Jujubae Fructus alleviates intestinal injury caused by toxic medicinals in Shizao Decoction based on correlation between intestinal flora and host metabolism / 中国中药杂志

Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia＿UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.

Effect of activation of canonical Wnt signaling by the Wnt-3a protein on the susceptibility of PC12 cells to oxidative and apoptotic insults

Wnt proteins are involved in tissue development and their signaling pathways play an important role during embryogenesis. Wnt signaling can promote cell survival, which is beneficial for neurons, but could also lead to tumor development in different tissues. The present study investigated the effects of a Wnt protein on the susceptibility of a neural tumor cell line (PC12 cells) to the cytotoxic compounds ferrous sulfate (10 mM), staurosporine (100 and 500 nM), 3-nitropropionic acid (5 mM), and amyloid β-peptide (Aβ25-35; 50 µM). Cells (1 x 10(6) cells/mL) were treated with the Wnt-3a recombinant peptide (200 ng/mL) for 24 h before exposure to toxic insults. The Wnt-3a protein partially protected PC12 cells, with a 6-15 percent increase in cell viability in the presence of toxic agents, similar to the effect measured using the MTT and lactate dehydrogenase cell viability assays. The Wnt-3a protein increased protein expression of β-catenin by 52 percent compared to control. These findings suggest that Wnt signaling can protect neural cells against apoptosis induced by toxic agents, which are relevant to the pathogenesis of Alzheimer’s and Huntington’s diseases.

pH-dependent modulation of intracellular free magnesium ions with ionselective electrodes in papillary muscle of guinea pig

A change in pH can alter the intracellular concentration of electrolytes such as intracellular Ca2+ and Na+ ([Na+]i) that are important for the cardiac function. For the determination of the role of pH in the cardiac magnesium homeostasis, the intracellular Mg2+ concentration ([Mg2+]i), membrane potential and contraction in the papillary muscle of guinea pigs using ion-selective electrodes changing extracellular pH ([pH]o) or intracellular pH ([pH]i) were measured in this study. A high CO2-induced low [pH]o causes a significant increase in the [Mg2+]i and [Na+]i, which was accompanied by a decrease in the membrane potential and twitch force. The high [pH]o had the opposite effect. These effects were reversible in both the beating and quiescent muscles. The low [pH]o-induced increase in [Mg2+]i occurred in the absence of [Mg2+]o. The [Mg2+]i was increased by the low [pH]i induced by propionate. The [Mg2+]i was increased by the low [pH]i induced by NH4Cl-prepulse and decreased by the recovery of [pH]i induced by the removal of NH4Cl. These results suggest that the pH can modulate [Mg2+]i with a reverse relationship in heart, probably by affecting the intracellular Mg2+ homeostasis, but not by Mg2+ transport across the sarcolemma.

Differential depression of spinal synaptic transmission in vitro by different hypoxic insults.

The effects of hypoxia (O2-free), aglycemia (glucose-free), ischemia (O2- and glucose-free) and chemical anoxia (by 3-nitropropionic acid; 3-NPA) were evaluated on the synaptic transmission in vitro. Stimulation of a dorsal root in hemisected spinal cord from neonatal rat, evoked monosynaptic (MSR) and polysynaptic reflexes (PSR) in the segmental ventral root. In all the hypoxic conditions, the reflexes were depressed in a time-dependent manner. Hypoxia took longer time (> 240 min) to abolish the reflexes where as, aglycemia and ischemia abolished them within 35 min. Recovery after wash was complete in hypoxia, 60-70% in aglycemia and 20-25% in ischemia. The time required for 50% depression of reflexes (T-50) was also in the same order (100, 23 and 13 min). The elimination of O2 in hypoxic or ischemic solution by N2 bubbling abolished the reflexes within 16 min. The T-50 values in both the conditions were between 5-8 min. Superfusion of 3-NPA (an irreversible inhibitor of succinate dehydrogenase) depressed the reflexes. The abolition time and T-50 values were shorter with the increasing concentrations of 3-NPA. The present results reveal that the energy production in hypoxic condition with normal glucose level can sustain the synaptic activity for a longer time while the glucose deficiency even in normoxic conditions drastically impair the synaptic activity. Further, aglycemia depressed the reflexes almost in a similar time as seen with ischemia.

Reactividad vascular pulmonar y formación de edema en presencia de inhibidores de prostaglandinas en el lóbulo canino aislado / Pulmonary vascular reactivity and edema formation in the presence of prostaglandins' inhibitors. Study in isolated canine pulmonary lobule

El propósito de este trabajao es el estudio de la reactividad vascular pulmonar y la formación de edema al acentuar la vasoconstricción arterial pulmonar a la hipoxia mediante un inhibidor de la producción de prostaglandinas: el ácido tiaprofénico. Se utilizó un modelo experimental ex-vivo de lóbulo canino aislado. La formación de edema fue cuantificada utilizando el método de espectrofotometría, previamente publicado por nosotros. Se estudiaron 6 lóbulos caninos, todos bajo dos condiciones: normoxia (FIO2 21 por ciento) e hipoxia (FIO2 5 por ciento); en cuatro de los seis experimentos de iniciaron con el periodo de normoxia y en dos en condición de hipoxia. El ácido tiaprofénico se administró en los 6 perros en forma intravenosa 2 horas antes de extraer los lóbulos. Resultados: No se observó con cambios significativos en la tasa de filtración, periodo de normoxia: 0.42 ñ 0.41, periodo de hipoxia: 0.37 ñ 0.51 ml/min/100 g de tejido pulmonar. La presión arterial pulmonar se incrementó significativamente, normoxia basal: 25.1 ñ 6.21 y durante la hipoxia: 37 ñ 7.19 cm de agua (delta de presión 12.0 ñ 1.2) con P< 0.001. Conclusiones: la reactividad vascular en hipoxia se acentuó significativamente con la administración de ácido tiaprofénico, no se demostró incremento en la permeabilidad vascular pulmonar o incremento en las tasas de filtración capilar

