Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Control metabólico de pacientes diabéticos tipo 2 tratados con empagliflozina: serie de casos / Metabolic control in type 2 diabetic patients treated with empagliflozin: A case series

Introducción La diabetes mellitus tipo 2 es una enfermedad de alta prevalencia y está asociada a mayor morbimortalidad. Debido al bajo porcentaje de compensación, se han buscado nuevas estrategias de tratamiento farmacológico, como los inhibidores del cotransportador sodio-glucosa tipo 2. Objetivo Describir la evolución de pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor, ubicado en el sector poniente de la Región Metropolitana, Chile. El objetivo primario fue evaluar la eficacia del medicamento respecto a hemoglobina glicosilada A1c. Los objetivos secundarios fueron registrar el logro de hemoglobina glicosilada A1c igual o menor a 7,5% según análisis de supervivencia. Luego, consignar el cambio en la velocidad de filtración glomerular y en la excreción urinaria de albúmina post tratamiento. Métodos Revisión de ficha clínica de todos los pacientes tratados con empagliflozina desde noviembre de 2019 a junio de 2023. Media de seguimiento de 19 (de 16,3 a 40) meses. Para comparación entre valores de hemoglobina glicosilada A1c según rangos de seguimiento, se utilizó prueba T de Student de términos pareados o prueba de Wilcoxon. Resultados Se estudió a 58 pacientes, 15 hombres y 43 mujeres (74,1%). Edad 58,5 ± 9,2 años, rango de 35 a 75 años. Hemoglobina glicosilada A1c basal de 10,3 ± 1,6% y 8,98% ± 2,2 en un rango de seguimiento de 18 a 24 meses post tratamiento, resultando en un descenso de 1,27% (p = 0,002; intervalo de confianza 95%: 0,5 a 2,03). El efecto adverso más frecuente fue infección del tracto urinario. Conclusiones Los pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor lograron un mejor control glicémico con pocos efectos adversos.

Background Type 2 diabetes mellitus is a highly prevalent disease and is associated with increased morbidity and mortality. Due to the low percentage of adequate glycemic control, new strategies for the treatment of type 2 diabetes mellitus have been sought, including sodium-glucose cotransporter type 2 inhibitorss. Objective To describe the evolution of patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital. The primary objective was to evaluate the efficacy of the medication regarding glycosylated hemoglobin A1c (HbA1c). The secondary objectives were: 1) achievement of HbA1c equal to or less than 7.5% according to survival analysis. 2) Change in glomerular filtration rate and urinary albumin excretion post treatment. Methods Review of clinical records of all patients treated with empagliflozin from November 2019 to June 2023. Average follow-up of 19 (16.3 to 40) months. To compare HbA1c values according to follow-up ranges, the paired T test or Wilcoxon test was used. Results We included 58 patients, 15 men and 43 women (74.1%), with an average age of 58.5 ± 9.2 years, ranging from 35 to 75 years. Baseline HbA1c of 10.3 ± 1.6% and 8.98% ± 2.2 in a follow-up of 18 to 24 months post-treatment, resulted in a decrease of 1.27% (p = 0.002; confidence interval 95%: 0.5 to 2.03). The most common adverse effect was urinary tract infection. Conclusions Patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital achieved better glycemic control with few adverse effects.

Sodium intake according to NOVA food classification in Brazil: trends from 2002 to 2018 / Ingestão de sódio segundo a classificação NOVA no Brasil: tendências de 2002 a 2018 / Ingesta de sodio según la clasificación NOVA en Brasil: tendencias del 2002 al 2018

Abstract: Excessive sodium intake is a major global public health issue and the identification of dietary sources and temporal trends in its consumption are a key to effective sodium reduction policies. This study aims to update estimates of sodium intake and its dietary sources in Brazil according to the NOVA food classification system. Records of 7-day food purchases of households from the Brazilian Household Budgets Survey of 2002-2003, 2008-2009, and 2017-2018 were converted into nutrients using food composition tables and the mean availability was estimated per 2,000kcal/day. Mean daily sodium available for consumption in Brazilian households has increased from 3.9 to 4.7g per 2,000kcal, from 2002-2003 to 2017-2018, over twice the recommended levels of sodium intake. From 2002-2003 to 2017-2018, the processed culinary ingredients, including table salt, represented the largest dietary source of sodium, although their participation in dietary sodium was reduced by 17% (66.6% to 55%), while the percentage of dietary sodium from processed foods increased by 20.3% and from ultra-processed foods increased by 47.6% (11.3% to 13.6% and 17% to 25.1%, respectively). In conclusion, the total household sodium availability remains high and has increased over time in Brazil, yet the participation of different dietary sources of sodium have gradually changed.

