RESUMEN
INTRODUCTION: Water and electrolyte disturbances associated with colistin are understudied adverse effects in the medical literature. We aim to evaluate their incidence in hospitalized older adult patients. MATERIALS AND METHODS: A longitudinal retrospective study of the interrupted time series type was conducted on patients admitted to Dr. César Milstein Hospital. We included adults aged 65 and older who received colistin with normal serum potassium, magnesium, and calcium at the outset. Electrolyte values were collected before, during and after suspending the antibiotic. Values were compared using non-parametric tests, and a multivariate linear regression model with robust intervals was performed to assess sociodemographic and clinical characteristics associated with serum concentrations. RESULTS: A total of 89 patients were included. The rate of hypokalemia was 77.5% (n=69), and factors associated with potassium decline included older age, increased creatinine levels, and longer colistin treatment duration. Serum magnesium disturbances were reported in 66 (79.5%) of the 83 patients evaluated. The decrease in both electrolytes was statistically significant in the measured times and both values normalized after 72 hours of stopping antibiotic therapy. The incidence of acute kidney injury during colistin treatment in patients with normal baseline creatinine was 63.6% (n = 42/66), and in those with abnormal baseline creatinine, it was 47.8% (n = 11/23). CONCLUSION: We report high rates of electrolyte disturbances in patients treated with colistin, with hypokalemia being the most frequent, showing resolution following discontinuation of antibiotic therapy. Continuous monitoring of electrolyte levels and renal function during colistin treatment is crucial.
Introducción: Los trastornos hidroelectrolíticos asociados a la colistina son efectos adversos poco estudiados en la literatura médica. Nos propusimos evaluar su incidencia en pacientes adultos mayores hospitalizados. Materiales y métodos: Se realizó un estudio longitudinal retrospectivo, del tipo serie de tiempo interrumpida, en pacientes internados mayores de 65 años que recibieron colistina, con potasio, magnesio y calcio séricos normales al inicio. Se recabaron valores de dichos electrolitos previo, durante y luego de suspender el antibiótico. Se compararon los valores mediante test no paramétricos y se realizó un modelo multivariado de regresión lineal con intervalos robustos para evaluar las características sociodemográficas y clínicas asociadas a las concentraciones séricas. Resultados: Se incluyeron 89 pacientes. La tasa de hipocalemia fue del 77.5% (n = 69) y las variables asociadas al descenso del potasio fueron mayor edad, aumento de creatininemia, y duración de tratamiento con colistina. Se informaron trastornos del magnesio en 66 (79.5%) de los 83 pacientes evaluados. El descenso de ambos electrolitos fue estadísticamente significativo en los tiempos medidos, y ambos normalizaron valores tras 72 horas de suspendida la antibioticoterapia. La incidencia de insuficiencia renal aguda en pacientes con creatinina basal normal fue del 63.6%, (42/66) y con creatinina basal anormal de 47.8% (11/23). Conclusión: En pacientes tratados con colistina, el trastorno más frecuente fue la hipocalemia, mostrando resolución tras la suspensión del antibiótico. Es importante la monitorización constante de los niveles de electrolitos y la función renal durante el tratamiento con colistina.
Asunto(s)
Antibacterianos , Calcio , Colistina , Hipopotasemia , Magnesio , Potasio , Humanos , Colistina/efectos adversos , Colistina/sangre , Masculino , Femenino , Anciano , Estudios Retrospectivos , Magnesio/sangre , Antibacterianos/efectos adversos , Hipopotasemia/sangre , Hipopotasemia/inducido químicamente , Hipopotasemia/epidemiología , Anciano de 80 o más Años , Potasio/sangre , Calcio/sangre , Estudios Longitudinales , Factores de Tiempo , Desequilibrio Hidroelectrolítico/inducido químicamente , Desequilibrio Hidroelectrolítico/sangre , Desequilibrio Hidroelectrolítico/epidemiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiologíaRESUMEN
BACKGROUND: Stroke is a leading cause of death worldwide, with oxidative stress and calcium overload playing significant roles in the pathophysiology of the disease. Ozone, renowned for its potent antioxidant properties, is commonly employed as an adjuvant therapy in clinical settings. Nevertheless, it remains unclear whether ozone therapy on parthanatos in cerebral ischemia-reperfusion injury (CIRI). This study aims to investigate the impact of ozone therapy on reducing parthanatos during CIRI and to elucidate the underlying mechanism. METHODS: Hydrogen peroxide (H2O2) was utilized to mimic the generation of reactive oxygen species (ROS) in SH-SY5Y cell reperfusion injury in vitro, and an in vivo ischemic stroke model was established. Ozone saline was introduced for co-culture or intravenously administered to mice. Apoptosis and oxidative stress were assessed using flow cytometry and immunofluorescence. Western blotting was utilized to examine the expression of parthanatos signature proteins. The mechanism by which ozone inhibits parthanatos was elucidated through inhibiting PPARg or Nrf2 activity. RESULTS: The findings demonstrated that ozone mitigated H2O2-induced parthanatos by either upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) or activating peroxisome proliferator-activated receptorg (PPARg). Furthermore, through the use of calcium chelators and ROS inhibitors, it was discovered that ROS directly induced parthanatos and facilitated intracellular calcium elevation. Notably, a malignant feedback loop between ROS and calcium was identified, further amplifying the induction of parthanatos. Ozone therapy exhibited its efficacy by increasing PPARg activity or enhancing the Nrf2 translation, thereby inhibiting ROS production induced by H2O2. Concurrently, our study demonstrated that ozone treatment markedly inhibited parthanatos in stroke-afflicted mice. Additionally, ozone therapy demonstrated significant neuroprotective effects on cortical neurons, effectively suppressing parthanatos. CONCLUSIONS: These findings contribute valuable insights into the potential of ozone therapy as a therapeutic strategy for reducing parthanatos during CIRI, highlighting its impact on key molecular pathways associated with oxidative stress and calcium regulation.
