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1
Fuentes, Yihajara, Claudia Giovagnoli-Vicuña, Mario Faúndez und Ady Giordano. „Microencapsulation of Chilean Papaya Waste Extract and Its Impact on Physicochemical and Bioactive Properties“. Antioxidants 12, Nr. 10 (23.10.2023): 1900. http://dx.doi.org/10.3390/antiox12101900.
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The microencapsulation of bioactive extracts of Chilean papaya waste, including both seeds and skin, was investigated. Papaya waste extract microcapsules utilizing maltodextrin at 10% (MD10), 20% (MD20), and 30% (MD30) (w/v) as the wall material through the freeze-drying process were obtained, and subsequently their physicochemical, antioxidant, and antimicrobial properties were evaluated. The TPC efficiency and yield values achieved were more than 60% for the microencapsulated seed and skin extracts, respectively. The best results for phenolic and antioxidant compounds were found in the microencapsulated seed extract with MD20, with a value of 44.20 ± 3.32 EAG/g DW for total phenols and an antioxidant capacity of 12.0 ± 0.32 mol ET/g DW for the DPPH and 236.3 ± 4.1 mol ET/g DW for the FRAP assay. In addition, the seed and skin samples reduced ROS generation in H2O2-treated Hek293 cells. In terms of antimicrobial activity, values ranging from 7 to 15 mm of inhibitory halos were found, with the maximum value corresponding to the inhibition of S. aureus, for both microencapsulated extracts. Therefore, the successful microencapsulation of the waste bioactive extracts (seed and skin) with the demonstrated antimicrobial and antioxidant properties highlight the bioactivity from Chilean papaya waste resources.
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Campo Fernández, Mercedes, Donna Fiorella Granja Rizzo, Nubia Lisbeth Matute Castro, Osmany Cuesta Rubio und Ingrid Márquez Hernández. „Microencapsulación mediante secado por atomización a partir de un extracto de los cálices de Hibiscus sabdariffa L.“ Revista Colombiana de Química 50, Nr. 1 (25.03.2021): 40–50. http://dx.doi.org/10.15446/rev.colomb.quim.v50n1.88424.
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La investigación tuvo como objetivo definir las mejores condiciones de extracción asistida por ultrasonido de los cálices de H. sabdariffa L. y la obtención de polvos microencapsulados, mediante secado por aspersión. Los extractos fueron analizados, considerando como variables: disolvente (agua y agua/etanol) y la relación temperatura/tiempo de extracción (25 ºC/60 min y 60 ºC/30 min). Para el secado se evaluaron las variables temperatura de entrada (150 ºC; 190 ºC) y la mezcla de encapsulantes goma arábiga (G) y maltodextrina (MD) (G40/MD60; G60/MD40). Los parámetros utilizados para el análisis fueron: rendimiento, pH, °Bx, composición química (fenoles y antocianinas totales, CLAE-EM) y capacidad antioxidante (DPPH). La mejor condición para la extracción de polifenoles resultó ser con agua:etanol (80:20), a 60 °C y durante 30 min. Se identificó la presencia de ácidos fenólicos, glicósidos de flavonoles y las antocianinas (delfinidina-3-sambubiósido y cianidina-3-sambubiósido), como las señales de mayor intensidad. Con el secado por atomización a 150 °C y con G60/MD40, se logró el mayor contenido de fenoles totales y antocianinas, sin embargo, la capacidad antioxidante se favoreció a 150 °C y con G40/MD60. Las micropartículas obtenidas podrían valorarse como materia prima para la elaboración de fitofármacos o alimentos funcionales, considerando su fácil manipulación, posible estabilidad y su valor antioxidante.
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Hejgaard, Jørn, William A. Laing, Salla Marttila, Andrew P. Gleave und Thomas H. Roberts. „Serpins in fruit and vegetative tissues of apple (Malus domestica): expression of four serpins with distinct reactive centres and characterisation of a major inhibitory seed form, MdZ1b“. Functional Plant Biology 32, Nr. 6 (2005): 517. http://dx.doi.org/10.1071/fp04220.
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Most serpins irreversibly inhibit serine proteinases of the chymotrypsin family using a suicide-substrate-based mechanism. Serpins are present in all domains of life, but physiological functions in the plant kingdom are yet to be elucidated. Inhibitory properties of many abundant cereal grain serpins are well characterised, but serpins have not been identified in eudicot seeds. In apple (Malus domestica Borkh.), the origin of 88 serpin expressed sequence tags (ESTs) identified among 160 000 ESTs from 30 cultivar-, tissue- and time-specific libraries showed that serpin genes are expressed in a wide variety of tissues, including developing and mature fruits, seeds and vegetative buds as well as developing, mature and senescing leaves. Analysis of 46 sequences, most full-length, identified serpins with four distinct reactive centres belonging to two subfamilies (MdZ1 and MdZ2) with ~85% amino acid sequence identity. MdZ1 included three molecular forms with identical reactive centre loop (RCL) sequences except for three different, but related, residues at P2 (Asp, Asn or Glu). A major seed serpin, MdZ1b, with P2–P1′ Glu–Arg–Arg was purified from decorticated seeds and characterised kinetically. MdZ1b was a fast inhibitor of bovine and porcine trypsin (second-order association rate constant k a ~4 × 106 m –1 s–1 and stoichiometry of inhibition SI = 1). Human plasmin and urokinase-type plasminogen activator (u-PA), but not thrombin, were inhibited at lower rates (k a ~104 m –1 s–1). Chymotrypsin was inhibited at the same site (k a~4 × 103 m –1 s–1), but a significant part of MdZ1b was cleaved as substrate (SI > 2). Unexpectedly, the MdZ1b-trypsin complex was relatively short-lived with a first-order dissociation rate constant k d in the order of 10−4 s–1. The bulk of mature seed MdZ1b was localised to the cotyledons. The content of MdZ1b in ripe apples was 5–26 µg per seed, whereas MdZ1b could not be detected in the cortex or skin. Localisation and inhibitory specificity of serpins in monocot and eudicot plants are compared and putative functions are discussed.
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Lacey, D. L., J. C. Chappel und S. L. Teitelbaum. „Interleukin 1 stimulates proliferation of a nontransformed T lymphocyte line in the absence of a co-mitogen.“ Journal of Immunology 139, Nr. 8 (15.10.1987): 2649–55. http://dx.doi.org/10.4049/jimmunol.139.8.2649.
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Abstract Although interleukin (IL) 2-responsive T cell lines provide an opportunity to study the cellular effects of this lymphokine on homogeneous T lymphocyte populations, T cell clones which proliferate in response to IL-1 alone have not been available. We have isolated from cultures of the nontransformed murine T helper cell line, D10 . G4 . 1, a variant (MD10 cells) which proliferates (no lectin or antigen needed) in response to IL-1 alone. The MD10 cells are markedly sensitive to either murine or human recombinant IL-alpha (HrIL-1 alpha) with half-maximal responses observed at monokine concentrations as low as 0.4 X 10(-12) M or 0.8 U/ml, respectively. MD10 cells show the maximal IL-1 effect at 72 hr where the response exceeds the base line by 100-fold (approximately 3,000----300,000 cpm of [3H]thymidine). Whereas both HrIL-2 and purified murine B cell-stimulatory factor 1 (MpBSF-1) induce MD10 proliferation, the maximal response to either is much lower (HrIL-2: 50X baseline; MpBSF-1: less than 20X base line) than to IL-1. Conditioned media from control, concanavalin A-, or IL-1-treated MD10 cells fail to stimulate CTLL or HT-2 cell proliferation alone or inhibit CTLL mitogenesis in the presence of added HrIL-2. Furthermore, monoclonal antibodies to BSF-1 fail to inhibit IL-1-stimulated MD10 replication, and neither HT-2 nor CTLL cells proliferate despite direct cell-to-cell contact with IL-1-treated MD10 cells. When combined, IL-1 (10(-13), 10(-12) M) and IL-2 (10(-13) to 10(-10) M) act synergistically in their MD10 cell growth-promoting effects. MD10 proliferation induced by either IL-1 or IL-2 is relatively resistant to cyclosporine A, with the ID50 of cyclosporine for both IL-1- and IL-2-exposed MD10 cells (ID50 5000 ng/ml) exceeding that for concanavalin A-activated splenocytes (ID50 20 ng/ml) by 2 to 3 orders of magnitude. Finally, MD10 cells bear the L3T4 antigen, IL-2 receptors, and the same clonotypic antigen receptor as the parent clone as recognized by monoclonal antibody 3D3. These data suggest that, in respect to this particular T cell line, IL-1 is directly growth-promoting or, alternatively, induces the production of undetectable, intermediate growth factor(s) resistant to inhibition by cyclosporine A.
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Civitelli, R., S. L. Teitelbaum, K. A. Hruska und D. L. Lacey. „IL-1 activates the Na+/H+ antiport in a murine T cell.“ Journal of Immunology 143, Nr. 12 (15.12.1989): 4000–4008. http://dx.doi.org/10.4049/jimmunol.143.12.4000.
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Abstract One of the early events following growth factor exposure is elevation of intracellular pH, a process mediated by the Na+/H+ antiport. We studied the effects of human rIL-1 alpha (HrIL-1 alpha) on intracellular pH (pHi) and calcium ([Ca2+]i) in a murine T cell line (MD10 cells), which proliferates in response to IL-1 alone. By using the intracellularly trapped fluorescent dyes (2(1),7(1)-bis-2-carboxyethyl)-5(and -6) carboxyfluorescein) and indo-1, we monitored immediate to early changes of pHi and [Ca2+]i in response to HrIL-1 alpha. Exposure to HrIL-1 alpha (120 pM) leads to an early, sustained intracellular alkalinization (delta pH = + 0.09 +/- 0.03) that plateaus within 20 min. Lower concentrations of the monokine (12 pM, 1.2 pM) have a positive but not statistically significant effect on pHi. These effects parallel the degree of MD10 IL-1R saturation predicted by the KD (49 pM) as assessed by 125I-HrIL-1 alpha binding by MD10 cells (Bmax = approximately 1300). Both the MD10 IL-1 receptor KD and the HrIL-1 alpha concentration required to induce early measurable alkaline pH shifts, however, exceed by three orders of magnitude the HrIL-1 alpha ED50 (50 fM) required for MD10 proliferation. The IL-1-induced rise in pHi is both sodium dependent and amiloride sensitive, indicative of activation of the Na+/H+ antiport. Additionally, PMA (100 nM) and IL-2 (2 nM) alkalinize MD10 cells, with the rise in pHi as a result of PMA exceeding the maximal IL-1 effect (delta pH = + 0.13 +/- 0.04). Furthermore, although PMA alkalinizes cells previously exposed to HrIL-1 alpha, the monokine does not alter the pHi of PMA-treated MD10 cells. Importantly, intracellular alkalinization induced by either HrIL-1 alpha or PMA is inhibited by staurosporine (1 mu iM). Finally, HrIL-1 alpha does not change MD10 [Ca2+]i, in either an acute or sustained fashion. These results indicate that IL-1 activates the Na+/H+ antiport in T cells by a mechanism that is unrelated to changes in [Ca2+]i but may involve protein kinase C activation.
