Reduction In Calcium Research Articles

Effects of azumolene on arrhythmia substrate in a model of recurrent long-duration ventricular fibrillation

BackgroundProarrhythmic risk of conventional anti-arrhythmic agents is linked to unintended modulation of membrane voltage dynamics. We have demonstrated that the anti-fibrillatory effect of azumolene is mediated via stabilization of the hyperphosphorylated ryanodine receptor (RyR2), leading to attenuation of diastolic calcium leak. However, the concomitant effects on membrane voltage dynamics have not been evaluated yet. MethodsAfter baseline optical mapping, Langendorff-perfused rabbit hearts treated with azumolene, or vehicle, were subjected to global ischemia-reperfusion (I/R) followed by two episodes of long-duration ventricular fibrillation (LDVF). Simultaneous dual epicardial calcium transient (CaT) and voltage dynamics were studied optically. ResultsPre-treatment with azumolene was associated with higher CaT amplitude alternans ratios (0.94 ± 0.02 vs. 0.78 ± 0.03 in control hearts, at 6 Hz; p = 0.005; and action potential amplitude alternans ratio (0.95 ± 0.02 vs. 0.78 ± 0.04 at 6.0 Hz; p = 0.02), and reduction of action potential duration (APD80) dispersion (9.0 ± 4.8 msec vs. 19.3 ± 6.6 msec at 6.0 Hz p = 0.02) and optical action potential upstroke rise time (26.3 ± 2.6 msec in control vs. 13.8 ± 0.6 msec at 6.0 Hz, p = 0.02) after LDVF. No change in action potential duration (APD) was noted with azumolene treatment. ConclusionIn a model of ischemic recurrent LDVF, treatment with azumolene led to reduction of cardiac alternans, i.e., calcium and voltage alternans. Unlike conventional anti-arrhythmic agents, reduction of action potential upstroke rise time and preservation of action potential duration following azumolene treatment may reduce the proarrhythmia risk.

Effects of Catha Edulis Forsk on spatial learning, memory and correlation with serum electrolytes in wild-type male white albino rats.

The burdens of psychostimulant use disorders are becoming a worldwide problem. One of the psychostimulants widely consumed in Ethiopia and East African countries is Catha edulis Forsk (khat). However, no studies have been conducted on the cognitive effects of khat and its correlation with serum electrolytes. The present study was aimed to evaluate the effects of khat on spatial learning and memory and their correlation with serum electrolytes. Diethyl ether and chloroform (3:1v/v ratio) were solvents used to obtain the crude khat extract in this study. T80W was used to prepare the khat juice, fresh khat leave extract. The rats were received crude khat extract subchronically (KESC) (100 mg/kg, 200 mg/kg and 300 mg/kg b.w), khat juice (KHJ 2.5 mL/kg), 2% tween 80 in distilled water (T80W- v/v, vehicle) and khat extract subacutely (KESA) (300 mg/kg). For subchronic treatment, each rat was administered for twelve weeks before Morris water maze experiment has been started, while it was administered for a week for acute treatment. Spatial learning and memory were measured using the Morris water maze model and serum sodium, calcium, potassium, and chloride were evaluated using Cobas 6000. Spatial learning was improved with trials across the groups, while average escape latency (s) of rats received KESC 200 mg/kg (p<0.001), KESC 300 mg/kg (p<0.01) and KHJ 2.5 mL/kg (p<0.05) was significantly greater than rats that received vehicle. There was no significant difference in the latency between rats that received KESA 300mg/kg and vehicle (p>0.05). Thigmotaxis was significantly higher in rats that received all doses of khat extract (p<0.001). The time spent in the target quadrant in rats that received KESC 300 mg/kg was significantly reduced (p<0.05). Serum calcium level was inversely correlated with the escape latency (R = -0.417, p<0.05) in rats that received khat. Khat extract and juice administered subchronically, but not subacutely, impaired learning and memory and was associated with serum calcium reduction. The neuronal basis for such alteration should be investigated.

