Cordycepin suppresses vascular inflammation, apoptosis and oxidative stress of arterial smooth muscle cell in thoracic aortic aneurysm with VEGF inhibition.

BACKGROUND: Thoracic aortic aneurysm (TAA) is a type of common and serious vascular disease, in which inflammation, apoptosis and oxidative stress are strongly involved in the progression. Cordycepin, a bioactive compound from Cordyceps militaris, exhibits anti-inflammatory and anti-oxidative activities. This study aimed to address the role and mechanism of cordycepin in TAA. METHODS: The thoracic aortas were perivascularly administrated with calcium chloride (CaCl2), and human aortic smooth muscle cells (HASMCs) were incubated with angiotensin II (Ang II) to simulate the TAA model in vivo and in vitro, respectively. The effect and mechanism of cordycepin in TAA were explored by hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, biochemical test, cell counting kit-8 (CCK-8), and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assays. RESULTS: Cordycepin improved the CaCl2-induced the aneurysmal alteration and disappearance of normal wavy elastic structures of the aorta tissues, TAA incidence and thoracic aortic diameter in rats, and Ang II-induced the cell viability of HASMCs. Cordycepin reversed the CaCl2-induced the relative protein expression of cleaved caspase 9, cleaved caspase 3, interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1ß, and the relative levels of glutathione (GSH), malonaldehyde (MDA) and reactive oxygen species (ROS) in vivo, or Ang II-induced these changes in vitro. Mechanically, cordycepin reduced the relative protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), cluster of differentiation 31 (CD31) and endothelial nitric oxide synthase (eNOS) in the Ang II-induced HASMCs. Correspondingly, overexpression of VEGF increased the levels of the indicators involved in apoptosis, inflammation and oxidative stress, which were antagonized with the cordycepin incubation in the Ang II-induced HASMCs. CONCLUSION: Cordycepin inhibited apoptosis, inflammation and oxidative stress of TAA through the inhibition of VEGF.

Ethanol Extract of Glycyrrhiza uralensis Fisch: Antidiarrheal Activity in Mice and Contraction Effect in Isolated Rabbit Jejunum.

OBJECTIVE: To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. METHODS: In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA). RESULTS: GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil. CONCLUSIONS: GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.

Antidiarrheal effect of the ethanol extract from Scutellaria barbata and its effect on the contraction of jejunum smooth muscles.

Scutellaria barbata (S. barbata), a traditional herbal medicine used in southern China, possesses anti-inflammatory, antitumor, spasmolytic and expectorant effects. However, there are not many recent studies on its gastrointestinal effects. This study aimed to evaluate the antidiarrheal effect of the ethanol extract of S. barbata (SBE) and its effect on the isolated jejunum smooth muscle. METHODS: The antidiarrheal effect of SBE (doses: 125, 250 and 500 mg/kg) on castor oil-induced diarrhea was investigated in vivo. The effect of SBE (0.01-10 mg/mL) on spontaneous or acetylcholine chloride (ACh, 10µM)/KCl (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was examined in vitro. The possible spasmolytic mechanism of SBE (1 and 3mg/mL) was analyzed by accumulating CaCl2 in a Ca2+-free high-K+ (60mM) solution. RESULTS: SBE (125, 250 and 500mg/kg) could delay the initial semi-solid onset time of mice and also reduce the diarrhea index in vivo. Furthermore, SBE (0.01-10mg/mL) could alleviate the spontaneous or ACh/KCl-induced contraction in vitro. SBE (1 and 3mg/mL) also inhibited the contraction induced by CaCl2, and the concentration-response curves of CaCl2 moved downward and to the right, similar to those of verapamil (0.01 and 0.1µM). CONCLUSIONS: SBE exerts antidiarrheal and spasmolytic effects, which provides a pharmacological basis for its use in functional gastrointestinal disorders.

Effect of Del Nido cardioplegia on ventricular arrhythmias after cardiovascular surgery.