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Vernillo, Anthony. „Using Patients as Participants in Dental Board Exams for Licensure — A Contemporary Demonstration of Reductio ad Absurdum“. Journal of the Academy of Distinguished Educators 6, Nr. 1 (2018): 10. http://dx.doi.org/10.33682/56xr-mdz4.
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In his commentary, Dr. Vernillo supports Dr. Schloss's argument and goes further. He asserts that given advances in current computer and informational technology, board examinations that adequately assess dental students' clinical skills without the use of human subjects are doable, ethically justified, and should be mandated.
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Foo, Ning-Ping, Yu-Fan Liu, Ping-Ching Wu, Chung-Hsi Hsing, Bu-Miin Huang und Edmund-Cheung So. „Midazolam’s Effects on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-lymphocytes“. International Journal of Molecular Sciences 22, Nr. 13 (04.07.2021): 7198. http://dx.doi.org/10.3390/ijms22137198.
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Midazolam (MDZ) could affect lymphocyte immune functions. However, the influence of MDZ on cell’s K+ currents has never been investigated. Thus, in the present study, the effects of MDZ on Jurkat T lymphocytes were studied using the patch-clamp technique. Results showed that MDZ suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in concentration-, time-, and state-dependent manners. The IC50 for MDZ-mediated reduction of IK(DR) density was 5.87 μM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on IK(DR) density was estimated with a dissociation constant of 5.14 μM. In addition, the inactivation curve of IK(DR) associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of IK(DR) was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both IK(DR) and IKCa-channel activity appeared to be independent from GABAA receptors and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes. In conclusion, MDZ suppressed current density of IK(DR) in concentration-, time-, and state-dependent manners in Jurkat T-lymphocytes and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes.
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Lu, Hsin-Ling, King-Chuen Wu, Char-Wen Chen, Hung-Kai Weng, Bu-Miin Huang, Ting-Yu Lin, Ming-Hsin Liu, Edmund-Cheung So, Ruey-Mo Lin und Yang-Kao Wang. „Anticancer Effects of Midazolam on Lung and Breast Cancers by Inhibiting Cell Proliferation and Epithelial-Mesenchymal Transition“. Life 11, Nr. 12 (13.12.2021): 1396. http://dx.doi.org/10.3390/life11121396.
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Despite improvements in cancer treatments resulting in higher survival rates, the proliferation and metastasis of tumors still raise new questions in cancer therapy. Therefore, new drugs and strategies are still needed. Midazolam (MDZ) is a common sedative drug acting through the γ-aminobutyric acid receptor in the central nervous system and also binds to the peripheral benzodiazepine receptor (PBR) in peripheral tissues. Previous studies have shown that MDZ inhibits cancer cell proliferation but increases cancer cell apoptosis through different mechanisms. In this study, we investigated the possible anticancer mechanisms of MDZ on different cancer cell types. MDZ inhibited transforming growth factor β (TGF-β)-induced cancer cell proliferation of both A549 and MCF-7 cells. MDZ also inhibited TGF-β-induced cell migration, invasion, epithelial-mesenchymal-transition, and Smad phosphorylation in both cancer cell lines. Inhibition of PBR by PK11195 rescued the MDZ-inhibited cell proliferation, suggesting that MDZ worked through PBR to inhibit TGF-β pathway. Furthermore, MDZ inhibited proliferation, migration, invasion and levels of mesenchymal proteins in MDA-MD-231 triple-negative breast cancer cells. Together, MDZ inhibits cancer cell proliferation both in epithelial and mesenchymal types and EMT, indicating an important role for MDZ as a candidate to treat lung and breast cancers.
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Harigaya, Hiroko, Risako Chiba-Ohkuma, Takeo Karakida, Ryuji Yamamoto, Keiko Fujii-Abe, Hiroshi Kawahara und Yasuo Yamakoshi. „Potential for Drug Repositioning of Midazolam as an Inhibitor of Inflammatory Bone Resorption“. International Journal of Molecular Sciences 25, Nr. 14 (12.07.2024): 7651. http://dx.doi.org/10.3390/ijms25147651.
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Drug repositioning is a method for exploring new effects of existing drugs, the safety and pharmacokinetics of which have been confirmed in humans. Here, we demonstrate the potential drug repositioning of midazolam (MDZ), which is used for intravenous sedation, as an inhibitor of inflammatory bone resorption. We cultured a mouse macrophage-like cell line with or without MDZ and evaluated its effects on the induction of differentiation of these cells into osteoclasts. For in vivo investigations, we administered lipopolysaccharide (LPS) together with MDZ (LPS+MDZ) to the parietal region of mice and evaluated the results based on the percentage of bone resorption and calvaria volume. Furthermore, we examined the effects of MDZ on the production of reactive oxygen species (ROS) in cells and on its signaling pathway. MDZ inhibited osteoclast differentiation and bone resorption activity. In animal studies, the LPS+MDZ group showed a decreasing trend associated with the rate of bone resorption. In addition, the bone matrix volume in the LPS+MDZ group was slightly higher than in the LPS only group. MDZ inhibited osteoclast differentiation by decreasing ROS production and thereby negatively regulating the p38 mitogen-activated protein kinase pathway. Thus, we propose that MDZ could potentially be used for treating inflammatory bone resorption, for example, in periodontal disease.
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Shrestha, Nikesh, Saba Khan, Yub Raj Neupane, Shweta Dang, Shadab Md, Usama A. Fahmy, Sabna Kotta, Nabil A. Alhakamy, Sanjula Baboota und Javed Ali. „Tailoring Midazolam-Loaded Chitosan Nanoparticulate Formulation for Enhanced Brain Delivery via Intranasal Route“. Polymers 12, Nr. 11 (04.11.2020): 2589. http://dx.doi.org/10.3390/polym12112589.
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In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ solution (Cmax 245.44 ± 12.83 ng/mL, tmax 1 h, and AUC0-480 1208.94 ng.min/mL) and IN administration of MDZ solution (Cmax 211.67 ± 12.82, tmax 2 h, and AUC0-480 1036.78 ng.min/mL). The brain–blood ratio of MDZ-CSNPs (IN) were significantly greater at all sampling time points when compared to that of MDZ solution (IV) and MDZ (IN), which indicate that direct nose-to-brain delivery by bypassing the blood–brain barrier demonstrates superiority in brain delivery. The drug-targeting efficiency (DTE%) as well as nose-to-brain direct transport percentage (DTP%) of MDZ-CSNPs (IN) was found to be comparatively higher than that for other formulations, suggesting better brain targeting potential. Thus, the obtained results demonstrated that IN MDZ-CSNP has come up as a promising approach, which exhibits tremendous potential to mark a new landscape for the treatment of status epilepticus.
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Liu, Li, Qi You, Yingfeng Tu, Quanyi Li, Lihong Zheng, Xuan Li, Jing Gu und Guonian Wang. „Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway“. Cellular Physiology and Biochemistry 35, Nr. 1 (2015): 126–36. http://dx.doi.org/10.1159/000369681.
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Background: There is an increasing interest in the role of astrocytes contributing to the intrinsic bioremediation of ischemic brain injury. The purpose of this study was to disclose the effects and mechanism of midazolam (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition. Methods: The astrocytes were assigned randomly into four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The astrocytes were treated with MDZ at dose of 10 μmol/L in OGD+MDZ group. And in OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10μmol/L and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry. Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and Caspase-3 proteins were determined by western blotting assay. Results: Astrocytes proliferation was decreased obviously in OGD group, while MDZ could increase astrocytes proliferation under OGD condition. Moreover, OGD could induce apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6, a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3 proteins decreased relative to OGD group. But IL-6 could counteract the anti-apoptotic effects of MDZ. Conclusion: Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. We firstly disclose the beneficial roles of midazolam in astrocytes under ischemic condition, which may be a rational treatment selection for ischemic cerebral protection.
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van Groen, BD, WHJ Vaes, BK Park, EHJ Krekels, E. van Duijn, L.-T. Kõrgvee, W. Maruszak et al. „O20 Dose-linearity of the pharmacokinetics of an intravenous [14C]midazolam microdose in children“. Archives of Disease in Childhood 104, Nr. 6 (17.05.2019): e9.1-e9. http://dx.doi.org/10.1136/archdischild-2019-esdppp.20.
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BackgroundDrug disposition in children may vary from adults due to age-related variation in drug metabolism, but paediatric pharmacokinetic (PK) studies are challenging. Microdose studies present an innovation to study PK in paediatrics, and can only be used when the PK of a microdose are dose-linear to a therapeutic dose. We aimed to assess dose-linearity of [14C]midazolam (MDZ), a marker for the activity of the developmentally regulated CYP3A enzyme, by comparing the PK of an intravenous (IV) [14C]MDZ microtracer given simultaneously with therapeutic MDZ, with the PK of a single IV [14C]MDZ microdose.MethodsPreterm to 2-year-old infants admitted to the intensive care unit received [14C]MDZ IV either as a microtracer during therapeutic MDZ infusion or as an isolated microdose. Dense blood sampling was done up to 36 hours after dosing. Plasma concentrations of [14C]MDZ and [14C]1-OH-MDZ were determined by accelerator mass spectrometry. A population PK model was developed with NONMEM 7.4 to study whether there was a difference in the PK of the microtracer versus those of a microdose [14C]MDZ.ResultsOf fifteen children (median gestational age 39.4 [range 23.9–41.4] weeks, postnatal age 11.4 [0.6–49.1] weeks), nine received a microdose and six a microtracer [14C]MDZ (111 Bq/kg; 37.6 ng/kg). In a two-compartment PK model, bodyweight was the most significant covariate for volume of distribution. There was no statistically significant difference in any PK parameter between the [14C]MDZ microdose or microtracer, suggesting the PK of MDZ to be linear within the range of the therapeutic doses and microdoses.ConclusionOur data supports the dose-linearity of an IV [14C]MDZ microdose in children, thus a [14C]MDZ microdosing approach can be used to study developmental changes in hepatic CYP3A activity.Disclosure(s)This project was funded by the ZonMw ERA-NET PRIOMEDCHILD programme (projectnumber 113205022). * both authors contributed equally
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Zhang, Xun, Zhiguo Li, Jing Gao, Zengming Wang, Xiang Gao, Nan Liu, Meng Li, Hui Zhang und Aiping Zheng. „Preparation of Nanocrystals for Insoluble Drugs by Top-Down Nanotechnology with Improved Solubility and Bioavailability“. Molecules 25, Nr. 5 (28.02.2020): 1080. http://dx.doi.org/10.3390/molecules25051080.