High efficiency desulfurization behavior by the sustainable low carbon utilization of carbide slag

For the purpose of the gradual decrease of calcium carbonate resources and reduction of carbon emissions in wet flue gas desulfurization process, the utilization process of carbide slag to replace limestone is systematically analyzed. The properties of carbide slag and limestone have been analyzed, and the mass transfer and reaction behaviors in desulfurization process have been calculated and comprehensively evaluated. Desulfurization performances have been also compared through response surface analysis method. The results show that the calcium content and specific surface area of carbide slag are higher than limestone, which is conducive to the dissolution and mass transfer rate. Therefore, carbide slag is suitable for the treatment of flue gas with high SO2 concentration. Desulfurization efficiencies of the two desulfurization agents of carbide slag and limestone under the optimal process are 99.15% and 96.53%, respectively. In conclusion, carbide slag can be used in desulfurization process to replace limestone. The consumption of carbide slag slurry in the desulfurization process is about half of limestone slurry at the same conditions, and the higher desulfurization efficiency of carbide slag is attributed to the higher mass transfer and dissolution rate. Utilization of carbide slag also reduces the carbon emission in desulfurization process and economic cost. The reduction amount of CO2 emission can reach to about 0.76 t /t carbide slag. This work provides a basis for the industrial application and desulfurization efficiency improvement of carbide slag as the desulfurizer.

Effect of controlled loss of 350 ml blood from human body on electrolytes and albumin levels – An observational study done in whole blood donors at a regional blood centre

Background: Researchers have studied the hemodynamic effect of hemorrhage widely but the biochemical alternations after blood loss are less explored. Knowledge about changes in electrolyte values after blood donation may help in assessing the effect on large quantity donations or massive hemorrhage. It may also be beneficial in donor counseling and reassurance. Aims and Objectives: Primary objective of the study was to quantify changes in plasma sodium, potassium, calcium, magnesium, and albumin before and after blood donation. Materials and Methods: Predonation electrolyte and albumin levels were tested in all study subjects as baseline and repeated after 45 min of completed blood donation. Both values were compared with paired t test in SPSS version 17. Results: After 45 min of donating 350 ml whole blood, no significant changes were observed in sodium and potassium levels. Reduction in calcium, magnesium, and albumin was 0.188 mg/dL, 0.0328 mg/dl, and 0.193 g/dl, respectively, which were statistically significant. About 15% of the blood donors were already deficient in magnesium. Conclusions: Calcium, magnesium, and albumin levels were reduced after blood donation but well maintained within the normal level and most of the donors had normal predonation levels. Hence, in large volume or repeated plasma donation and massive blood loss, baseline evaluation, and monitoring of these parameters may be worthwhile.

Clinico-pathological investigation of inflammatory mammary carcinomas in bitches

A study was conducted to elucidate the altered clinico-pathological parameters in diagnosis and prognosis of inflammatory mammary carcinomas in bitches. Blood and serum samples were collected from 30 each normal and tumor bearing bitches for haemato-biochemical analysis. A significant (P<0.05) reduction of total erythrocyte count and highly significant (P<0.01) reduction of packed cell volume were noticed in tumor affected bitches. A significant (P<0.05) elevation of mean corpuscular haemoglobin and highly significant (P<0.01) elevation of mean corpuscular haemoglobin concentration and total leucocyte count were observed in mammary tumor affected dogs. A significant (P<0.05) increase in total cholesterol and highly significant (P<0.01) increase in alanine transaminase, aspartate transaminase, alkaline phosphatase and potassium values were noticed in tumor bearing bitches. Highly significant (P<0.01) reduction in albumin and significant (P<0.05) reduction in calcium were also noticed. An elevation of superoxide dismutase, reduced glutathione, glutathione peroxidase and lipid peroxidase values whereas reduction of catalase value were noticed in the tumor tissues. Histopathologically, the tumors were classified as benign (2) and malignant (28) tumors with infiltration of inflammatory cells in 18 cases. The haemato-biochemical alterations due to antioxidants and lipid peroxidase were consistent in the diagnosis and management of mammary tumors in bitches.

