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1.
Pflugers Arch ; 476(4): 427-443, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38282081

RESUMEN

Maintaining an appropriate acid-base equilibrium is crucial for human health. A primary influencer of this equilibrium is diet, as foods are metabolized into non-volatile acids or bases. Dietary acid load (DAL) is a measure of the acid load derived from diet, taking into account both the potential renal acid load (PRAL) from food components like protein, potassium, phosphorus, calcium, and magnesium, and the organic acids from foods, which are metabolized to bicarbonate and thus have an alkalinizing effect. Current Western diets are characterized by a high DAL, due to large amounts of animal protein and processed foods. A chronic low-grade metabolic acidosis can occur following a Western diet and is associated with increased morbidity and mortality. Nutritional advice focusing on DAL, rather than macronutrients, is gaining rapid attention as it provides a more holistic approach to managing health. However, current evidence for the role of DAL is mainly associative, and underlying mechanisms are poorly understood. This review focusses on the role of DAL in multiple conditions such as obesity, cardiovascular health, impaired kidney function, and cancer.


Asunto(s)
Acidosis , Dieta , Animales , Humanos , Equilibrio Ácido-Base , Riñón/metabolismo , Acidosis/metabolismo , Obesidad/metabolismo
2.
Am J Physiol Regul Integr Comp Physiol ; 325(6): R725-R734, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37811714

RESUMEN

Exercise is associated with the development of oxidative stress, but the specific source and mechanism of production of pro-oxidant chemicals during exercise has not been confirmed. We used equine skeletal muscle mitochondria to test the hypothesis that hyperthermia and acidosis affect mitochondrial oxygen consumption and production of reactive oxygen species (ROS). Skeletal muscle biopsies were obtained at rest, after an acute episode of fatiguing exercise, and after a 9-wk conditioning program to increase aerobic fitness. Mitochondrial oxygen consumption and ROS production were measured simultaneously using high-resolution respirometry. Both hyperthermia and acidosis increased nonphosphorylating (LEAK) respiration (5.8× and 3.0×, respectively, P < 0.001) and decreased efficiency of oxidative phosphorylation. The combined effects of hyperthermia and acidosis resulted in large decreases in phosphorylating respiration, further decreasing oxidative phosphorylation efficiency from 97% to 86% (P < 0.01). Increased aerobic fitness reduced the effects of acidosis on LEAK respiration. Hyperthermia increased and acidosis decreased ROS production (2× and 0.23×, respectively, P < 0.001). There was no effect of acute exercise, but an aerobic conditioning program was associated with increased ROS production during both nonphosphorylating and phosphorylating respiration. Hyperthermia increased the ratio of ROS production to O2 consumption during phosphorylating respiration, suggesting that high-temperature impaired transfer of energy through the electron transfer system despite relatively low mitochondrial membrane potential. These data support the role of skeletal muscle mitochondria in the development of exercise-induced oxidative stress, particularly during forms of exercise that result in prolonged hyperthermia without acidosis.NEW & NOTEWORTHY The results of this study provide evidence for the role of mitochondria-derived ROS in the development of systemic oxidative stress during exercise as well as skeletal muscle diseases such as exertional rhabdomyolysis.


Asunto(s)
Acidosis , Hipertermia Inducida , Animales , Caballos , Especies Reactivas de Oxígeno/metabolismo , Mitocondrias/metabolismo , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Acidosis/metabolismo , Consumo de Oxígeno/fisiología , Hipertermia/metabolismo
3.
Front Immunol ; 14: 1197133, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37275885

RESUMEN

Liver damage is common in ruminants with subacute ruminal acidosis (SARA). Disodium fumarate (DF) could regulate rumen microbial community and neutralize ruminal organic acids. This study aimed to evaluate the effect of dietary DF supplementation on SARA-induced liver damage and investigate the underlying mechanism. The results showed that feeding a high-concentrate diet induced decreased rumen fluid pH and increased ruminal LPS. The rumen fluid pH in the HC group was less than 5.6 at 4 time points, indicating that SARA was successfully induced. The histopathological analysis showed that in the HC group, hemorrhage and inflammatory cell infiltration were observed in liver tissue. Using ELISA kits and biochemical analyzer, we identified that the contents of interleukin 1beta (IL-1ß), interleukin 18 (IL-18), caspase-1, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in hepatic vein were elevated in the HC group. However, DF supplementation increased rumen fluid pH value, decreased ruminal LPS, attenuated hemorrhage and inflammatory cell infiltration in the liver tissue, and decreased contents of IL-1ß, IL-18, caspase-1, AST, and ALT in the hepatic vein. Real-time PCR and western blot analysis displayed that SARA-induced increased expression of pyroptosis-related proteins (GSDMD-NT) was attenuated in the HCDF group. Meanwhile, SARA induced increased expression of mitophagy and inflammasome-related proteins (MAP1LC3-II, PINK1, Parkin, cleaved-caspase-11, cleaved-caspase-1, NLRP3, and ASC) and elevated expression of inflammasome-related genes (NLRP3, CASP1, and ASC), which was reversed by DF supplementation. Moreover, SARA activated toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) signaling pathway and inhibited the entry of forkhead box A2 (FOXA2) into the nucleus, which was reversed by DF supplementation. Collectively, our data suggest that dietary DF supplementation inhibited hepatocyte pyroptosis by regulating the mitophagy-NLRP3 inflammasome pathway and the NF-κB signaling pathway, thus alleviating SARA-induced liver damage in Hu sheep.