BACKGROUND: Del Nido cardioplegia (DNC) has been proven safe and effective in pediatric patients. However, the use of DNC in adult undergoing cardiovascular surgery lacks support with substantial evidence. This study aimed to evaluate the efficacy of DNC as a cardioplegia of prophylaxis to ventricular arrhythmias associated to cardiovascular surgery in adult patients. METHODS: This study recruited nine hundred fifty-four patients who underwent cardiopulmonary bypass surgeries in Nanjing Hospital affiliated to Nanjing Medical University between January 2019 and December 2019. Among 954 patients, 324 patients were treated with DNC (DNC group), and 630 patients were treated with St. Thomas cardioplegia (STH group). The incidence of postoperative arrhythmia as well as other cardiovascular events relavant to the surgery were investigated in both groups. RESULTS: In DNC group, the incidence of postoperative ventricular arrhythmias was lower (12.4% vs. 17.4%, P = 0.040), and the length of ICU stay was shorter (1.97 ± 1.49 vs. 2.26 ± 1.46, P = 0.004). Multivariate logistic regression demonstrated that the use of DNC helped to reduce the incidence of postoperative ventricular arrhythmias (adjusted odds ratio 0.475, 95% CI 0.266-0.825, P = 0.010). The propensity score-based analysis and subgroup analysis indicated that DNC has the same protecting effects towards myocardial in all kinds of cardiopulmonary bypass surgeries. CONCLUSIONS: Del Nido cardioplegia may potentially reduce the incidence of postoperative ventricular arrhythmias, shorten the length of ICU stay and improve the overall outcome of the patients undergoing cardiovascular surgery.

Extravasation of calcium solution in the child: Value of negative-pressure wound therapy.

The extravasation of a calcium solution into soft tissue constitutes a medical emergency, and a lack of adequate management can lead to significant functional and cosmetic sequelae. Here, we report on the management of and long-term outcome in two children who experienced calcium infusion leakage. We also describe the emergency procedures used in cases of extravasation and discuss the role of negative pressure wound therapy as an appropriate adjunct to conventional techniques for dealing with serious extravasation-related injuries.

The Effect of Long-term Dressing with Calcium Hydroxide on the Fracture Susceptibility of Teeth.

INTRODUCTION: Calcium hydroxide has been widely used to treat immature teeth to achieve periodontal healing and to promote the formation of an apical barrier. However, retrospective clinical studies have shown a high incidence of cervical root fractures with long-term calcium hydroxide dressing. The alkalinity of calcium hydroxide has been suggested to weaken the root. In vitro studies using ovine teeth show conflicting results on fracture strength of dentine, although different commercial products may have influenced the results. The purpose of this study was to investigate the effects of 2 commercial products used in prior studies (Calasept Plus and UltraCal XS), as well as a new product (Calmix) that uses a nonaqueous vehicle that allows for a higher pH, on the fracture strength of dentine over time. METHODS: A total of 330 lamb incisor teeth were collected and the canals prepared so that 3 commercial calcium hydroxide products as well as a positive control of pure calcium hydroxide slurry that filled the root canal from the open apex and a negative control of saline was tested. The teeth were loaded until fracture with a universal testing machine at time points 0, 3, 6, and 9 months and the force to fracture was calculated. The data were analyzed with Friedman analysis of variance and Mann-Whitney t tests. RESULTS: No statistical differences were observed between the different calcium hydroxide products and the negative controls. CONCLUSIONS: Thin and fragile roots could be the cause of fracture rather than the calcium hydroxide dressing.

Effects of chemical castration using 20% CaCl2 with 0.5% DMSO in tomcats: Evaluation of inflammatory reaction by infrared thermography and effectiveness of treatment.

This study used infrared thermography to monitor the immediate inflammatory reaction to an intratesticular injection of 20% (calcium chloride) CaCl2 with 0.5% dimethyl sulfoxide (DMSO) for chemical castration and to provide evidence of the treatment's clinical viability. Six animals received a 0.25 mL intratesticular injection of 20% CaCl2 with 0.5% DMSO in each testis. Thermographic imaging, testicular measurement, penile spine evaluation, electroejaculation, and sperm analysis were performed before the injection. Eighty days post-injection, the cats were evaluated again, then received an orchiectomy followed by histological analysis. Infrared thermography of the testicular area was performed before (M0) and after anesthesia (M0A); after electroejaculation (M0E); 10 min (M1), 1 h, (M2) and 6 h (M3) after the injection for seven consecutive days (M4-10); after 15 (M11) and 30 days (M12); and after 80 days, before and after anesthesia and after electroejaculation (M13, M13A and M13E). No cats had a significant increase in testicular temperature or behavioral changes. All animals were azoospermic and had a 50% reduction in total testicular volume after 80 days. Histologically, the testes showed different degrees of degeneration, necrosis, calcification and replaced connective tissue, as well as Leydig cell hyperplasia in 7/12 of the testes. Infrared thermography efficiently diagnosed and monitored scrotal inflammation caused by intratesticular injection of 20% CaCl2 solution with 0.5% DMSO, and it is suggested that a single injection of this compound can cause azoospermia after 80 days. We concluded by infrared thermography with a clinical exam, that the adverse reactions were minimal and did not interfere with animal welfare.

