Tag: M.W=200-350

Demirdag, Hatice Gamze published the artcileEvaluation of relationship between antihypertensive drug usage and dermatoscopic features in patients with keratinizing skin cancer, SDS of cas: 21829-25-4, the main research area is hydrochlorothiazide antihypertensive diagnosis keratinizing skin cancer; actinic keratosis; antihypertensive drug; cSCC; dermatoscopy; dermoscopy; intraepidermal carcinoma; keratoacanthoma; squamous cell carcinoma.

Keratinizing skin cancers including actinic keratoses (AK), in situ squamous cell carcinoma/Bowens disease/intraepidermal carcinoma (IEC), invasive cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma share similar dermatoscopic features and also reveal different patterns that assist in their diagnosis. Recently epidemiol. studies reveal the association between antihypertensive drugs and skin cancer risk, especially cSCC. This study aims to determine the dermatoscopic features of keratinizing skin cancer in patients using antihypertensive drug and compare with non-users. A total of 46 patients with 64 keratinizing skin cancer lesions were included in the study. The demog., clin. characteristic of patients, the number, duration, localization and dermatoscopic features from each lesion were collected. First, we evaluated the dermatoscopic features according to the histopathol. diagnosis. Then, all patients were divided into two groups as users of antihypertensive drugs and non-users. The dermatoscopic features were compared in terms of antihypertensive drug usage and histopathol. diagnosis in antihypertensive drug users and non-users, sep. The users of anti-hypertensive drugs were 22 (47,8%) and non-users 24 (52,2%). Of the total 64 lesions including 47 AK, 5 IEC, 10 cSCC, and 2 keratoacanthoma were evaluated. White structureless area was found statistically significant in cSCC lesions of patients using antihypertensive drugs (P = .004). This finding in cSCC may be a clue for antihypertensive drug usage and these drugs may be a predisposan factor for dermal fibrosis. Regardless of histopathol., dermatoscopic features show no statistically difference between antihypertensive drug users and non-users (P > .05). Clearer results can be obtained by conducting more detailed and long-term studies.

Dermatologic Therapy published new progress about Actinic keratosis. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, SDS of cas: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Perkins, Emma M. published the artcileAltered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction, Synthetic Route of 21829-25-4, the main research area is human cortical neuron synaptic dysfunction CORF network property; ALS; C9ORF72; Cortical; Electrophysiology; FTD; Hyperexcitability; Network; Neuron; Repeat expansion; Synaptic.

Physiol. disturbances in cortical network excitability and plasticity are established and widespread in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those harbouring the C9ORF72 repeat expansion (C9ORF72RE) mutation – the most common genetic impairment causal to ALS and FTD. Noting that perturbations in cortical function are evidenced pre-symptomatically, and that the cortex is associated with widespread pathol., cortical dysfunction is thought to be an early driver of neurodegenerative disease progression. However, our understanding of how altered network function manifests at the cellular and mol. level is not clear. To address this we have generated cortical neurons from patient-derived iPSCs harbouring C9ORF72RE mutations, as well as from their isogenic expansion-corrected controls. We have established a model of network activity in these neurons using multi-electrode array electrophysiol. We have then mechanistically examined the physiol. processes underpinning network dysfunction using a combination of patch-clamp electrophysiol., immunocytochem., pharmacol. and transcriptomic profiling. We find that C9ORF72RE causes elevated network burst activity, associated with enhanced synaptic input, yet lower burst duration, attributable to impaired pre-synaptic vesicle dynamics. We also show that the C9ORF72RE is associated with impaired synaptic plasticity. Moreover, RNA-seq anal. revealed dysregulated mol. pathways impacting on synaptic function. All mol., cellular and network deficits are rescued by CRISPR/Cas9 correction of C9ORF72RE. Our study provides a mechanistic view of the early dysregulated processes that underpin cortical network dysfunction in ALS-FTD. These findings suggest synaptic pathophysiol. is widespread in ALS-FTD and has an early and fundamental role in driving altered network function that is thought to contribute to neurodegenerative processes in these patients. The overall importance is the identification of previously unidentified defects in pre and postsynaptic compartments affecting synaptic plasticity, synaptic vesicle stores, and network propagation, which directly impact upon cortical function.