Asunto(s)
Acidosis , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Femenino , Acidosis/metabolismo , Caspasas , Suplementos Dietéticos , Inflamasomas , Interleucina-18 , Lactancia , Lipopolisacáridos , Hígado/patología , Mitofagia , FN-kappa B/metabolismo , Piroptosis , Ovinos
4.
Res Vet Sci ; 160: 30-38, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37263098

RESUMEN

Subacute ruminal acidosis (SARA) in feedlot cattle during the feed transition to grain-based diets is a significant constraint to animal health and productivity. This experiment assessed an antibiotic-free supplement (ProTect®) effects on ruminal pH variability and methane (CH4) emissions of cattle during the challenge of SARA. Ten 18-month-old Angus steers (472 ± 4.8 kg) were randomly allocated into monensin (n = 5) and ProTect® groups (n = 5) and progressively introduced to grain diets incorporating monensin or ProTect® for 36 days of the experiment [starter (7 days; 45% grain), T1 (7 days; 56% grain), T2 (7 days; 67% grain), finisher (15 days; 78% grain)]. The pH variability on the finisher period was reduced by the ProTect® supplement (6.6% vs. 5.2%; P < 0.01), with CH4 emissions being significantly higher relative to the monensin group [88.2 g/day (9.3 g CH4/kg DMI) vs. 133.7 g/day (14.1 g CH4/kg DMI); P < 0.01]. There was no difference between treatments in the time spent on the ruminal pH < 5.6 or < 5.8 (P > 0.05). The model evaluation for the ruminal pH variation indicated that the mean absolute error (MAE) proportion for both groups was good within the same range [4.05% (monensin) vs. 4.25% (ProTect®)] with identical root mean square prediction error (RMSPE) (0.34). It is concluded that the ProTect® supplement is an effective alternative to monensin for preventing SARA in feedlot cattle by managing ruminal pH variation during the transition to high-grain diets. Both monensin and ProTect® supplemented cattle exhibited lower CH4 yield compared to cattle fed forages and low-concentrate diets.


Asunto(s)
Acidosis , Enfermedades de los Bovinos , Bovinos , Animales , Monensina/farmacología , Monensina/metabolismo , Alimentación Animal/análisis , Antibacterianos/farmacología , Antibacterianos/metabolismo , Metano , Rumen/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Dieta/veterinaria , Suplementos Dietéticos , Acidosis/prevención & control , Acidosis/veterinaria , Acidosis/metabolismo , Grano Comestible , Concentración de Iones de Hidrógeno , Fermentación , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/metabolismo
5.
BMC Vet Res ; 18(1): 356, 2022 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-36151574

RESUMEN

BACKGROUND: In recent years, researchers have become increasingly interested in developing natural feed additives that can stabilize ruminal pH and thus prevent or eliminate the risk of severe subacute rumen acidosis. Herein, 3 experiments were conducted using a semi-automated in vitro gas production technique. In the experiment (Exp.) 1, the efficacy of 9 plant extracts (1.5 mg/ml), compared to monensin (MON; 12 µg/ml), to counteract ruminal acidosis stimulated by adding glucose (0.1 g/ml) as a fermentable carbohydrate without buffer was assessed for 6 h. In Exp. 2, cinnamon extract (CIN) and MON were evaluated to combat glucose-induced acidosis with buffer use for 24 h. In Exp. 3, the effect of CIN and MON on preventing acidosis when corn or barley grains were used as substrate was examined. RESULTS: In Exp. 1, cinnamon, grape seeds, orange, pomegranate peels, propolis, and guava extracts significantly increased (P < 0.05) pH compared to control (CON). Both CIN and MON significantly increased the pH (P < 0.001) but reduced cumulated gas production (P < 0.01) compared to the other treatments. In Exp. 2, the addition of CIN extract increased (P < 0.01) pH value compared to CON at the first 6 h of incubation. However, no significant differences in pH values between CIN and CON at 24 h of incubation were observed. The addition of CIN extract and MON decreased (P < 0.001) lactic acid concentration and TVFA compared to CON at 24 h. The CIN significantly (P < 0.01) increased acetate: propionate ratio while MON reduced it. In Exp. 3, both CIN and MON significantly increased (P < 0.05) ruminal pH at 6 and 24 h and reduced lactic acid concentration at 24 h compared to CON with corn as substrate. However, CIN had no effect on pH with barley substrate at all incubation times. CONCLUSIONS: It can be concluded that CIN can be used effectively as an alternative antibiotic to MON to control ruminal acidosis when corn is used as a basal diet.