Resumo: A ingestão excessiva de sódio é um dos principais problemas de saúde pública em todo o mundo e a identificação de fontes alimentares e tendências temporais no seu consumo são fundamentais para a elaboração de políticas eficazes de redução de sódio. Este estudo tem como objetivo atualizar as estimativas de ingestão de sódio e suas fontes alimentares no Brasil de acordo com o sistema de classificação NOVA. Os registros de compras de alimentos no período de 7 dias de famílias das Pesquisas de Orçamentos Familiares de 2002-2003, 2008-2009 e 2017-2018 foram convertidos em nutrientes utilizando tabelas de composição de alimentos. A disponibilidade média foi estimada em 2.000kcal/dia. A média diária de sódio disponível para consumo nos domicílios brasileiros aumentou de 3,9 para 4,7g por 2.000kcal, de 2002-2003 a 2017-2018, mais do que o dobro dos níveis recomendados de ingestão desse nutriente. De 2002-2003 a 2017-2018, os ingredientes culinários processados, incluindo o sal de cozinha, representaram a maior fonte de sódio, embora a sua participação no sódio dietético tenha sido reduzida em 17% (de 66,6% para 55%), enquanto a porcentagem de sódio dietético dos alimentos processados aumentou 20,3% e dos alimentos ultraprocessados aumentou 47,6% (11,3% para 13,6% e 17% para 25,1%, respectivamente). Concluindo, a disponibilidade total de sódio nos domicílios permanece alta e tem aumentado ao longo do tempo no Brasil, mas a participação de diferentes fontes dietéticas de sódio mudou gradualmente.

Resumen: La ingesta excesiva de sodio es uno de los principales problemas de salud pública en todo el mundo, y la identificación de las fuentes alimentarias y tendencias temporales en su consumo son esenciales para desarrollar políticas efectivas de reducción de sodio. Este estudio tiene como objetivo actualizar las estimaciones de la ingesta de sodio y sus fuentes alimentarias en Brasil según el sistema de clasificación NOVA. Los registros de compras de alimentos en el período de 7 días de familias de las Encuestas de Presupuestos Familiares de Brasil de 2002-2003, 2008-2009 y 2017-2018 se convirtieron en nutrientes utilizando tablas de composición de alimentos. La disponibilidad media se estimó en 2.000kcal/día. El promedio diario de sodio disponible para el consumo en los hogares brasileños aumentó de 3,9 a 4,7g por 2.000kcal, entre 2002-2003 y 2017-2018, más del doble de los niveles de ingesta recomendados de este nutriente. Entre 2002-2003 y 2017-2018, los ingredientes culinarios procesados, incluida la sal de mesa, representaron la mayor fuente de sodio, aunque su participación en el sodio dietético se redujo en un 17% (del 66,6% al 55%), mientras que el porcentaje de sodio dietético de los alimentos procesados aumentó un 20,3% y de los alimentos ultraprocesados aumentó un 47,6% (11,3% a 13,6% y 17% a 25,1%, respectivamente). En conclusión, la disponibilidad total de sodio en los hogares sigue siendo alta y ha aumentado a lo largo del tiempo en Brasil, pero la proporción de diferentes fuentes dietéticas de sodio ha cambiado gradualmente.

Effect of sodium hypochlorite and calcium hypochlorite on the apical sealing ability of endodontic sealers

Aim: This study aimed to compare the influence of sodium hypochlorite (NaOCl) and calcium hypochlorite [Ca(OCl)2 ] on the apical sealing capacity of AH Plus (Dentsply Maillefer) and Bio-C Sealer (Angelus) endodontic sealers. Methods: Sixty permanent human lower incisors were randomly allocated (http://www.randomized.org), according to the irrigant used, into three groups (n=20): 0.9% sodium chloride (NaCl/Control); 2.5% NaOCl; and 2.5% Ca(OCl)2 . The root canal was prepared with rotary files under 10 mL of the solution corresponding to the experimental group. Each group was subdivided into two (n=10) according to the sealer used for filling: AH Plus (Dentsply Maillefer) or Bio-C Sealer (Angelus). Then, all samples were immersed in black India ink for one week. After the storage period, the roots were then grooved longitudinally and split, and the ink penetration was measured from the apical part to the coronal part of the root canal into which the ink penetrated using a stereomicroscope. Data were analyzed by one-way ANOVA and Tukey's post-hoc tests. Results: There was no statistical difference in ink penetration between the different endodontic sealers tested for the same irrigating solution (p > 0.05). However, when the Bio-C Sealer (Angelus) was used, the group treated with 2.5% Ca(OCl)2 was associated with lower values of apical leakage, compared to 2.5% NaOCl (p < 0.05). For the AH Plus sealer (Dentsply Maillefer), there was no difference between the irrigants (p > 0.05). Conclusions: Associating Ca(OCl)2 irrigant with Bio-C Sealer (Angelus) seems to be a good option to reduce apical leakage

Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Effects of sodium pyruvate on the morphology, structure and function of erythrocytes stored in vitro in type 2 diabetes rats / 中国临床药理学与治疗学

AIM: To observe the effect of RBC preservation solution with sodium pyruvate on the morphology, structure and function of RBC stored in vitro in type 2 diabetes rats. METHODS: Thirty SPF male SD rats, were randomly divided into 3 groups (n=10): non-T2DM conventional RBC preservation solution (group A), T2DM conventional RBC preservation solution (group B) and T2DM sodium pyruvate RBC preservation solution (group C). The leukoreduced RBC from the tail vein and stored for 0 d (T0), 7 d (T1), 14 d (T2), 21 d (T3) and 28 d (T4) to detect the morphology, structure and the contents of 2, 3-DPG, reactive oxygen species (ROS), malondialdehyde (MDA) and lactic acid (LA) of RBC in group A, B and C. The RBC stored for 14 days in vitro were labeled with PKH26, and its survival rate were tested in vivo at 1, 4, 10 and 16 hours after intravenous infusion. RESULTS: At T0, the RBC morphology of group A was intact, which was better than that of group B and group C. With the extension of storage time, the morphology of RBC in each group gradually transformed into a spindle-spherical shape. Compared with group A, the incidence of acanthocytes in group B and group C was higher, and the incidence of acanthocytes in group C was lower than that in group B. Compared with group A, the content of 2, 3-DPG in group B and group C decreased, while ROS and MDA increased at different time points (P<0.05). The content of 2,3-DPG in group C was higher than that in group B (P<0.05), and the contents of ROS and MDA were lower than those in group B (P<0.05). LA content in group B was higher than that in group A and group C (P<0.05). At T2-T4, the LA content in group C was lower than that in group A (P<0.05). The survival rate of RBC in group A was higher than that in group B and C, and the survival rate of RBC in group B was lower than that in group C (P<0.05). CONCLUSION: Sodium pyruvate added RBC preservation solution has a certain protective effect on RBC stored in vitro in type 2 diabetic rats, and its mechanism may be related to its antioxidant effect.

Resistance to deltamethrin and its association with mutation sites in the sodium iron channel domain III gene in Rhipicephalus microplus in Huaihua City of Hunan Province / 中国血吸虫病防治杂志

Objective To investigate the level of deltamethrin resistance and mutation sites in the sodium iron channel gene in Rhipicephalus microplus in Huaihua City, Hunan Province, and to examine the correlation between deltamethrin resistance and mutation sites in the sodium iron channel gene in Rh. microplus. Methods Rh. microplus was sampled from multiple yellow cattle farms in Huaihua City, Hunan Province from June to September 2022, and the level of resistance to deltamethrin was determined in ticks using the adult immersion test. The sodium iron channel domain III gene was amplified in deltamethrin-resistant and wild-type Rh. microplus using PCR assay. Following sequencing and sequence alignment, mutation sites were detected in bases. The sodium iron channel domain III gene in Rh. microplus was translated, and the signal peptide, transmembrane domain, and phosphorylation and glycosylation sites were detected in amino acid sequences. The tertiary structures of the sodium iron channel domain III protein of deltamethrin-resistant and wild-type Rh. microplus were deduced and compared, and the association be tween mutation sites in bases and resistance to deltamethrin was examined in Rh. microplus according the level of deltamethrin resistance, sequence alignment and protein tertiary structure. Results The median (LC50) and 95% lethal concentrations (LC95) of deltamethrin were 121.39 mg/L and 952.61 mg/L against Rh. microplus, with a resistance factor of 9.24 and level II resistance. The sequence of the sodium ion channel domain III gene was 1 010 bp in size, and mutation sites were detected in two neighboring bases in the sequence of the sodium ion channel domain III gene in deltamethrin-resistant Rh. microplus. Although no signal peptides were found in the sodium iron channel domain III protein of deltamethrin-resistant or wild-type Rh. microplus, 6 trans-membrane domains, 42 phosphorylation sites and 8 glycosylation sites were identified, with a significant difference in the tertiary structure of the sodium iron channel domain III protein between deltamethrin-resistant and wild-type Rh. microplus. Conclusions Level II resistance to deltamethrin is detected in Rh. microplus in Huaihua City, Hunan Province, and two mutation sites that correlate with the emergence of deltamethrin resistance are identified in the sequence of the sodium iron channel domain III gene in deltamethrin-resistant Rh. microplus.

