acidosis also comes with a range of additional benefits such as lipid profile control, increased vitamins, and antioxidants intake. In our review, we evaluated the main dietary-nutritional regimens useful to counteract metabolic acidosis, such as the Mediterranean diet, the alkaline diet, the low-protein diet, and the vegan low-protein diet, analyzing the potentialities and limits of every dietary-nutritional treatment. Literature data suggest that the Mediterranean and alkaline diets represent a valid nutritional approach in the prevention and correction of metabolic acidosis in CKD early stages, while the low-protein diet and the vegan low-protein diet are more effective in CKD advanced stages. In conclusion, we propose that tailored nutritional approaches should represent a valid therapeutic alternative to counteract metabolic acidosis.


Assuntos
Acidose/dietoterapia , Dieta/métodos , Terapia Nutricional/métodos , Insuficiência Renal Crônica/dietoterapia , Equilíbrio Ácido-Base , Acidose/etiologia , Acidose/prevenção & controle , Dieta Mediterrânea , Dieta com Restrição de Proteínas , Dieta Vegana , Humanos , Insuficiência Renal Crônica/complicações
12.
Kidney Int ; 100(4): 850-869, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252449

RESUMO

Adverse effects of calcineurin inhibitors (CNI), such as hypertension, hyperkalemia, acidosis, hypomagnesemia and hypercalciuria, have been linked to dysfunction of the distal convoluted tubule (DCT). To test this, we generated a mouse model with an inducible DCT-specific deletion of the calcineurin regulatory subunit B alpha (CnB1-KO). Three weeks after CnB1 deletion, these mice exhibited hypomagnesemia and acidosis, but no hypertension, hyperkalemia or hypercalciuria. Consistent with the hypomagnesemia, CnB1-KO mice showed a downregulation of proteins implicated in DCT magnesium transport, including TRPM6, CNNM2, SLC41A3 and parvalbumin but expression of calcium channel TRPV5 in the kidney was unchanged. The abundance of the chloride/bicarbonate exchanger pendrin was increased, likely explaining the acidosis. Plasma aldosterone levels, kidney renin expression, abundance of phosphorylated sodium chloride-cotransporter and abundance of the epithelial sodium channel were similar in control and CnB1-KO mice, consistent with a normal sodium balance. Long-term potassium homeostasis was maintained in CnB1-KO mice, but in-vivo and ex-vivo experiments indicated that CnB1 contributes to acute regulation of potassium balance and sodium chloride-cotransporter. Tacrolimus treatment of control and CnB1-KO mice demonstrated that CNI-related hypomagnesemia is linked to impaired calcineurin-signaling in DCT, while hypocalciuria and hyponatremia occur independently of CnB1 in DCT. Transcriptome and proteome analyses of isolated DCTs demonstrated that CnB1 deletion impacts the expression of several DCT-specific proteins and signaling pathways. Thus, our data support a critical role of calcineurin for DCT function and provide novel insights into the pathophysiology of CNI side effects and involved molecular players in the DCT.


Assuntos
Acidose , Magnésio , Animais , Calcineurina/genética , Túbulos Renais Distais , Camundongos , Proteoma/genética , Transcriptoma
13.
Eur J Obstet Gynecol Reprod Biol ; 264: 173-177, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34304026

RESUMO

BACKGROUND: S100B and cardiac troponin T (c-TnT) are relevant biomarkers at birth of hypoxic-ischemic encephalopathy (HIE) and myocardial ischemia secondary to metabolic acidosis during labor, respectively. The purpose was to assess in-utero changes in S100B and c-TnT levels in an experimental model of labor-like acidosis. METHODS: Repeated umbilical cord occlusions (UCOs) in ten experiments were performed in mild (phase A, 1 UCO/5 mn), moderate (phase B, 1 UCO/3 mn), and severe (phase C, 1 UCO/2 mn) period. The experiments were stopped if arterial pH reached 6.90. RESULTS: UCOs resulted in fetal acidosis with pH dropping to 6.99 ±0.13. When compared to the baseline period fetal S100B increased between phases A and B (7% ± 4 vs 17% ± 13, p = 0.030) and between phases A and C (7% ± 4 vs 24% ± 8, p < 0.001). Fetal c-TnT serum levels increased during occlusions: 102 ng/L (58-119) in phase A, vs 119 ng/L (103-198) in phase B vs 169 ng / L (128-268) in phase C (p < 0.05, for all). When compared to the baseline control period, fetal ΔcTnT was significantly modified throughout UCO series: 5.0% (-3; 45) in phase A, 51% (4; 263) in phase B, and 77% (56.5; 269) in phase C (p < 0.05 for all). CONCLUSIONS: S100B and c-TnT increased when fetal acidosis occurred, which reflects the potential neurological damage and fetal cardiovascular adaptation.