Asunto(s)
Acidosis , Própolis , Acidosis/metabolismo , Acidosis/prevención & control , Acidosis/veterinaria , Alimentación Animal/análisis , Animales , Antibacterianos/farmacología , Carbohidratos/farmacología , Cinnamomum zeylanicum , Dieta , Digestión , Fermentación , Glucosa/metabolismo , Ácido Láctico/metabolismo , Monensina/farmacología , Extractos Vegetales/farmacología , Propionatos/metabolismo , Própolis/metabolismo , Própolis/farmacología , Rumen/metabolismo
6.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33658363

RESUMEN

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.


Asunto(s)
Acidosis/sangre , Proteína HMGB1/sangre , Sepsis/sangre , Sialoglicoproteínas/sangre , Zinc/sangre , Acidosis/inmunología , Acidosis/metabolismo , Acidosis/patología , Proteínas Portadoras , Proteína HMGB1/farmacología , Humanos , Concentración de Iones de Hidrógeno , Inmunidad Innata , Lipopolisacáridos/farmacología , Polisacáridos/química , Sepsis/inmunología , Sepsis/patología , Ácidos Siálicos/química , Sialoglicoproteínas/química , Zinc/metabolismo
7.
Mol Genet Metab ; 132(2): 146-153, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33485800

RESUMEN

TRMU is a nuclear gene crucial for mitochondrial DNA translation by encoding tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase, which thiolates mitochondrial tRNA. Biallelic pathogenic variants in TRMU are associated with transient infantile liver failure. Other less common presentations such as Leigh syndrome, myopathy, and cardiomyopathy have been reported. Recent studies suggested that provision of exogenous L-cysteine or N-acetylcysteine may ameliorate the effects of disease-causing variants and improve the natural history of the disease. Here, we report six infants with biallelic TRMU variants, including four previously unpublished patients, all treated with exogenous cysteine. We highlight the first report of an affected patient undergoing orthotopic liver transplantation, the long-term effects of cysteine supplementation, and the ability of the initial presentation to mimic multiple inborn errors of metabolism. We propose that TRMU deficiency should be suspected in all children presenting with persistent lactic acidosis and hypoglycemia, and that combined N-acetylcysteine and L-cysteine supplementation should be considered prior to molecular diagnosis, as this is a low-risk approach that may increase survival and mitigate the severity of the disease course.


Asunto(s)
Enfermedad de Leigh/terapia , Fallo Hepático/terapia , Proteínas Mitocondriales/genética , Biosíntesis de Proteínas , ARNt Metiltransferasas/genética , Acetilcisteína/administración & dosificación , Acetilcisteína/metabolismo , Acidosis/genética , Acidosis/metabolismo , Cisteína/administración & dosificación , Cisteína/metabolismo , ADN Mitocondrial/genética , Femenino , Humanos , Lactante , Enfermedad de Leigh/genética , Enfermedad de Leigh/metabolismo , Enfermedad de Leigh/patología , Fallo Hepático/genética , Fallo Hepático/metabolismo , Fallo Hepático/patología , Trasplante de Hígado/métodos , Masculino , Mitocondrias/enzimología , Proteínas Mitocondriales/deficiencia , ARN de Transferencia/genética , ARNt Metiltransferasas/deficiencia
8.
J Am Soc Nephrol ; 32(1): 229-237, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33093193

