A Study of Hypomagnesemia in Patients Admitted in Medical ICU and Its Correlation with Final Outcome

Introduction: Magnesium is the second most common intracellular cation found in the body that is required as cofactor in numerous enzymatic reactions, smooth functioning of cardiac and neurological systems. Magnesium deficiency is often overlooked in critically ill patients and is linked with risk of electrolyte imbalance, difficulty weaning off ventilator, sudden cardiac deaths and poorer outcome. Objective- To assess prevalence of magnesium deficiency in critically ill patients admitted to Medical ICU and its association with requirement & duration of mechanical ventilation, ICU stay, APACHE-II & mortality. Methods- Prospective descriptive study was conducted on 69 critically ill patients admitted in medical ICU. After taking informed consent serum magnesium level of patients were collected and entered in spreadsheet and final analysis was done with help of Open EPI and SPSS software. Results-It was concluded that patients having hypomagnesemia were at increased risk of electrolyte abnormalities, longer ventilatory support, longer hospital and ultimately poorer outcome stay as compared to patients with normal magnesium levels. Conclusion- Magnesium remains an important but often side-lined cation in critically ill patients. However, Hypomagnesemia is a repeated finding seen in critically ill patients and is significantly associated with a higher mortality rate and frequent need for mechanical ventilation.

A Schiff base of 2-((E)-(2-amino-5-methylphenylimino)methyl)- 5-(difluoromethoxy)phenol and its applications on fluorescent chemosensor for selection of Mg2+ ion, molecular docking, and anticancer activity

A novel Schiff base of 2-((E)-(2-amino-5-methylphenylimino)methyl)-5-(difluoromethoxy)phenol (R) wassynthesized and characterized by FTIR, 1H&13C-NMR, and mass spectrometry. The receptor turned yellow and thengreen in the presence of Mg2+ molecules, with the intervention of different metal ions. The selectivity and sensitivityof Mg2+ ion caused the maximum fluorescence emission intensity at 524 nm, with an excitation wavelength at 378nm. Further experiments confirmed that receptor R binds with Mg2+. Job’s plot conforms to a 1:1 stoichiometrycomplex formation. The strong fluorescence is owing to the photoinduced electron/energy transfer effect. The receptorwas recovered by an ethylenediaminetetraacetic acid titration and the emission intensity also returned to a valueequivalent to the unbound ligand. protein data bank: 4J96 was used for the molecular docking of receptor R. Thecytotoxicity effect treatment was carried out by increasing the concentration of HeLa cells to predict IC50 value. Thehighest occupied molecular orbital/lowest unoccupied molecular orbita energy gap calculated and compared betweenR results as 3.48 eV and R-Mg2+ alpha and the beta value calculated a low energy value at 2.27 eV.

Research progress of trpm7 channel and tumor development / 中国药理学通报

Transient receptor potential melastatin-subfamily member 7(TRPM7) is a non-selective cation channel fused with a functional kinase domain. Studies have shown that TRPM7 is aberrantly expressed in tumor cells. TRPM7 plays a variety of functional roles in cancer cells including survival t cell cycle progression, proliferation, invasion, epithelial-mesenchymal transition (EMT) and angiogenesis. The high correlation between TR-PM7 and tumorigcnesis makes TRPM7 a prognostic indicator and a potential therapeutic target for malignant tumors. In this arti cle , we review the research progress of TRPM7 and tumor progression, explore the mechanism of TRPM7-mediated tumor development and the clinical treatment of tumor strategy targeting TRPM7, and provide some reference for follow-up research and clinical treatment.

Correlation Of Serum Mg2+ Levels With Duration Of T2dm

INTRODUCTION: Diabetes is the most common serious metabolic disease. The hallmark of Diabetes is elevated blood glucose concentration, just one of many biochemical & physiological alterations that occur in the disease. In Diabetics there is a association between serum magnesium levels & cellular glucose disposal independent of insulin secretion. DIRECT etion. This change in glucose disposal is found to be associated with INCREASED SENSITIVITY of the tissues to insulin in the presence of sufficient magnesium levels. Magnesium deficiency has been found to be related with DIABETIC MICROVASCULAR DISEASE. Hypomagnesaemia has been reported to occur in 25-38% patients with T2DM without metabolic control. Hence the present study is conducted to find any 1 correlation with DURATION of T2DM & Serum Magnesium.