Normokalemic nondepolarizing long-acting blood cardioplegia.

Objective Blood cardioplegia, the gold-standard cardioprotective strategy, requires frequent dosing, resulting in hyperkalemia-induced myocardial edema. The aim of our study was to compare the efficacy and safety of a long-acting blood-based cardioplegia with physiological potassium levels versus the well-established cold blood St. Thomas' Hospital no. 1 cardioplegia solution in multivalve surgeries. Methods One hundred patients undergoing simultaneous elective aortic and mitral valve replacement ± tricuspid valve repair were randomized in two groups. In group 1, adenosine 12 mg was given via the aortic root after crossclamping, followed by a single dose of long-acting solution at 14℃ (30 mLckg-1); in group 2, an initial 30 mLckg-1 of St. Thomas' cardioplegia at 14℃ was administered, followed by 15 mLckg-1 every 20 min. Duration of cardiopulmonary bypass, inotropic score, arrhythmias, ventilation time, and the levels of interleukin-6, creatinine kinase-MB, and troponin I were compared. Results Mean cardiopulmonary bypass and crossclamp times were 134.04 ± 36.12 vs. 154.34 ± 34.26 ( p = 0.004) and 110.37 ± 24.80 vs. 132.48 ± 31.68 min ( p = 0.002), respectively, in the long-acting and St. Thomas' groups. Cardiac index, creatinine kinase-MB and troponin I levels were comparable. Interleukin-6 levels post-bypass were 61.72 ± 15.33 and 75.44 ± 31.78 pgcmL-1 ( p = 0.007) in the long-acting and St. Thomas' cardioplegia groups, respectively. Conclusions Single-dose long-acting cardioplegia gives a cardioprotective effect comparable to repeated doses of the well-established St. Thomas' Hospital no. 1 cold blood cardioplegia.

A combination of additives can synergically decrease acrylamide content in gingerbread without compromising sensory quality.

BACKGROUND: The present study tested whether replacement of the leavening agent ammonium carbonate by sodium hydrogen carbonate in combination with calcium cation and acidifying agent will synergically decrease acrylamide (AA) content in gingerbread. RESULTS: The type of leavening agent and the presence of Ca2+ and citric acid accounted for 33.6%, 13.2% and 53.2% of the explained variability of the AA content, respectively (P < 0.01). The AA content in gingerbread produced with (NH4 )2 CO3 alone was 186.5 µg kg-1 . Irrespective of other tested additives, NaHCO3 decreased (P < 0.05) AA content to 42% compared to (NH4 )2 CO3 . Combination of NaHCO3 + CaCl2 + citric acid in dough reduced (P < 0.05) AA content below the limit of detection (25 µg kg-1 ). The AA content in gingerbread (y; µg kg-1 ) decreased with an increasing number of additives used (x) according to the equation y = 158.8 - 47.94x (r2 = 0.42; P < 0.0001). A comprehensive sensory analysis did not indicate any significant deterioration (P > 0.05) in the organoleptic quality of gingerbread produced using calcium cation and citric acid. CONCLUSION: The present study demonstrates that the combination of additives NaHCO3 /Ca2+ /citric acid synergically decreases AA content in gingerbread without compromising the sensory quality. © 2016 Society of Chemical Industry.

Salinization triggers a trophic cascade in experimental freshwater communities with varying food-chain length.

The application of road deicing salts in northern regions worldwide is changing the chemical environment of freshwater ecosystems. Chloride levels in many lakes, streams, and wetlands exceed the chronic and acute thresholds established by the United States and Canada for the protection of freshwater biota. Few studies have identified the impacts of deicing salts in stream and wetland communities and none have examined impacts in lake communities. We tested how relevant concentrations of road salt (15, 100, 250, 500, and 1000 mg Cl- /L) interacted with experimental communities containing two or three trophic levels (i.e., no fish vs. predatory fish). We hypothesized that road salt and fish would have a negative synergistic effect on zooplankton, which would then induce a trophic cascade. We tested this hypothesis in outdoor mesocosms containing filamentous algae, periphyton, phytoplankton, zooplankton, several macroinvertebrate species, and fish. We found that the presence of fish and high salt had a negative synergistic effect on the zooplankton community, which in turn caused an increase in phytoplankton. Contributing to the magnitude of this trophic cascade was a direct positive effect of high salinity on phytoplankton abundance. Cascading effects were limited with respect to impacts on the benthic food web. Periphyton and snail grazers were unaffected by the salt-induced trophic cascade, but the biomass of filamentous algae decreased as a result of competition with phytoplankton for light or nutrients. We also found direct negative effects of high salinity on the biomass of filamentous algae and amphipods (Hyalella azteca) and the mortality of banded mystery snails (Viviparus georgianus) and fingernail clams (Sphaerium simile). Clam mortality was dependent on the presence of fish, suggesting a non-consumptive interactive effect with salt. Our results indicate that globally increasing concentrations of road salt can alter community structure via both direct and indirect effects.