RESUMEN

BACKGROUND: The precise origin of phosphate that is removed during hemodialysis remains unclear; only a minority comes from the extracellular space. One possibility is that the remaining phosphate originates from the intracellular compartment, but there have been no available data from direct assessment of intracellular phosphate in patients undergoing hemodialysis. METHODS: We used phosphorus magnetic resonance spectroscopy to quantify intracellular inorganic phosphate (Pi), phosphocreatine (PCr), and ßATP. In our pilot, single-center, prospective study, 11 patients with ESKD underwent phosphorus (31P) magnetic resonance spectroscopy examination during a 4-hour hemodialysis treatment. Spectra were acquired every 152 seconds during the hemodialysis session. The primary outcome was a change in the PCr-Pi ratio during the session. RESULTS: During the first hour of hemodialysis, mean phosphatemia decreased significantly (-41%; P<0.001); thereafter, it decreased more slowly until the end of the session. We found a significant increase in the PCr-Pi ratio (+23%; P=0.001) during dialysis, indicating a reduction in intracellular Pi concentration. The PCr-ßATP ratio increased significantly (+31%; P=0.001) over a similar time period, indicating a reduction in ßATP. The change of the PCr-ßATP ratio was significantly correlated to the change of depurated Pi. CONCLUSIONS: Phosphorus magnetic resonance spectroscopy examination of patients with ESKD during hemodialysis treatment confirmed that depurated Pi originates from the intracellular compartment. This finding raises the possibility that excessive dialytic depuration of phosphate might adversely affect the intracellular availability of high-energy phosphates and ultimately, cellular metabolism. Further studies are needed to investigate the relationship between objective and subjective effects of hemodialysis and decreases of intracellular Pi and ßATP content. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy (CIPHEMO), NCT03119818.


Asunto(s)
Adenosina Trifosfato/metabolismo , Fosfatos/metabolismo , Diálisis Renal , Acidosis/metabolismo , Adulto , Anciano , Calcio/metabolismo , Metabolismo Energético , Femenino , Hemodinámica , Humanos , Concentración de Iones de Hidrógeno , Fallo Renal Crónico/metabolismo , Cinética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Fosfocreatina/metabolismo , Fósforo , Isótopos de Fósforo , Proyectos Piloto , Estudios Prospectivos
9.
Microb Pathog ; 137: 103781, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31593757

RESUMEN

Sub-acute ruminal acidosis (SARA) [1] is one of the most common problems of dairy animals causing great economical loss due to decreased milk production. Here we determined the antioxidant effect of sodium butyrate (NaB) [2] in experimentally induced SARA and its effects on mammary epithelial tissues of goat. Goats (n = 12) were equally divided into two groups: high-concentrate (HC) as control group fed with HC diet (concentrate: forage = 6:4) whereas HC + NaB as treatment group fed HC diet with NaB at 1% by weight for 24 weeks. Mammary epithelial tissue samples were analyzed for the expression of genes and proteins responsible for oxidative stress as well as biochemical markers of antioxidant activity in the form of Reactive Oxygen Species (ROS). The total antioxidant capacity (T-AOC) of antioxidant enzymes was also calculated. Butyrate induced antioxidant effect by increasing mRNA and protein abundance of antioxidants in mammary gland of HC + NaB group compared to HC group. Likewise, the total antioxidant capacity (T-AOC) was significantly increased and Malondialdehyde (MDA) concentration was decreased in HC + NaB group compared to HC group. It is concluded that oxidative stress in mammary gland of goats induced by high concentrate diet was alleviated by NaB supplementation.


Asunto(s)
Acidosis/metabolismo , Acidosis/veterinaria , Ácido Butírico/administración & dosificación , Enfermedades de las Cabras/tratamiento farmacológico , Glándulas Mamarias Animales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Acidosis/tratamiento farmacológico , Acidosis/fisiopatología , Animales , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Femenino , Enfermedades de las Cabras/genética , Enfermedades de las Cabras/metabolismo , Enfermedades de las Cabras/fisiopatología , Cabras , Lactancia/efectos de los fármacos , Malondialdehído/metabolismo , Glándulas Mamarias Animales/metabolismo , Leche/química , Leche/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo
10.
J Dairy Sci ; 102(7): 6518-6531, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31030914

RESUMEN

We investigated the effects of active dried Saccharomyces cerevisiae (ADSC) on ruminal pH, fermentation, and the fluid bacterial community during the short-term ruminal acidosis challenge. Five rumen-fistulated male Holstein calves (147.0 ± 5.8 kg of body weight; 3.6 ± 0.2 mo of age) were used in a crossover design, and 0 g (control group, n = 5) or 2 g (SC group, n = 5) of ADSC (1 × 1010 cfu/g) was administered twice daily for 21 consecutive days. Calves were fed a high-forage diet during the first 15 d (d -14 to d 0; prechallenge), a high-grain diet for 2 d (d 1 and 2; ruminal acidosis challenge), and a high-forage diet for 4 d (d 3 to 6; postchallenge). Ruminal pH was measured continuously. Rumen fluid samples were collected once daily (0800 h) on d 0, 3, 4, and 6 and twice daily (0800 and 1100 h) on d 1 and 2. Bacterial DNA was extracted from fluid samples collected on d 0 and 3. The 24-h and 1-h mean ruminal pH was significantly depressed during the ruminal acidosis challenge in each group, although the changes were more severe in the SC group, consistent with a significant increase in lactic acid on d 2 (1100 h) compared with d 0 and a significantly higher proportion of butyric acid on d 2 (1100 h) compared with the control group. Feeding a high-grain diet caused a decrease in bacterial diversity due to high acidity in both groups. The relative abundances of the genus Bifidobacterium and operational taxonomic unit (OTU) 3 (Bifidobacterium species) increased significantly in both groups but were higher in the SC group. Correlation analyses indicated that OTU3 (Bifidobacterium species) were positively correlated with lactic acid concentration and that OTU1 (Prevotella species) and OTU5 (Succinivibrio species) were correlated with the proportion of butyric acid. These results suggest that ADSC supplementation induced the intense decreases in ruminal pH by increased butyric and lactic acid production through a high-grain diet fermentation by rumen fluid bacterial species during the short-term ruminal acidosis challenge in Holstein calves after weaning.