Meta-analysis of Angong Niuhuang Pill Combined with Chemical Drug in the Treatment of Severe Craniocerebral Injury and Its Effect on Patient's Mg2+ Concentration in Peripheral Blood / 中国药房

OBJECTIVE:To evaluate clinical efficacy of Angong niuhuang pill combined with chemical drug in the treatment of severe craniocerebral injury and its effect on the concentration of Mg2+ in peripheral blood,and to provide evidence-based reference in clinic.METHODS:Retrieved from Chinese Journal Full-text Database,China Science and Technology Journal Database,China Bxdxiology Medicine disc,Wanfang Database,Chinese Clinical Trial Registry,PubMed,Excerpta Media Database,The Cochrane Library,Web of Science,Clinical Trials,and related literatures of intemet searched by Google Scholar,randomized controlled trials (RCT) about Angong niuhuang pill combined with chemical drug (trial group) vs.chemical drug (control group) in the treatment of severe craniocerebral injury and its effects on the concentration of Mg2+ in peripheral blood were collected.After literature screening,data extraction,quality evaluation with modified Jadad scale,meta-analysis of Glasgow Coma Scale (GCS) scores and Mg2+ concentration in peripheral blood were conducted by using Rev Man 5.3 statistical software after 7 d of treatment.RESULTS:A total of 6 RCTs were included,involving 773 patients.Results of meta-analysis showed that GCS [MD=2.87,95％CI (1.64,4.10),P＜0.01] and Mg2+ concentration in peripheral blood [MD=0.11,95％CI(0.06,0.16),P＜0.01] of trial group were significantly higher than those of control group,with statistical significance.CONCLUSIONS:Therapeutic efficacy of Angong niuhuang pill combined with chemical drug is better than that of chemical drug alone in the treatment of severe craniocerebral injury,can improve clinical symptom and prognosis.

Ardipusilloside-I stimulates gastrointestinal motility and phosphorylation of smooth muscle myosin by myosin light chain kinase

Ardipusilloside-I is a natural triterpenoid saponin, which was isolated from Ardisia pusilla A. DC. The aim of the study was to evaluate the stimulation of ardipusilloside-I on gastrointestinal motility in vitro and in vivo. The experiment of smooth muscle contraction directly monitored the contractions of the isolated jejunal segment (IJS) in different contractile states, and the effects of ardipusilloside-I on myosin were measured in the presence of Ca²⁺-calmodulin using the activities of 20 kDa myosin light chain (MLC₂₀) phosphorylation and myosin Mg²⁺-ATPase. The effects of ardipusilloside-I on gastro emptying and intestinal transit in constipation-predominant rats were observed, and the MLCK expression in jejuna of constipated rats was determined by western blot. The results showed that, ardipusilloside-I increased the contractility of IJS in a dose-dependent manner and reversed the low contractile state (LCS) of IJS induced by low Ca²⁺, adrenaline, and atropine respectively. There were synergistic effects on contractivity of IJS between ardipusilloside-I and ACh, high Ca²⁺, and histamine, respectively. Ardipusilloside-I could stimulate the phosphorylation of MLC₂₀ and Mg²⁺-ATPase activities of Ca²⁺- dependent phosphorylated myosin. Ardipusilloside-I also stimulated the gastric emptying and intestinal transit in normal and constipated rats in vivo, respectively, and increased the MLCK expression in the jejuna of constipation-predominant rats. Briefly, the findings demonstrated that ardipusilloside-I could effectively excite gastrointestinal motility in vitro and in vivo.

Brief low Mg2+o-induced Ca2+ spikes inhibit subsequent prolonged exposure-induced excitotoxicity in cultured rat hippocampal neurons

Reducing [Mg2+]o to 0.1 mM can evoke repetitive [Ca2+]i spikes and seizure activity, which induces neuronal cell death in a process called excitotoxicity. We examined the issue of whether cultured rat hippocampal neurons preconditioned by a brief exposure to 0.1 mM [Mg2+]o are rendered resistant to excitotoxicity induced by a subsequent prolonged exposure and whether Ca2+ spikes are involved in this process. Preconditioning by an exposure to 0.1 mM [Mg2+]o for 5 min inhibited significantly subsequent 24 h exposure-induced cell death 24 h later (tolerance). Such tolerance was prevented by both the NMDA receptor antagonist D-AP5 and the L-type Ca2+ channel antagonist nimodipine, which blocked 0.1 mM [Mg2+]o-induced [Ca2+]i spikes. The AMPA receptor antagonist NBQX significantly inhibited both the tolerance and the [Ca2+]i spikes. The intracellular Ca2+ chelator BAPTA-AM significantly prevented the tolerance. The nonspecific PKC inhibitor staurosporin inhibited the tolerance without affecting the [Ca2+]i spikes. While Go6976, a specific inhibitor of PKCalpha had no effect on the tolerance, both the PKCepsilon translocation inhibitor and the PKCzeta pseudosubstrate inhibitor significantly inhibited the tolerance without affecting the [Ca2+]i spikes. Furthermore, JAK-2 inhibitor AG490, MAPK kinase inhibitor PD98059, and CaMKII inhibitor KN-62 inhibited the tolerance, but PI-3 kinase inhibitor LY294,002 did not. The protein synthesis inhibitor cycloheximide significantly inhibited the tolerance. Collectively, these results suggest that low [Mg2+]o preconditioning induced excitotoxic tolerance was directly or indirectly mediated through the [Ca2+]i spike-induced activation of PKCepsilon and PKCxi, JAK-2, MAPK kinase, CaMKII and the de novo synthesis of proteins.

Secretory expression and characterization of heat sensitive nuclease in Pichia pastoris / 生物工程学报

Nucleases is an important enzyme widely used in biotechnology. A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. On the basis of multi-copy recombinant strain, we further optimized the expression condition and characterized SNU. SNU was highly expressed and stable after 1% methanol induction for 72 h, yield reached 1.4×10⁵ U/mL. SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. Functional analysis on the nuclease activity indicated that it was stimulated by bivalent iron, such as Ca²⁺, Mn²⁺, Co²⁺ and Mg²⁺, but inhibited by Zn²⁺, Cu²⁺ and high salt. Meanwhile, it was irreversibly inactivated at 70 ℃ for 10 min.

A comparative study of serum calcium, magnesium and its ratio in women of menopausal and reproductive age group.

Background: The menstrual cycle is the result of complex interacting processes within the hypothalamus, the hypophysis, the ovaries and the uterus. Patterns of change in plasma concentrations of various minerals have been the subject of several research endeavours. Therefore, the present study has been conducted to study and compare the serum calcium, magnesium and its ratio in menopausal and reproductive age group. Methods: The study was performed in two groups of subjects with a control group of 30 healthy women of reproductive age group and a postmenopausal group of 30 women with varying durations of menopause (less than and more than 10 years after menopause). Three blood samples were obtained from the control group –one each in early follicular phase, ovulatory phase and during luteal phase for estimation of calcium and magnesium. One sample was taken from the menopausal age group for the estimation of calcium and magnesium using commercially available kit. The values are expressed as mean ± S.D. The comparison between the different phases of menstrual cycle in reproductive age group with menopausal women was performed using student t-test. P value less than 0.05 was considered significant. Result: The serum Ca2+, Mg2+ and Calcium/ Magnesium ratio was found to be statistically insignificant (p=1.00), during different phases of menstrual cycle in normal cycling women is statistically insignificant. Discussion: The cyclical changes of serum Ca2+ and Serum Mg2+ levels in women of reproductive age may be due to the cyclical changes in the level of sex hormones during different phases of menstrual cycle

Contrastive study on the effect of 3, 5-diiodotyrosine and potassium iodide on myocardial ATPase in hyperthyroidism Wistar rats / 中华地方病学杂志