Multicenter study on the efficacy and safety of 3 kinds of Cephalosporin for injection from centralized procurement or non-centralized procurement / 中国药房

OBJECTIVE To compare the efficacy and safety of Cefazolin sodium for injection， Cefuroxime sodium for injection， and Ceftazidime for injection from nationally organized centralized drug procurement （hereinafter referred to as “centralized procurement”） and non-centralized procurement in patients with bacterial infection. METHODS The case data of hospitalized patients who had used 3 kinds of Cephalosporins for injection from centralized procurement or non-centralized procurement in the treatment of bacterial infections were retrospectively collected from 19 medical institutions in Kunming from January 2020 to September 2022. After balancing the baseline differences between the groups with the propensity score matching method， the effectiveness and safety differences of 3 kinds of Cephalosporins for injection from centralized procurement or non- centralized procurement were compared respectively. RESULTS After balancing the baseline differences among the groups， 394 cases in each group of Cefazolin sodium for injection from centralized procurement or non-centralized procurement， 472 cases in each group of Cefuroxime sodium for injection from centralized procurement or non-centralized procurement， 504 cases in group of Ceftazidime for injection from centralized procurement and 590 cases in group of non-centralized procurement were included in the analysis. In terms of effectiveness， there were no significant differences in clinical response rate， 72 h response rate， bacterial clearance rate， and the recovery rate of body temperature， white blood cell count， neutrophil count， neutrophil percentage， C-reactive protein， procalcitonin recovery between the centralized procurement group and non-centralized procurement group of Cefazolin sodium for injection and Cefuroxime sodium for injection （P＞0.05）. The proportion of patients in centralized procurement group of Ceftazidime for injection with C-reactive protein restored to normal reference range was significantly higher than that in non-centralized procurement group （46.9% vs. 27.9%， P＜0.05）， but there were no statistically significant differences in other effectiveness indicators among groups （P＞0.05）. In terms of safety， there was no statistical difference in the incidence of adverse drug reactions between centralized procurement group and non-centralized procurement group of 3 kinds of Cephalosporins for injection （P＞0.05）； the incidence of platelet count reduction in centralized procurement group of Cefazolin sodium for injection was significantly higher than non-centralized procurement group （20.7% vs. 7.1%， P＜0.05）， the incidence of eosinophilia elevation in centralized procurement group of Ceftazidime for injection was significantly higher than non-centralized procurement group （5.3% vs. 1.9%， P＜0.05）. In addition， there was no statistically significant difference in the abnormal rates of other laboratory indicators among the three types of injection Cephalosporins （P＞ 0.05）. CONCLUSIONS The efficacy of 3 kinds of Cephalosporin for injection from centralized procurement is not inferior to non- centralized procurement varieties， and the safety is equivalent to that of non-centralized procurement varieties.

Neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating SIRT1/NF-κB signaling pathway / 中国药房

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role.

Advances in research on treatment of tympanosclerosis / 临床耳鼻咽喉头颈外科杂志

Tympanosclerosis is the hyaline degeneration and calcium deposition of the lamina propria of tympanic membrane and the submucosa of middle ear under long-term chronic inflammatory stimulation. At present, treatment primarily involves the surgical removal of sclerotic foci and reconstruction of auditory ossicular chain. However, excision of sclerotic lesions near critical structures like the facial nerve canal and vestibular window may result in complications like facial paralysis, vertigo, and sensorineural hearing loss. Developing safer and more effective treatments for tympanosclerosis has become an international research focus. Recent years have seen novel explorations in the treatment of tympanosclerosis. Therefore, this article reviews the latest advancements in research on the treatment of tympanosclerosis.

Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases / 临床肝胆病杂志

Apical sodium-dependent bile acid transporter （ASBT） is a key transporter responsible for intestinal reabsorption of bile acid and plays an important role in maintaining bile acid and cholesterol homeostasis， and its expression is regulated by various factors including transcription factors， nuclear receptors， and intestinal microflora. The abnormal expression and function of ASBT can lead to disorders in the metabolism of bile acid and cholesterol， causing a variety of hepatobiliary diseases. At present， ASBT has attracted wide attention as a therapeutic target. This article elaborates on the biological characteristics and expression regulation mechanism of ASBT and reviews the role of ASBT in hepatobiliary diseases， in order to provide a new direction for the treatment of related diseases.