Asunto(s)
Acidosis/veterinaria , Enfermedades de los Bovinos/microbiología , Rumen/microbiología , Saccharomyces cerevisiae/metabolismo , Acidosis/metabolismo , Acidosis/microbiología , Alimentación Animal , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Butiratos/metabolismo , Bovinos , Enfermedades de los Bovinos/metabolismo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Grano Comestible , Fermentación , Concentración de Iones de Hidrógeno , Masculino , Rumen/química , Rumen/metabolismo , Levadura Seca
11.
Clin Biochem ; 65: 53-54, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30578759

RESUMEN

A 35-month-old female with nonketotic hyperglycinemia (NKH) presented to the Emergency department with severe hypoglycemia, fever, and several episodes of seizures. Due to worsening respiratory status, additional seizures and anion gap worsening metabolic acidosis the patient was transferred to the pediatric intensive care unit. The useful mnemonics for causes of high anion gap metabolic acidosis are the classic MUDPILES (representing Methanol, Uraemia, Diabetes, Paraldehyde, Iron (and Isoniazid), Lactate, Ethylene glycol, and Salicylate) and the more recently proposed GOLD MARK (Glycols [ethylene and propylene], Oxoproline, l-lactate, d-lactate, Methanol, Aspirin, Renal failure, and Ketoacidosis) as causes of the anion gap metabolic acidosis were all ruled out. Relatively stable concentrations of salicylate (approximately 10 mg/dL, 0.7 mmol/L) were noted, despite no evidence the patient received aspirin Therefore further laboratory testing was performed. A Basic-Acid-Neutral (BAN) gas chromatography mass-spectroscopy (GC-MS) Drug screen of urine was undertaken. A large benzoic acid peak was identified by spectral match, which supported the clinical history that the patient was taking sodium benzoate powder 1175 mg as a dietary supplement three times a day. However, salicylate was not identified. This patient had benzoic acid concentration in excess of 2000 µg/mL. Given that benzoic acid is a weak acid, with a pK of approximately 4 it is almost completely ionized at pH 7. Therefore, the large amount of benzoic acid was not only thought to be contributing to the patient's anion gap metabolic acidosis, but the source of the interference in the salicylate assay.


Asunto(s)
Acidosis/metabolismo , Equilibrio Ácido-Base/fisiología , Ácido Benzoico/metabolismo , Preescolar , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos
12.
J Agric Food Chem ; 66(38): 9995-10002, 2018 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-30173520

RESUMEN

The present study aims to reveal the mechanisms of hepatocyte apoptosis induced by dietary feeding. Eighteen midlactating goats were randomly divided into three groups: the low concentrate group (LC), the high concentrate group (HC), and the sodium butyrate (SB)-supplemented group (SHC). After 10 weeks, the HC diet successfully induced subacute ruminal acidosis (SARA), which increased the lipopolysaccharide (LPS) and cytokine concentrations and the expression of genes and proteins related to inflammation and apoptosis. The addition of SB to the HC diet notably decreased the levels of those parameters. Additionally, Bcl2 mRNA and protein expression was lower in the HC group than those in the LC and SHC groups. Furthermore, the HC diet reduced the percentages of caspase 3 and 8 promoter methylation compared to those of goats fed the LC diet, whereas the SHC diet partially recovered the methylation ratio to reduce caspase 3 and 8 expression. Collectively, HC diet-induced SARA caused hepatocyte apoptosis via activating the extrinsic apoptosis pathway, whereas dietary addition of SB depressed the inflammatory response and attenuated hepatocyte apoptosis. DNA methylation contributed to regulation of the expression of key apoptotic genes in the livers of lactating goats.