Asunto(s)
Modelos Animales de Enfermedad , Accidente Cerebrovascular Isquémico , Estrés Oxidativo , Ozono , Especies Reactivas de Oxígeno , Ozono/farmacología , Ozono/uso terapéutico , Animales , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Ratones , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión , Masculino , Peróxido de Hidrógeno/metabolismo , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Calcio/metabolismoRESUMEN
Calcium (Ca) is an essential mineral for eggshell formation and muscle contraction, and a lack of it can result in poor egg quality and decreased egg output in laying ducks. This study aims to see how feeding the mineral Ca in a ration containing Shrimp head meal and Bilis fish head affects the laying performance and quality of hatching eggs in Mojosari ducks. A total of 105 female and 15 male Mojosari ducks, aged 78 weeks, were raised for three months and randomly divided into 15 flocks (each flock containing seven females and one male duck). There were three kinds of treatment, namely P0 (control, without mineral), P1 (ratio of Shrimp head meal and Bilis fish head 2:1 + 1% mineral), and P2 ((ratio of Shrimp head meal and Bilis fish head 1:2 + 1% mineral). The findings revealed that adding mineral Ca to feed, including Shrimp head meal and Bilis fish head, had no significant influence (P>0.05) on laying Mojosari duck performance in terms of feed intake, egg production, egg weight, egg quality, ducklings produced, and income over feed cost (IOFC). Furthermore, Ca addition in the ration did not result in substantial increases (P>0.05) in fertility, hatchability, or egg size characteristics. Based on the findings of this study, feeding ducks with shrimp head meal and Bilis fish head can be used as an alternate calcium-free feed formulation.
Asunto(s)
Alimentación Animal , Calcio , Patos , Animales , Patos/fisiología , Femenino , Alimentación Animal/análisis , Masculino , Calcio/análisis , Oviposición/efectos de los fármacos , Oviposición/fisiología , Óvulo/efectos de los fármacos , Óvulo/fisiología , Distribución AleatoriaRESUMEN
The papaya (Carica papaya L.) is among the mainly fruit species produced in tropical and subtropical climate. The salinity of water in agricultural areas is considered a limiting factor for the expansion of papaya. This study aimed to evaluate calcium-enriched microalgae extract (EMa-Ca) as an attenuator of saline stress in irrigation water on the growth and physiology of Formosa papaya seedlings, hybrid Tainung. The experiment was conducted in a protected environment, with treatments distributed in a 5 × 2 factorial scheme, comprising five electrical conductivities of irrigation water (0.50; 1.10; 2.50; 3.90 and 4.50 dSm-1) with the presence and absence of EMa-Ca in the substrate. Evaluated characteristics were: plant height, number of leaves, stem diameter, leaf area, dry masses weight of roots, aboveground parts and total. Gas exchanges and chlorophyll indices (a, b and total) were also evaluated. The application of EMa-Ca resulted in an increase of 6.05% in height and 6.33% in trunk diameter. The number of leaves decreased with an increase in electrical conductivity, and the leaf area was reduced by 33%. All seedling dry masses showed greater declines in the absence of EM-Ca. The EMa-Ca increased net photosynthesis, CO2 concentration, transpiration and stomatal conductance by 39.13%, 30.43%, 38.88% and 42.85%, respectively. For chlorophyll without the use of EMa-Ca, a decrease rate of 1.21%, 0.41% and 1.62% was observed for Chla, Chlb and Chlt, respectively. Therefore, the EMa-Ca application (1.0 ml/L) significantly enhance the vegetative development, gas exchanges, and chlorophyll indices of papaya seedlings under saline stress conditions.