Assuntos
Acidose , Trabalho de Parto , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Troponina/sangue , Animais , Feminino , Feto , Gravidez , Ovinos , Cordão Umbilical
14.
J Dairy Sci ; 104(10): 10780-10795, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34253359

RESUMO

Rumen microbiota intervention has long been used to cure ruminal indigestion in production and has recently become a research hotspot. However, how it controls the remodeling of rumen bacterial homeostasis and the restoration of rumen fermentation in cows of subacute ruminal acidosis (SARA) remains poorly understood. This study explored changes in rumen fermentation and bacterial communities in SARA cows following rumen content transplantation (RCT). The entire experiment comprised 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were selected and allocated into 2 groups at random, fed either a conventional diet [CON; n = 4; 40% concentrate, dry matter (DM) basis] or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). After the SARA induction period, the RCT period began. The HG cows were randomly divided into 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group, and their rumen contents were removed completely before RCT. For the DR group, cows received 70% rumen content from the CON cows, paired based on comparable body weight; for the SR group, each cow received 70% rumen content, self-derived. The results showed that nearly all rumen fermentation parameters returned to the normal levels that the cows had before SARA induction after 6 d of transplantation, regardless of RCT. The concentrations of acetate, valerate, and total volatile fatty acids (VFA) were not recovered in the SR cows, whereas all of them were recovered in the DR cows. The amplicon sequencing results indicated that both the SR and DR cows rebuild their rumen bacterial homeostasis quickly within 4 d after RCT, and the DR group showed a higher level of bacterial community diversity. At the genus level, the DR cows displayed an improved proportion of unclassified Ruminococcaceae and Saccharofermentans compared with the SR cows. Correlation analysis between the rumen bacteria and rumen fermentation suggested some potential relationships between the predominant transplantation-sensitive operational taxonomic units and VFA. Co-occurrence network analysis revealed that RCT affected only those rumen bacterial taxa that showed weak interactions with other taxa and did not affect the pivotal rumen bacteria with high levels of co-occurrence. Our findings indicate that RCT contributes to the restoration of rumen bacterial homeostasis and rumen fermentation in cows suffering from SARA without affecting the core microbiome.


Assuntos
Acidose , Doenças dos Bovinos , Acidose/metabolismo , Acidose/veterinária , Ração Animal , Animais , Bactérias , Bovinos , Doenças dos Bovinos/metabolismo , Dieta/veterinária , Feminino , Fermentação , Concentração de Íons de Hidrogênio , Lactação , Leite , Rúmen/metabolismo
15.
Biomed Pharmacother ; 139: 111615, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243598