Asunto(s)
Acidosis/veterinaria , Apoptosis/efectos de los fármacos , Ácido Butírico/administración & dosificación , Suplementos Dietéticos/análisis , Enfermedades de las Cabras/tratamiento farmacológico , Hepatocitos/citología , Rumen/metabolismo , Acidosis/tratamiento farmacológico , Acidosis/metabolismo , Acidosis/fisiopatología , Alimentación Animal , Animales , Enfermedades de las Cabras/metabolismo , Enfermedades de las Cabras/fisiopatología , Cabras , Hepatocitos/efectos de los fármacos , Hígado/citología , Hígado/efectos de los fármacos
13.
Orphanet J Rare Dis ; 13(1): 120, 2018 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-30025539

RESUMEN

BACKGROUND: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy. RESULTS: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers. CONCLUSIONS: Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin.


Asunto(s)
Acidosis/genética , Acidosis/metabolismo , Acil-CoA Deshidrogenasa/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/metabolismo , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/metabolismo , Debilidad Muscular/genética , Debilidad Muscular/metabolismo , Riboflavina/uso terapéutico , Acidosis/patología , Actividades Cotidianas , Acil-CoA Deshidrogenasa/genética , Acil-CoA Deshidrogenasa/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/patología , Cardiomiopatía Hipertrófica/patología , Complejo I de Transporte de Electrón/metabolismo , Femenino , Humanos , Masculino , Enfermedades Mitocondriales/patología , Debilidad Muscular/tratamiento farmacológico , Debilidad Muscular/patología , Pronóstico
14.
Clin Perinatol ; 45(1): 129-141, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29406002

RESUMEN

Most bone formation and mineralization occurs late in gestation. Accretion of adequate minerals is a key element of this process and is often interrupted through preterm birth. In utero, mineral transport is accomplished via active transport across the placenta and does not require fetal hormone input. Postnatal mineral homeostasis requires a balance of actions of parathyroid hormone, calcitonin, and vitamin D on target organs. Preterm birth, asphyxia, acidosis, and prolonged parenteral nutrition increase the risk of mineral imbalance and metabolic bone disease (MBD). Aggressive postnatal nutrition is key to preventing and treating MBD in preterm infants.


Asunto(s)
Enfermedades Óseas Metabólicas/metabolismo , Calcificación Fisiológica , Calcitonina/metabolismo , Calcio/metabolismo , Hormona Paratiroidea/metabolismo , Fósforo/metabolismo , Vitamina D/metabolismo , Acidosis/metabolismo , Asfixia Neonatal/metabolismo , Homeostasis , Humanos , Recién Nacido , Recien Nacido Prematuro , Nutrición Parenteral , Raquitismo/metabolismo
15.
Clin Exp Hypertens ; 40(4): 370-377, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29420074

RESUMEN

Vascular calcification such as arteriosclerosis, which is characterized by a calcification of the tunica media, is a severe complication of chronic kidney disease (CKD), contributing to the high prevalence of cardiovascular morbidity and mortality in patients with CKD. An essential step during the development of arteriosclerosis is the transdifferentiation/calcification of vascular smooth muscle cells (VSMCs), resembling osteogenesis. Metabolic acidosis, a common clinical manifestation in CKD, is known to decrease vascular calcification. To understand the underlying regulatory mechanisms of acidosis, we investigated whether the acidosis-decreased VSMC calcification involves altered signaling of the LTCC/Ca2+/Runx2 pathway. Vascular calcifications, calcium content, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), L-type calcium channel (LTCC) ß3 subunits, and calcium influx were measured in vivo or in vitro. Calcified nodules and calcium content increased either in aorta sections of vascular calcified rats or in VSMCs induced by ß-GP. The expression of Runx2 and ALP activity markedly rose, accompanied by the increasing expression of LTCC ß3 subunits and calcium influx. However, acidosis supplementation successfully attenuated VC and VSMC calcification and inhibited Runx2, ALP, LTCC ß3 subunits, and calcium influx. In conclusion, acidosis significantly attenuated vascular calcification in association with downregulation of the LTCC/Ca2+/Runx2 pathway.


Asunto(s)
Acidosis/metabolismo , Canales de Calcio Tipo L/metabolismo , Calcio/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Aorta/metabolismo , Células Cultivadas , Masculino , Redes y Vías Metabólicas , Ratas
16.
Biochim Biophys Acta Mol Basis Dis ; 1864(1): 162-177, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28986307