Asunto(s)
Calcio , Carica , Microalgas , Plantones , Carica/química , Carica/efectos de los fármacos , Plantones/efectos de los fármacos , Calcio/análisis , Microalgas/efectos de los fármacos , Microalgas/fisiología , Clorofila/análisis , Estrés Salino/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , SalinidadRESUMEN
Background: Calcium intake is below recommendations in several parts of the world. Improving calcium intake has benefits not only for bone health but also helps to prevent pregnancy hypertension disorders. Calcium concentration of tap water is usually low The aim of the present study was to determine the maximum amount of calcium that can be added to tap water while complying with drinking water Argentine regulations. Methods: Tap water samples were collected from the Province of Buenos Aires (Argentina). Physicochemical properties and saturation index were measured. Different incremental concentrations of calcium chloride were added to the experimental aliquots. Results: Baseline water had a mean calcium concentration of 22.00 ± 2.54 mg/L, water hardness of 89.9 ± 6.4 mg/L CaCO 3, and a saturation index of -1.50 ± 0.11. After the addition of 0.4554 ± 0.0071 g of salt, water hard-ness reached 355.0 ± 7.1 mg/L CaCO 3, a calcium concentration of 140.50 ± 2.12 mg/L, and a saturation index -0.53 ± 0.02. Conclusions: This study shows that at laboratory level it is feasible to increase calcium concentration of drinking water by adding calcium chloride while complying with national standards. Calcium concentration of drinking tap water could be evaluated and minimum calcium concentration of tap water regulated so as to improve calcium intake in populations with low calcium intake.
Asunto(s)
Calcio , Agua Potable , Agua Potable/química , Agua Potable/normas , Humanos , Argentina , Calcio/análisis , Estudios de Factibilidad , Calcio de la Dieta/análisis , Calidad del Agua/normas , Abastecimiento de Agua/normas , FemeninoRESUMEN
Familial Alzheimer's disease (FAD) is a chronic neurological condition that progresses over time. Currently, lacking a viable treatment, the use of multitarget medication combinations has generated interest as a potential FAD therapy approach. In this study, we examined the effects of 4-phenylbutyric acid (4-PBA) and methylene blue (MB) either separately or in combination on PSEN1 I416T cholinergic-like neuron cells (ChLNs), which serve as a model for FAD. We found that MB was significantly efficient at reducing the accumulation of intracellular Aß, phosphorylation of TAU Ser202/Thr205, and increasing Δψm, whereas 4-PBA was significantly efficient at diminishing oxidation of DJ-1Cys106-SH, expression of TP53, and increasing ACh-induced Ca2+ influx. Both agents were equally effective at blunting phosphorylated c-JUN at Ser63/Ser73 and activating caspase 3 (CASP3) into cleaved caspase 3 (CC3) on mutant cells. Combination of MB and 4-PBA at middle (0.1, 1) concentration significantly reduced iAß, p-TAU, and oxDJ-1 and augmented the ACh-induced Ca2+ influx compared to combined agents at low (0.05, 0.5) or high (0.5, 5) concentration. However, combined MB and 4-PBA were efficient only at dropping DJ-1Cys106-SO3 and increasing ACh-induced Ca2+ inward in mutant ChLNs. Our data show that the reagents MB and 4-PBA alone possess more than one action (e.g., antiamyloid, antioxidant, anti-TAU, antiapoptotic, and ACh-induced Ca2+ influx enhancers), that in combination might cancel or diminish each other. Together, these results strongly argue that MB and 4-PBA might protect PSEN1 I416T ChLNs from Aß-induced toxicity by working intracellularly as anti-Aß and anti-Tau agents, improving Δψm and cell survival, and extracellularly, by increasing ACh-induced Ca2+ ion influx. MB and 4-PBA are promising drugs with potential for repurposing in familial AD.
Asunto(s)
Enfermedad de Alzheimer , Antioxidantes , Apoptosis , Azul de Metileno , Fenilbutiratos , Presenilina-1 , Presenilina-1/genética , Presenilina-1/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Azul de Metileno/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Humanos , Fenilbutiratos/farmacología , Proteínas tau/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Péptidos beta-Amiloides/metabolismo , Calcio/metabolismo , Animales , Fosforilación/efectos de los fármacosRESUMEN
Trypanosoma evansi is a unicellular protozoan responsible for causing a disease known as "surra," which is found in different regions of the world and primarily affects horses and camels. Few information is known about virulence factors released from the parasite within the animals. The organism can secrete extracellular vesicles (EVs), which transport a variety of molecules, including proteins. Before being considered exclusively as a means for eliminating unwanted substances, extracellular vesicles (EVs) have emerged as key players in intercellular communication, facilitating interactions between cells, host cells, and parasites, and even between parasites themselves. Thus, they may be used as potential biomarkers. This study aimed to assess the induction of EVs production by Ca+2, conduct a proteomic analysis of the EVs released by T. evansi, and identify epitopes that could serve as biomarkers. The findings indicated that Ca+2 is not an effective promoter of vesiculation in T. evansi. Furthermore, the proteomic analysis has identified multiple proteins that have been investigated as biomarkers or vaccine antigens, previously. A total of 442 proteins were identified, with 7 of them specifically recognizing 9 epitopes that are unique to T. evansi. At least one of these epitopes of TevSTIB805.9.11580 have been previously identified, which increases the possibility of further investigating its potential as a biomarker.