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Midazolam is a rapidly effective benzodiazepine drug that is widely used as a sedative worldwide. Due to its poor solubility in a neutral aqueous solution, the clinical use of midazolam is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have drawn worldwide attention. We prepared a stable nanosuspension system that causes little muscle irritation. The particle size of the midazolam nanocrystals (MDZ/NCs) was 286.6 ± 2.19 nm, and the crystalline state of midazolam did not change in the size reduction process. The dissolution velocity of midazolam was accelerated by the nanocrystals. The pharmacokinetics study showed that the AUC0–t of the MDZ/NCs was 2.72-fold (p < 0.05) higher than that of the midazolam solution (MDZ/S), demonstrating that the bioavailability of the MDZ/NC injection was greater than that of MDZ/S. When midazolam was given immediately after the onset of convulsions, the ED50 for MDZ/NCs was significantly more potent than that for MDZ/S and DZP/S. The MDZ/NCs significantly reduced the malondialdehyde content in the hippocampus of the seizures model rats and significantly increased the glutathione and superoxide dismutase levels. These results suggest that nanocrystals significantly influenced the dissolution behavior, pharmacokinetic properties, anticonvulsant effects, and neuroprotective effects of midazolam and ultimately enhanced their efficacy in vitro and in vivo.
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Karakida, Takeo, Kazuo Onuma, Mari Saito, Ryuji Yamamoto, Toshie Chiba, Risako Chiba, Yukihiko Hidaka, Keiko Fujii-Abe, Hiroshi Kawahara und Yasuo Yamakoshi. „Potential for Drug Repositioning of Midazolam for Dentin Regeneration“. International Journal of Molecular Sciences 20, Nr. 3 (04.02.2019): 670. http://dx.doi.org/10.3390/ijms20030670.
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Drug repositioning promises the advantages of reducing costs and expediting approvalschedules. An induction of the anesthetic and sedative drug; midazolam (MDZ), regulatesinhibitory neurotransmitters in the vertebrate nervous system. In this study we show the potentialfor drug repositioning of MDZ for dentin regeneration. A porcine dental pulp-derived cell line(PPU-7) that we established was cultured in MDZ-only, the combination of MDZ with bonemorphogenetic protein 2, and the combination of MDZ with transforming growth factor-beta 1. Thedifferentiation of PPU-7 into odontoblasts was investigated at the cell biological and genetic level.Mineralized nodules formed in PPU-7 were characterized at the protein and crystal engineeringlevels. The MDZ-only treatment enhanced the alkaline phosphatase activity and mRNA levels ofodontoblast differentiation marker genes, and precipitated nodule formation containing a dentinspecificprotein (dentin phosphoprotein). The nodules consisted of randomly orientedhydroxyapatite nanorods and nanoparticles. The morphology, orientation, and chemicalcomposition of the hydroxyapatite crystals were similar to those of hydroxyapatite that hadtransformed from amorphous calcium phosphate nanoparticles, as well as the hydroxyapatite inhuman molar dentin. Our investigation showed that a combination of MDZ and PPU-7 cellspossesses high potential of drug repositioning for dentin regeneration.
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González-García, Jaime, Manuel Conejero und Jorge Gutiérrez-Hellín. „Assessing Jump Performance: Intra- and Interday Reliability and Minimum Difference of Countermovement Jump and Drop Jump Outcomes, Kinetics, Kinematics, and Jump Strategy“. Applied Sciences 14, Nr. 6 (21.03.2024): 2662. http://dx.doi.org/10.3390/app14062662.
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Understanding the reliability of jump testing is essential to determine the neuromuscular progress of athletes and make informed decisions. This study aimed to assess the reliability of several countermovement jump (CMJ) and drop jump (DJ) test metrics in female volleyball players. Sixteen (n = 16) semi-professional female volleyball players participated in this test-retest study. Intrasession and intersession reliability of CMJ and DJ metrics were evaluated using a randomized cross-over design. A dual force platform was used to collect CMJ and DJ data, and several dependent variables were calculated using forward dynamics. Intraclass correlation coefficients (ICC), coefficients of variation (CV), and minimum difference (MD) were calculated to assess intra- and interday reliability. During the same testing, the third attempt consistently yielded the highest values for both tests in jump height but presented excellent reliability (CMJ: ICC [95%CI] = 0.97 [0.93–0.99]; CV [95%CI] = 4.1% [1.2–7.0]; MD95 = 3.5 cm; MD90 = 2.9 cm; DJ: ICC [95%CI] = 0.91 [0.77–0.97]; CV [95%CI] = 6.7% [1.9–11.5]; MD95 = 6.0 cm; MD90 = 5.0 cm). CMJ height exhibited excellent reliability between sessions (ICC [95%CI] = 0.93 [0.81–0.97]; CV [95%CI] = 3.8% [1.1–6.4]; MD95 = 3.5 cm; MD90 = 3.0 cm), whereas DJ height demonstrated slightly lower but still acceptable intersession reliability (ICC [95%CI] = 0.81 [0.55–0.93]; CV [95%CI] = 6.1% [1.7–10.4]; MD95 = 5.2 cm; MD90 = 4.4 cm). Intersession reliability for CMJ kinetics and kinematics was excellent for 13 of the 24 metrics assessed. For DJ, only concentric (ICC [95%CI] = 0.91 [0.76–0.97]; CV [95%CI] = 3.0% [0.9–5.2]; MD95 = 15 Ns; MD90 = 12.6 Ns) and eccentric impulses (ICC [95%CI] = 0.99 [0.96–0.99]; CV [95%CI] = 1.7% [0.5–2.9]; MD95 = 9.2 Ns; MD90 = 7.7 Ns) demonstrated excellent intersession reliability. Most CMJ variables showed excellent reliability within sessions, while DJ had lower reliability in most metrics. These findings provide valuable information to physical trainers to select the metrics to assess athletes’ performance as well as to identify a minimum cut-off value that serves as a reference for each of the metrics reported in both tests.
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Hidaka, Yukihiko, Risako Chiba-Ohkuma, Takeo Karakida, Kazuo Onuma, Ryuji Yamamoto, Keiko Fujii-Abe, Mari M. Saito, Yasuo Yamakoshi und Hiroshi Kawahara. „Combined Effect of Midazolam and Bone Morphogenetic Protein-2 for Differentiation Induction from C2C12 Myoblast Cells to Osteoblasts“. Pharmaceutics 12, Nr. 3 (02.03.2020): 218. http://dx.doi.org/10.3390/pharmaceutics12030218.
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In drug repositioning research, a new concept in drug discovery and new therapeutic opportunities have been identified for existing drugs. Midazolam (MDZ) is an anesthetic inducer used for general anesthesia. Here, we demonstrate the combined effects of bone morphogenetic protein-2 (BMP-2) and MDZ on osteogenic differentiation. An immortalized mouse myoblast cell line (C2C12 cell) was cultured in the combination of BMP-2 and MDZ (BMP-2+MDZ). The differentiation and signal transduction of C2C12 cells into osteoblasts were investigated at biological, immunohistochemical, and genetic cell levels. Mineralized nodules formed in C2C12 cells were characterized at the crystal engineering level. BMP-2+MDZ treatment decreased the myotube cell formation of C2C12 cells, and enhanced alkaline phosphatase activity and expression levels of osteoblastic differentiation marker genes. The precipitated nodules consisted of randomly oriented hydroxyapatite nanorods and nanoparticles. BMP-2+MDZ treatment reduced the immunostaining for both α1 and γ2 subunits antigens on the gamma-aminobutyric acid type A (GABAA) receptor in C2C12 cells, but enhanced that for BMP signal transducers. Our investigation showed that BMP-2+MDZ has a strong ability to induce the differentiation of C2C12 cells into osteoblasts and has the potential for drug repositioning in bone regeneration.
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Qulu, Wenkosi Perez, Gugulethu Mzobe, Andile Mtshali, Marothi Peter Letsoalo, Farzana Osman, James Emmanuel San, Asavela Olona Kama et al. „Metronidazole Treatment Failure and Persistent BV Lead to Increased Frequencies of Activated T- and Dendritic-Cell Subsets“. Microorganisms 11, Nr. 11 (27.10.2023): 2643. http://dx.doi.org/10.3390/microorganisms11112643.
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Metronidazole (MDZ) treatment failure and bacterial vaginosis (BV) recurrence rates are high among African women. This cohort study identified genital immune parameters associated with treatment response by comparing vaginal microbiota and immune cell frequencies in endocervical cytobrushes obtained from 32 South African women with symptomatic BV pre- and post-metronidazole treatment. Cervical T- and dendritic-cell subsets were phenotyped using multiparameter flow cytometry and the composition of vaginal microbial communities was characterized using 16S rRNA gene sequencing. MDZ treatment led to a modest decrease in the relative abundance of BV-associated bacteria, but colonization with Lactobacillus species (other than L. iners) was rare. At 6 and 12 weeks, MDZ-treated women had a significant increase in the frequencies of CCR5+ CD4+ T cells and plasmacytoid dendritic cells compared to the pre-treatment timepoint. In addition, MDZ non-responders had significantly higher frequencies of activated CD4 T cells and monocytes compared to MDZ responders. We conclude that MDZ treatment failure was characterized by an increased expression of activated T- and dendritic-cell subsets that may enhance HIV susceptibility. These data suggest the need to further assess the long-term impact of MDZ treatment on mucosal immune response and the vaginal microbiota.
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Nguyen, Nghi M., Daniel Meyer, Luke Meyer, Subhash Chand, Sankarasubramanian Jagadesan, Maireen Miravite, Chittibabu Guda, Sowmya V. Yelamanchili und Gurudutt Pendyala. „Identification of YWHAH as a Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure during Early Development“. Cells 12, Nr. 6 (22.03.2023): 966. http://dx.doi.org/10.3390/cells12060966.
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Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics the exposure of MDZ in the NICU using an increasing dosage regimen, we isolated BDEVs from postnatal 21-days-old control and MDZ groups using a differential sucrose density gradient. BDEVs from the control and MDZ groups were then characterized using a ZetaView nanoparticle tracking analyzer and transmission electron microscopy analysis. Next, using RT-qPCR, we examined the expression of key ESCRT-related genes involved in EV biogenesis. Lastly, using quantitative mass spectrometry-based proteomics, we mined the BDEV protein cargo that revealed key differentially expressed proteins and associated molecular pathways to be altered post long-term MDZ exposure. Our study characterized the proteome in BDEV cargo from long-term MDZ exposure at early development. Importantly, we identified and validated the expression of YWHAH as a potential target for further characterization of its downstream mechanism and a potential biomarker for the early onset of neurodevelopment and neurodegenerative diseases. Overall, the present study demonstrated long-term exposure to MDZ at early development stages could influence BDEV protein cargo, which potentially impact neural functions and behavior at later stages of development.