Hemostatic Wound Dressing for Postinterventional Hemostasis in Large Femoral Artery Access Sites: An Initial Efficacy and Safety Study.

PURPOSE: To present the results of a prospective single-center study that evaluated the safety and efficacy of a hemostatic dressing following femoral artery access. METHODS: Within a 9-month period, 80 patients (mean age 68±14 years; 55 men) were treated with a hemostatic dressing patch (Hematrix Active Patch) containing aminocaproic acid, calcium chloride, and thrombin after endovascular procedures via a 6- to 8-F femoral artery access. After removing the sheath, the wound dressing was placed on the puncture site followed by constant manual compression adapted to the sheath size (specified pressure times: 8 minutes for 6-F, 9 minutes for 7-F, and 10 minutes for 8-F). Patients were treated with an additional pressure bandage for 24 hours. Hemostasis was checked clinically and with duplex ultrasound after patch removal and at 24 hours. Patient characteristics [platelets, systolic blood pressure, international normalized ratio (INR), and partial thromboplastin time (PTT)], sheath sizes, and approach direction were compared among patients with successful hemostasis (within specified pressure times) vs those with prolonged compression. RESULTS: A total of 39 6-F, 19 7-F, and 22 8-F sheaths were employed. In 73 (91.2%) of 80 patients, hemostasis was reached within the prespecified pressure times (mean 8.8±0.8 minutes). In 7 patients (4 6-F, 1 7-F, 2 8-F) a longer compression time was necessary (mean 34±30 minutes). No serious major complication occurred. Twelve (15.0%) minor and 5 (6.3%) moderate subcutaneous hematomas were observed. Two (2.5%) false aneurysms were treated successfully. Ambulation and discharge was possible within 24 hours in 79 (98.7%) cases. Patients with initial hemostasis and those with prolonged compression did not differ substantially (p>0.05) according to sheath size, approach direction, INR (1.09±0.3 vs 1.11±0.3), platelets (234±47×10(3)/µL vs 249±93×10(3)/µL), systolic blood pressure (150±26 vs 152±17 mm Hg), or PTT (31±7.9 vs 34.8±10.0 seconds). CONCLUSION: The evaluated wound dressing seems to be safe and effective in reducing time to hemostasis in large arterial access sites. However, a randomized trial with a larger population and an active control group is necessary to confirm these preliminary data. Moreover, additional focus on shortening the time to ambulation is required in future studies.

Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms.

Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture and subsequent high mortality. Establishment of medical therapies for the prevention of AAAs requires further understanding of the molecular pathogenesis of this condition. This report details the possible involvement of Osteoprotegerin (OPG) in the prevention of AAAs through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In CaCl2-induced AAA models, both internal and external diameters were significantly increased with destruction of elastic fibers in the media in Opg knockout (KO) mice, as compared to wild-type mice. Moreover, up-regulation of TRAIL expression was observed in the media by immunohistochemical analyses. Using a culture system, both the TRAIL-induced expression of matrix metalloproteinase-9 in smooth muscle cells (SMCs) and the chemoattractive effect of TRAIL on SMCs were inhibited by OPG. These data suggest that Opg may play a preventive role in the development of AAA through its antagonistic effect on Trail.

Effect of calcium chloride treatments on calcium content, anthracnose severity and antioxidant activity in papaya fruit during ambient storage.