RESUMO

BACKGROUND: Severe acidosis deteriorates cardiac injury. Rat coronary arteries (RCAs) are unusually hypercontractive to extracellular (o) acidosis (EA). TMEM16A-encoded anoctamin 1 (ANO1), a Ca2+-activated chloride channel (CaCC), plays an important role in regulating coronary arterial tension. PURPOSE: We tested the possibility that the activation of CaCCs in the arterial smooth muscle cell (ASMC) contributes to EA-induced RCA constriction. METHODS: ANO1 expression was detected with immunofluorescence staining and Western blot. TMEM16A mRNA was assessed with quantitative Real-Time PCR. Cl- currents and membrane potentials were quantified with a patch clamp. The vascular tension was recorded with a myograph. Intracellular (i) level of Cl- and Ca2+ was measured with fluorescent molecular probes. RESULTS: ANO1 was expressed in all tested arterial myocytes, but was much more abundant in RCA ASMCs as compared with ASMCs isolated from rat cerebral basilar, intrarenal and mesenteric arteries. EA reduced [Cl-]i levels, augmented CaCC currents exclusively in RCA ASMCs and depolarized RCA ASMCs to a greater extent. Cl- deprivation, which depleted [Cl-]i by incubating the arteries or their ASMCs in Cl--free bath solution, decreased EA-induced [Cl-]i reduction, diminished EA-induced CaCC augmentation and time-dependently depressed EA-induced RCA constriction. Inhibitor studies showed that these EA-induced effects including RCA constriction, CaCC current augmentation, [Cl-]i reduction and/or [Ca2+]i elevation were depressed by various Cl- channel blockers, [Ca2+]i release inhibitors and L-type voltage-gated Ca2+ channel inhibitor nifedipine. ANO1 antibody attenuated all observed changes induced by EA in RCA ASMCs. CONCLUSION: The greater activity of RCA ASMC CaCCs complicated with an enhanced Ca2+ mobilization from both [Ca2+]i release and [Ca2+]o influx plays a pivotal role in the distinctive hypercontractility of RCAs to acidosis. Translation of these findings to human beings may lead to a new conception in our understanding and treating cardiac complications in severe acidosis.


Assuntos
Acidose/metabolismo , Anoctamina-1/metabolismo , Vasos Coronários/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Vasoconstrição/fisiologia , Acidose/tratamento farmacológico , Animais , Cálcio/metabolismo , Canais de Cloreto/metabolismo , Cloretos/metabolismo , Vasos Coronários/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Nifedipino/farmacologia , Técnicas de Patch-Clamp/métodos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Vasoconstrição/efeitos dos fármacos
16.
Nutrients ; 13(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206629

RESUMO

A perinatal high-salt (HS) diet was reported to elevate plasma triglycerides. This study aimed to investigate the hypothesis that a perinatal HS diet predisposed offspring to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of abnormal lipid metabolism, and the possible mechanism. Female C57BL/6 mice were fed a control diet (0.5% NaCl) or HS diet (4% NaCl) during pregnancy and lactation and their offspring were sacrificed at weaning. The perinatal HS diet induced greater variation in fecal microbial beta-diversity (ß-diversity) and increased bacteria abundance of Proteobacteria and Bacteroides. The gut microbiota dysbiosis promoted bile acid homeostasis disbalance, characterized by the accumulation of lithocholic acid (LCA) and deoxycholic acid (DCA) in feces. These alterations disturbed gut barrier by increasing the expression of tight junction protein (Tjp) and occludin (Ocln), and increased systemic lipopolysaccharide (LPS) levels and hepatic inflammatory cytokine secretion (TNF-α and IL-6) in the liver. The perinatal HS diet also inhibited hepatic expression of hepatic FXR signaling (CYP7A1 and FXR), thus triggering increased hepatic expression of pro-inflammatory cytokines (TNF-α and IL-6) and hepatic lipid metabolism-associated genes (SREBP-1c, FAS, ACC), leading to unique characteristics of NAFLD. In conclusion, a perinatal HS diet induced NAFLD in weanling mice offspring; the possible mechanism was related to increased bacteria abundance of Proteobacteria and Bacteroides, increased levels of LCA and DCA in feces, and increased expressions of hepatic FXR signaling.


Assuntos
Dieta/efeitos adversos , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal/etiologia , Sódio na Dieta/efeitos adversos , Acidose/etiologia , Animais , Animais Recém-Nascidos , Ácidos e Sais Biliares/metabolismo , Dieta/métodos , Disbiose/etiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Homeostase/fisiologia , Lactação/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Gravidez , Transdução de Sinais/fisiologia , Triglicerídeos/sangue , Desmame
17.
Mayo Clin Proc ; 96(7): 2005-2007, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34218872
18.
Malar J ; 20(1): 282, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172046