Asunto(s)
Vesículas Extracelulares , Proteómica , Proteínas Protozoarias , Trypanosoma , Trypanosoma/metabolismo , Trypanosoma/genética , Vesículas Extracelulares/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Animales , Calcio/metabolismo , Biomarcadores , Tripanosomiasis/parasitología , Proteoma , Epítopos/inmunologíaRESUMEN
TRPM4 is a non-selective cation channel activated by intracellular Ca2+ but only permeable to monovalent cations, its activation regulates membrane potential and intracellular calcium. This channel participates in the migration and adhesion of non-excitable cells and forms an integral part of the focal adhesion complex. In neurons, TRPM4 expression starts before birth and its function at this stage is not clear, but it may function in processes such as neurite development. Here we investigate the role of TRPM4 in neuritogenesis. We found that neurons at DIV 0 express TRPM4, the inhibition of TRPM4 using 9-Ph reduces neurite number and slows the progression of neurite development, keeping neurons in stage 1. The genetic suppression of TRPM4 using an shRNA at later stages (DIV2) reduces neurite length. Conversely, at DIV 0, TRPM4 inhibition augments the Cch-induced Ca2 + i increase, altering the calcium homeostasis. Together, these results show that TRPM4 participates in progression of neurite development and suggest a critical role of the calcium modulation during this stage of neuronal development.
Asunto(s)
Calcio , Corteza Cerebral , Neuritas , Neurogénesis , Canales Catiónicos TRPM , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/antagonistas & inhibidores , Animales , Neuritas/metabolismo , Neuritas/efectos de los fármacos , Calcio/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Neuronas/metabolismoRESUMEN
OBJECTIVE: In the context of postoperative anal pain, understanding the intricate mechanisms and effective interventions is paramount. This study investigates the role of Muscarinic Acetylcholine Receptors (mAChRs) and the IP3-Ca2+-CaM signaling pathway in a rat model of postoperative anal pain, exploring the potential analgesic effects of electroacupuncture. METHODS: Comprehensive approaches involving mechanical sensitivity assays, Western blotting, immunohistochemistry, and intracellular calcium concentration measurement were used. RESULTS: The authors found elevated mAChRs expression in the postoperative pain model. Antagonizing mAChRs reduced pain sensitivity and attenuated the IP3-Ca2+-CaM pathway. Remarkably, electroacupuncture treatment further mitigated pain, potentially by suppressing this signaling cascade. INTERPRETATION: These findings reveal a novel connection between mAChRs and the IP3-Ca2+-CaM pathway in postoperative anal pain and suggest electroacupuncture as a promising avenue for pain relief through these mechanisms, offering insights into innovative strategies for postoperative pain management.
Asunto(s)
Electroacupuntura , Hemorreoidectomía , Dolor Postoperatorio , Ratas Sprague-Dawley , Receptores Muscarínicos , Transducción de Señal , Animales , Electroacupuntura/métodos , Dolor Postoperatorio/terapia , Masculino , Hemorreoidectomía/métodos , Receptores Muscarínicos/metabolismo , Puntos de Acupuntura , Canal Anal/cirugía , Modelos Animales de Enfermedad , Western Blotting , Ratas , Inmunohistoquímica , Calcio/metabolismo , Resultado del TratamientoRESUMEN
Background and Objective. This study addresses the Force-Frequency relationship, a fundamental characteristic of cardiac muscle influenced byß1-adrenergic stimulation. This relationship reveals that heart rate (HR) changes at the sinoatrial node lead to alterations in ventricular cell contractility, increasing the force and decreasing relaxation time for higher beat rates. Traditional models lacking this relationship offer an incomplete physiological depiction, impacting the interpretation of in silico experiment results. To improve this, we propose a new mathematical model for ventricular myocytes, named 'Feed Forward Modeling' (FFM).Methods. FFM adjusts model parameters like channel conductance and Ca2+pump affinity according to stimulation frequency, in contrast to fixed parameter values. An empirical sigmoid curve guided the adaptation of each parameter, integrated into a rabbit ventricular cell electromechanical model. Model validation was achieved by comparing simulated data with experimental current-voltage (I-V) curves for L-type Calcium and slow Potassium currents.Results. FFM-enhanced simulations align more closely with physiological behaviors, accurately reflecting inotropic and lusitropic responses. For instance, action potential duration at 90% repolarization (APD90) decreased from 206 ms at 1 Hz to 173 ms at 4 Hz using FFM, contrary to the conventional model, where APD90 increased, limiting high-frequency heartbeats. Peak force also showed an increase with FFM, from 8.5 mN mm-2at 1 Hz to 11.9 mN mm-2at 4 Hz, while it barely changed without FFM. Relaxation time at 50% of maximum force (t50) similarly improved, dropping from 114 ms at 1 Hz to 75.9 ms at 4 Hz with FFM, a change not observed without the model.Conclusion. The FFM approach offers computational efficiency, bypassing the need to model all beta-adrenergic pathways, thus facilitating large-scale simulations. The study recommends that frequency change experiments include fractional dosing of isoproterenol to better replicate heart conditionsin vivo.