ST-Segment Elevation Mimicking STEMI Due to Hypercalcemia: A Case Report

ST-segment elevation myocardial infarction (STEMI) is an important, life-threatening diagnosis that requires quick diagnosis and treatment, characteristic ECG of which shows ST-segment elevation. Unfortunately, ST-segment elevation is nonspecific, which can be misleading if not careful to be interpreted, as in this case of hypercalcemia seen by us. A 48-year-old male was admitted to our emergency department with recurrent chest pain, nausea and vomiting. Medical history includes hypertension and diabetes. ST-segment elevation in V1 - V4 mimicking STEMI was present on admission. However, immediate coronary angiography revealed nearly normal coronary arteries, his troponin was negative in 6 hours and calcium was 2.95 mmol/L. It was thought that the ECG changes were not indicative of cardiac ischemia but hypercalcemia. He was managed with calcium reduction treatment such as intravenous normal saline and furosemide, with subsequent resolution of ST-segment changes.

Morpho-physiological and phytochemical responses of basil (Ocimum basilicum L.) to toxic heavy metal cadmium

Cadmium (Cd) is a particularly noteworthy metal that may change the secondary metabolism efficacy of pharmaceutical valuable plants. This study aimed to explore the influence of Cd (0, 25, 75, 100, and 150 µM) on the morpho-physiological traits, mineral contents, essential oil composition, and morphology of secretory glands in basil (Ocimum basilicum L.). The exposure to Cd reduced significantly shoot and root dry weight, shoot and root lengths, total chlorophyll, number, and length of secretory gland compared to control plants, while increased peroxidase activity, proline content, and number of stomata. Essential oil compositions were varied in the Cd-treated plants in a dose-dependent manner. The main compounds of the essential oil were Estragole followed by Linalool and Geranial which the highest percentages were observed in the plants treated with Cd 150 µM. The Cd-treated plants exhibited reductions in calcium (Ca) and iron (Fe) concentrations in both leaves and roots. Cd contents in roots and shoots progressively enhanced with increasing Cd concentrations In general, basil showed good tolerance to Cd stress, so that 50% reduction in shoot dry weight occurred in above 100 μm treatments, which can be related to physiological reactions such as increased antioxidant activity, proline content, number of leaves stomata, and changes in other morpho-physiological factors.

Abstract 12627: Effects Of Lipid Control On Coronary Calcification

Introduction: Lipid lowering drugs are some of the most prescribed medications to control coronary artery disease (CAD). The long-term lipid lowering effects on coronary artery calcium (CAC) progression remain a subject of controversy with inconclusive results from multiple literature reviews. The purpose of this meta-analysis is to elucidate the relationship between lipid control and CAC progression. Methods: A computerized search of MEDLINE was conducted using the search terms “coronary”, “calcification”, “statin”, and “lipid lowering.” Studies were included if they measured mean value changes from baseline in coronary calcium using cardiac computed tomography. Data were extracted from the articles using the Cochrane method. RevMan 5.4 was used to aggregate the studies and report statistics. Results: A total of 13 studies were included with a total of 6671 patients. LDL reduction amongst the studies was significant as compared to placebo or lower dose lipid lowering therapy (standardized mean difference [SMD]: -0.71; 95% CI: -0.79, -0.64; p&lt;0.00001). A small increase in CAC was not statistically significant (standardized mean difference [SMD]: 0.10; 95% CI: 0.02, 0.17; p=0.19). Conclusions: Lipid lowering therapy shows efficacy in LDL reduction however, it does not lead to coronary calcium reduction. Further studies are needed to elucidate the long-term effects of lipid powering on CAC and the prognostic value of CAC in CAD parents receiving optimal therapy.