BACKGROUND: There have been no reports on the effects of preharvest calcium application on anthracnose disease severity, antioxidant activity and cellular changes during ambient storage of papaya, and therefore the objective of this study was to investigate these effects. RESULTS: Higher calcium concentrations (1.5 and 2% w/v) increased calcium concentration in the peel and pulp tissues, maintained firmness, and reduced anthracnose incidence and severity. While leakage of calcium-treated fruit was lower for 1.5 and 2% calcium treatments compared to the control, microscopic results confirmed that pulp cell wall thickness was higher after 6 days in storage, for the 2% calcium treatment compared to the control. Calcium-treated fruit also had higher total antioxidant activity and total phenolic compounds during storage. CONCLUSION: Calcium chloride, especially at higher concentrations, is effective in maintaining papaya fruit quality during ambient storage. © 2015 Society of Chemical Industry.

[ANTIARRHYTHMIC EFFECTS OF 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE HEMISUCCINATE IN COMPARISON TO MEXIDOL.]

Based on the results of experiments on nonlinear white awake male rats it is established that 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate and mexidol exhibit a pronounced antiarrhythmic (antifibrillatory) activity on the calcium chloride arrhythmia model. The maximum effect was observed for hemisuccinate 2-ethyl-6-methyl-3-hydroxypyridine. This substaned; unlike mexidol, also showed high activity on the model of aconitine arrhythmia, which is typical of class I antiarrhytmics. Mexidol did not show this activity. Consequently, 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate possesses a wider therapeutic spectrum than the well-known antiarrhythmic drugs of class I (lidocaine, procainamide) and is comparable in this respect with class IV drug verapamil.

The effects of CaCl2 and CaBr2 on the reproduction of Daphnia magna Straus.

Concentrated CaCl2 and CaBr2 salt solutions of densities up to 2.3 kg L-1 are regularly used to control hydrostatic pressure in oil wells during special operations in the exploration and production of natural gas and crude oil. Various concentrations of high density salts are frequently left in mud pits near the drilling site as waste, polluting fresh and ground waters by spillage and drainage. The toxic effects of these salts have already been observed. This study investigated the effects of CaCl2 and CaBr2 on water flea Daphnia magna Straus in a 21-day reproduction test. The three tested concentrations of CaCl2 (240, 481, and 1925 mg L-1) caused a significant dose-response decrease of reproduction (p<0.001). With CaBr2 (533 and 1066 mg L-1), only aborted eggs were produced, demonstrating the embryotoxicity of the substance. The results suggest that high concentrations of the tested chemicals are harmful to Daphnia's reproduction and could reduce its abundance.

Fabrication and characterization of the nano-composite of whey protein hydrolysate chelated with calcium.

The nano-composites of whey protein hydrolysate (WPH) chelated with calcium were fabricated in aqueous solution at 30 °C for 20 min, with the ratio of hydrolysate to calcium 15 : 1 (w/w). UV scanning spectroscopy, fluorescent spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering and atomic force microscopy were applied to characterize the structure of the WPH-calcium chelate. The nano-composites showed the successful incorporation of calcium into the WPH, indicating the interaction between calcium and WPH. The chelation of calcium ions to WPH caused molecular folding and aggregation which led to the formation of a WPH-calcium chelate of nanoparticle size, and the principal sites of calcium-binding corresponded to the carboxyl groups and carbonyl groups of WPH. The WPH-calcium chelate demonstrated excellent stability and absorbability under both acidic and basic conditions, which was beneficial for calcium absorption in the gastrointestinal tract of the human body. Moreover, the calcium absorption of the WPH-calcium chelate on Caco-2 cells was significantly higher than those of calcium gluconate and CaCl2 in vitro, suggesting the possible increase in calcium bioavailability. The findings suggest that the WPH-calcium chelate has the potential in making dietary supplements for improving bone health of the human body.

Alginate gelation-induced cell death during laser-assisted cell printing.

Modified laser-induced forward transfer has emerged as a promising bioprinting technique. Depending on the operating conditions and cell properties, laser cell printing may cause cell injury and even death, which should be carefully elucidated for it to be a viable technology. This study has investigated the effects of alginate gelation, gelation time, alginate concentration, and laser fluence on the post-transfer cell viability of NIH 3T3 fibroblasts. Sodium alginate and calcium chloride are used as the gel precursor and gel reactant solution to form cell-laden alginate microspheres. It is found that the effects of gelation depend on the duration of gelation. Two-minute gelation is observed to increase the cell viability after 24 h incubation, mainly due to the protective cushion effect of the forming gel membrane during droplet landing. Despite the cushion effect from 10 min gelation, it is observed that the cell viability decreases after 24 h incubation because of the forming thick gel membrane that reduces nutrient and oxygen diffusion from the culture medium. In addition, the cell viability after 24 h incubation decreases as the laser fluence or alginate concentration increases.