Molecular Neurodegeneration published new progress about Alzheimer disease. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Synthetic Route of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ma, Xiangyu published the artcileInfluence of mechanical and thermal energy on nifedipine amorphous solid dispersions prepared by hot melt extrusion: Preparation and physical stability, Application In Synthesis of 21829-25-4, the main research area is nifedipine amorphous solid dispersion extrusion stability; Amorphous solid dispersion; Homogeneity; Hot melt extrusion; Physical stability; Specific mechanical energy; Thermal energy.

Hot melt extrusion (HME) has been used to prepare solid dispersions, especially molecularly dispersed amorphous solid dispersions (ASDs) for solubility enhancement purposes. The energy generated by the extruder in the form of mech. and thermal output enables the dispersion and dissolution of crystalline drugs in polymeric carriers. However, the impact of this thermal and mech. energy on ASD systems remains unclear. We selected a model ASD system containing nifedipine (NIF) and polyvinylpyrrolidone vinyl acetate (PVP/VA 64) to investigate how different types of energy input affect the preparation and phys. stability of ASDs. Formulations were prepared using a Leistritz Nano-16 extruder, and we varied the screw design, barrel temperature, screw speed, and feed rate to control the mech. and thermal energy input. Specific mech. energy (SME) was calculated to quantitate the mech. energy input, and the thermal energy was estimated using barrel temperature We find that both mech. and thermal energy inputs affect the conversion of crystalline NIF into an amorphous form, and they also affect the level of mixing and the degree of homogeneity in NIF ASDs. However, for small size extruders (e.g., Leistritz Nano-16), thermal energy is more efficient than mech. energy in preparing NIF ASDs that have better stability.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Amorphous materials. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Sarpal, Kanika published the artcileAmorphous Solid Dispersions of Felodipine and Nifedipine with Soluplus: Drug-Polymer Miscibility and Intermolecular Interactions, Application In Synthesis of 21829-25-4, the main research area is felodipine nifedipine soluplus miscibility polymer; Amorphous solid dispersions; Hydrogen bonding; Phase heterogeneity; Solid-state nuclear magnetic resonance spectroscopy; Thermodynamic miscibility.

The objective of this study was to investigate thermodn. and kinetic miscibility for two structurally similar model compounds nifedipine (NIF) and felodipine (FEL) when formulated as amorphous solid dispersions (ASDs) with an amphiphilic polymer Soluplus. Thermodn. miscibility was studied via m.p. depression approach for the two systems. The Flory Huggins theory was used to calculate the interaction parameter and generate the phase diagrams. It was shown that NIF was more miscible in Soluplus than FEL. The nature of drug-polymer interactions was studied by fourier transform infra-red spectroscopy (FTIR) and solid-state NMR spectroscopy (ssNMR). The data from spectroscopic analyses showed that both the drugs interacted with Soluplus through hydrogen bonding interactions. Furthermore, 13C ssNMR data was used to get quant. estimate of the extent of hydrogen bonding for ASDs samples. Proton relaxation measurements were carried out on ASDs in order to evaluate phase heterogeneity on two different length scales of mixing. The data suggested that better phase homogeneity in NIF:SOL systems especially for lower Soluplus content ASDs on smaller domains. This could be explained by understanding the extent of hydrogen bonding interactions for these two systems. This study highlights the need to consider thermodn. and kinetic mixing, when formulating ASDs with the goal of understanding phase mixing between drug and polymer.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Amorphous materials. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Turkes, Cuneyt published the artcileAnti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity, Application In Synthesis of 21829-25-4, the main research area is cinnarizine calcium channel blocker antidiabetic agent aldose reductase; Aldose reductase; Calcium channel blockers; Inhibition; Purification.

Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some calcium channel blockers and the enzyme. It was found that calcium channel blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87-8.77μM and Ki constants in the range of 2.07 ± 0.72-5.62 ± 1.53μM. The calcium channel blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (Ki: 2.07 ± 0.72μM). They may be useful in the treatment and/or prevention of diabetic complications.