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Rixe, Olivier, John Sarantopoulos, Chung-Tsen Hsueh, A. Craig Lockhart, Sharona Ross, Sanjiv S. Agarwala, Wendy Zhang et al. „Absence of interaction of cabazitaxel on the pharmacokinetics of midazolam: Results of a drug–drug interaction study in patients with advanced solid tumors.“ Journal of Clinical Oncology 31, Nr. 6_suppl (20.02.2013): 126. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.126.
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126 Background: Cabazitaxel (Cbz) is approved in combination with prednisone/prednisolone for the treatment of men with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen. In vitro studies showed that Cbz is mainly metabolized through CYP3A, resulting in inhibition of this family of enzymes. Midazolam (Mdz) is primarily metabolized by CYP3A4. We aimed to determine the effect of Cbz on CYP3A activity by comparing the pharmacokinetic (PK) properties of Mdz when administered alone and following co-administration with Cbz. Methods: An ongoing safety and PK study of Cbz in patients with metastatic or locally advanced solid tumors and varying degrees of hepatic impairment (NCT01140607) included a cohort with normal hepatic function to assess the effect of a single Cbz dose on the PK profile of a single dose of Mdz. This was an open-label, two-period, fixed-sequence study in patients aged between 45 and 60 years with advanced solid tumors and normal hepatic function. A single dose of Mdz (2 mg) was administered orally alone (Day –1) and at the end of a 1-hour infusion of Cbz (25 mg/m2) (Day 1), with a 24-hour interval between the two administrations of Mdz. Endpoints included AUC and AUClastof Mdz with and without Cbz administration, and safety evaluations. Results: Of the 13 patients enrolled and treated in the cohort, 11 patients were included in the PK analysis. Exposure (AUC and AUClast) and other PK parameters after a single administration of Mdz alone and in combination with Cbz (Day 1) were similar. The AUC ratio for Mdz administered alone or with Cbz was 0.97 (90% CI: 0.76–1.23). The AUClast ratio for Mdz administered alone or with Cbz was 1.04 (90% CI: 0.81–1.34). All 13 patients had ≥1 adverse event (AE), 11 (84.6%) experienced a Grade 3–4 AE, and 4 (30.8%) experienced a serious AE. The majority of Grade 3–4 AEs were haematological and no new or unexpected safety findings were observed. Conclusions: In this study, Cbz did not increase the plasma exposure of Mdz. This indicates that Cbz is not a CYP3A inhibitor in the clinical setting and can be administered in combination with drugs metabolized by CYP3A. Clinical trial information: NCT01140607.
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Lacey, D. L., und J. M. Erdmann. „IL-1 and IL-4 modulate IL-1 receptor expression in a murine T cell line.“ Journal of Immunology 145, Nr. 12 (15.12.1990): 4145–53. http://dx.doi.org/10.4049/jimmunol.145.12.4145.
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Abstract The combination of IL-1 and IL-4 stimulates the proliferation of certain murine T cell populations. Although this effect has been best characterized for a number of murine type 2 Th cell (Th2) clones, the mechanism(s) by which these cytokines effect this response is unclear. We have examined the effects of IL-1 and IL-4 on IL-1R expression by MD10 cells, and IL-1-responsive murine T cell line. These cells bear specific IL-1R, which bind human and murine IL-1 alpha and -beta. The measured apparent IL-1R dissociation constant ranged from 41 to 255 pM using 125I-HrIL-1 alpha. Cross-linking studies demonstrated two different 125I-HrIL-1 alpha binding complexes having Mr of 70,000 and 130,000 to 156,000. When removed from passage conditions and placed in non-growth factor-supplemented media, MD10 IL-1R expression spontaneously increased two- to fourfold over the first 11 to 12 h of culture followed by a decline. This phenomenon is partially inhibitable by cycloheximide suggesting that protein synthesis is involved. In agreement with other reports, HrIL-1 alpha down-regulated the expression of its own receptor with an ED50 of between 1 and 10 pM HrIL-1 alpha for this effect. In most experiments, low amounts of HrIL-1 alpha (1.0, 0.1 pM) significantly augmented IL-1R expression. Scatchard analysis of data obtained with all HrIL-1 alpha treatment conditions showed that the effects were due to a change in receptor number, not affinity. Significantly, purified murine IL-4 (MpIL-4) augmented MD10 IL-1R expression in both a time- and dose-dependent fashion. In the presence of 50 U/ml MpIL-4, MD10 IL-1R expression increased two- to threefold after 24 h without a change in receptor affinity. When MpIL-4 (50 U/ml) and various amounts of HrIL-1 alpha (.01-1000 pM) were co-added, the down-regulatory effect of high levels of HrIL-1 alpha was significantly antagonized. When added to cultures after 24 h of HrIL-1 alpha (100 pM) treatment, MpIL-4 reversed the IL-1R down-regulatory effect induced by high levels of HrIL-1 alpha. Finally, when combined in MD10 proliferation assays, MpIL-4 synergistically enhanced the proliferation of MD10 cells treated with suboptimal levels of HrIL-1 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
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Wakita, Ryo, Hikaru Kohase und Haruhisa Fukayama. „A Comparison of Dexmedetomidine Sedation With and Without Midazolam for Dental Implant Surgery“. Anesthesia Progress 59, Nr. 2 (01.06.2012): 62–68. http://dx.doi.org/10.2344/11-11.1.
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Dexmedetomidine (DEX) has a minimal respiratory depressive effect, which is beneficial for dentistry; however, it has the disadvantage of permitting an intraoperative arousal response such that the patient appears to be suddenly no longer sedated, and it has a variable amnestic effect. Since midazolam (MDZ) in an appropriate dose has a profound amnesic effect, we investigated whether additional MDZ compensates for the disadvantage of DEX and enables a better quality of sedation. Forty-three subjects were randomly divided into 4 groups. In group 1, MDZ (0.02 mg/kg) was administered intravenously, followed by a dose of 0.01 mg/kg every 45 minutes. After the first dose of MDZ, preloading with DEX (2 µg/kg/h for 10 minutes) was started and maintained with a dosage of 0.5 µg/kg/h. In group 2, MDZ was infused in the same manner as in group 1, followed by preloading with DEX (1 µg/kg/h for 10 minutes) and maintenance (0.3 µg/kg/h). In group 3, MDZ was infused 0.03 mg/kg, and a dose of 0.01 mg/kg was given every 30 minutes; DEX was administered at the same as in group 2. In group 4, DEX was infused using the same method as in group 1 without MDZ. The sedation levels, amnesia, and patient satisfaction were also investigated. Group 2 had a lower sedation level and a poor evaluation during the first half of the operation. Group 4 did not exhibit an amnesic effect at the beginning of the operation. An evaluation of the degree of patient satisfaction did not reveal any differences among the groups. Optimal sedation was achieved through the combined use of MDZ (0.02 mg/kg with the addition of 0.01 mg/kg every 45 minutes) and DEX (2 µg/kg/h for 10 minutes followed by 0.5 µg/kg/h).
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Nguyen, Nghi M., Neetha N. Vellichirammal, Chittibabu Guda und Gurudutt Pendyala. „Decoding the Synaptic Proteome with Long-Term Exposure to Midazolam during Early Development“. International Journal of Molecular Sciences 23, Nr. 8 (08.04.2022): 4137. http://dx.doi.org/10.3390/ijms23084137.
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The intensive use of anesthetic and sedative agents in the neonatal intensive care unit (NICU) has raised controversial concerns about the potential neurodevelopmental risks. This study focused on midazolam (MDZ), a common benzodiazepine regularly used as a sedative on neonates in the NICU. Mounting evidence suggests a single exposure to MDZ during the neonatal period leads to learning disturbances. However, a knowledge gap that remains is how long-term exposure to MDZ during very early stages of life impacts synaptic alterations. Using a preclinical rodent model system, we mimicked a dose-escalation regimen on postnatal day 3 (P3) pups until day 21. Next, purified synaptosomes from P21 control and MDZ animals were subjected to quantitative mass-spectrometry-based proteomics, to identify potential proteomic signatures. Further analysis by ClueGO identified enrichment of proteins associated with actin-binding and protein depolymerization process. One potential hit identified was alpha adducin (ADD1), belonging to the family of cytoskeleton proteins, which was upregulated in the MDZ group and whose expression was further validated by Western blot. In summary, this study sheds new information on the long-term exposure of MDZ during the early stages of development impacts synaptic function, which could subsequently perturb neurobehavioral outcomes at later stages of life.
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Juárez, Graciela de la Fuente, Ismael Jiménez, María Cristina Márquez Orozco+ und Amalia Márquez Orozco. „Alteraciones locomotoras de crías de ratón inducidas por exposición posnatal a midazolam“. Archives of Health 3, Nr. 4 (02.06.2022): 619–27. http://dx.doi.org/10.46919/archv3n4-002.
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El midazolam (MDZ) se emplea en pediatría como medicación previa a la anestesia y para producir amnesia anterógrada. Se emplea en prematuros y recién nacidos con problemas respiratorios severos que requieren cuidados intensivos o con crisis epilépticas. Se investigó si las crías de ratón machos de 21 días de edad tratadas del día 6 al 9 postnatales modifican su actividad locomotora y exploratoria medidas en un campo abierto. Dos grupos de crías macho de ratón de la cepa ICR fueron inyectadas del día 6 al 9 posnatales el primero (MDZ) con dosis únicas diarias de MDZ (1 mg/kg/pc/sc) y el segundo (C) con solución salina. La actividad locomotora y la exploratoria se midieron durante 5 min en un campo abierto de 50 x 50 x 20 cm. Las pruebas se videograbaron. Sobre un monitor se dividió el campo abierto en nueve cuadros numerados. Se registró el número de veces que cada ratón visitó los cuadros en 5 min. La distancia (cm) y la velocidad (cm/s) se analizaron con el sistema digital del Departamento de Fisiología, Biofísica y Neurociencias del CINVESTAV-IPN. En los machos del grupo MDZ el promedio de la distancia recorrida, la velocidad, el número de cuadros visitados y la actividad exploratoria fueron mayores en el grupo MDZ que en el grupo C (p<0.05). Los resultados podrían correlacionarse con las alteraciones de la corteza cerebelar causadas por el MDZ observadas en estos animales. Se sabe que el MDZ administrado a crías de rata de 7 días de edad causa neurodegeneración apoptótica en el cerebro y alteraciones de aprendizaje y memoria.