Objective To study the effects of 3,5-diiodotyrosine (DIT) and potassium iodide (KI) on myocardial ATPase activity in hyperthyroidism Wistar rats induced by thyroid tablets.Methods Seventy-two Wistar rats were divided into 8 groups according to body weight by the random number table method (9 rats in each group),respectively,which were control group,hyperthyroidism model group,low,medium and high doses groups (both DIT and KI contents were 25.0,166.7,500.1 μg/kg).Physiological saline was intragastrically administrated to the control group;the hyperthyroidism model group was given thyroid tablet suspension (200.0 mg/kg);DIT and KI groups were given thyroid tablet suspension with corresponding doses of iodine simultaneously.The medicine was given once a day for a mouth,all the rats were sacrificed and heart tissue was collected.The colorimetric method was used to examine the activity of ATPases (Na+-K+-ATPase,Mg2+-ATPase,Ca2+-ATPase).Results The activities of Na+-K+-ATPase,Mg2+-ATPase,Ca2+-ATPase were significantly different statistically between groups (F =2.99,3.03,6.18,all P ＜ 0.01).Compared with the control group [(4.01 ± 0.22),(4.28 ± 0.28),(4.46 ± 0.35) μmol/mg·h],the activities of ATPases (Na+-K+-ATPase,Mg2+-ATPase,Ca2+-ATPase included) were reduced significantly in hyperthyroidism model group [(3.60 ± 0.25),(3.42 ± 0.31),(3.85 ± 0.17)μ mol/mg·h,all P ＜ 0.01];the activities of Mg2+-ATPase in DIT medium dose group [(3.89 ± 0.35)μmol/mg ·h],Ca2+-ATPase in DIT medium and high doses groups [(4.12 ± 0.20),(4.09 ± 0.21)μ mol/mg·h] were reduced significantly (all P ＜ 0.05);the activities of Na+-K+-ATPases,Ca2+-ATPase were decreased significantly in three KI groups [(3.64 ± 0.32),(3.60 ± 0.32),(3.53 ± 0.33),(3.93 ± 0.22),(3.90 ± 0.23),(3.85 ± 0.26)μmol/mg·h],Mg2+-ATPase in KI high dose group [(3.65 ± 0.49)μmol/mg·h] was decreased significantly (P ＜ 0.05or ＜ 0.01).Compared with the hyperthyroidism model group,the activities of ATPase were increased in most of the DIT groups [Mg2+-ATPase in low,medium doses groups:(4.06 ± 0.51),(3.89 ± 0.35)μmol/mg·h;Ca2+-ATPase in low,medium,high doses groups (4.15 ± 0.26),(4.12 ± 0.20),(4.09 ± 0.21)μmol/mg·h,all P ＜ 0.05].Conclusion Supplementation of thyroid tablets in the process of hyperthyroidism formation in Wistar rats will reduce myocardial damage by DTT compared with the same dose of KI.

Screening of effective parts in Jiaoai Decoction with blood enriching function in blood deficiency model rats / 中草药

Objective: To screen the active parts with enriching the blood effects of different solvent extraction parts from Jiaoai Decoction (JAD) by comparing the peripheral blood, immune organ index, interleukin 2 (IL-2), and erythropoietin (EPO) and the effect of content of erythrocyte membrane and energy metabolism enzyme activity of blood deficiency model rats. Methods: Taking the fundus venous plexus blood 5 mL/kg every day, continuous bleeding for 12 d, to establish the rat model of blood deficiency; The model animals in each group were ig given JAD and n-butanol, petroleum ether, ethyl acetate, parts of water extract (12 g/kg crude drug) with compound E-Jiao slurry as a positive control. On day 12 of modeling, the erythrocyte count (RBC), hemoglobin (HGB), red blood cell hematocrit (HCT), platelet count (PLT) were detected in rats and immune organ indexes of spleen and thymus were calculated, the levels of IL-2 and EPO content were detected, energy metabolism enzymes (Na+, K+-ATPase and Ca2+, Mg2+-ATPase) activity were investigated; The difference of the chemical constituents in the different solvent extraction of JAD was analyzed by UPLC. Results: Compared with the control group, the RBC, HGB, HCT, PLT, thymus index, and IL-2 levels of rats in the model group decreased significantly, Na+, K+-ATPase and Ca2+, Mg2+-ATPase activity weakened significantly, the spleen index and EPO levels were significantly increased, indicating that blood deficiency model was successfully established. Compared with the model group, HCT, RBC, HGB, and PLT (P<0.05, 0.01) of rats in n-butyl alcohol group could be significantly increased; The spleen index and the content of EPO (P<0.05, 0.01) were reduced; The thymus index and the content of IL-2 (P<0.01) were increased, the erythrocyte Ca2+, Mg2+-ATPase and Na+, K+-ATPase activity (P<0.05, 0.01) was elevated. The contents of PLT and IL-2 (P<0.01) in petroleum ether group could be obviously increased; The content of EPO and the spleen index (P<0.05, 0.01) were decreased. The ethyl acetate fractions could obviously reduce the spleen index and the content of EPO (P<0.01), increase Ca2+, Mg2+-ATPase activity in erythrocytes (P<0.05). In water group PLT (P<0.05) could be significantly increased and the content of EPO (P<0.01) be decreased. There were no coffee acid, benzoyl paeoniflorin, and ammonium glycyrrhizinate in other solvent extracts of JAD, while the content of gallic acid, protocatechuic acid, ligustrazine phosphate, and chlorogenic acid in n-butanol extract were higher than those in ethyl acetate and water extract parts of JAD. Conclusion: The n-butanol extract is the most active part of JAD for enriching the blood.