Nutritional cost reduction and increase profitability in commercial broiler production using phytase superdosing

ABSTRACT The objective of the present study was to evaluate the reduction of calcium (Ca), crude protein (CP), metabolizable energy (ME), and available phosphorus (aP) in the nutritional matrix of Brazilian commercial broiler diets supplemented with both phytase superdosing (1500 FTU/kg) or conventional doses (500 FTU/kg) on the feed cost and profitability, performance, bone mineralization, and carcass yield of broiler from 1 to 42 d. A total 1200 one-day-old chicks (Cobb 500) were randomly distributed in a commercial feeding program [...]

Application of ion exchange resins to reduce hardness and scaling of drinking water: Experimental and modeling

In this research, the performance of strong cationic Purolite C-100 Na+, Ambersep IR252 H+, Amberlite IR120 H+ ion exchange resins and an IRA402 OH- anionic resin have investigated to the reduction of hardness and TDS of drinking water in Bushehr, Iran. Also, to demonstrate the efficiency of these resins, the experimental variables affecting the ion exchange process such as contact time and adsorbent consumption were investigated. The results showed that the maximum adsorption capacity in the best operating condition was 48.01, 45 and 36.01 mg.g-1 for Purolite, Ambersep, and Amberlite resins, respectively. The maximum percentage of total hardness reduction parameters, calcium and magnesium ions reduction at best operating condition was 90.086%, 93.085%, 77.27% for Purolite ion exchange resins, 83.84%, 86.70%, 71.59% for Ambersep ion exchange resins and 69.83, 69.41, 69.32 for Amberlite ion exchange resins, respectively. Also, in the compound stage (the combination of cationic and anionic resins), at the best condition, 3 g/L of cationic resin and 12 g/L of anionic resin had the best efficiency in adjusting pH and reducing TDS. To study the adsorption kinetic process of calcium and magnesium ions by three strong cationic ion exchange resins, three pseudo-first-order, pseudo-second-order, and Morris-Weber models were employed. Among these models, the pseudo-second-order kinetic model had the best agreement with the experimental data. The models of Langmuir, Freundlich, Temkin, and Dobinin-Radskvich were utilized for the equilibrium study of hardened ions adsorption (calcium and magnesium). From the equilibrium study of the absorption process, it was founded that this process involves both chemical and physical absorption and the Langmuir model has the best agreement with the experimental data.

Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons.

BackgroundThe analgesic effects of Cannabis sativa are mediated by ∆9 tetrahydrocannabinol (THC), but the contributions of other bioactive complex components, including cannabigerol (CBG) and cannabidiol (CBD), are unclear. We describe the individual and combined effects of CBG, CBD and THC, on blocking capsaicin responses in dorsal root ganglion (DRG) neurons, in an in vitro model of nociceptor hypersensitivity.Materials and MethodsAdult rat DRG were dissected and enzyme digested to obtain a neuronal suspension in BSF2 medium containing 2% fetal calf serum, and the neurotrophic factors NGF and GDNF. After 48 h, cultured neurons were loaded with Fura-2 AM, to determine the effects of cannabinoids on capsaicin responses using calcium imaging. In control experiments, neurons were treated with vehicle, followed by 1 µM capsaicin. In cannabinoid treated cultures, CBG, CBD or THC were applied individually, or combined (1:1:1 ratio), followed by 1 µM capsaicin. Data from n = 6 experiments were analysed with Student’s t-test and Pearson’s correlation coefficient.ResultsCBG, CBD and THC, applied individually, elicited dose-related calcium influx in a subset of DRG neurons, and a corresponding dose-related reduction of subsequent responses to capsaicin. Maximum inhibition of capsaicin responses was observed at 30 µM CBG, 100 µM CBD, and 100 µM THC individually, and with combined CBD+CBG+THC (1:1:1) at 90 µM. THC+CBD+CBG combined in a 1:1:1 proportion has the potential to enhance the potency of these compounds applied individually. There was a high correlation between cannabinoid-mediated calcium influx and reduction of capsaicin responses: CBG = −0.88, THC = −0.97, CBD = −0.99 and combined CBG + THC + CBD = −1.00.ConclusionCBG, CBD and THC demonstrated potent dose-related inhibition of capsaicin responses in DRG neurons when applied individually in vitro, and enhanced when applied in combination, being most effective at 90 μM. Thus, efficacy and tolerability of THC could be improved in combination with CBG and CBD at optimal concentrations, which deserve further studies in vivo.