Asunto(s)
Potenciales de Acción , Simulación por Computador , Ventrículos Cardíacos , Contracción Miocárdica , Miocitos Cardíacos , Conejos , Animales , Miocitos Cardíacos/fisiología , Contracción Miocárdica/fisiología , Modelos Cardiovasculares , Frecuencia Cardíaca/fisiología , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Nodo Sinoatrial/fisiología , Modelos TeóricosRESUMEN
Neurotransmission is critical for brain function, allowing neurons to communicate through neurotransmitters and neuropeptides. RVD-hemopressin (RVD-Hp), a novel peptide identified in noradrenergic neurons, modulates cannabinoid receptors CB1 and CB2. Unlike hemopressin (Hp), which induces anxiogenic behaviors via transient receptor potential vanilloid 1 (TRPV1) activation, RVD-Hp counteracts these effects, suggesting that it may block TRPV1. This study investigates RVD-Hp's role as a TRPV1 channel blocker using HEK293 cells expressing TRPV1-GFP. Calcium imaging and patch-clamp recordings demonstrated that RVD-Hp reduces TRPV1-mediated calcium influx and TRPV1 ion currents. Molecular docking and dynamics simulations indicated that RVD-Hp interacts with TRPV1's selectivity filter, forming stable hydrogen bonds and van der Waals contacts, thus preventing ion permeation. These findings highlight RVD-Hp's potential as a therapeutic agent for conditions involving TRPV1 activation, such as pain and anxiety.
Asunto(s)
Endocannabinoides , Canales Catiónicos TRPV , Humanos , Calcio/metabolismo , Endocannabinoides/farmacología , Endocannabinoides/metabolismo , Endocannabinoides/química , Células HEK293 , Hemoglobinas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/metabolismo , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/antagonistas & inhibidoresRESUMEN
Pelgipeptins, tridecaptins, and elgicins are among the antimicrobials produced by Paenibacillus elgii. Growth in complex media is commonly applied to obtain lipopeptides from culture's supernatant, but it requires further purification. This study aimed to improve the yield of pelgipeptins and tridecaptins using chemically defined media. The kinetics of antimicrobial lipopeptide yield in chemically defined media were evaluated in P. elgii AC13. Pelgipeptins were detected in the supernatant and the culture pellet, but tridecaptins were mainly associated with cell debris or endospores. We investigated whether removing Ca2+ would impair P. elgii sporogenesis, consequently improving the yield of tridecaptin. The kinetics of both lipopeptides in the presence and absence of Ca2+ were quantitatively and qualitatively evaluated and further correlated with the cell cycle. The impairment of P. elgii AC13 sporogenesis had no effect on tridecaptin production, which remained undetected in the supernatant of the culture. On the other hand, the yield of pelgipeptin in a Ca2+-free medium increased. We showed for the first time that the removal of Ca2+ interrupted the sporogenesis in P. elgii and improved the yield of pelgipeptins. However, Ca2+ absence had no effect on tridecaptin yield, which is possibly degraded or associated with other cell debris components.
Asunto(s)
Medios de Cultivo , Lipopéptidos , Paenibacillus , Paenibacillus/metabolismo , Paenibacillus/crecimiento & desarrollo , Lipopéptidos/biosíntesis , Lipopéptidos/metabolismo , Medios de Cultivo/química , Calcio/metabolismo , Esporas Bacterianas/crecimiento & desarrollo , Antibacterianos/biosíntesis , Antibacterianos/farmacologíaRESUMEN
Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.