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Feng, Ji-Feng, Xiao-Xia Wang, Yan-Yan Lu, Deng-ge Pang, Wei Peng und Jian-lan Mo. „Effects of dexmedetomidine versus midazolam for premedication in paediatric anaesthesia with sevoflurane: A meta-analysis“. Journal of International Medical Research 45, Nr. 3 (20.04.2017): 912–23. http://dx.doi.org/10.1177/0300060517704595.
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Background Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, produces ideal sedation and early postoperative recovery for premedication in paediatric surgery, reducing preoperative anxiety and facilitating smooth induction of anaesthesia. We performed a meta-analysis to compare the effects of DEX and midazolam (MDZ) in paediatric anaesthesia with sevoflurane. Methods PubMed, Ovid, Web of Science, and Public Health Management Corporation were searched through December 2016 for randomized controlled trials (RCTs) that compared DEX and MDZ in children undergoing sevoflurane anaesthesia. The risk ratio (RR) with 95% incidence interval (95%CI) was used for dichotomous variables. Results Twelve RCTs involving 422 patients in the DEX group and 448 patients in the MDZ group were included. Patients in the DEX group had a significantly lower incidence of unsatisfactory sedation (RR [95%CI] = 0.71 [0.57–0.89]), unsatisfactory parental separation (RR [95%CI] = 0.56 [0.35–0.87]), and rescue analgesia (RR [95%CI] = 0.52 [0.35–0.77]) than patients in the MDZ group. However, both groups had a similar incidence of unsatisfactory mask acceptance, emergence agitation, and postoperative nausea and vomiting. Conclusion Compared with MDZ, DEX is beneficial in paediatric anaesthesia with sevoflurane because of its lower incidence of unsatisfactory sedation, parental separation, and rescue analgesia.
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LEE, L., A. NAFZIGER und J. BERTINO. „The ratio of 1-hydroxymidazolam (1-OH MDZ) to midazolam (MDZ) plasma concentrations is not an accurate measurement for CYP3A activity when using oral (PO) MDZ“. Clinical Pharmacology & Therapeutics 77, Nr. 2 (Februar 2005): P32. http://dx.doi.org/10.1016/j.clpt.2004.12.016.
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Denisov, Ilia G., Yelena V. Grinkova, Mark A. McLean, Tyler Camp und Stephen G. Sligar. „Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4“. Biomolecules 12, Nr. 6 (20.06.2022): 853. http://dx.doi.org/10.3390/biom12060853.
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Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions (DDI). In order to develop a method for the detection and prediction of the possible involvement of new drug candidates in CYP3A4-mediated DDI, we evaluated the application of midazolam (MDZ) as a probe substrate. MDZ is hydroxylated by CYP3A4 in two positions: 1-hydroxy MDZ formed at lower substrate concentrations, and up to 35% of 4-hydroxy MDZ at high concentrations. The ratio of the formation rates of these two products (the site of metabolism ratio, SOM) was used as a measure of allosteric heterotropic interactions caused by effector molecules using CYP3A4 incorporated in lipid nanodiscs. The extent of the changes in the SOM in the presence of effectors is determined by chemical structure and is concentration-dependent. MD simulations of CYP3A4 in the lipid bilayer suggest that experimental results can be explained by the movement of the F-F’ loop and concomitant changes in the shape and volume of the substrate-binding pocket. As a result of PGS binding at the allosteric site, several residues directly contacting MDZ move away from the substrate molecule, enabling the repositioning of the latter for minor product formation.
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Barari, Ahmad, Hoda A. ElMaraghy und George K. Knopf. „Search-Guided Sampling to Reduce Uncertainty of Minimum Deviation Zone Estimation“. Journal of Computing and Information Science in Engineering 7, Nr. 4 (17.08.2007): 360–71. http://dx.doi.org/10.1115/1.2798114.
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Integrating computational tasks in coordinate metrology and its effect on the inspection’s uncertainty is studied. It is shown that implementation of an integrated inspection system is crucial to reduce the uncertainty in minimum deviation zone (MDZ) estimation. An integrated inspection system based on the iterative search procedure and online MDZ estimation is presented. The search procedure uses the Parzen Windows technique to estimate the probability density function of the geometric deviations between the actual and substitute surfaces. The computed probability density function is used to recognize the critical points in the MDZ estimation and to identify portions of the surface that require further iterative measurements until the desired level of convergence is achieved. Reduction of the uncertainty in the MDZ estimation using the developed search method compared to the MDZ estimations using the traditional sampling methods is demonstrated by presenting experiments including both actual and virtual inspection data. The proposed search method can be used for assessing any geometric deviations when no prior assumptions about the fundamental form and distribution of the underlying manufacturing errors are required. The search method can be used to inspect and evaluate both primitive geometric features and complicated sculptured surfaces. Implementation of this method reduces inspection cost as well as the cost of rejecting good parts or accepting bad parts.
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A, Kishman, Sholjakova M, Kartalov A, Kuzmanovska B, Angjushev D, Demjanski V und Durnev V. „Comparative study of the effects of dexmedetomidin and midazolam on respiration and hemodynamics used during facial surgery“. Journal of Anesthesia & Critical Care: Open Access 15, Nr. 6 (17.11.2023): 167–70. http://dx.doi.org/10.15406/jaccoa.2023.15.00574.
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Background: The interventions in facial surgery are specific, short, and very painful. The place of the surgery can compromise a patient’s airway. Surgeons prefer to give local infiltrative anesthetics, but during the surgery patients are nervous, stressed, restless and ask for drugs to be asleep/ask for sleep medication. Dexmedetomidine (Dex) as an agent for analgosedation can meet the needs of those patients. Dex is an alpha 2 adrenergic agonist with sedative, anxiolytic and analgesic properties; Midazolam (Mdz) is the most often used drug for classical sedation, a drug from the benzodiazepine group. Aims: The aim of this study was to compare the effects on circulation and respiration of two drugs, dexmedetomidine (Dex) and midazolam (Mdz). Blood pressure, Puls/min, respiration/min, SpO2, incidents of bradycardia, hypotension, hypoxia, and other complications were measured and compared in the two groups. Material and methods: Sixty patients for facial surgery who met the inclusion criteria were enrolled in the study. Due to a computed choice/option, patients were allocated to be sedated with Dex (n=30) or Mdz (n=30). After signing a written consent for inclusion in the study, prior to surgery all patients got two venous lines and were preoperatively monitored. Patients of Dex group received a bolus of Dex 1 mcg/kg given in 10 minutes. The sedation was maintained with an additional dose of Dex of 0.5 mcg/kg/h, which was disconnected at the end of the surgery. Patients of Mdz group received a bolus of Mdz of 0.03 mg/kg followed by an infusion of Mdz of 0.2 mg/kg/h, which was disconnected at the end of the surgery. The vital signs (ECG, BP, P/min, Res/min, SpO2, ETCO2, BIS) were monitored and noted on 5-minute intervals. Results: The obtained results were statistically analyzed. Demographic data showed homogeneity between the groups. All patients prior to procedural sedation got local infiltrative anesthesia with lidocaine 1%. There was insignificant difference in duration of the surgical procedure between the groups (p>0.05) and prolonged induction to sedation in the Dex group (10.6±2.7* vs. 1.9±1.7); p=0.01. Blood pressure of patients in the Dex group showed a significant decrease and was lower than that in the Mdz group (p=0.05). Also, P/min in the Dex group was lower than in the Mdz group (74.45±14.84*vs. 84.13±12.88) p=0.03. The results from the monitored respiration showed a statistically significant decrease in respiration/minute in the Mdz group (p=0.05) and decrease in SpO2, (p=0.02). Conclusion: We found that Dex, used as an agent for analgosedation for facial surgery, is a safe drug providing hypotension and mild bradycardia which are easy for treatment with vasoconstrictors and a sedation without effects on respiration. Patients in the Dex group were more comfortable, and their satisfaction was higher than in patients in the Mdz group.
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Bhide, S., S. Gulliford, R. A'Hern, E. Hall, K. Newbold, K. Harrington und C. Nutting. „Quantitative estimates of the effects of concomitant chemotherapy on acute dysphagia in patients receiving radical treatment for head and neck cancer“. Journal of Clinical Oncology 27, Nr. 15_suppl (20.05.2009): e22134-e22134. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22134.
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e22134 Purpose: To generate quantitative parameters describing the effect of concomitant chemotherapy on incidence of grade 3 dysphagia (CTCAE v3.0, assisted feeding) using dose response curves in patients receiving radical treatment for head and neck cancer. Methods: Patients treated at a single centre in prospective phase I and II trials of concomitant chemo-IMRT (CRT) (n=85) and the phase III trial of IMRT vs. conventional radiotherapy (PARSPORT) (n=82) formed the basis of this non-randomized comparison. Patients in the PARSPORT trial received radiation alone (RT). Radiation dose for all patients was radiobiologically equivalent to at least 70Gy in 35 fractions. Concomitant chemotherapy was cisplatin (100 mg/m2) on days 1 and 29. G3 dysphagia was recorded prospectively. Dose volume histograms (DVH) were generated for the pharyngeal mucosa. The mean dose (converted to equivalent dose in 2Gy/fraction, MD2) was used as a univariate descriptor of the DVH, for the generation of the dose response curves. A logistic function of the form p=1/[1+(MD50/D)k] was fitted where, p is the probability of the incidence of toxicity, D is the mean dose, MD50 is the mean dose at which 50% of patients experience toxicity and k describes the increase in incidence with increasing dose. The dose response curves were fitted using non-linear logistic regression. Results: The mean MD2 to the pharyngeal mucosa were 56Gy and 55.8Gy respectively, in the CRT and RT groups. There was a statistically significant difference of 25% (95% CI: 10–38, p=0.002) in the incidence of G3 dysphagia between the CRT (68%) and RT (43%) groups. Fitting dose response curves to the clinical data yielded parameter values (95% CIs) of MD50=46 Gy (42–49), k=4.8 (2.3–7.2) for the CRT group and MD50= 58 Gy (55–61), k=3 (1.6-.45) for RT group. Dose response gradients for CRT and RT showed approximately 1.95% and 1.3% increase (respectively) in probability of G3 dysphagia resulting from an increase in mean dose of 1Gy between doses of 30Gy to 70Gy. Conclusions: Addition of concomitant chemotherapy increases the incidence of G3 dysphagia by 0.65% for every 1 Gy increase in radiation dose. The observed MD50 for G3 dysphagia is lower for RT alone (46 Gy vs. 58 Gy). No significant financial relationships to disclose.