Effects of percutaneous midband pulse current stimulation in hepatic region on the activity of hepatic mitochondrial Na+-K+-ATPase and Ca2+-Mg2+-ATPase in exercise-induced fatigued rats / 解放军医学杂志

Objective To explore the effects of percutaneous impulsive current stimulation in hepatic region on the activity of hepatic mitochondrial Na+-K+-ATPase and Ca2+-Mg2+-ATPase in exercise-induced fatigued rats, in order to investigate the effect of exercise-induced fatigue. Methods Seventy-two 8-week old male Wistar rats were randomly divided into 4 groups (18 each): control group (group A), fatigue group (group B), stimulation before fatigue group (group C) and stimulation after fatigue group (group D). Exhaustion of animals in B, C and D groups were reproduced by prolonged swimming. Current stimulation (1024Hz, 10mA, current cycle 1sec) for 20 minutes was given to the rats of group C before swimming, and to those in group D after exhaustion. At the weekend of 1st, 3rd and 5th week after modeling, the rats were sacrificed in batches from each group (6 each). The activities of hepatic mitochondrial Na+-K+-ATPase and Ca2+-Mg2+-ATPase were determined by spectrophotometry, and Bradfood protein quantification was employed to quantitate the protein in rats' hepatic mitochondria. Results No significant difference was found in swimming-exhaustion time among 3 groups at the first weekend (P>0.05), while the swimming-exhaustion time was significantly prolonged at the 3rd and 5th weekends in group D than in group B and C (P+-K+-ATPase and Ca2+-Mg2+-ATPase among the 4 groups (including group A) at the weekend of the 1st week (P>0.05), while the enzyme activities were obviously lower at the 3rd and 5th weekend in group B than that in groups A, C and D (P+-K+-ATPase and Ca2+-Mg2+-ATPase. Percutaneous pulsive current stimulating hepatic region of exercise-induced fatigued rats may improve the enzyme activity, reduce the concentration of free calcium and calcium overload in mitochondria, stimulate the oxidative phosphorylation, accelerate the rate of respiratory chain, promote exercise endurance and score, and relieve exercise-induced fatigue rapidly.

Effects of Kangshuai Yizhi Capsule on Activity of ATP in Brain Tissues and IL-6, TNF-α in Serum of Aging Rats / 中国中医药信息杂志

Objective To observe effects of Kangshuai Yizhi Capsule on ATP in brain tissue and IL-6, TNF-α in serum of aging model rats, and explore the protective effects of the capsule on brain tissue.Methods Totally 72 rats were randomly divided into a normal group and a model group. The subacutely aging model rats were made by injectingD-gal, then aging rats were numbered and grouped by random number table into the model group, Kangshuai Yizhi high-dose group, Kangshuai Yizhi Capsule low-dose group and Naofukang group. All dose groups were received gavage by giving corresponding doses, while normal group and model group were given the same amount of saline everyday. After treated for 60 days, the activity of Na+-K+-ATP and Ca2+-Mg2+-ATP in brain tissue, and IL-6, TNF-α in serum were detected.Results Compared with normal group, Na+-K+-ATP and Ca2+-Mg2+-ATP were less active (P<0.05), but levels of IL-6 and TNF-α in model group were significantly higher, with statistical significance (P<0.05). Compared with model group, after treated with Kangshuai Yizhi Capsule, Na+-K+-ATP and Ca2+-Mg2+-ATP were more active, and IL-6 and TNF-α levels were down-regulated significantly in dose groups, with statistical significance (P<0.05). Meanwhile, Kangshuai Yizhi Capsule high-dose group showed the most obvious effect among dose groups.ConclusionKangshuai Yizhi Capsule has effects of enhancing activity of ATP in brain tissue and reducing level of proinflammatory factors.

Modulation of Na+/K+, Mg2+ and Ca2+ ATPase activity in different regions of rat brain during rotenone induced parkinson's disease and protective role of bacopa monnieri.