Asunto(s)
Astrocitos , Cuerpo Estriado , Animales , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/efectos de los fármacos , Femenino , Embarazo , Ratas , Ácido Valproico/farmacología , Ratas Wistar , Picrotoxina/farmacología , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Modelos Animales de Enfermedad , Masculino , Calcio/metabolismo , Trastorno del Espectro Autista/metabolismo , Trastorno Autístico/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismoRESUMEN
High-intensity interval training (HIIT) has shown significant results in addressing adiposity and risk factors associated with obesity. However, there are no studies that investigate the effects of HIIT on contractility and intracellular Ca2+ handling. The purpose of this study was to explore the impact of HIIT on cardiomyocyte contractile function and intracellular Ca2+ handling in rats in which obesity was induced by a saturated high-fat diet (HFD). Male Wistar rats were initially randomized into a standard diet and a HFD group. The experimental protocol spanned 23 weeks, comprising the induction and maintenance of obesity (15 weeks) followed by HIIT treatment (8 weeks). Performance was assessed using the maximum oxygen consumption test ( V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ ). Evaluation encompassed cardiac, adipose and skeletal muscle histology, as well as contractility and intracellular Ca2+ handling. HIIT resulted in a reduction in visceral area, an increase in V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ , and an augmentation of gastrocnemius fibre diameter in obese subjects. Additionally, HIIT led to a decrease in collagen fraction, an increase in percentage shortening, and a reduction in systolic Ca2+/percentage shortening and systolic Ca2+/maximum shortening rates. HIIT induces physiological cardiac remodelling, enhancing the contractile function of cardiomyocytes and improving myofilament sensitivity to Ca2+ in the context of obesity. This approach not only enhances cardiorespiratory and physical performance but also reduces visceral area and prevents interstitial fibrosis.
Asunto(s)
Calcio , Entrenamiento de Intervalos de Alta Intensidad , Contracción Miocárdica , Miocitos Cardíacos , Miofibrillas , Obesidad , Condicionamiento Físico Animal , Ratas Wistar , Animales , Masculino , Obesidad/fisiopatología , Obesidad/metabolismo , Obesidad/terapia , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Calcio/metabolismo , Condicionamiento Físico Animal/fisiología , Ratas , Entrenamiento de Intervalos de Alta Intensidad/métodos , Contracción Miocárdica/fisiología , Miofibrillas/metabolismo , Dieta Alta en Grasa , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Consumo de Oxígeno/fisiologíaRESUMEN
This study describes the association of non-esterified fatty acids (NEFA) and calcium concentrations at calving with early lactation disease, reproductive performance and culling in 646 dairy cows from 13 commercial grazing dairy herds in Uruguay. During one year, health events were recorded from calving to 30 days in milk (DIM). The first author visited each farm every 20 days. During each visit, body condition score (BCS) was recorded (scale 1-5), defining BCS < 3 as suboptimal and BCS > 3 as optimal, and a blood sample was taken from cows between 0 and 4 DIM for metabolite determination. To evaluate the association between health events (i.e., retained placenta-metritis and clinical mastitis) and risk factors (parity, BCS, high NEFA (> 0.6â¯mmol/L) and subclinical hypocalcemia (SCH) (< 2.10â¯mM)) data were analysed using multivariable logistic regression models. To evaluate the association of health events and risk factors with reproductive performance and culling, data were analysed using Cox proportional hazard regression models. A risk factor and an outcome of interest were assumed to be associated at P < 0.05 and a tendency to be associated was defined at P < 0.10. Overall, 47â¯% (n = 303) of the cows showed elevated NEFA concentration and 77â¯% (n = 499) had SCH. In addition, 21.5â¯% (n = 139) of the cows recorded at least one clinical disease. Cumulative incidence was 17â¯% (n = 109) for clinical mastitis, 4.2â¯% (n = 27) for retained placenta (RP)-metritis and 1.4â¯% (n = 7) for lameness. Clinical mastitis was associated with parity, with lower odds in primiparous (PP) cows (OR = 0.42, P < 0.01). Cows in an optimal BCS also tended to have lower odds (OR = 0.66, P = 0.07). Moreover, high NEFA and SCH cows had higher odds of CM (OR = 4.5, P = 0.01 and OR = 1.75, P = 0.04, respectively). Retained placenta-metritis tended to be associated with high NEFA concentration (OR = 2.2, P = 0.06). Primiparous cows with suboptimal BCS showed an increased first insemination rate (HR = 2.34; P < 0.01). The risk of culling was lower in PP cows (HR = 0.19; P < 0.01) and in cows with optimal BCS and low NEFA concentration (HR = 0.38; P = 0.03). Our data show that metabolic challenge (defined as peripartum suboptimal BCS, high NEFA or SCH) is associated with increased odds of clinical mastitis and RP-metritis, decreased probability of insemination and increased hazard of culling. Under grazing conditions, we suggest that farm management to improve the metabolic adaptation to lactation represents an opportunity to enhance cow performance in terms of health, fertility and longevity.