RESUMO

BACKGROUND: Severe metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings. METHODS: A retrospective analysis of the 'Artesunate versus quinine in the treatment of severe falciparum malaria in African children' (AQUAMAT) trial was conducted to identify clinical features of severe metabolic acidosis and uraemia in 5425 children from nine African countries. Separate models were fitted for uraemia and severe metabolic acidosis. Separate univariable and multivariable logistic regression were performed to identify prognostic factors for severe metabolic acidosis and uraemia. Both analyses adjusted for the trial arm. A forward selection approach was used for model building of the logistic models and a threshold of 5% statistical significance was used for inclusion of variables into the final logistic model. Model performance was assessed through calibration, discrimination, and internal validation with bootstrapping. RESULTS: There were 2296 children identified with severe metabolic acidosis and 1110 with uraemia. Prognostic features of severe metabolic acidosis among them were deep breathing (OR: 3.94, CI 2.51-6.2), hypoglycaemia (OR: 5.16, CI 2.74-9.75), coma (OR: 1.72 CI 1.17-2.51), respiratory distress (OR: 1.46, CI 1.02-2.1) and prostration (OR: 1.88 CI 1.35-2.59). Features associated with uraemia were coma (3.18, CI 2.36-4.27), Prostration (OR: 1.78 CI 1.37-2.30), decompensated shock (OR: 1.89, CI 1.31-2.74), black water fever (CI 1.58. CI 1.09-2.27), jaundice (OR: 3.46 CI 2.21-5.43), severe anaemia (OR: 1.77, CI 1.36-2.29) and hypoglycaemia (OR: 2.77, CI 2.22-3.46) CONCLUSION: Clinical and laboratory parameters representing contributors and consequences of severe metabolic acidosis and uraemia were independently associated with these outcomes. The model can be useful for identifying patients at high risk of these complications where laboratory assessments are not routinely available.


Assuntos
Acidose/diagnóstico , Malária Falciparum/complicações , Uremia/diagnóstico , Acidose/parasitologia , África ao Sul do Saara , Criança , Pré-Escolar , República Democrática do Congo , Feminino , Gâmbia , Gana , Humanos , Lactente , Quênia , Malária Falciparum/parasitologia , Masculino , Moçambique , Nigéria , Prognóstico , Estudos Retrospectivos , Ruanda , Tanzânia , Uganda , Uremia/parasitologia
19.
Diabetes Care ; 44(9): 2061-2068, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34187840

RESUMO

OBJECTIVE: Fluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment. RESEARCH DESIGN AND METHODS: The current analysis involved moderate or severe DKA episodes (n = 714) in children age <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration). RESULTS: The rate of change of pH did not differ by treatment arm, but Pco2 increased more rapidly in the fast versus slow fluid infusion arms during the initial 4 h of treatment. The anion gap also decreased more rapidly in the fast versus slow infusion arms during the initial 4 and 8 h. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 h. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% versus 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) versus the slow arms (35.2%). CONCLUSIONS: In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco2 than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.


Assuntos
Acidose , Cetoacidose Diabética , Acidose/etiologia , Acidose/terapia , Adolescente , Criança , Cetoacidose Diabética/tratamento farmacológico , Cetoacidose Diabética/terapia , Eletrólitos , Hidratação , Humanos , Sódio
20.
J Int Med Res ; 49(6): 3000605211024480, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34162258

RESUMO

Compared with monopolar transurethral resection of the prostate (TURP), which requires electrolyte-free irrigation fluid, normal saline can be used as the irrigation solution in bipolar and laser TURP. The risk of TURP syndrome and severe electrolyte disturbance is minimized when normal saline is used as the irrigation fluid. However, the use of isotonic saline also causes acid-base imbalance and electrolyte disturbance. We experienced two patients who developed hyperchloremic metabolic acidosis during bipolar TURP. After proper intervention, hemodynamic instability resolved, and laboratory test results normalized. Anesthesiologists must pay attention to acid-base and electrolyte status when rapid absorption of excessive isotonic solution is suspected, even during bipolar and laser TURP, which use normal saline as the irrigation fluid.


Assuntos
Acidose , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Acidose/etiologia , Humanos , Masculino , Próstata , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos
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