RESUMEN

The acute-phase proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1ß and TNF-α in acid-induced apoptosis of chondrocytes remain unclear. Rat adjuvant arthritis and primary articular chondrocytes were used as in vivo and in vitro model systems, respectively. ASIC1a expression in articular cartilage was increased and highly colocalized with nuclear factor (NF)-κB expression in vivo. IL-1ß and TNF-α could upregulate ASIC1a expression. These cytokines activated mitogen-activated protein kinase and NF-κB pathways in chondrocytes, while the respective inhibitors of these signaling pathways could partially reverse the ASIC1a upregulation induced by IL-1ß and TNF-α. Dual luciferase and gel-shift assays and chromatin immunoprecipitation-polymerase chain reaction demonstrated that IL-1ß and TNF-α enhanced ASIC1a promoter activity in chondrocytes by increasing NF-κB DNA-binding activities, which was in turn prevented by the NF-κB inhibitor ammonium pyrrolidinedithiocarbamate. IL-1ß and TNF-α also decreased cell viability but enhanced LDH release, intracellular Ca2+ concentration elevation, loss of mitochondrial membrane potential, cleaved PARP and cleaved caspase-3/9 expression, and apoptosis in acid-stimulated chondrocytes, which effects could be abrogated by the specific ASIC1a inhibitor psalmotoxin-1 (PcTX-1), ASIC1a-short hairpin RNA or calcium chelating agent BAPTA-AM. These results indicate that IL-1ß and TNF-α can augment acidosis-induced cytotoxicity through NF-κB-dependent up-regulation of ASIC1a channel expression in primary articular chondrocytes.


Asunto(s)
Acidosis/patología , Apoptosis/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Interleucina-1beta/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Canales Iónicos Sensibles al Ácido/genética , Canales Iónicos Sensibles al Ácido/metabolismo , Acidosis/genética , Acidosis/metabolismo , Animales , Apoptosis/genética , Artritis Experimental/genética , Artritis Experimental/metabolismo , Artritis Experimental/patología , Cartílago Articular/fisiología , Células Cultivadas , Condrocitos/fisiología , Masculino , FN-kappa B/metabolismo , FN-kappa B/fisiología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética
17.
Adv Chronic Kidney Dis ; 24(5): 298-304, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-29031356

RESUMEN

Subjects with CKD and reduced glomerular filtration rate are at risk for chronic metabolic acidosis, and CKD is its most common cause. Untreated metabolic acidosis, even in its mildest forms, is associated with increased mortality and morbidity and should therefore be treated. If reduced glomerular filtration rate or the tubule abnormality causing chronic metabolic acidosis cannot be corrected, it is typically treated with dietary acid (H+) reduction using Na+-based alkali, usually NaHCO3. Dietary H+ reduction can also be accomplished with the addition of base-producing foods such as fruits and vegetables and limiting intake of H+-producing foods like animal-sourced protein. The optimal dose of Na+-based alkali that prevents the untoward effects of metabolic acidosis while minimizing adverse effects and the appropriate combination of this traditional therapy with dietary strategies remain to be determined by ongoing studies. Recent emerging evidence supports a phenomenon of H+ retention, which precedes the development of metabolic acidosis by plasma acid-base parameters, but further studies will be needed to determine how best to identify patients with this phenomenon and whether they too should be treated with dietary H+ reduction.


Asunto(s)
Acidosis/dietoterapia , Acidosis/tratamiento farmacológico , Dieta , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Bicarbonato de Sodio/uso terapéutico , Equilibrio Ácido-Base , Acidosis/etiología , Acidosis/metabolismo , Acidosis Tubular Renal/tratamiento farmacológico , Animales , Bicarbonatos/sangre , Proteínas en la Dieta , Frutas , Tasa de Filtración Glomerular , Humanos , Verduras
18.
Am J Kidney Dis ; 70(5): 725-728, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28739329

RESUMEN

Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in which a somatostatin analogue (a small peptide) is coupled with a radioligand so that the radiation dose is selectively administered to somatostatin receptor-expressing metastasized neuroendocrine tumors, particularly gastroenteropancreatic. Reported toxicities include myelotoxicity and nephrotoxicity, the latter manifesting as decreased kidney function, often developing months to years after treatment completion. We present a case of PRRT-induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with preserved kidney function. Because profound hypokalemia and hypocalcemia can lead to life-threatening arrhythmias, we highlight the necessity for careful monitoring of serum and urine electrolytes in patients receiving PRRT.


Asunto(s)
Síndrome de Gitelman/inducido químicamente , Neoplasias del Íleon/radioterapia , Tumores Neuroendocrinos/radioterapia , Octreótido/análogos & derivados , Compuestos Organometálicos/efectos adversos , Desequilibrio Hidroelectrolítico/inducido químicamente , Acidosis/inducido químicamente , Acidosis/metabolismo , Acidosis/terapia , Anciano , Calcitriol/uso terapéutico , Carbonato de Calcio/uso terapéutico , Quimioradioterapia Adyuvante , Procedimientos Quirúrgicos del Sistema Digestivo , Fluidoterapia , Síndrome de Gitelman/metabolismo , Síndrome de Gitelman/terapia , Humanos , Hipocalcemia/inducido químicamente , Hipocalcemia/metabolismo , Hipocalcemia/terapia , Hipopotasemia/inducido químicamente , Hipopotasemia/metabolismo , Hipopotasemia/terapia , Sulfato de Magnesio/uso terapéutico , Masculino , Octreótido/efectos adversos , Vitaminas/uso terapéutico , Desequilibrio Hidroelectrolítico/metabolismo , Desequilibrio Hidroelectrolítico/terapia
19.
Sci Rep ; 6: 35334, 2016 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-27734955