Applied Biochemistry and Biotechnology published new progress about Antidiabetic agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Seo, Mi Seon published the artcileEmpagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K+ channels, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is empagliflozin antidiabetic agent vasodilatory; Aorta; Empagliflozin; Protein kinase G; Voltage-dependent K(+) (Kv) channel.

We investigated the vasodilatory effects of empagliflozin (a sodium-glucose co-transporter 2 inhibitor) and the underlying mechanisms using rabbit aorta. Empagliflozin induced vasodilation in a concentration-dependent manner independently of the endothelium. Likewise, pretreatment with the nitric oxide synthase inhibitor L-NAME or the SKca inhibitor apamin together with the IKca inhibitor TRAM-34 did not impact the vasodilatory effects of empagliflozin. Pretreatment with the adenylyl cyclase inhibitor SQ22536 or a guanylyl cyclase inhibitor ODQ or a protein kinase A (PKA) inhibitor KT5720 also did not alter the vasodilatory response of empagliflozin. However, the vasodilatory effects of empagliflozin were significantly reduced by pretreatment with the protein kinase G (PKG) inhibitor KT5823. Although application of the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide, large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline, or inwardly rectifying K+ (Kir) channel inhibitor Ba2+ did not impact the vasodilatory effects of empagliflozin, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of empagliflozin. Pretreatment with DPO-1 (Kv1.5 channel inhibitor), guangxitoxin (Kv2.1 channel inhibitor), or linopirdine (Kv7 channel inhibitor) had little effect on empagliflozin-induced vasodilation. Application of nifedipine (L-type Ca2+ channel inhibitor) or thapsigargin (sarco-endoplasmic reticulum Ca2+-ATPase pump inhibitor) did not impact empagliflozin-induced vasodilation. Therefore, empagliflozin induces vasodilation by activating PKG and Kv channels.

Toxicology and Applied Pharmacology published new progress about Antidiabetic agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yamazaki, Kei published the artcileHepatocyte growth factor exhibits anti-fibrotic effects in an in vitro model of nifedipineinduced gingival overgrowth, Related Products of pyridine-derivatives, the main research area is gingiva nifedipine hepatocyte growth factor antifibrotic; drug-induced gingival overgrowth; hepatocyte growth factor; nifedipine.

Purpose: The aim of this study was to establish an in vitro model of nifedipine-induced gingival overgrowth and characterize the anti-fibrotic effect of hepatocyte growth factor (HGF) using this model. Methods: Human gingival fibroblasts were cultured-treated with 0.1, 1, or 10μg/mL nifedipine or 10 ng/mL IL-1β + 0.1, 1, or 10μg/mL nifedipine (0.1N, 1N, 10N, IL + 0.1N, IL + 1N, IL + 10N). Cell proliferation and levels of type I collagen, TGF-β1, CCN2/CTGF, and α-SMA were measured 48 h after the simultaneous addition of 10 and 50 ng/mL HGF (10 and 50HGF) along with IL-1β and nifedipine. Type I collagen was measured after administration of anti-HGF neutralizing antibody. Results: Significant increases in type I collagen, TGF-β1, and CCN2/ CTGF were observed after treatment in the 1N and IL + 0.1N groups. Levels of type I collagen and CCN2/CTGF differed significantly between the IL + 0.1N group and the IL + 0.1N + 50HGF group. Production of type I collagen increased significantly following addition of anti-HGF antibody. Conclusion: This study demonstrated the establishment of an in vitro model of nifedipine-induced gingival overgrowth by showing increased collagen levels. Experiments using this model suggested that HGF exerts anti-fibrotic effects.

Journal of Oral Science published new progress about Antifibrotic agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Jian-Qi published the artcileEffects of allisartan isoproxil on blood pressure and target organ injury in patients with mild to moderate essential hypertension, COA of Formula: C17H18N2O6, the main research area is essential hypertension organ injury blood pressure allisartan isoproxil.