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Magliocco, Gaëlle, Jules Desmeules, Marija Bosilkovska, Aurélien Thomas und Youssef Daali. „The 1β-Hydroxy-Deoxycholic Acid to Deoxycholic Acid Urinary Metabolic Ratio: Toward a Phenotyping of CYP3A Using an Endogenous Marker?“ Journal of Personalized Medicine 11, Nr. 2 (20.02.2021): 150. http://dx.doi.org/10.3390/jpm11020150.
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In this study, we assessed the potential use of the 1β-hydroxy-deoxycholic acid (1β-OH-DCA) to deoxycholic acid (DCA) urinary metabolic ratio (UMR) as a CYP3A metric in ten male healthy volunteers. Midazolam (MDZ) 1 mg was administered orally at three sessions: alone (control session), after pre-treatment with fluvoxamine 50 mg (12 h and 2 h prior to MDZ administration), and voriconazole 400 mg (2 h before MDZ administration) (inhibition session), and after a 7-day pre-treatment with the inducer rifampicin 600 mg (induction session). The 1β-OH-DCA/DCA UMR was measured at each session, and correlations with MDZ metrics were established. At baseline, the 1β-OH-DCA/DCA UMR correlated significantly with oral MDZ clearance (r = 0.652, p = 0.041) and Cmax (r = −0.652, p = 0.041). In addition, the modulation of CYP3A was reflected in the 1β-OH-DCA/DCA UMR after the intake of rifampicin (induction ratio = 11.4, p < 0.01). During the inhibition session, a non-significant 22% decrease in 1β-OH-DCA/DCA was observed (p = 0.275). This result could be explained by the short duration of CYP3A inhibitors intake fixed in our clinical trial. Additional studies, particularly involving CYP3A inhibition for a longer period and larger sample sizes, are needed to confirm the 1β-OH-DCA/DCA metric as a suitable CYP3A biomarker.
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Dalla Costa, Bádila Regina, Charize Dallazem Bertol, Daiane Anzilaggo, Hellen Karine Stulzer und Luciana Grazziotin Rossato-Grando. „STABILITY-INDICATING LC METHOD FOR THE QUANTIFICATION OF MIDAZOLAM ACTIVE PHARMACEUTICAL INGREDIENT AND IN PHARMACEUTICAL FORMULATIONS“. Drug Analytical Research 2, Nr. 2 (16.12.2018): 44–48. http://dx.doi.org/10.22456/2527-2616.86375.
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A stability-indicating LC method was validated for the quantification of midazolam (MDZ) active pharmaceutical ingredient (API) and in pharmaceutical formulations. Isocratic chromatography was performed on C18 column with mobile phase containing methanol/acetonitrile/water (45:35:20 v/v/v) with 0.4% of triethylamine pH 6.5. The validation included specificity, linearity, accuracy, precision and robustness. In specificity, after acid, basic, neutral, oxidant and thermal degradation, it was found that the concentration of MDZ decreased substantially, with the appearance of peaks representatives of the degradation products, proving the stability-indicating power of the method. The response was linear in the range 50.0 – 250.0 µg.mL-1, with 11.73 µg.mL-1 and 3.87 µg.mL-1 as LOQ and LOD, respectively. Recoveries ranged between 98.68 and 100.41%. The relative standard deviation values for intra and interday precision were 1.11%, 0.82% and 1.47%, respectively. The tablets and injections containing MDZ were approved in the assay and content uniformity. The method can be adopted by pharmacopeias and for routine quality control for analysis of MDZ API, tablets and injection.
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Figueiredo, Taiza H., Vassiliki Aroniadou-Anderjaska, Volodymyr I. Pidoplichko, James P. Apland und Maria F. M. Braga. „Antiseizure and Neuroprotective Efficacy of Midazolam in Comparison with Tezampanel (LY293558) against Soman-Induced Status Epilepticus“. Toxics 10, Nr. 8 (22.07.2022): 409. http://dx.doi.org/10.3390/toxics10080409.
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Acute exposure to nerve agents induces status epilepticus (SE), which can cause death or long-term brain damage. Diazepam is approved by the FDA for the treatment of nerve agent-induced SE, and midazolam (MDZ) is currently under consideration to replace diazepam. However, animal studies have raised questions about the neuroprotective efficacy of benzodiazepines. Here, we compared the antiseizure and neuroprotective efficacy of MDZ (5 mg/kg) with that of tezampanel (LY293558; 10 mg/kg), an AMPA/GluK1 receptor antagonist, administered 1 h after injection of the nerve agent, soman (1.2 × LD50), in adult male rats. Both of the anticonvulsants promptly stopped SE, with MDZ having a more rapid effect. However, SE reoccurred to a greater extent in the MDZ-treated group, resulting in a significantly longer total duration of SE within 24 h post-exposure compared with the LY293558-treated group. The neuroprotective efficacy of the two drugs was studied in the basolateral amygdala, 30 days post-exposure. Significant neuronal and inter-neuronal loss, reduced ratio of interneurons to the total number of neurons, and reduction in spontaneous inhibitory postsynaptic currents accompanied by increased anxiety were found in the MDZ-treated group. The rats treated with LY293558 did not differ from the control rats (not exposed to soman) in any of these measurements. Thus, LY293558 has significantly greater efficacy than midazolam in protecting against prolonged seizures and brain damage caused by acute nerve agent exposure.
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Hunt, Ann R., Shana Frederickson, Christopher Hinkel, Katherine S. Bowdish und John T. Roehrig. „A humanized murine monoclonal antibody protects mice either before or after challenge with virulent Venezuelan equine encephalomyelitis virus“. Journal of General Virology 87, Nr. 9 (01.09.2006): 2467–76. http://dx.doi.org/10.1099/vir.0.81925-0.
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A humanized monoclonal antibody (mAb) has been developed and its potential to protect from or cure a Venezuelan equine encephalomyelitis virus (VEEV) infection was evaluated. The VEEV-neutralizing, protective murine mAb 3B4C-4 was humanized using combinatorial antibody libraries and phage-display technology. Humanized VEEV-binding Fabs were evaluated for virus-neutralizing capacity, then selected Fabs were converted to whole immunoglobulin (Ig) G1, and stable cell lines were generated. The humanized mAb Hy4-26C, designated Hy4 IgG, had virus-neutralizing capacity similar to that of 3B4C-4. Passive antibody protection studies with purified Hy4 IgG were performed in adult Swiss Webster mice. As little as 100 ng Hy4 IgG protected 90 % of mice challenged with 100 intraperitoneal (i.p.) mean morbidity (MD50) doses of virulent VEEV (Trinidad donkey) 24 h after antibody transfer; also, 500 μg Hy4 IgG protected 80 % of mice inoculated with 100 intranasal MD50 doses of VEEV. Moreover, 10 μg passive Hy4 IgG protected 70 % of mice from a VEEV challenge dose as great as 107 i.p. MD50. Hy4 IgG also protected mice from challenge with another epizootic VEEV variety, 1C (P676). Importantly, therapeutic administration of the humanized mAb to mice already infected with VEEV cured 90 % of mice treated with Hy4 IgG within 1 h of VEEV inoculation and 75 % of mice treated 24 h after virus infection.
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Peng, Jing, Fujuan He, Chenguang Qin, Yuanyuan Que, Rui Fan und Bin Qin. „Intraoperative Dexmedetomidine Versus Midazolam in Patients Undergoing Peripheral Surgery With Mild Traumatic Brain Injuries: A Retrospective Cohort Analysis“. Dose-Response 18, Nr. 2 (01.04.2020): 155932582091634. http://dx.doi.org/10.1177/1559325820916342.
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Background: The intra- and postoperative effects of dexmedetomidine are not completely consistent and midazolam/fentanyl is most widely used in peripheral surgeries. The objectives of the study were to evaluate the sedative, analgesic, hemodynamic, anti-inflammatory, and antioxidant effects of dexmedetomidine against midazolam in patients undergoing peripheral surgeries with mild traumatic brain injuries. Methods: Medical records of patients who underwent peripheral surgeries with mild traumatic brain injury were included in the analysis. Patients received intraoperative midazolam (MDZ cohort, n = 225) or dexmedetomidine (DEX cohort, n = 231). Pre-, intra-, and postoperative characteristics of patients were collected and analyzed. Results: After administration of anesthesia, up to 40 minutes, patients of the MDZ group had lower modified observer’s assessment of alertness/sedation score than those of the DEX group ( P = .041), but after 40 minutes, patients of the MDZ group had a higher score than those of the DEX group throughout surgeries ( P = 0.048). The DEX group has less requirements of postoperative morphine/equivalent doses than the MDZ group (4 ± 1 vs 5 ± 1, P < .0001, q = 18.451). Conclusions: Intraoperative DEX offers better sedation, postoperative analgesia, and clinical recovery for peripheral surgeries and suppresses inflammatory response. Level of Evidence: III.
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Li, Zaiyuan, Consolatha Chambi, Tianhua Du, Cong Huang, Fulian Wang, Guifen Zhang, Chuanren Li und Mohamed Juma Kayeke. „Effects of Water Immersion and Soil Moisture Content on Larval and Pupal Survival of Bactrocera minax (Diptera: Tephritidae)“. Insects 10, Nr. 5 (14.05.2019): 138. http://dx.doi.org/10.3390/insects10050138.
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Bactrocera minax, one of the most devastating citrus pests in Asia, has two developmental stages (mature larva and pupa) that complete their life cycle in the soil. Currently, southern China has a climate with abundant autumn rains, and soil moisture can be a major factor affecting the survival of larvae and pupae of B. minax. In the present study, we evaluated the effects of water immersion and high soil moisture content on the development of mature larvae and pupae of B. minax. When immersed in water for 1 d, 100% of mature larvae of B. minax were knocked out. When larvae were immersed for less than 6 d, however, more than 92% of knocked-out larvae recovered within 24 h. The days of water immersion with 50% and 90% recovery ratios (indicated as RD50 and RD90) were 10.3 d and 6.4 d, respectively. When larvae were immersed less than 6 d, the mortality ratios of larvae were not significantly different from those that were not immersed at all. The days of immersion causing 50% and 90% mortality of larvae (MD50 and MD90, respectively) were 7.6 d and 11.1 d, respectively. The pupation ratios of larvae were also observed to be not significantly different compared to non-immersion, and the days of immersion causing 50% and 90% pupation (PD50 and PD90, respectively) were 6.6 d and 0.8 d, respectively. Larval respiration rates were reduced after water immersion as a strategy for larval survival. High water content was not detrimental to pupae of B. minax. Adult emergence did not significantly decrease in soil with high water content, even though pupae were under those conditions for 161–175 d. The respiration rates of pupae were lower in soil with different moisture levels and were not significantly different, which ensured the survival of pupae in high water content. Reduced respiration rate is a strategy for survival of larvae and pupae, and remarkable tolerance to high moisture conditions could explain the high rate of spread and geographical distribution of B. minax. The results of this study provide a reference for the occurrence and control of B. minax.