Effect of propionic acid on fungal growth and aflatoxin production in moist inshell groudnuts

O efeito do ácido propiônico nas concentraçöes de 3,0 g/kg (AP1) e 5,0 g./kg (AP2) foi avaliado em laboratório para verificar sua eficiência sobre o crescimento fúngico e produçäo de aflatoxinas quando aplicado sobre amendoim em casca úmido. As avaliaçöes, crescimento fúngico sobre as vagens e seus gräos e as análises de aflatoxinas, foram realizadas antes da incubaçäo e aos 7, 14, 21 e 28 dias de incubaçäo. O tratamentoAP1 foi ineficiente no controle do crescimento fúngico a partir de 14§ dia

Evaluación preclínica del fenbufen, capsulas de producción nacional / Preclinical evaluation of fenbufen. Capsules from national production

Se realizó un estudio comparativo del fenbufén, cápsulas de producción nacional, lote 2001, en relación con el producto importado Cincopal, lote A-07. Para ello se evaluó su actividad antiinflamatoria en el edema agudo por carraganina en ratas Wistar, el efecto analgésico al inducir contorsiones por ácido acético en ratones suizos, ambas especies presedentes de la colonia del Laboratorio Control Biológico, así como la toxicidad aguda tanto en ratas como en ratones. Se comprueba que no aparece diferencia significativa en la potenciaantiinflamatoria y analgésica, ni en la toxicidad aguda en ratas; no sucede así en ratones donde la formulación nacional mostró menor toxicidad. Las alteraciones histológicas aparecen en el hígado y riñón para ambos preparados y en el tracto gastrointestinal al emplear la formulación nacional en ratones dañados

Ensaio biologico de novos derivados do acido 3-fosfonopropionico contra o TRYPANOSOMA CRUZI / Biological assay of new derivatives of 3-phosphonopropionic acid against TRYPANOSOMA CRUZI

Diversos derivados do acido 3-fosfonopropionico foram submetidos a ensaios in vivo e in vitro, contra formas tripomastigotas da cepa Y de Trypanosoma Cruzi. Nos ensaios in vivo, realizados em camundongos previamente infectados,os derivados ensaiados se mostraram inativos, sendo que os acidos (R,S)-3-fenil-3-fosfonopropionico e (R,S)-3-fenil-3-(0,0-dietilfosfono)-propionico foram letais para alguns dos animais. Nos ensaios in vitro efetuados em cultura de tecido os compostos ensaiados foram inativos, com excecao do (R,S)-3-fenil-3-(0,0-dietilfosfono)-propionato de etila, que apresentou alguma atividade.

Novos agentes antiinflamatorios analgesicos no campo odontológico: substituem os tradicionalmente conhecidos

O presente trabalho visa dar ao clínico um apanhado sobre os mais recentes antiinflamatórios näo-esteróides lançados no mercado bem como suas aplicaçöes em clínica odontológica. Tenciona fornecer informaçöes que possibilitem uma decisäo mais apropriada sobre a escolha dos medicamentos em funçäo das diversas situaçöes clínicas com as quais o clínico se depara

Farmacodinamia clínica del ácido tiaprofénico / Clinical pharmacodynamics of the tiaprofenic acid

El ácido tiaprofénico [ácido alfa-benzoil-5-thienil- 2 propiónico ha demostrado ser un activo inhibidor reversible de la ciclooxigenasa. La evidencia de que ciertas prostaglandinas (PGs), enzimas lisozómicas y otros autacoides producían injuria articular y reacciones sinoviales, nos sugirió la investigación de la eficacia a corto plazo del ácido tiaprofénico, en el tratamiento de la artritis reumatoidea. El estudio fue realizado sobre 20 pacientes adultos, portadores de sinovitis con derrame, a los cuales fue suspendida toda otra medicación antiinflamatoria, 7 días antes de comenzar el estudio. En todos los pacientes se analizó la concentración de: PGE2 2, P6F2-alfa fosfatasa ácida, dehidrogenasa láctica y cantidad de células en el líquido sinovial, antes y después de 8 días de tratamiento con 600mg/día/vía oral, de ácido tiaprofénico. La detección de los niveles de las PGs se realizó por cromatografía sobre capa fina y ensayo biológico sobre fundus gástrico de rata, contra testigo. Luego del 5§ día se observó una disminución progresiva de la reacción inflamatoria. En corto tiempo el ácido tiaprofénico provocó una caída significativa en los valores de LDH (p<0,02), PGE2 (p<0,001), fosfatasa ácida (p<0,005)., PGF2-alfa (p<0,001) y en el número de células (p<0,02). Concluimos en que el ácido tiaprofénico es una droga anti-PGs y antiinflamatoria efectiva a corto período de tratamiento