Experimental study of Lentinan antagonizes against hepatic lipid deposition induced by sodium arsenite in mice / 公共卫生与预防医学

Objective To investigate the ameliorative effect of Lentinan (LNT) on sodium arsenite (SA)-induced hepatic lipid deposition in mice. Methods C57BL/6 mice were used as the experimental subjects, which were divided into control group, SA-exposed group, LNT + SA-exposed group and LNT control group. Blood and liver tissue samples were collected at the end of the experiment, and serum glutathione transaminase (ALT) and glutathione aminotransferase (AST) levels were detected by enzyme-linked immunosorbent assay (ELISA). A part of liver tissues was stained with hematoxylin-eosin (HE) or oil red O to observe the characteristics of liver pathological damage and lipid deposition, and another part of liver tissues was used to detect triglyceride (TG) and Adiponectin (APN) levels by ELISA. Results Compared with control group or LNT control group, SA-exposed group showed the increased levels of AST and ALT, showing the characteristics of liver histopathological damage and lipid deposition, and the APN level decreased while the TG level increased (P<0.05). Compared with SA-exposed group, the levels of AST and ALT decreased in LNT + SA-exposed group, showing the reduced degree of liver tissue damage and lipid deposition, and APN level upregulated while TG level downregulated (P<0.05). Conclusion Chronic SA exposure induces liver function damage, APN downregulation and lipid deposition in C57BL/6 mice, while LNT intervention leads to the significantly improvement of hepatic damage and lipid deposition, which may be related to the elevated APN level in liver.

Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes / 药学学报

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Effect of low concentration of sodium fluoride on osteogenic/odontogenic differentiation of human dental pulp cells / 口腔疾病防治

Objective@#To study the effect of low concentrations of sodium fluoride on the osteogenic/odontogenic differentiation of human dental pulp cells (hDPCs) in vitro.@*Methods@#This study was reviewed and approved by the Ethics Committee. hDPCs were cultured using a modified tissue explant technique in vitro. The effects of different concentrations of sodium fluoride on the proliferation of hDPCs were measured by methylthiazol tetrazolium (MTT) assay. Appropriate concentrations were added to the osteogenic/odontogenic differentiation induction medium, and the cells were induced in vitro. Alizarin red S staining was used to detect the osteoblastic/odontogenic differentiation ability of the cells, and the mRNA expression of the key differentiation factors was detected by RT-qPCR. Moreover, the expression of key molecules of endoplasmic reticulum stress (ERS) was detected by RT-qPCR and Western blot. The data were analyzed with the SPSS 18.0 software package.@*Results@#Low concentration of NaF (0.1 mmol/L) could stimulate cell proliferation in vitro, while a high concentration (5-10 mmol/L) could inhibit cell proliferation (P<0.05). According to the literature and the experimental data, 0.1 mmol/L NaF was selected as the following experimental concentration. The levels of alizarin red S staining were increased after NaF induction of mixed osteogenic/odontogenic differentiation in vitro. The mRNA expression levels of key molecules for osteogenic/odontogenic differentiation, dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP) and osteocalcin (OCN), were increased (P<0.05). The mRNA levels of ERS markers (splicing x-box binding protein-1 (sXBP1), glucose-regulated protein 78 (GRP78) and activating transcription Factor 4 (ATF4) were increased in NaF-treated cells. The protein expression levels of key ER stress molecules (phosphorylated RNA-activated protein kinase-like ER-resident kinase (p-PERK), phosphorylated eukaryotic initiation factor-2α (p-eIF2α) and ATF4) were higher in NaF-treated cells.@*Conclusion@#A low concentration of NaF promotes the osteogenic/odontogenic differentiation of hDPCs and increases the level of ER stress.

Acidente de hipoclorito de sódio durante retratamento endodôntico / Sodium hypochlorite accident during endodontic retreatment / Accidente con hipoclorito de sodio durante retratamiento