Bacopa monnieri (BM; Family: Scrophulariaceae), also referred as Brahmi or Jalbrahmi has been used for centuries in Ayurvedic system of medicine as a brain tonic, memory enhancer, revitaliser of sensory organs, anti-anxiety, cardio-tonic, diuretic, antidepressant and anticonvulsant agent, and the pharmacological actions are mainly attributed to the saponin compounds present in the alcoholic extract of the plant. The present study was carried out with a specific aim to examine the neuroprotective effect of Bacopa monnieri during Rotenone (RT) induced Parkinson’s disease (PD) with particular reference to Na+/K+, Mg2+ and Ca2+ -ATPase activities in different regions of rat brain. In the experiment conducted rats were divided into four groups of six in each group, group 1 received Saline water (1 ml/kg), group 2 received RT (2.5 mg/kg) through i.p. route administration for 60 days to induce PD. The third group received BM extract (180 mg/kg/day) for 20 days orally before induction of PD and group 4 received Levodopa (LD) (10 mg/kg/day) orally which is referred as drug control. The levels of Na+/K+, Mg2+ and Ca2+ -ATPase activities were measured. Na+/K+, Mg2+ and Ca2+ -ATPase activities were significantly depleted in different brain regions of rat during RT induced PD when compared to control rats. Treatment with BM and LD caused significant elevation in the activity levels of Na+/K+, Mg2+ and Ca2+ -ATPase in different brain regions of rats when compared to induced PD rats. Our results suggest the ability of BM extract to modulate Na+/K+, Mg2+ and Ca2+ - ATPase activities in different brain regions of RT induced rodent model of PD and thus offers effective management in the treatment of PD.

Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase / Influencia de los iones Mg+2 sobre la interacción entre el ácido 3,5- dicafeoilquínico y la integrasa del HTLV-I / Influência dos íons Mg2+ sobre a interação entre o ácido 3,5-dicafeoilquínico e a integrase do HTLV-I

Objective. Using molecular simulation, we studied the influence of Mg2+ ions on the binding mode of HTLV-I Integrase (IN) catalytic domain (modeled by homology) with the 3,5- Dicaffeoylquinic Acid (DCQA). HTLV-I Integrase homology model was built using template-like crystallographic data of the IN catalytic domain solved for Avian Sarcoma Virus (VSA, pdb: 1VSD). Materials and methods. In order to analyze the role of Mg2+ in the interaction or coupling between 3,5-DCQA and Integrase, three models were created: i) in the absence of Mg2+ ions, ii) with a Mg2+ ion coordinated at Asp15 and Asp72 and iii) model with two Mg2+ ions coordinated at Asp15-Asp72 and Asp72-Glu108. Coupling force and binding free energy between 3,5-DCQA and HTLV-I IN were assessed in the three models. Results. The lowest docking score and free energy binding were obtained for the second model. Mg2+ ion strongly affected the coupling of the inhibitor 3,5-DCQA with HTLV-I catalytic domain of Integrase, thus revealing a strong interaction in the ligand-protein complex regardless of the ligand-catalytic interaction sites for all three models. Conclusion. Altogether, these results strengthen the hypothesis that the presence of one Mg2+ ion could enhance the interaction in the complex by decreasing free energy, therefore increasing the affinity. Moreover, we propose 3,5-DCQA as an important pharmacophore in the rational design of new antiretroviral drugs.

Objetivo: Usando simulación molecular, estudiamos la influencia de los iones Mg2+ en la interacción del dominio catalítico de la integrasa HTLV-I (IN) (modelado por homología) con el ácido 3,5-Dicafeoilquínico (DCQA). Materiales y métodos. El modelo por homología de la HTLV-I IN fue construido usando como molde la estructura cristalina de la IN del virus del sarcoma aviar (VSA, pdb: 1VSD). Para analizar el rol de los iones Mg2+ en la interacción con el DCQA y la integrasa, tres modelos fueron creados: i) en ausencia de iones Mg2+, ii) con un ion Mg2+ coordinado con Asp15 y Asp72 y iii) con dos iones Mg2+ coordinados con Asp15-Asp72 y Asp72-Glu108. Las fuerzas de interacción y la energía libre de unión entre el DCQA y la HTLV-I IN fueron calculadas en los tres modelos. Resultados. El puntaje más bajo en el docking y la menor energía libre fueron obtenidos para el modelo con un solo ion de Mg2+. El Mg2+ afecta fuertemente el acoplamiento del inhibidor DCQA con el dominio catalítico de la HTLV-I IN, revelando una fuerte interacción entre el complejo ligando-proteína que es independiente del sitio catalítico de los tres modelos usados. Conclusión. Los resultados sugieren que la presencia de un ion de Mg² + podría incrementar la interacción en el complejo debido a la disminución de la energía libre, intensificando así la afinidad. Por lo que, proponemos al DCQA como farmacóforo para el diseño de drogas antiretrovirales.