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Doi, Hiroyoshi, Taito Matsuda, Atsuhiko Sakai, Shuzo Matsubara, Sumio Hoka, Ken Yamaura und Kinichi Nakashima. „Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition“. Proceedings of the National Academy of Sciences 118, Nr. 38 (15.09.2021): e2107596118. http://dx.doi.org/10.1073/pnas.2107596118.
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Linkage between early-life exposure to anesthesia and subsequent learning disabilities is of great concern to children and their families. Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and the expression of quiescence-associated genes in neural stem cells (NSCs) in the mouse hippocampus. The alterations led to a sustained restriction of NSC proliferation toward adulthood, resulting in a reduction of neurogenesis that was associated with the impairment of hippocampal-dependent memory functions. Moreover, we found that voluntary exercise restored hippocampal neurogenesis, normalized the MDZ-perturbed transcriptome, and ameliorated cognitive ability in MDZ-exposed mice. Our findings thus explain how pediatric anesthesia provokes long-term adverse effects on brain function and provide a possible therapeutic strategy for countering them.
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Xiangshen, Tian, Zhu Longfei, Cai ZhengYu und Kong Hui. „The Relationship between MnS Precipitation and Induced Nucleation Effect of Mg-Bearing Inclusion“. High Temperature Materials and Processes 37, Nr. 8 (28.08.2018): 711–16. http://dx.doi.org/10.1515/htmp-2016-0259.
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AbstractThe relationship between MnS precipitation and induced nucleation effect of Mg-bearing inclusion has been explored through scanning electron microscope and energy dispersive spectrometer (EDS). Results indicate that MnS prefers to precipitate on Mg-bearing inclusions. Statistical analysis suggests that MgAl2O4 and MgO may coexist in inclusion. After etching, it is found that Mg-bearing inclusions can induce the nucleation of intragranular acicular ferrites. Based on EDS line analysis and comparison with Al-Mn-Si-O inclusion in non-Mg-treated sample, this effect can be explained by Mn-depletion zone (MDZ), which is due to the vacancy property and crystal structure of MgAl2O4. In the same sample, similar induced nucleation effect and MDZ are not observed around pure MnS. This comparison implies that the formation of MDZ may be independent of MnS precipitation.
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Vuković, Ivan, Božidar Duplančić, Benjamin Benzon, Zoran Đogaš, Ruben Kovač und Renata Pecotić. „Midazolam versus Dexmedetomidine in Patients at Risk of Obstructive Sleep Apnea during Urology Procedures: A Randomized Controlled Trial“. Journal of Clinical Medicine 11, Nr. 19 (02.10.2022): 5849. http://dx.doi.org/10.3390/jcm11195849.
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Benzodiazepines are the most commonly used sedatives for the reduction of patient anxiety. However, they have adverse intraoperative effects, especially in obstructive sleep apnea (OSA) patients. This study aimed to compare dexmedetomidine (DEX) and midazolam (MDZ) sedation considering intraoperative complications during transurethral resections of the bladder and prostate regarding the risk for OSA. This study was a blinded randomized clinical trial, which included 115 adult patients with a mean age of 65 undergoing urological procedures. Patients were divided into four groups regarding OSA risk (low to medium and high) and choice of either MDZ or DEX. The doses were titrated to reach a Ramsay sedation scale score of 4/5. The intraoperative complications were recorded. Incidence rates of desaturations (44% vs. 12.7%, p = 0.0001), snoring (76% vs. 49%, p = 0.0008), restlessness (26.7% vs. 1.8%, p = 0.0044), and coughing (42.1% vs. 14.5%, p = 0.0001) were higher in the MDZ group compared with DEX, independently of OSA risk. Having a high risk for OSA increased the incidence rates of desaturation (51.2% vs. 15.7%, p < 0.0001) and snoring (90% vs. 47.1%, p < 0.0001), regardless of the sedative choice. DEX produced fewer intraoperative complications over MDZ during sedation in both low to medium risk and high-risk OSA patients.
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Liu, Shuhui, Qingchuan Zheng und Fuquan Bai. „Differences of Atomic-Level Interactions between Midazolam and Two CYP Isoforms 3A4 and 3A5“. Molecules 28, Nr. 19 (01.10.2023): 6900. http://dx.doi.org/10.3390/molecules28196900.
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CYP 3A4 and CYP 3A5 are two important members of the human cytochrome P450 family. Although their overall structures are similar, the local structures of the active site are different, which directly leads to obvious individual differences in drug metabolic efficacy and toxicity. In this work, midazolam (MDZ) was selected as the probe substrate, and its interaction with two proteins, CYP 3A4 and CYP 3A5, was studied by molecular dynamics simulation (MD) along with the calculation of the binding free energy. The results show that two protein–substrate complexes have some similarities in enzyme–substrate binding; that is, in both complexes, Ser119 forms a high occupancy hydrogen bond with MDZ, which plays a key role in the stability of the interaction between MDZ and the enzymes. However, the complex formed by CYP 3A4 and MDZ is more stable, which may be attributed to the sandwich structure formed by the fluorophenyl group of the substrate with Leu216 and Leu482. Our study interprets the binding differences between two isoform–substrate complexes and reveals a structure–function relationship from the atomic perspective, which is expected to provide a theoretical basis for accurately measuring the effectiveness and toxicity of drugs for individuals in the era of precision medicine.
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Sievers, Theresa D., John D. Yee, Mary E. Foley, Peter J. Blanding und Charles B. Berde. „Midazolam for Conscious Sedation During Pediatric Oncology Procedures: Safety and Recovery Parameters“. Pediatrics 88, Nr. 6 (01.12.1991): 1172–79. http://dx.doi.org/10.1542/peds.88.6.1172.
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Multiple bone marrow aspirations or biopsies and lumbar punctures are a necessary part of the diagnosis and treatment of many pediatric cancer patients. Pharmacologic sedation may decrease the distress associated with these procedures. Midazolam (MDZ, Versed) is a water-soluble, rapid-onset, short-duration benzodiazepine that has not been studied widely in children. We prospectively evaluated safety and recovery parameters for intravenous MDZ used for conscious sedation by oncologists (without an anesthesiologist in attendance) for 70 procedures (bone marrow aspirations, lumbar punctures, or bone marrow aspirations plus lumbar punctures) in 24 ambulatory pediatric cancer patients, aged 1.5 to 15.5 years. MDZ was used alone or in combination with morphine or fentanyl. Respiratory rate, oxygen saturation, blood pressure, and heart rate were monitored. Sedation, anxiolysis, and recovery were assessed with a behavior score and a modified recovery room discharge score. Restraint was not required in 45% of the procedures. In no case was a respiratory rate < 12 observed. In nine procedures (13%), an oxygen saturation ≤ 90 occurred, all within 10 minutes after the last dose of MDZ. Ten procedures (14%) required verbal stimulation to take deeper breaths. Two patients did not respond immediately to verbal stimulation and received face-mask oxygen. Hypoxemia was not correlated with opioid use. Hypoxemia appears to be related to total MDZ dose and may occur with normal respiratory rates; all cases resolved with verbal stimulation or face-mask oxygen without specific airway maneuvers or assisted ventilation. Heart rate and blood pressure remained stable in all 70 procedures. In all 70 procedures a satisfactory discharge score was achieved by 60 minutes after the last dose of MDZ. Full or partial amnesia was reported in 90% of the procedures. No long-term adverse effects were reported on follow-up. Midazolam appeared to offer effective sedation and amnesia in children undergoing bone marrow aspirations or lumbar punctures. Safe administration requires constant observation, use of pulse oximetry, and availability of supplemental oxygen and resuscitation equipment because significant hypoxemia can occur in patients breathing room air. A recovery period of 60 minutes appeared to be adequate.
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SAWAMURA, MORIO. „A NOVEL IL-5 AND IL-6 SENSITIVE PLASMACYTOMA CLONE, MD90“. KITAKANTO Medical Journal 42, Nr. 6 (1992): 545–53. http://dx.doi.org/10.2974/kmj1951.42.545.
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Singh, Geetika, und Indu Chhabra. „Discriminative Moment Feature Descriptors for Face Recognition“. International Journal of Computer Vision and Image Processing 5, Nr. 2 (Juli 2015): 81–97. http://dx.doi.org/10.4018/ijcvip.2015070105.
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Zernike Moment (ZM) is a promising technique to extract invariant features for face recognition. It has been modified in previous studies to Discriminative ZM (DZM), which selects most discriminative features to perform recognition, and shows improved results. The present paper proposes modification of DZM, named Modified DZM (MDZM), which selects coefficients based on their discriminative ability by considering extent of variability between their class-averages. This reduces within-class variations while maintaining between-class differences. The study also investigates this idea of feature selection on recently introduced Polar Complex Exponential Transform (PCET) (named discriminative or DPCET). Performance of the techniques is evaluated on ORL, Yale and FERET databases against pose, illumination, expression and noise variations. Accuracy improves up to 3.1% by MDZM at reduced dimensions over ZM and DZM. DPCET shows 1.9% of further improvement at less computational complexity. Performance is also tested on LFW database and compared with many other state-of-art approaches.
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Chatzaras, Vasileios, Basil Tikoff, Seth C. Kruckenberg, Sarah J. Titus, Christian Teyssier und Martyn R. Drury. „Stress variations in space and time within the mantle section of an oceanic transform zone: Evidence for the seismic cycle“. Geology 48, Nr. 6 (27.03.2020): 569–73. http://dx.doi.org/10.1130/g47137.1.
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Abstract The Bogota Peninsula shear zone in New Caledonia (southwest Pacific Ocean) is the exhumed mantle section of an oceanic transform zone. Ductile fabrics in this zone formed at temperatures >820 °C, and differential stresses estimated from microstructures vary spatially and temporally. Along a transform-perpendicular transect, stresses increase toward the high-strain areas. We attribute this stress gradient to an increase in strain rate caused by imposed rather than intrinsic strain localization. Temporal stress variations are indicated by the formation of fine-grained microdeformation zones (MDZs) that truncate and offset coarser grains. We interpret the MDZs to result from zones of brittle deformation caused by earthquake fracture propagation downward in the upper mantle, which are in turn overprinted by ductile deformation at stresses 2–6 times higher (22–81 MPa) than their surrounding steady-state fabrics. We interpret the spatial and temporal variations in microstructures and stresses as reflecting different stages of the seismic cycle in oceanic lithosphere.