O retratamento endodôntico é uma intervenção executada em um dente que já apresenta um tratamento realizado anteriormente que foi mal sucedido clínica e/ou radiograficamente. O objetivo deste trabalho foi o de relatar um caso de retratamento endodôntico na clínica de Atenção Básica III da Faculdade de Odontologia de Pernambuco devido ao desconforto estético do incisivo lateral superior que estava fraturado e necessitando de prótese fixa. Após anamnese, exames extra e intra-oral e exames radiográficos, constatou-se o canal do dente 12 havia sido tratado endodonticamente há aproximadamente quatro anos. A remoção da gutta percha contaminada foi realizada com as limas rotatórias EasyLogic RT® 25mm sequência 30.10 torque 4N e 900 RPM, 25.08 torque 4Ne 900 RPM. Após remoção da guta-percha, realizou-se o protocolo de irrigação com solução de hipoclorito de sódio a 2,5% (Biodinâmic). A odontometria foi realizada com localizador apical e confirmada por radiografia periapical e o repreparo do canal radicular confeccionado com a Lima EasyLogic 2® de número 35.06 e posterior irrigação com a solução de Labarraque. Nesse momento, o paciente relatou dor e após aspiração com sugador endodôntico, notou-se sangramento abundante, correspondendo ao extravasamento do hipoclorito de sódio (Enfizema por hipoclorito de sódio. O paciente foi medicado com Amoxacilina 875mg de 12 em 12 horas durante sete dias, Predisin 20mg ­ Corticóide - um comprimido pela manhã por 4 dias e Nimesulida 100mg de 12 em 12 horas durante 5 dias. Após 24 horas o paciente não relatou dor nem edema. Na segunda sessão, 10 dias após o acidente, a obturação foi realizada com cone único de guta-percha 35.06 HBassi (Easy, associado ao cimento Bio C Sealer Fillapex (Angelus®). Concluiu-se que a conduta terapêutica imediata instituída para este caso, foi efetiva para o controle da dor e prevenção de complicações adicionais após injeção acidental de hipoclorito de sódio.

Endodontic retreatment is an intervention performed on a tooth that already has a previously performed treatment that was clinically and/ or radiographically unsuccessful. The objective of this study was to report a case of endodontic retreatment at the Primary Care Clinic III of the Faculty of Dentistry of Pernambuco due to the aesthetic discomfort of the maxillary lateral incisor that was fractured and required a fixed prosthesis. After anamnesis, extra and intraoral exams and radiographic exams, it was found that the root canal of tooth 12 had been endodontically treated for approximately four years. Removal of contaminated gutta percha with those performed with EasyLogic RT® 25mm rotary files sequence 30.10 torque 4N and 900 RPM, 25.08 torque 4N and 900 RPM. After removing the gutta-percha, the irrigation protocol was performed with a 2.5% sodium hypochlorite solution (Biodynamic). Odontometry was performed with an apex locator and confirmed by periapical radiography and root canal re-preparation made with EasyLogic 2® File number 35.06 and subsequent irrigation with Labarraque's solution. At that moment, the patient reported pain and after aspiration with an endodontic sucker, there was profuse bleeding, corresponding to sodium hypochlorite extravasation (Sodium hypochlorite emphysema. The patient was medicated with Amoxicillin 875mg every 12 hours for seven days, Predisin 20mg - Corticosteroid - one tablet in the morning for 4 days and Nimesulide 100mg every 12 hours for 5 days. After 24 hours the patient did not report pain or swelling. In the second session, 10 days after the accident, the filling was performed with a single cone of gutta-percha 35.06 HBassi (Easy, associated with Bio C Sealer Fillapex cement (Angelus®). It was concluded that the immediate therapeutic approach instituted for this case was effective for pain control and prevention of complications. additional doses after accidental injection of sodium hypochlorite.

El retratamiento endodóntico es una intervención que se realiza sobre un diente que ya tiene un tratamiento realizado previamente que resultó clínica y/o radiográficamente fallido. El objetivo de este estudio fue relatar un caso de retratamiento endodóntico en la Clínica de Atención Básica III de la Facultad de Odontología de Pernambuco debido a la incomodidad estética del incisivo lateral maxilar que estaba fracturado y requirió prótesis fija. Después de anamnesis, exámenes extraorales, intraorales y exámenes radiográficos, se encontró que el conducto radicular del diente 12 había sido tratado endodónticamente durante aproximadamente cuatro años. Eliminación de gutapercha contaminada con las realizadas con limas rotatorias EasyLogic RT® 25mm secuencia 30.10 torque 4N y 900 RPM, 25.08 torque 4N y 900 RPM. Tras retirar la gutapercha, se realizó el protocolo de irrigación con una solución de hipoclorito de sodio al 2,5% (Biodynamic). Se realizó odontometría con localizador de ápices y se confirmó mediante radiografía periapical y repreparación del conducto radicular realizada con EasyLogic 2® File número 35.06 y posterior irrigación con solución de Labarraque. En ese momento el paciente refirió dolor y luego de aspiración con ventosa endodóntica presentó sangrado profuso, correspondiente a extravasación de hipoclorito de sodio (Enfisema por hipoclorito de sodio. El paciente fue medicado con Amoxicilina 875mg cada 12 horas por siete días. Predisin 20mg - Corticosteroide - una tableta por la mañana por 4 días y Nimesulida 100mg cada 12 horas por 5 días, luego de 24 horas el paciente no refirió dolor ni hinchazón, en la segunda sesión, 10 días después del accidente, se realizó el relleno con un solo cono de gutapercha 35.06 HBassi (Easy, asociado al cemento Bio C Sealer Fillapex (Angelus®). Se concluyó que el abordaje terapéutico inmediato instituido para este caso fue eficaz para el control del dolor y la prevención de complicaciones. dosis adicionales después de accidente inyección de hipoclorito de sodio.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study / Dapagliflozina em pacientes com doença crítica: justificativa e desenho do estudo DEFENDER

ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098

RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098

Antimicrobial effect of phytosphingosine in acrylic resin

Abstract This study evaluated color stability (CS), anti-adherence effect (AAE), and cell viability of microorganisms on acrylic resin (AR) surface, treated associated or not with sodium percarbonate (SP). AR specimens were prepared, and color analysis was performed before and after the treatments and the CS was calculated. For analysis of AAE, the samples were sterilized by radiation in a microwave oven. Then samples were randomly distributed: phosphate-buffered saline (PBS - control), 0.5% sodium hypochlorite (SH), phytosphingosine (PHS), and phytosphingosine + SP (PHS+Na2CO3). The specimens remained in contact with solutions for 30 minutes and were later contaminated by Candida albicans. Aliquots were seeded in Petri dishes with Sabouraud Dextrose agar and incubated at 37°C for 24 hours. After the incubation, the number of colonies was counted. The cell viability of adhered microorganisms on the AR was evaluated and 20 fields were observed under an epifluorescence microscope, and the percentage of adhered viable cells was calculated. Data were compared (One-way ANOVA, Tukey, p<.05). As for CS, PHS+ Na2CO3 (0.4±0.1) resulted in less change than PBS (0.9±0.2), similar to the other groups (SH [1.0±0.3)]; PHS [0.9±0.2)]). There was no difference for all tested solutions regarding the ability to avoid microorganism adherence (p>0.05), but PHS (11.2±4.1) resulted in a smaller area of adhered viable cells, statistically different from SH (18.2±7.6) and PBS (26.4±10.8). It was concluded that PHS resulted in lower adhered viable cells and when associated with Na2CO3, also shows a lower effect on the CS of AR.

Resumo Este estudo avaliou estabilidade de cor (EC), efeito antiaderente (EAA) e viabilidade celular de microrganismos em superfície de resina acrílica (RA), tratada com solução de fitoesfingosina, associada ou não ao percarbonato de sódio (PS). Espécimes RA foram preparados e análise de cor foi realizada antes e após os tratamentos e EC foi calculada. Para análise de EAA, as amostras foram esterilizadas por radiação em forno de micro-ondas. Então foram distribuídas aleatoriamente: solução salina tamponada com fosfato (PBS - controle), hipoclorito de sódio 0,5% (SH), fitoesfingosina (PHS) e fitoesfingosina + SP (PHS+Na2CO3). Os espécimes permaneceram em contato com as soluções por 30 minutos e posteriormente foram contaminados por Candida albicans. Alíquotas foram semeadas em placas de Petri com ágar Sabouraud Dextrose e incubadas a 37°C por 24 horas. Após a incubação, o número de colônias foi contado. A viabilidade celular dos microorganismos aderidos na RA foi avaliada e 20 campos foram observados em microscópio de epifluorescência, e a porcentagem de células viáveis aderidas foi calculada. Os dados foram comparados (One-way ANOVA, Tukey, p<0,05). Quanto a EC, o PHS+ Na2CO3 [0,4 (0,1)] resultou em menor alteração que o PBS [0,9 (0,2)], semelhante aos demais grupos (SH [1,0 (0,3)]; PHS [0,9 (0,2)]). Não houve diferença para todas as soluções testadas quanto à capacidade de evitar a aderência de microorganismos (p>0,05), mas o PHS [11,2 (4,1)] resultou em uma área menor de células viáveis aderidas, estatisticamente diferente do SH [18,2 (7,6)] e PBS [26,4 (10,8)]. Concluiu-se que o PHS resultou em menor número de células viáveis aderidas e, quando associado ao Na2CO3, também apresenta menor efeito sobre o EC da RA.