Asunto(s)
Calcio , Enfermedades de los Bovinos , Ácidos Grasos no Esterificados , Lactancia , Animales , Bovinos/fisiología , Femenino , Ácidos Grasos no Esterificados/sangre , Lactancia/fisiología , Uruguay/epidemiología , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/sangre , Calcio/sangre , Embarazo , Factores de Riesgo , Fertilidad/fisiología , Mastitis Bovina/epidemiología , Industria Lechera , Hipocalcemia/veterinaria , Hipocalcemia/epidemiología , Endometritis/veterinaria , Endometritis/epidemiología , Retención de la Placenta/veterinaria , Retención de la Placenta/epidemiología , Retención de la Placenta/sangreRESUMEN
The mitochondrial permeability transition (MPT) pore regulates necrotic cell death following diverse cardiac insults. While the componentry of the pore itself remains controversial, Cyclophilin D (CypD) has been well-established as a positive regulator of pore opening. We have previously identified Complement 1q-binding protein (C1qbp) as a novel CypD-interacting molecule and a negative regulator of MPT-dependent cell death in vitro. However, its effects on the MPT pore and sensitivity to cell death in the heart remain untested. We therefore hypothesized that C1qbp would inhibit MPT in cardiac mitochondria and protect cardiac myocytes against cell death in vivo. To investigate the effects of C1qbp in the myocardium we generated gain- and loss-of-function mice. Transgenic C1qbp overexpression resulted in decreased complex protein expression and reduced mitochondrial respiration and ATP production but MPT was unaffected. In contrast, while C1qbp+/- mice did not exhibit any changes in mitochondrial protein expression, respiration, or ATP, the MPT pore was markedly sensitized to Ca2+ in these animals. Neither overexpression nor depletion of C1qbp significantly affected baseline heart morphology or function at 3 months of age. When subjected to myocardial infarction, C1qbp transgenic mice exhibited similar infarct sizes and cardiac remodeling to non-transgenic mice, consistent with the lack of an effect on MPT. In contrast, cardiac scar formation and dysfunction were significantly increased in the C1qbp+/- mice compared to C1qbp+/+ controls. Our results suggest that C1qbp is required for normal regulation of the MPT pore and mitochondrial function, and influences cardiac remodeling following MI, the latter more likely being independent of C1qbp effects on the MPT pore.
Asunto(s)
Ratones Transgénicos , Poro de Transición de la Permeabilidad Mitocondrial , Infarto del Miocardio , Miocitos Cardíacos , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Poro de Transición de la Permeabilidad Mitocondrial/metabolismo , Ratones , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Remodelación Ventricular , Mitocondrias Cardíacas/metabolismo , Calcio/metabolismo , Peptidil-Prolil Isomerasa F/metabolismo , Peptidil-Prolil Isomerasa F/genética , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/genética , Necrosis por Permeabilidad de la Transmembrana Mitocondrial , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Adenosina Trifosfato/metabolismo , Proteínas MitocondrialesRESUMEN
Complement mediated interference with the detection of antibodies targeting HLA is a known limitation of the single antigen bead (SAB) Luminex assay. Ethylenediaminetetraacetic acid (EDTA) is currently the serum treatment of choice in most histocompatibility laboratories to block complement activation by chelating calcium. The purpose of this study was to investigate a serum with an antibody reactivity to HLA-DQ6, 7, 8 and 9 molecules, in the Luminex SAB assay, that was inhibited by treatment with EDTA. Serum was from a 55-year-old highly sensitised female renal transplant candidate that contained, among others, antibodies to an epitope containing the 74EL eplet, shared by HLA-DQ6, DQ7, DQ8 and DQ9 molecules. Serum samples were treated with EDTA, dithiothreitol (DTT), or heat prior to testing by SAB assay. EDTA-treated serum was also tested after the addition of calcium chloride (CaCl2). HLA-DQ-specific antibodies were isolated by adsorption/elution method using three informative donor cells and were tested in the absence or presence of EDTA. The antibody reactivity against HLA-DQ6, DQ7, DQ8 and DQ9 in the SAB assay was significantly inhibited by treating serum and eluates with EDTA and was restored by addition of CaCl2. The study represents the first description of a calcium-dependent epitope in HLA molecules. The relevance of this finding is that the treatment of sera with EDTA could lead to false-negative reactions in the SAB assay, which may compromise virtual crossmatching.
Asunto(s)
Calcio , Ácido Edético , Epítopos , Antígenos HLA-DQ , Prueba de Histocompatibilidad , Humanos , Ácido Edético/farmacología , Ácido Edético/química , Epítopos/inmunología , Femenino , Prueba de Histocompatibilidad/métodos , Antígenos HLA-DQ/inmunología , Persona de Mediana Edad , Isoanticuerpos/inmunología , Isoanticuerpos/sangre , Trasplante de RiñónRESUMEN
The aim of this study was to explore maternity care providers' knowledge, attitudes, and perceptions about the use of calcium supplements during pregnancy for the prevention of preeclampsia in three hospitals from Metropolitan Buenos Aires, Argentina. We conducted semi-structured interviews and followed a thematic analysis framework. Maternity care providers' knowledge, attitudes, and practices regarding calcium supplementation during pregnancy are linked to barriers to the potential implementation of calcium supplementation. Free provision of calcium supplements by the government, coupled with training that reinforces the scientific evidence supporting their use to prevent preeclampsia, along with documented recommendations from credible sources, would be crucial to ensure that health providers adopt the use of calcium supplements in antenatal care. Future studies should assess pregnant women and policymakers' perceptions about calcium supplementation during pregnancy, as well as local infrastructure to provide access to free-of-charge calcium supplements in antenatal care settings. Economic evaluation with local information could inform policymakers and advocate for the implementation of strategies to reduce preeclampsia.