RESUMEN

Excessive pig manure application probably degrades arable soil quality in some intensive pig farming areas. The responses of the nematode community to dosages of pig manure were investigated in Ferric Acrisols under 3-season peanut monoculture. Varying dosages of manure (1.75, 3.5, 7, 14 and 28 t·ha-1·yr-1) in combination with chemical fertilizer were applied to field plots, and chemical fertilizer alone was also applied as a control. With increasing manure application, the abundance of bacterivores and omnivores-predators increased, the abundance of plant parasites decreased, and fungivores abundance exhibited hump-shaped variation. Simpson diversity index and plant parasite index/maturity index of the nematode communities increased to a maximum level at a manure application rate of 3.5 t·ha-1·yr-1 and then sharply decreased. The changes in the soil nematode community were further determined to be correlated with chemical properties; available phosphorus had the strongest quadratic correlation with the two indices, implying that available phosphorus had a better indicative effect than other soil properties to nematode community. Available phosphorus in soil was deduced from 49 to 64 mg·kg-1 with the best nematode communities. Our results emphasized the importance of regular applications of manure in agriculture field to balance nematode diversity and build healthy agro-ecosystems.


Asunto(s)
Acidosis/metabolismo , Hierro/química , Estiércol , Nematodos/fisiología , Suelo/química , Agricultura , Animales , Productos Agrícolas , Ecosistema , Monitoreo del Ambiente , Fertilizantes , Concentración de Iones de Hidrógeno , Análisis Multivariante , Fósforo/química , Porcinos
20.
J Anim Sci ; 94(2): 709-17, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27065141

RESUMEN

The objectives were to determine the optimum inclusion of NaOH necessary to buffer the acidity of dried distillers' grains with solubles (DDGS) and its effects on digestibility, ruminal metabolism, and metabolic acidosis in feedlot steers. Rumen cannulated Angus-crossed steers were blocked by BW (small: 555 ± 42 kg initial BW, = 4; large: 703 ± 85 kg initial BW, = 4) over four 21-d periods in a replicated 4 × 4 Latin square design. Steers were assigned to 1 of 4 dietary treatments: 1) 50% untreated DDGS, 2) 50% DDGS treated with 0.5% (DM basis) sodium hydroxide (NaOH), 3) 50% DDGS treated with 1.0% (DM basis) NaOH, and 4) 50% DDGS treated with 1.5% (DM basis) NaOH. The remainder of the diets, on a DM basis, was composed of 20% corn silage, 20% dry-rolled corn, and 10% supplement. Ruminal pH was not affected by treatments ( = 0.56) or by a treatment × time interaction ( = 0.15). In situ NDF and ruminal DM disappearance did not differ ( ≥ 0.49 and ≥ 0.47, respectively) among treatments. Similar to in situ results, apparent total tract DM and NDF digestibility were not affected ( ≥ 0.33 and ≥ 0.21, respectively) by increasing NaOH inclusion in the diets. Urinary pH increased (linear, < 0.01) with increasing NaOH concentration in the diet. Blood pH was not affected ( ≥ 0.20), and blood total CO and partial pressure of CO were similar ( ≥ 0.56 and ≥ 0.17, respectively) as NaOH increased in the diet. Increasing NaOH in the diet did not affect ( ≥ 0.21) ruminal concentrations of total VFA. There were no linear ( = 0.20) or quadratic ( = 0.20) effects of treatment on ruminal acetate concentrations, nor was there a treatment × time interaction ( = 0.22) for acetate. Furthermore, there were no effects ( ≥ 0.90) of NaOH inclusion on ruminal propionate concentration. However, there was a quadratic response ( = 0.01) of ruminal butyrate concentrations as NaOH inclusion increased in the diet; ruminal butyrate concentrations were greatest with the 0.5 and 1.0% NaOH treatments of DDGS. In the current study, feeding DDGS treated with NaOH did not increase fiber digestibility nor was it necessary to alleviate a possible metabolic acidosis. Alkali treatment of DDGS did not increase average ruminal pH or blood pH.


Asunto(s)
Ensilaje/análisis , Hidróxido de Sodio/química , Acidosis/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Fibras de la Dieta/metabolismo , Suplementos Dietéticos , Digestión/fisiología , Conducta Alimentaria , Fermentación , Concentración de Iones de Hidrógeno , Masculino , Zea mays
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