Month: December 2022

Kjalarsdottir, Lilja published the artcile1,25-Dihydroxyvitamin D3 enhances glucose-stimulated insulin secretion in mouse and human islets: a role for transcriptional regulation of voltage-gated calcium channels by the vitamin D receptor, Product Details of C17H18N2O6, the main research area is insulin peptide hormone vitamin D3 VDR calcium channel islet; Calcitriol; Insulin secretion; Islet; Transcriptional regulation; Vitamin D; Voltage-gated calcium channels.

Vitamin D deficiency in rodents neg. affects glucose-stimulated insulin secretion (GSIS) and human epidemiol. studies connect poor vitamin D status with type 2 diabetes. Previous studies performed primarily in rat islets have shown that vitamin D can enhance GSIS. However the mol. pathways linking vitamin D and insulin secretion are currently unknown. Therefore, experiments were undertaken to elucidate the transcriptional role(s) of the vitamin D receptor (VDR) in islet function. Human and mouse islets were cultured with vehicle or 1,25-dihydroxyvitamin-D3 (1,25D3) and then subjected to GSIS assays. Insulin expression, insulin content, glucose uptake and glucose-stimulated calcium influx were tested. Microarray anal. was performed. In silico anal. was used to identify VDR response elements (VDRE) within target genes and their activity was tested using reporter assays. Vdr mRNA is abundant in islets and Vdr expression is glucose-responsive. Preincubation of mouse and human islets with 1,25D3 enhances GSIS and increases glucose-stimulated calcium influx. Microarray anal. identified the R-type voltage-gated calcium channel (VGCC) gene, Cacna1e, which is highly upregulated by 1,25D3 in human and mouse islets and contains a conserved VDRE in intron 7. Results from GSIS assays suggest that 1,25D3 might upregulate a variant of R-type VGCC that is resistant to chem. inhibition. These results suggest that the role of 1,25D3 in regulating calcium influx acts through the R-Type VGCC during GSIS, thereby modulating the capacity of beta cells to secrete insulin.

Journal of Steroid Biochemistry and Molecular Biology published new progress about Adipose tissue. 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, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Yuanliang published the artcileZearalenone exposure mediated hepatotoxicity via mitochondrial apoptotic and autophagy pathways: Associated with gut microbiome and metabolites, Category: pyridine-derivatives, the main research area is Lactococcus hepatotoxicity zearalenone mitochondria apoptosis autophagy hepatocyte gut microbiota; Gut microbiome; Hepatotoxicity; Metabolomics; Zearalenone.

Zearalenone (ZEN), a mycotoxin is frequently detected in different food products and has been widely studied for its toxicity. However, the underlying mechanisms of hepatotoxic effects, relationship between gut microbiome and liver metabolite mediated hepatotoxicity mechanisms induced by ZEN are still not clear. Here, we reported that the different microscopic changes like swelling of hepatocyte, disorganization of hepatocytes and extensive vacuolar degeneration were observed, and the mitochondrial functions decreased in exposed mice. Results exhibited up-regulation in expression of signals of apoptosis and autophagy in liver of treated mice via mitochondrial apoptotic and autophagy pathway (Beclin1/p62). The diversity of gut microbiome decreased and the values of various microbiome altered in treated mice, including 5 phyla (Chloroflexi, Sva0485, Methylomirabilota, MBNT15 and Kryptonia) and genera (Frankia, Lactococcus, Anaerolinea, Halomonas and Sh765B-TzT-35) significantly changed. Liver metabolism showed that the concentrations of 91 metabolite including lipids and lipid like mols. were significantly changed. The values of phosphatidylcholine, 2-Lysophosphatidylcholine and phosphatidate concentrations suggestive of abnormal glycerophosphate metabolism pathway were significantly increased in mice due to exposure to ZEN. In conclusion, the findings suggest that the disorders in gut microbiome and liver metabolites due to exposure to ZEN in mice may affect the liver.

Toxicology published new progress about Actinobacteria. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wells, Jeffrey L. published the artcileOn the electrophilic reactivities of α-carbonyl heterocycles and arenes, Quality Control of 71255-09-9, the main research area is heterocyclic aldehyde hemi acetal formation electrophilic reactivity LUMO.

A series of heterocyclic aldehydes and substituted benzaldehydes were studied for their tendencies to form hemiacetal products with methanol. The equilibrium ratios were compared with DFT calculated MO levels and the hemi-acetal content was found to correlate roughly to the energy level of the lowest unoccupied MOs (LUMOs). Hemi-acetal formation is enhanced by intramol. hydrogen bonds and diminished by steric effects.

Pharma Chemica published new progress about Acid catalysis. 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Quality Control of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Huang, Jessica published the artcileAngiotensin axis antagonists increase the incidence of haemodynamic instability in dihydropyridine calcium channel blocker poisoning, Quality Control of 72509-76-3, the main research area is dihydropyridine calcium channel blocker angiotensin antagonist haemodynamic bsu; Angiotensin II receptor blockers; amlodipine; angiotensin converting enzyme inhibitors; overdose; toxicity.

Context Amlodipine, a dihydropyridine calcium channel blocker (CCB), is the leading cause of cardiovascular drug-related overdose deaths in the USA. In contrast, angiotensin-II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) cause minimal toxicity in overdose. ACEIs/ARBs are often combined with dihydropyridines in hypertension treatment. Co-ingested ARBs/ACEIs may significantly contribute to the toxicity of dihydropyridine, but this has not been investigated. Objective To investigate the clin. outcomes from dihydropyridine overdoses with ARBs/ACEIs vs. dihydropyridine overdoses alone. Methods This was a retrospective study of patients reported to the New South Wales Poisons Information Center (NSW PIC) and 3 toxicol. units (Jan 2016 to Jun 2019) in Australia. Patients >14 years who took an overdose of dihydropyridines (amlodipine, felodipine, lercanidipine, nifedipine) were included. Concurrent overdoses with non-dihydropyridine CCBs, alpha-blockers and beta-blockers were excluded. Patient demographics, drugs exposure details, serial vital signs, treatments and outcome were collected.Results There were 100 patients. 68 took mixed overdoses of dihydropyridines with ARBs/ACEIs and 32 took single overdoses of dihydropyridines without ARBs/ACEIs. The mixed group had lower median nadir mean arterial pressures (62 vs 75 mmHg, p < 0.001), more frequently had hypotension (OR 4.5, 95%CI: 1.7-11.9) or bradycardia (OR 8.8, 95%CI: 1.1-70). Multivariable anal. indicated the mixed overdoses had an 11.5 mmHg (95%CI: 4.9-18.1) lower min. systolic blood pressure (SBP) compared with the single group; other factors associated with a lower min. SBP were higher doses [2.3 mmHg (95%CI: 1.1-3.5) lower per 10 defined daily doses] and younger age [2.2 mmHg (95%CI: 0.3-4.2) higher per decade]. A larger proportion of the mixed ingestion group received i.v. fluids (OR 5.7, 95%CI: 1.8-18.6) and antidotes and/or vasopressors (OR 2.9, 95%CI: 1.004-8.6). Conclusion Combined overdoses of dihydropyridines with ARBs/ACEIs caused more significant hypotension and required more haemodynamic support than overdoses of dihydropyridines alone. Clinical Toxicology published new progress about Abdominal pain. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Sahoo, Arpita published the artcileA comprehensive review on Siragata vata w.s.r to Raynaud’s disease, Application In Synthesis of 21829-25-4, the main research area is review nifedipine prazocin glycerin trinitrate Siragata Vata Raynaud disease.

Siragata Vata is an Ekanga (localized) Vatavyadhi described by Maharshis. It is better correlated with Raynaud’s disease in modern medical science. Vasospasm or obstruction of blood vessels results cessation of blood flow to the fingers, hand, lips, nose and toes make worse the condition. Shita Ahara Vihar, Chinta, Shoka, Srota Avarodha are causative factors. Pallor or blanching, dusky cyanosis and painful red engorgement are common symptoms. Modern medicines like nifedipine, prazocin, glycerin trinitrate are advised for treatment of Raynaud’s disease but these medicines may affect other organs functions and produce side effects. Ayurvedic therapies described for Siragata Vata can be beneficial for the treatment of Raynaud’s disease without any alteration of other organs functions. Leech therapy has vasodilator effect which can improve the vasospasm. In this review paper detail comparison between Siragata Vata and Raynaud’s disease has been described.

World Journal of Pharmacy and Pharmaceutical Sciences published new progress about Raynaud 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, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kawata, Tsutomu published the artcileCharacteristics of viologen derivatives for electrochromic display, Application of 1,1-Di-n-octyl-4,4-bipyridinium Dibromide, the main research area is viologen derivative polarog optical absorption; electrochromic display viologen derivative.

The polarog. half-wave potentials (E1/2, in aqueous solutions with pH 3.29 at 25°) and the absorption spectra (at λ = 250-700 nm) in various media (aqueous solution, MeOH, glycerin) were determined to characterize the electrochromic behavior of the viologen derivatives X-RN+C5H4-C5H4N+RX- [= Viol] (R = Pr, C6H13, or C7H15 for X = Br; X = Cl, Br, or I for R = PhCH2). Two polarog. waves were observed for each derivative: the 1st E1/2 [= 0.568-0.710 V vs. SCE] was attributed to the reduction, dication of Viol (I, colorless) + e- ⇄ radical cation (II, colored); and the 2nd E1/2 [= 0.775-0.965 V] was attributed to II + e- ⇄ biradical (III, colored). The E1/2 values were smaller for the PhCH2 derivatives than for the alkyl derivatives For R = PhCH2, the observed absorption maximum were at λ (in nm) ≈ 260 for I, ≈ 260, 400, and 630 for II, and ≈ 380 for III. With a viologen derivative in an electrochromic display device (having a transparent SnO2 cathode and a Pt anode), the writing time decreased with increasing applied voltage, and was ∼0.4-0.8 sec for obtaining a transmittance of 80%. An applied voltage greater than the 2nd E1/2 caused the color to change from purple to yellow; on open circuit, the color changed back to purple.

Japanese Journal of Applied Physics published new progress about Electrochromism. 36437-30-6 belongs to class pyridine-derivatives, name is 1,1-Di-n-octyl-4,4-bipyridinium Dibromide, and the molecular formula is C26H42Br2N2, Application of 1,1-Di-n-octyl-4,4-bipyridinium Dibromide.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lal, Chiman published the artcilePharmacokinetic and Pharmacodynamic Studies of Nifedipine Loaded Microspheres for the Treatment of Hypertension, Formula: C17H18N2O6, the main research area is pharmacokinetic pharmacodynamic nifedipine microsphere hypertension; Hypertension; blood pressure; mucoadhesive microspheres; nifedipine; pharmacodynamic; pharmacokinetic.

The purpose of this research work was to evaluate the Pharmacokinetic (PK), Pharmacodynamic (PD), and the distribution pattern of mucoadhesive microspheres of nifedipine. Firstly, the emulsion solvent evaporation technique was used to prepare the mucoadhesive microspheres. The microspheres were characterized by Fourier Transform IR Spectroscopy (FTIR) and in vivo studies were carried on Wistar rats. Blood samples of rats were withdrawal at 2, 4, and 8 h time interval, after the administration of Mucoadhesive microspheres of nifedipine (Mm-N) and the Saline solution of nifedipine (Ss-N) sep. The Area Under the Curve (AUC) of Mm-N was seven foaled and Cmax around four foaled high when compared with Ss-N with a significant difference P<0.005. Hypertension induced with DOCA (deoxycorticosterone acetate) and the Blood Pressure (BP) of hypertensive rats were recorded at 0, 0.5, 1, 2, 3, 4, 5, 6 h time interval after given Mm-N and Ss-N to different groups. The BP of rats was better control with Mm-N and regular after 2 h with high significant difference P<0.0001 however, the Ss-N have an insignificant difference with P>0.05. The Mm-N was distributed in the upper part of the Gastrointestinal Tract (GIT) after 8 h confirmed with the help of the fluorescence microscopic examination Conclusion: This study indicates that the nifedipine was present in the blood for a more extended period, and the blood pressure was easily controlled with mucoadhesive microspheres of nifedipine. Therefore, mucoadhesive microspheres of nifedipine would be an excellent alternative over conventional drug delivery for the treatment of hypertension.

Current Drug Delivery published new progress about Digestive tract. 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

Koli, Akshay R. published the artcileOral bioavailability improvement of felodipine using tailored microemulsion: Surface science, ex vivo and in vivo studies, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is felodipine microemulsion delivery capmul Tween polyethylene glycol oral bioavailability; Felodipine; Microemulsion; Oral bioavailability; Pharmacokinetic studies; Surface science.

Felodipine is a calcium channel blocker, which shows low oral bioavailability (<15%) owing to poor water solubility and high first pass metabolism The aim of the present investigation was to study the surface science (dynamic surface tension) and characteristics of microemulsion (Capmul MCM, Tween 20 and polyethylene glycol) to enhance the oral bioavailability of felodipine by improving permeability of the drug in the intestine. The paper is the first attempt to study the stability of oil-water interface of microemulsion using bubble tensiometer. The Smix at 2:1 ratio showed the maximum microemulsion area which did not alter in the presence of drug. The microemulsion batch coded Fe-O5-Smix45 (5% Capmul MCM and 45% Smix) was selected based on transmittance (>99%), dilution (stable after 100 times dilution with water), size (15.1 nm), dispersibility (grade A) and thermodn. stability studies. The dynamic surface tension at newly created surface indicate the stability of surfactant film at the oil/water interface. The microemulsion was also stable in the presence of drug and in different buffer phases. The ex vivo intestinal permeability studies showed significant increase in the microemulsion permeation (74.1% after 1 h) in comparison to the felodipine suspension (16.9% after 1 h). The in vivo pharmacokinetic parameters in the rat model confirmed the improvement in oral bioavailability with microemulsion (relative bioavailability = 21.9) in comparison to the felodipine suspension, due to high surface area of oil droplets and its lymphatic uptake via transcellular route. In conclusion, the stable microemulsion offers a promising approach to improve the oral bioavailability of felodipine which can help to reduce the dose and its associated side effects.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Digestive tract. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Koerber, Thomas published the artcileSystematic differences in the relaxation stretching of polar molecular liquids probed by dielectric vs magnetic resonance and photon correlation spectroscopy, Product Details of C18H19Cl2NO4, the main research area is relaxation stretching polar liquid NMR dielec photon correlation spectroscopy.

Relaxation spectra of mol. glass formers devoid of secondary relaxation maxima, as measured by dielec. spectroscopy (DS), NMR relaxometry, photon correlation spectroscopy (PCS), and Fabry-Perot interferometry, are quant. compared in terms of the Kohlrausch stretching parameter βK. For a reliable estimate of βK, the excess wing contribution has to be included in the spectral anal. The relaxation stretching probed by PCS and NMR varies only weakly among the liquids (βK = 0.58 ± 0.06). It is similar to that found in DS, provided that the liquid is sufficiently nonpolar (relaxation strength Δε≲6). For larger strengths, larger βDSK (narrowed relaxation spectra) are found when compared to those reported from NMR and PCS. Frequency-temperature superposition (FTS) holds for PCS and NMR. This is demonstrated by data scaling and, for the few glass formers for which results are available, by the equivalence of the susceptibilities χ′′PCS(ωτ) ∼ χ′′NMR(τ) ∼ χ′′NMR(ω), i.e., measuring at a constant frequency is equivalent to measuring at a constant temperature or constant correlation time. In this context, a plot of the spin-lattice relaxation rate R1(T) as a function of the spin-spin relaxation rate R2(T) is suggested to reveal the stretching parameter without the need to perform frequency-dependent investigations. Dielec., we identify a trend of increasing deviations from FTS with increasing Δε. Depending on the technique and glass former, the relative relaxation strength of the excess wing varies, whereas its exponent appears to be method independent for a given substance. For polar liquids, we discuss possible reasons for the discrepancy between the results from PCS and NMR as compared to those from DS.

Journal of Chemical Physics published new progress about Dielectric loss. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Product Details of C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

McCarthy, Carly J. published the artcileATP transients accompany spontaneous contractions in isolated guinea-pig detrusor smooth muscle, Application In Synthesis of 21829-25-4, the main research area is ATP spontaneous contraction detrusor smooth muscle; ATP; detrusor smooth muscle; spontaneous contractions.

New Findings : What is the central question of this study Overactive bladder is associated with enhanced spontaneous contractions, but their origins are unclear. The aim of this study was to characterize the accompanying ATP transients. What is the main finding and its importance Spontaneous detrusor contractions were accompanied by transient increases of ATP, and their appearance was delayed by previous activation of efferent nerves to the detrusor. This indicates that spontaneous ATP release from nerve terminals supports spontaneous contractions. ATP is a functional excitatory neurotransmitter in human bladder only in pathologies such as overactive bladder. A potential drug target is revealed to manage this condition. Abstract : Spontaneous contractions are characteristic of the bladder wall, but their origins remain unclear. Activity is reduced if the mucosa is removed but does not disappear, suggesting that a fraction arises from the detrusor. We tested the hypothesis that spontaneous detrusor contractions arise from spontaneous ATP release. Guinea-pig detrusor strips, without mucosa, were superfused with Tyrode solution at 36°C. Preparations were subjected to elec. field stimulation (EFS; 3 s trains at 90 s intervals) to produce nerve-mediated contractions, abolished by 1μm TTX. Amperometric ATP electrodes on the preparation surface recorded any ATP released. Spontaneous contractions and ATP transients were recorded between EFS trains. Nerve-mediated contractions were attenuated by atropine and α,β-methylene ATP; in combination, they nearly abolished contractions, as did nifedipine. Contractions were accompanied by ATP transients that were unaffected by atropine but inhibited by TTX and greatly attenuated by nifedipine. Spontaneous contractions were accompanied by ATP transients, with a close correlation between the magnitudes of both transients. ATP and contractile transients persisted with TTX, atropine and nifedipine. Immediately after a nerve-mediated contraction and ATP transient, there was a longer interval than normal before spontaneous activity resumed. Spontaneous contractions and ATP transients are proposed to arise from ATP leakage from nerve terminals innervating the detrusor. Extracellular ATP has a greater functional significance in humans who suffer from detrusor overactivity (spontaneous bladder contractions associated with incontinence) owing to its reduced hydrolysis at the nerve-muscle interface. This study shows the origin of spontaneous activity that might be exploited to develop a therapeutic management of this condition.

Experimental Physiology published new progress about Detrusor muscle. 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