Asunto(s)
Suplementos Dietéticos , Conocimientos, Actitudes y Práctica en Salud , Hospitales Públicos , Preeclampsia , Atención Prenatal , Investigación Cualitativa , Humanos , Embarazo , Femenino , Argentina , Atención Prenatal/métodos , Preeclampsia/prevención & control , Adulto , Actitud del Personal de Salud , Personal de Salud/psicología , Calcio de la Dieta/administración & dosificación , Calcio/administración & dosificación , MasculinoRESUMEN
Accurately predicting phosphorous (P) and calcium (Ca) dietary requirements is critical for optimizing dairy cattle performance, and minimizing mineral excretions and ecosystems eutrophication. This study provides a new factorial system to determine net and dietary P and Ca requirements for maintenance and lactation, derived from a meta-regression of mineral trials involving lactating dairy cows. A comprehensive global database was constructed from 57 peer-reviewed articles of mineral balance trials, with a wide range of dietary and animal performance data. We estimated the net requirements for maintenance from the intercept of a nonlinear equation between mineral intake and the sum of total fecal and urinary excretions, which is an estimate of endogenous mineral loss. Mineral secreted in milk was used to obtain net requirements for lactation. The mineral metabolizable coefficient was quantified through observed (treatment means) mineral intake and total fecal and urinary excretions, discounting the estimated endogenous excretions from our proposed models. The nonlinear models of total fecal and urinary mineral excretion were evaluated (observed versus predicted values) using a 5-fold cross validation approach. The models to estimate the sum of endogenous fecal and urinary excretions of P (0.135±0.043 g P/kg BW0.75) and Ca (0.360±0.144 g Ca/kg BW0.75) exhibited suitable precision and accuracy; r = 0.89 and 0.79, concordance correlation coefficient = 0.85 and 0.77, and root mean square prediction error = 24.1 and 20.5% observed means, respectively. Dietary variables (forage level, fiber, starch, crude protein, and ether extract) did not affect the metabolizable coefficient (MC) of P and Ca; therefore, an overall dietary MC of P (0.69±0.01) and Ca (0.65±0.02) were proposed. Our new system estimates lower net and dietary P requirements for lactating dairy cows compared to the NASEM-2021 and NRC-2001 models, but slightly higher Ca requirements than NASEM-2021.This proposed system holds potential to reduce the use of phosphorus in diets for dairy cows, and thus to enhance economic efficiency and environmental sustainability of the dairy industry.
Asunto(s)
Calcio , Lactancia , Fósforo , Animales , Bovinos , Femenino , Fósforo/metabolismo , Fósforo/orina , Calcio/orina , Calcio/metabolismo , Calcio/análisis , Heces/química , Calcio de la Dieta/metabolismo , Calcio de la Dieta/análisis , Alimentación Animal/análisis , Industria Lechera , Leche/metabolismo , Leche/química , Fenómenos Fisiológicos Nutricionales de los Animales , Fósforo Dietético/metabolismo , Fósforo Dietético/orina , Necesidades Nutricionales , Dieta/veterinariaRESUMEN
The α9α10 nicotinic cholinergic receptor (nAChR) is a ligand-gated pentameric cation-permeable ion channel that mediates synaptic transmission between descending efferent neurons and mechanosensory inner ear hair cells. When expressed in heterologous systems, α9 and α10 subunits can assemble into functional homomeric α9 and heteromeric α9α10 receptors. One of the differential properties between these nAChRs is the modulation of their ACh-evoked responses by extracellular calcium (Ca2+). While α9 nAChRs responses are blocked by Ca2+, ACh-evoked currents through α9α10 nAChRs are potentiated by Ca2+ in the micromolar range and blocked at millimolar concentrations. Using chimeric and mutant subunits, together with electrophysiological recordings under two-electrode voltage-clamp, we show that the TM2-TM3 loop of the rat α10 subunit contains key structural determinants responsible for the potentiation of the α9α10 nAChR by extracellular Ca2+. Moreover, molecular dynamics simulations reveal that the TM2-TM3 loop of α10 does not contribute to the Ca2+ potentiation phenotype through the formation of novel Ca2+ binding sites not present in the α9 receptor. These results suggest that the TM2-TM3 loop of α10 might act as a control element that facilitates the intramolecular rearrangements that follow ACh-evoked α9α10 nAChRs gating in response to local and transient changes of extracellular Ca2+ concentration. This finding might pave the way for the future rational design of drugs that target α9α10 nAChRs as otoprotectants.