Irrigants and irrigation activation systems in Endodontics

Abstract Root canal infections are typically polymicrobial and involve strong bacterial interactions. The goal of endodontic treatment is to remove infected content from the root canal system to allow the healing of a pre-existing periapical lesion or to prevent infection of the periradicular tissues. Instrumentation alone is not capable of touching all of the root canal walls. Therefore, the irrigation process is an essential step in the endodontic treatment. However, due to the complex anatomy of the root canal system, this cleaning is very challenging. Although syringe and needle irrigation associated with the use of chemical substances is still the most used method, it does not guarantee optimal cleaning of the root canals. As a result, not only alternative irrigating substances but also numerous activation systems - which are technologies that aim to optimize the action of irrigating substances, both chemically and physically - have been developed. This work aimed to review the characteristics of both classic and current alternatives of irrigating substances and irrigation activation systems.

Resumo As infecções dos canais radiculares são tipicamente polimicrobianas e envolvem fortes interações bacterianas. O objetivo do tratamento endodôntico é remover o conteúdo infeccioso do sistema de canais radiculares, a fim de permitir a cicatrização de uma lesão periapical pré-existente ou prevenir a infecção dos tecidos perirradiculares. A instrumentação por si só não é capaz de tocar todas as paredes dos canais radiculares, desta forma a irrigação é uma etapa essencial no tratamento endodôntico. No entanto, devido à complexa anatomia do sistema de canais radiculares, essa limpeza é muito desafiadora. Embora a irrigação convencional com seringa e agulha, fazendo o uso de substâncias auxiliares seja o método mais utilizado, ela não garante a limpeza ideal dos canais radiculares. Como resultado, foram desenvolvidos inúmeros sistemas de ativação que visam otimizar a ação das substâncias irrigadoras, tanto química quanto fisicamente. O objetivo deste artigo foi revisar as características das substâncias irrigadoras (clássicas e alternativas) e dos sistemas de ativação destas substâncias.

Sodio urinario como factor pronóstico para mortalidad en pacientes con falla cardiaca aguda descompensada

Introducción. En los pacientes con falla cardíaca, el sodio urinario se ha propuesto como marcador de gravedad y resistencia a los diuréticos, pero los resultados de los estudios reportados son heterogéneos. Objetivo. Evaluar el sodio en orina ocasional como factor pronóstico de mortalidad en pacientes con falla cardiaca descompensada. Materiales y métodos. Se realizó un análisis anidado de casos y controles de una cohorte prospectiva de falla cardíaca descompensada. El desenlace primario fue mortalidad a los 180 días. Se hizo un análisis bivariado para evaluar las variables que se asocian con la mortalidad. Se analizaron las diferencias de las variables clínicas entre los grupos con sodio urinario mayor o menor de 70 mEq/L. Resultados. Se incluyeron 79 pacientes de los cuales 15 fallecieron a los 180 días. La edad promedio fue de 68,9 años (DE: ±13,8), 30 eran mujeres (38 %). Quince pacientes (18,9 %) tuvieron un sodio en orina inferior a 70 mEq/L. En el análisis bivariado se encontró una asociación significativa de la mortalidad con las hospitalizaciones, la presión arterial sistólica inferior a 90 mm Hg, el uso de inotrópicos y el sodio urinario inferior a 70 mEq/L. Los pacientes con sodio urinario bajo habían estado hospitalizados con mayor frecuencia en el último año, tenían menores valores de sodio sérico y presión arterial al ingreso. Conclusión. Los pacientes con sodio urinario inferior a 70 mEq/L tienen características de mayor gravedad. En el análisis bivariado, el sodio urinario se asoció con mortalidad a los 180 días.

Introduction. Urinary sodium has been proposed as a prognostic marker and indicator of the diuretic response in patients with heart failure. However, study results are heterogeneous. Objective. To evaluate the spot urinary sodium level as a risk factor for mortality in patients with decompensated heart failure. Materials and methods. We conducted a case-control study nested in a prospective cohort of patients with decompensated heart failure. The primary outcome was mortality at 180 days. The risk factors associated with mortality were evaluated through a bivariate analysis. Differences in clinical variables between groups with urinary sodium greater than or lesser than 70 mEq/L were analyzed. Results. The study included 79 patients; 15 died at 180 days. Their mean age was 68.9 years (SD=± 13.8); 30 were women (38%), and 15 (18.9%) had urinary sodium <70 mEq/L. In the bivariate analysis, a significant association was found between mortality and past medical history of hospitalizations, SBP<90 mm Hg, the use of inotropes, and urinary sodium <70 mEq/L. Regarding clinical characteristics, patients with low urinary sodium level in the last year were hospitalized more frequently with hyponatremia and hypotension at admission. Conclusion. Patients with urinary sodium <70 mEq/L had more severe signs. In a bivariate analysis, urinary sodium was associated with mortality at 180 days.