Objetivo. Usando simulação molecular, estudamos a influência dos íons Mg2+ na interação do domínio catalítico da integrase HTLV-I (IN) (modelado por homologia) com o ácido 3,5-dicafeoilquínico (3,5-diCQA). Materiais e métodos. O modelo de homologia da HTLV-I IN foi construído utilizando como fôrma a estrutura cristalina da IN de vírus do sarcoma aviário (VSA, pdb: 1VSD). Para analisar o papel dos íons Mg2+ na interação com o 3,5-diCQA e a integrase, três modelos foram criados: i) na ausência de íons Mg2+, ii) com um íon Mg2+ coordenado com Asp15 e Asp72 e, iii) com dois íons Mg2+ coordenados com Asp15-Asp72 e Asp72-Glu108. As forças de interação e a energia livre de ligação entre o 3,5-diCQA e a HTLV-I IN foram calculadas nos três modelos. Resultados. A pontuação mais baixa no docking e a menor energia livre foram obtidas para o modelo com um único íon de Mg2+. O Mg2+ afeta fortemente o acoplamento do inibidor 3,5-diCQA com o domínio catalítico da HTLV-I IN, revelando uma forte interação entre o complexo ligando-proteína que é independente do sítio catalítico dos três modelos utilizados. Conclusão. Os resultados sugerem que a presença de um íon Mg2+ poderia aumentar a interação no complexo devido à diminuição da energia livre, aumentando assim a afinidade. Assim, propomos ao 3,5-diCQA como farmacóforo para a fabricação de medicamentos antirretrovirais.

Effect of sevoflurane postconditioning on activities of Na+-K+-ATPase and Ca2+ -Mg2+ -ATPase during myocardial ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To investigate the effect of sevoflurane postconditioning on the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase during myocardial ischemia-reperfusion (I/R) in rats and the possible mechanism. Methods Forty-five healthy male Wistar rats weighing 250-280 g were randomly divided into 3 groups ( n = 15 each): sham operation group (group S), I/R group and sevoflurane postconditioning group (group Spo). Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion. In group S the anterior descending branch was only exposed but not ligated. Group Spo received 5 min inhlation of 2.5% sevoflurane 1 min before reperfusion. The myocardial tissues were taken at 2 h of reperfusion for determination of infarct size and activities of Na+ -K+ -ATPase and Ca2 * -Mg2 * -ATPase. Results The infarct size was significantly larger and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were signifi cantly lower in group I/R than in group S ( P ＜ 0.05). The infarct size was significantly smaller and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were significantly higher in group Spo than in group I/R (P ＜ 0.05 ). Conclusion Sevoflurane postconditioning can reduce myocardial I/R injury through increasing the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase.

Effects of Divalent Mg2+ and Monovalent Na+ on Cleavage Reactions by Multiribozyme System in vitro / 中国生物化学与分子生物学报

To better understand the cleavage efficiency of muhiribozyme system on its RNA substrate in the presence and absence of divalent magnesium and monovalent sodium ions.we constructed pGEM-Coat'A,pGEM-Coat'A196Rz plasmids and pGEM-MDRl target plasmid.They were applied to transcribe RNAs with SP6/T7 transcription kit.Cleavage reactions were carried out in cell-free system and reaction products were analyzed by electrophoresis on 6% denaturing polyacrylamide gels in TBS buffer.The gels were dried and exposed to X-ray films for autoradiography.The Image J software was employed to analyze the dried gels.The results indicated that the cleavage efficiency of the muhiribozyme was dependent on the concentration of divalent Mg2+.The cleavage products increased with the concentrations of divalent Mg2+ and were Mg2+ concentration and time dependent.No cleavage product was obtained in the presence of lower than 200 mmol/L Na+ alone.On the contrary,monovalent Na+ inhibited the Mg2+ -induced cleavage reaction in Na+ and Mg2+ coexistance.The cleavage rate was significantly lower than that observed with divalent Mg2+ alone.These results suggested that divalent Mg2+ was required for muhiribozyme on substrate cleavage reaction in the physical condition,whereas monovalent Na+ was not.