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May, Roger A., und Kenneth C. Sink. „DIRECT SOMATIC EMBRYOGENESIS FROM PROTOPLASTS DERIVED FROM EMBRYOGENIC SUSPENSION CULTURES OF ASPARAGUS OFFICINALIS L.“ HortScience 28, Nr. 5 (Mai 1993): 499b—499. http://dx.doi.org/10.21273/hortsci.28.5.499b.
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Embryogenic callus from four asparagus genotypes (JG8, MD10, MD22, and 86SOM1) was initiated from micropropagated spears placed on semisolid LS medium containing 5 μM 2,4-D or 50 μM NAA, concomitantly. After three subcultures such cells were used to initiate suspensions in liquid medium of the same composition. The eight sets of suspensions were used as sources of protoplasts at two months of age and again at five months. Protoplasts were immobilized at 105/ml density in MS medium with 0.6% agarose and overlaid with liquid KM medium containing the auxin of the corresponding donor suspension or no hormones. Plating efficiencies were recorded at 14 days and ranged from 0% to 40% depending on the genotype, suspension medium, and inclusion or exclusion of hormones in the protoplast plating medium. All four genotypes were capable of forming somatic embryos directly from protoplasts; however, conversion was greatest from MD10 and MD22 derived cultures and occurred as rapidly as six weeks after initial protoplast culture.
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Reyes-Ortiz, Oscar Javier, Javier Fernando Camacho-Tauta und Angie Londoño León. „Caracterización mecánica de mezclas asfálticas en función del origen y gradación del agregado pétreo“. Revista Científica General José María Córdova 11, Nr. 12 (30.07.2013): 215. http://dx.doi.org/10.21830/19006586.194.
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El objetivo principal de la investigación es profundizar el conocimiento acerca de la influencia que el origen y gradación del agregado pétreo pueden tener en el comportamiento de mezclas asfálticas. Se realizó el análisis petrográfico macroscópico de gravas y arenas provenientes de la cantera del río Coello-Tolima (Cantol) y de la fuente aluvial del río Tunjuelito-Cundinamarca (Cancun). Se seleccionaron dos tipos de granulometría según las especificaciones del Instituto de Desarrollo Urbano (md12 y md20). El porcentaje óptimo de asfalto se determinó mediante la metodología Marshall. Los ensayos realizados a las mezclas asfálticas fueron la Resistencia a la Tracción Indirecta (RTI) en estados seco y húmedo, la Resistencia Conservada (RC) y el Módulo Resiliente (MR). La mitad de las muestras fueron envejecidas mediante el empleo de un horno a 80ºC, con circulación de aire. Dentro de los resultados encontrados se pudo establecer que las probetas con granulometría md20 (independiente del origen del granular) tienen mayor densidad (RTI y MR) que las probetas md12. Así mismo, los resultados de RTI de las probetas Cantol en comparación con las probetas Cancun fueron mayores para los estados seco y envejecido a 48 horas. En el estado húmedo, tanto para la mezcla asfáltica md20 como la md12, los valores de RTI y RC de las probetas Cancun fueron mayores. Finalmente se determinó que los módulos resilientes de las probetas Cancun fueron considerablemente menores en comparación con las probetas Cantol, sin distinción de estado. Estos resultados ponen de manifiesto en el caso de estudio, que el origen del granular y la granulometría afectan las propiedades mecánicas y dinámicas de las mezclas asfálticas.
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Gojanovich, Greg S., Denise L. Jacobson, Carly Broadwell, Brad Karalius, Brian Kirmse, Mitchell E. Geffner, Jennifer Jao et al. „Associations of FGF21 and GDF15 with mitochondrial dysfunction in children living with perinatally-acquired HIV: A cross-sectional evaluation of pediatric AIDS clinical trials group 219/219C“. PLOS ONE 16, Nr. 12 (31.12.2021): e0261563. http://dx.doi.org/10.1371/journal.pone.0261563.
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Background In persons living with HIV, mitochondrial disease (MD) is difficult to diagnose, as clinical signs are non-specific with inconsistent patterns. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are mitokines elevated in MD patients without HIV, and associated with cardiometabolic comorbidities in adults living with HIV. We assessed relationships of these biomarkers with MD in children living with perinatally-acquired HIV infection (CPHIV). Setting Cross-sectional study of CPHIV from Pediatric ACTG 219/219C classified by Mitochondrial Disease Criteria (MDC) that defines scores 2–4 as “possible” MD. Methods Each case with MDC equaling 4 (MDC4; n = 23) was matched to one randomly selected control displaying no MDC (MDC0; n = 23) based on calendar date. Unmatched cases with MDC equaling 3 (MDC3; n = 71) were also assessed. Plasma samples proximal to diagnoses were assayed by ELISA. Mitokine distributions were compared using Wilcoxon tests, Spearman correlations were calculated, and associations with MD status were assessed by conditional logistic regression. Results Median FGF21 and GDF15 concentrations, respectively, were highest in MDC4 (143.9 and 1441.1 pg/mL), then MDC3 (104.0 and 726.5 pg/mL), and lowest in controls (89.4 and 484.7 pg/mL). Distributions of FGF21 (paired Wilcoxon rank sum p = 0.002) and GDF15 (paired Wilcoxon rank sum p<0.001) differed in MDC4 vs MDC0. Mitokine concentrations were correlated across all participants (r = 0.33; p<0.001). Unadjusted odds ratios of being MDC4 vs MDC0 were 5.2 [95% confidence interval (CI): 1.06–25.92] for FGF21 and 3.5 (95%CI: 1.19–10.25) for GDF15. Relationships persisted after covariate adjustments. Conclusion FGF21 and GDF15 levels may be useful biomarkers to screen for CPHIV with mitochondrial dysfunction.
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Sevrioukova, Irina F., und Thomas L. Poulos. „Structural basis for regiospecific midazolam oxidation by human cytochrome P450 3A4“. Proceedings of the National Academy of Sciences 114, Nr. 3 (28.12.2016): 486–91. http://dx.doi.org/10.1073/pnas.1616198114.
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Human cytochrome P450 3A4 (CYP3A4) is a major hepatic and intestinal enzyme that oxidizes more than 60% of administered therapeutics. Knowledge of how CYP3A4 adjusts and reshapes the active site to regioselectively oxidize chemically diverse compounds is critical for better understanding structure–function relations in this important enzyme, improving the outcomes for drug metabolism predictions, and developing pharmaceuticals that have a decreased ability to undergo metabolism and cause detrimental drug–drug interactions. However, there is very limited structural information on CYP3A4–substrate interactions available to date. Despite the vast variety of drugs undergoing metabolism, only the sedative midazolam (MDZ) serves as a marker substrate for the in vivo activity assessment because it is preferentially and regioselectively oxidized by CYP3A4. We solved the 2.7 Å crystal structure of the CYP3A4–MDZ complex, where the drug is well defined and oriented suitably for hydroxylation of the C1 atom, the major site of metabolism. This binding mode requires H-bonding to Ser119 and a dramatic conformational switch in the F–G fragment, which transmits to the adjacent D, E, H, and I helices, resulting in a collapse of the active site cavity and MDZ immobilization. In addition to providing insights on the substrate-triggered active site reshaping (an induced fit), the crystal structure explains the accumulated experimental results, identifies possible effector binding sites, and suggests why MDZ is predominantly metabolized by the CYP3A enzyme subfamily.
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Liang, Xiao Ping, Shao Bo Xin, Xiao Hui Wang und Zheng Fang Yang. „Wear Properties of Y-TZP Ceramics Dispersed with Second Phase Particles“. Key Engineering Materials 368-372 (Februar 2008): 744–47. http://dx.doi.org/10.4028/www.scientific.net/kem.368-372.744.
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The wear properties of ADZ (alumina dispersed in Y-TZP) and MDZ (mullite dispersed in Y-TZP) were investigated by using a ring-on-block tribometer. The results showed that for Y-TZP ceramic, the addition of alumina phase (with 10-20% in mass fraction) leads to an improved wear resistance. With the increase of the normal load, the wear rates of ADZ ceramics increase. Under low and medium normal load (100N and 300N), the wear resistance is controlled by the hardness of ceramics, and under high normal load (500N) the fracture toughness is obviously contributed to the wear resistance of the ceramics. For MDZ ceramic, the wear resistance of 15MDZ (15wt% mullite dispersed in Y-TZP) is better than that of 20 MDZ (20wt% mullite) under the normal load from 100 N to 500 N. The mechanical properties of 15MDZ are worse than that of Y-TZP ceramic, but the wear resistance is enhanced due to the action of “needle roller bearing” of the fractured rod-like mullite particles.
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Silva-Caldeira, Priscila Pereira, Andressa Castro Terto Vilas Boas, Bárbara Paiva Machado, Diogo Émerson Leite de Carvalho und Kláudia Maria Machado Neves Silva. „LIBERAÇÃO CONTROLADA DO FÁRMACO MEBENDAZOL A PARTIR DE UMA MATRIZ POLIMÉRICA NATURAL“. Iniciação Científica Cesumar 21, Nr. 1 (24.06.2019): 37. http://dx.doi.org/10.17765/1518-1243.2019v21n1p37-44.
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Sistemas de liberação controlada de fármacos têm por objetivos principais minimizar a necessidade de doses tóxicas e propiciar melhor controle da liberação do princípio ativo ao longo do tempo quando comparado à forma convencional de administração. Neste trabalho foi preparado um sistema de liberação controlada do fármaco mebendazol (MDZ), que apresenta baixa absorção gastrointestinal pela sua baixa solubilidade em água, a partir de uma matriz polimérica biodegradável formada por alginato de sódio. O teste de intumescimento e a avaliação temporal da liberação do ativo in vitro foram realizados em meio que simula as condições do corpo humano. A avaliação da resistência ao meio fisiológico pela matriz polimérica com MDZ incorporado mostrou que a mesma permaneceu por mais de 72 h no meio fisiológico, enquanto que a avaliação do comportamento de dissolução e liberação do MDZ durante 8 h mostrou-se satisfatória com a liberação do ativo de forma lenta de gradual, o que demonstra o potencial dessa matriz para ser usado como um dispositivo oral de liberação controlada desse fármaco.
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Zhao, Hong-Ying, Ramasamy Anbuchezhian, Wei Sun, Chang-Lun Shao, Feng-Li Zhang, Ying Yin, Zhi-Sheng Yu, Zhi-Yong Li und Chang-Yun Wang. „Cytotoxic Nitrobenzoyloxy-substituted Sesquiterpenes from Spongederived Endozoic Fungus Aspergillus insulicola MD10-2“. Current Pharmaceutical Biotechnology 17, Nr. 3 (06.02.2016): 271–74. http://dx.doi.org/10.2174/1389201017666151223123424.
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