Evidence has shown that angiotensin II type 1 receptor antagonists have lower blood pressure and have target organ protective effects, but this is not the case for the drug allisartan isoproxil. The aim of this study was to evaluate the effects of allisartan isoproxil on blood pressure and target organ injury in patients with mild to moderate essential hypertension.In total, 80 essential hypertensive participants were randomly divided into an allisartan group and a nifedipine group (n=40 per group), and their blood pressure was measured once per mo for 6 mo. A 2-dimensional echocardiogram was performed at baseline and at the end of the study. The serum levels of renal injury indexes, endothelial function markers, inflammatory factors, blood biochem. assays and urinary measurements were determined at baseline and at 6 mo.At the end of the study, both systolic and diastolic blood pressure were significantly decreased in the allisartan group compared with baseline and showed the same antihypertensive effect as the nifedipine group. Meanwhile, the left ventricular remodeling, 24-h levels of urinary microalbumin, endothelial dysfunction, and arterial stiffness were all significantly improved compared with that of the baseline and the nifedipine group (all P<.05).The present study showed that allisartan isoproxil had favorable blood pressure lowering and heart, renal, and endothelial protective effects in patients with mild to moderate essential hypertension. Medicine (Philadelphia, PA, United States) published new progress about Antiglaucoma agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, COA of Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Peng, De-wei published the artcileConnexin 43 participates in atrial electrical remodelling through colocalization with calcium channels in atrial myocytes, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is connexin 43 calcium channel atrial elec remodelling fibrillation myocyte; HL-1 cells; L type calcium channel current; T type calcium channel current; atrial fibrillation; connexin 43.

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by elec. and/or structural remodelling. In the present study, author hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.2 and connexin 43 (Cx43) and basal ICa,L were decreased in AF subjects compared to sinus rhythm (SR) controls. In cultured atrium-derived myocytes (HL-1 cells), knocking-down of Cx43 or incubation with 30 mmol/L glycyrrhetinic acid significantly inhibited protein levels of Cav1.2 and Cav3.1 and the c.d. of ICa,L and ICa,T. Incubation with nifedipine or mibefradil decreased the protein level of Cx43 in HL-1 cells. Moreover, Cx43 was colocalized with Cav1.2 and Cav3.1 in atrial myocytes. Therefore, Cx43 might regulate the ICa,L and ICa,T through colocalization with calcium channel subunits in atrial myocytes, representing a potential pathogenic mechanism in AF.

Clinical and Experimental Pharmacology and Physiology published new progress about Atrial fibrillation. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Feric, Nicole T. published the artcileEngineered cardiac tissues generated in the biowire II: a platform for human-based drug discovery, Formula: C17H18N2O6, the main research area is heart tissue cardiomyocyte drug discovery; Cardiomyocytes; contractility; drug discovery; drug safety; engineered cardiac tissue; in vitro models.

Recent advances in techniques to differentiate human induced pluripotent stem cells (hiPSCs) hold the promise of an unlimited supply of human derived cardiac cells from both healthy and disease populations. That promise has been tempered by the observation that hiPSC-derived cardiomyocytes (hiPSC-CMs) typically retain a fetal-like phenotype, raising concern about the translatability of the in vitro data obtained to drug safety, discovery, and development studies. The Biowire II platform was used to generate 3D engineered cardiac tissues (ECTs) from hiPSC-CMs and cardiac fibroblasts. Long term elec. stimulation was employed to obtain ECTs that possess a phenotype like that of adult human myocardium including a lack of spontaneous beating, the presence of a pos. force-frequency response from 1 to 4 Hz and prominent postrest potentiation. Pharmacol. studies were performed in the ECTs to confirm the presence and functionality of pathways that modulate cardiac contractility in humans. Canonical responses were observed for compounds that act via the β-adrenergic/cAMP-mediated pathway, eg, isoproterenol and milrinone; the L-type calcium channel, eg, FPL64176 and nifedipine; and indirectly effect intracellular Ca2+ concentrations, eg, digoxin. Expected pos. inotropic responses were observed for compounds that modulate proteins of the cardiac sarcomere, eg, omecamtiv mecarbil and levosimendan. ECTs generated in the Biowire II platform display adult-like properties and have canonical responses to cardiotherapeutic and cardiotoxic agents that affect contractility in humans via a variety of mechanisms. These data demonstrate that this human-based model can be used to assess the effects of novel compounds on contractility early in the drug discovery and development process.

Toxicological Sciences published new progress about Cardiac contraction. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem