Electrospinning-modified Pt/CeO2 nano bandage as a promising therapy to reduce secondary brain injury

Traumatic brain injury (TBI) continues to be a major contributor to morbidity, disability, and mortality in all age groups. Initial brain damage is accompanied by acute and irreversible primary damage to the parenchyma, while subsequent secondary brain damage often progresses slowly over months to years, thus providing a window for therapeutic intervention. The most frequent case which happened is excessive oxidative stress and calcium release after brain injury. Although some traditional antioxidants have been clinically approved, the efficacy is far from satisfactory due to their low ROS-scavenging efficiency, instability, toxicity, or inadequate penetration of the blood-brain barrier. Moreover, the combination of Nanozyme based-bandage with Pt/CeO2 atom catalysis with electrospinning nanofibers N-type voltage-gated calcium channel blocker (SNX-185) is predicted to be as promising as a potential novel to reduce secondary injury of TBI. Therefore, the duo could cut down morbidity and mortality rates because of TBI in the future, noninvasively.

Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells

Thanks to the crosstalk between Na+ and Ca2+ channels, Na+ and Ca2+ homeostasis interplay in so-called excitable cells enables the generation of action potential in response to electrical stimulation. Here, we investigated the impact of persistent activation of voltage-gated Na+ (NaV) channels by neurotoxins, such as veratridine (VTD), on intracellular Ca2+ concentration ([Ca2+]i) in a model of excitable cells, the rat pituitary GH3b6 cells, in order to identify the molecular actors involved in Na+-Ca2+ homeostasis crosstalk. By combining RT-qPCR, immunoblotting, immunocytochemistry, and patch-clamp techniques, we showed that GH3b6 cells predominantly express the NaV1.3 channel subtype, which likely endorses their voltage-activated Na+ currents. Notably, these Na+ currents were blocked by ICA-121431 and activated by the β-scorpion toxin Tf2, two selective NaV1.3 channel ligands. Using Fura-2, we showed that VTD induced a [Ca2+]i increase. This effect was suppressed by the selective NaV channel blocker tetrodotoxin, as well by the selective L-type CaV channel (LTCC) blocker nifedipine. We also evidenced that crobenetine, a NaV channel blocker, abolished VTD-induced [Ca2+]i elevation, while it had no effects on LTCC. Altogether, our findings highlight a crosstalk between NaV and LTCC in GH3b6 cells, providing a new insight into the mode of action of neurotoxins.

Solubility of Nifedipine by Shake Flask UV-Spectrometry; Review of Safety Concerns in Pregnancy

Nifedipine is chemically dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, a dihydropyridine derivative used frequently as anti-hypertensive. It is a L- type calcium channel blocker (CCB). Few analogical discrepancies were found between Nifedipine’s clinical output report and chemical analysis of solubility. The ambition of this research is to conduct a re-check and proper quantification of partition co-efficient (logP) of Nifedipine and clarify the discrepancy and rectify if any mistake has been done in recent past. The method used is the “gold standard” shake-flask method followed by analysis through UV-scpectrophotmetry.

Protective Actions of Cilnidipine: Dual L/N-Type Calcium Channel Blocker Against Hypertensive Renal Injury in Rats

Background: Cilnidipine belongs to fourth generation dihydropyridine calcium channel blocker (CCB). It is a dual L & N-type CCB. L- type calcium channels are present on the vascular smooth muscle and N-type calcium channels are present on the presynaptic nerve terminals. Cilnidipine has a vasodilating effect, its action is slow and long lasting. Aim and objectives: Aim of present study was to demonstrate the beneficial effects of cilnidipine on the hypertensive renal injury rats. And our objectives is to assess renal injury parameters (Proteinuria, Creatinine clearance, Renal fibrosis/glomerulosclerosis) in response to chronic NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) treatment in the presence or absence of cilnidipine treatment. Material and methods: Male albino Wister rats were procured from institutional animal house, divided into 4 groups (n=6 in each group). Group1 treated with vehicle (control), group2 treated with cilnidipine, group3 treated with L-NAME, group4 treated with L-NAME & cilnidipine. 24 hour urinary protein and creatinine clearance were measured. Serum urea and creatinine levels are also measured. Urinary and serum Angiotensin II levels were measured. Histopathological examination of kidneys was performed. Results: Our results demonstrate that treatment with cilnidipine (group4) there is reduction in 24hr urinary protein, improvement in creatinine clearance. We observed there was renal glomerulosclerosis and tubular degeneration of kidney tubules in group3 rats and reduction of renal injury in group4 rats. We also found reduced urinary and serum Angiotensin II level in cilnidipine treated (group 4) rats. Conclusion: These findings indicated that cilnidipine act as renoprotective agent and reduces glomerular damage in L-NAME induced hypertensive rats.

L-type calcium channel blocker increases VEGF concentrations in retinal cells and human serum

Objective: Vascular endothelial growth factor (VEGF) plays a key role in diabetic retinopathy (DR). L-type calcium channel blockers (LTCCBs) have been widely used as antihypertensive medication (AHM), but their association with VEGF and DR is still unclear. Therefore, we explored the effect of LTCCBs compared to other AHMs on VEGF concentrations in retinal cells and human serum. Furthermore, we evaluated the association between the use of LTCCBs and the risk of severe diabetic eye disease (SDED). Research design and methods: Muller cells (MIO-M1) were cultured as per recommended protocol and treated with LTCCBs and other AHMs. VEGF secreted from cells were collected at 24 hours intervals. In an interventional study, 39 individuals received LTCCBs or other AHM for four weeks with a four-week wash-out placebo period between treatments. VEGF was measured during the medication and placebo periods. Finally, we evaluated the risk of SDED associated with LTCCB usage in 192 individuals from the FinnDiane Study in an oberservational setting. Results: In the cell cultures, medium VEGF concentration increased time-dependently after amlodipine (p<0.01) treatment, but not after losartan (p>0.01), or lisinopril (p>0.01). Amlodipine, but no other AHM, increased serum VEGF concentration (p<0.05) during the interventional clinical study. The usage of LTCCB was not associated with the risk of SDED in the observational study. Conclusions: LTCCB increases VEGF concentrations in retinal cells and human serum. However, the usage of LTCCBs does not appear to be associated with SDED in adults with type 1 diabetes.

LaCl3 Treatment Improves Agrobacterium-mediated Immature Embryo Genetic Transformation Frequency of Maize

Agrobacterium-mediated genetic transformation of immature embryos is important for gene-function studies and molecular breeding of maize. However, the relatively low genetic transformation frequency remains a bottleneck for applicability of this method, especially on commercial scale. We report that pretreatment of immature embryos with LaCl3 (a Ca2+ channel blocker) improves the infection frequency of Agrobacterium tumefaciens, increases the proportion of positive calluses, yields more positive regenerated plantlets, and increases the transformation frequency from 8.40% to 17.60% for maize. This optimization is a novel method for improving the frequency of plant genetic transformations mediated by Agrobacterium tumefaciens.

Outcomes of Radial Artery Grafts Without Postoperative Calcium Channel Blocker Administration

Background: Guidelines encourage oral pharmacologic antispasmodic therapy for patients receiving a radial artery conduit during coronary artery bypass grafting. We review our experience with radial artery conduits without the postoperative use of calcium channel blocker therapy. Methods: A single-center, retrospective review patients undergoing isolated coronary artery bypass grafting with at least one radial artery conduit over a three-year period was performed. Patient demographic, operative, and post-discharge data were collected. Development of angina or angina equivalent symptoms, imaging suggestive of radial conduit failure, or percutaneous intervention to the territory grafted by a radial artery was considered to represent graft failure. Patients were evaluated for primary outcomes through 90 days postoperatively and followed for 1 year overall. Results: 264 adult patients underwent first-time, isolated coronary artery bypass grafting with use of a radial artery conduit. Three patients were observed to have radial graft occlusions during the first 90 days, all of which were attributed to technical issues. No patients required addition of a calcium channel blocker & no additional patients underwent imaging or intervention for radial graft failure during 1 year of follow up. Conclusions: Avoidance of postoperative calcium channel blocker therapy in patients receiving a radial artery graft was not associated with a high incidence of imaging-confirmed or clinically suggested conduit failure.

Formulation and Characterization of Nimodipine Nanoparticles for the Enhancement of solubility and dissolution rate

Nimodipine (NMD) is a dihydropyridine calcium channel blocker useful for the prevention and treatment of delayed ischemic effects. It belongs to class ? drugs, which is characterized by low solubility and high permeability. This research aimed to prepare Nimodipine nanoparticles (NMD NPs) for the enhancement of solubility and dissolution rate. The formulation of nanoparticles was done by the solvent anti-solvent technique using either magnetic stirrer or bath sonicator for maintaining the motion of the antisolvent phase. Five different stabilizers were used to prepare NMD NPs( TPGS, Soluplus®, HPMC E5, PVP K90, and poloxamer 407). The selected formula F2, in which Soluplus has been utilized as a stabilizer, has a particle size (77 nm) and polydispersity index (PDI) (0.016). The formulas with the smallest particle size were freeze dried with the addition of 1 % w/w mannitol as cryoprotectant. The saturation solubility of NMD in the prepared nanoparticles was increased twenty four-folds, and the complete dissolution was achieved at 90 minutes compared with pure NMD, which reaches only 6%. The formation of hydrogen bonding between NMD and the polymer or the cryoprotectant, as confirmed by the FTIR study. In conclusion, the preparation of NMD as polymeric nanoparticles is a useful technique for enhancing the solubility and dissolution rate.