Effects of Yiqihuoxuejiedu Formula on the Activity of G-6-Pase and Mg~(2+)-ATPase of Mice with Lewis Lung Cancer / 中国中医药信息杂志

Objective To observe the effect of Yiqihuoxuejiedu formula on the activity of G-6-Pase and Mg2+-ATPase of Lewis cells of mice with Lewis lung cancer. Method Enzyme cytochemistry was used to detect the activity of G-6-Pase and Mg2+-ATPase of the mice lung cancer of Lewis cells. Result The response granules of G-6-Pase and Mg2+-ATPase in the mice lung cancer of Lewis cells became smaller after the treatment of the Yiqihuoxuejiedu formula, the amount of the granules became fewer, the density was lower, which indicated the activity of enzyme reduced evidently. Conclusion Yiqihuoxuejiedu formula can decrease the activity of the G-6-Pase and Mg2+-ATPase.

Vipoxin specificity studied by gas chromatographic determination of enzymatic reaction products. Influence of Ca2+, Mg2+ and Sr2+

Gas chromatographic procedure with mass spectrometric detection was applied to quantitatively determine the enzymatic specificity and activity of vipoxin (a neurotoxin from the Vipera ammodytes meridionalis venom) as well as the influence of Ca2+, Mg2+ and Sr2+ on these properties.

The Effects of Lamotrigine on Epileptiform Discharges Induced by Mg2+ -free Medium and 4-aminopyridine in Hippocampal Slices of Immature Rats

PURPOSE: In order to elucidate the actual mechanism and the optimal concentration of Lamotrigine(LTG) that suppresses epileptiform discharges, we observed epileptiform discharges from hippocampal slices of immature rat in 4-aminopyridine(4-AP) added Mg2+ - free medium of artificial cerebrospinal fluid(aCSF) with various LTG concentrations. METHODS: We divided 19-23 day-old Sprague-Dawley rats into 4 groups; control group(n=12) and 3 LTG groups depending on the concentrations of LTG such as 400 (n=9), 800(n=7), and 1,000(n=8) microM. The rats were anesthetized and their brains were taken, soaked in aCSF(NaCl 125 mM, KCl 2.5 mM, NaH2PO4 2 mM, MgSO4 1.25 mM NaHCO3 25 mM, CaCl2 2 mM, Glucose 10 mM, pH 7.3-7.4). And then the brains were cut into 400 microm hippocampal slices by a vibratome. The slices of control group were soaked in 200 microM 4-AP added Mg2+ -free medium of aCSF for 1 hour, and then extracellular recordings were performed in hippocampal CA1 pyramidal region. The slices of LTG groups were soaked in the solution containing 400, 800, and 1,000 microM LTG, then extracellular recordings were performed. RESULTS: Interictal discharges were observed in all the control and the LTG groups. The latency to the first interictal discharges after 4-AP addition was 52.7+/-26.9 sec in control group, but was 225.0+/-28.2 sec in 800 microM and 322.1+/-116.4 sec in 1,000 microM group of LTG(P<0.05). The duration of interictal discharges was 64.6+/-35.6 sec in control group, but was the shortest in 800 microM group of LTG at 39.3+/-12.6 sec. Ictal discharges were observed in all of control and 400 microM group, but the frequency was decreased as the concentration of LTG increases, 57.1% in 800 microM, 12.5% in 1,000 microM group. The latency to ictal discharge after 4-AP addition was 142.1+/-52.6 sec in control group, but increased as the concentration of LTG increases, 304.4+/-84.5 sec in 400 microM group and 689.8+/-213.1 sec in 800 microM group(P<0.05). The duration of ictal discharges was 1,534.7/-339.3 sec in control group, but decreased as the concentration of LTG increases, it was 126.5+/-76.1 sec in 800 microM group(P <0.05) and 42 sec in 1,000 microM group. CONCLUSION: The antiepileptic effects of LTG were most significant when the concentration, inhibiting epileptiform discharges induced by 4-AP and Mg2+ -free medium in hippocampal slices of immature rats, was 800 microM or higher. Although the basic pharmacologic mechanism of LTG is the inhibition of sodium channel, it may also work on potassium channel at higher concentrations.