Influence of dietary emamectin benzoate on the biological responses of monosex (all-male) Oreochromis niloticus (L.) fries

The application of antiparasitic drugs plays a crucial role in the removal of infectious parasites in aquaculture. Emamectin benzoate (EB) is predominantly used as a feed premix against ectoparasites on temperate fish. This study evaluated the influence of 14 days of EB-dosing at 0–10 times the recommended dose (1X: 50 μg/kg biomass/day) on the biological responses and accrual/depletion of EB-residues in a tropical fish monosex Oreochromis niloticus fries. A significant dose-dependent reduction in feed intake by 3.50% in 1X and 43.00% in 10X groups, and an increase in mortalities from 2.92% (1X) to 11.25% (10X) during the EB-dosing period was noted. A significant increase in glucose and alkaline phosphatase and reduction in calcium and chloride ions, superoxide dismutase (SOD) and acetylcholinesterase levels in the muscle and/or brain tissue was observed. On day 21 post-EB-dosing, the levels of muscle glucose and SOD reached normalcy in the 1X group, while the levels of other biomarkers failed to recuperate. The EB-residue levels peaked on day 14 EB-dosing (2.77 ng/g) in the 1X group and decreased later with detectable levels (0.03 ng/g) even on day 21 post-EB-dosing. The EB-residue levels were within the permissible limits of the Canadian Food Inspection Agency and the European Commission. The EB-dosing negatively influenced the health of O. niloticus by altering the physiological state in a dose- and time-dependent way. The results suggested that the use of EB might be plausibly risky in tropical aquaculture.

FDA approved L-type channel blocker Nifedipine reduces cell death in hypoxic A549 cells through modulation of mitochondrial calcium and superoxide generation

As hypoxia is a major driver for the pathophysiology of COVID-19, it is crucial to characterize the hypoxic response at the cellular and molecular levels. In order to augment drug repurposing with the identification of appropriate molecular targets, investigations on therapeutics preventing hypoxic cell damage is required. In this work, we propose a hypoxia model based on alveolar lung epithelial cells line using chemical inducer, CoCl2 that can be used for testing calcium channel blockers (CCBs). Since recent studies suggested that CCBs may reduce the infectivity of SARS-Cov-2, we specifically select FDA approved calcium channel blocker, nifedipine for the study. First, we examined hypoxia-induced cell morphology and found a significant increase in cytosolic calcium levels, mitochondrial calcium overload as well as ROS production in hypoxic A549 cells. Secondly, we demonstrate the protective behaviour of nifedipine for cells that are already subjected to hypoxia through measurement of cell viability as well as 4D imaging of cellular morphology and nuclear condensation. Thirdly, we show that the protective effect of nifedipine is achieved through the reduction of cytosolic calcium, mitochondrial calcium, and ROS generation. Overall, we outline a framework for quantitative analysis of mitochondrial calcium and ROS using 3D imaging in laser scanning confocal microscopy and the open-source image analysis platform ImageJ. The proposed pipeline was used to visualize mitochondrial calcium and ROS level in individual cells that provide an understanding of molecular targets. Our findings suggest that the therapeutic value of nifedipine may potentially be evaluated in the context of COVID-19 therapeutic trials.

Flotation separation of apatite and calcite using gum arabic as a depressant

Flotation separation of apatite and calcite has always been difficult because of their similar physiochemical properties. To realize the flotation separation of the two minerals, many inorganic depressants are usually used, which contaminate the environment. In this study, the behavior of the polymer molecule gum arabic (GA) as a depressant of calcite in the apatite flotation was investigated by the pure mineral flotation experiments, and the mechanism was discussed by the contact angle measurement, adsorption tests, Fourier transform infrared (FTIR) spectroscopy and X–ray photoelectron spectroscopy (XPS). The flotation results showed that GA had a significant depressive effect on calcite but not on apatite. The separation of apatite from calcite was realized by adding 50 mg/L of the depressant GA followed by 0.5 × 10−4 mol/L of the collector sodium oleate (NaOl) at pH 7–11. The contact angle measurements showed that GA considerably enhanced the hydrophilicity of the calcite surface but had no significant effect on that of the apatite surface. The adsorption tests showed that the amount of GA adsorbed on the calcite surface was obviously greater than that on the apatite surface, indicating that calcite had a stronger affinity for GA. The FTIR and XPS analysis indicated that GA was adsorbed weakly on the apatite surface, but strongly adsorbed on the calcite surface. After GA was strongly adsorbed on the calcite surface, the abundant free –OH and –COOH groups in the GA molecule made the calcite surface more hydrophilic. Subsequently, it was hard for NaOl to be adsorbed on the calcite surface due to the reduction of active site calcium as well as the steric hindrance and electrostatic repulsion effect of GA on the NaOl molecule, which resulted in the selective depression of calcite in the apatite flotation.

Abstract P123: Effects Of Lipid Control On Coronary Calcification

Introduction: Lipid lowering drugs are some of the most prescribed medications to control coronary artery disease (CAD). The long-term lipid lowering effects on coronary artery calcium (CAC) progression remain a subject of controversy with inconclusive results from multiple literature reviews. The purpose of this meta-analysis is to elucidate the relationship between lipid control and CAC progression. Methods: A computerized search of MEDLINE was conducted using the search terms “coronary”, “calcification”, “statin”, and “lipid lowering.” Search filters included studies in English performed on human subjects, clinical trials, and journal articles. Studies were included if they measured mean value changes from baseline in coronary calcium using cardiac computed tomography. Data were extracted from the articles according to the Cochrane manual. RevMan 5.4 was used to aggregate the studies and report statistics. Results: A total of 13 studies were included with a total of 6671 patients. LDL reduction amongst the studies was significant as compared to placebo or lower dose lipid lowering therapy (standardized mean difference [SMD]: -0.71; 95% CI: -0.79, -0.64; p&lt;0.00001). Study heterogeneity was not significant amongst the CAC progression studies (p=0.19). An increase in CAC was statistically significant (standardized mean difference [SMD]: 0.10; 95% CI: 0.02, 0.17; p=0.009). Conclusion: Lipid lowering therapy shows efficacy in LDL reduction however, it does not lead to coronary calcium reduction. Further studies are needed to elucidate the long-term effects of lipid powering on CAC and the prognostic value of CAC in CAD parents receiving optimal therapy.

Sensitivity Analysis of Ion Channel Conductance on Myocardial Electromechanical Delay: Computational Study.

It is well known that cardiac electromechanical delay (EMD) can cause dyssynchronous heart failure (DHF), a prominent cardiovascular disease (CVD). This work computationally assesses the conductance variation of every ion channel on the cardiac cell to give rise to EMD prolongation. The electrical and mechanical models of human ventricular tissue were simulated, using a population approach with four conductance reductions for each ion channel. Then, EMD was calculated by determining the difference between the onset of action potential and the start of cell shortening. Finally, EMD data were put into the optimized conductance dimensional stacking to show which ion channel has the most influence in elongating the EMD. We found that major ion channels, such as L-type calcium (CaL), slow-delayed rectifier potassium (Ks), rapid-delayed rectifier potassium (Kr), and inward rectifier potassium (K1), can significantly extend the action potential duration (APD) up to 580 ms. Additionally, the maximum intracellular calcium (Cai) concentration is greatly affected by the reduction in channel CaL, Ks, background calcium, and Kr. However, among the aforementioned major ion channels, only the CaL channel can play a superior role in prolonging the EMD up to 83 ms. Furthermore, ventricular cells with long EMD have been shown to inherit insignificant mechanical response (in terms of how strong the tension can grow and how far length shortening can go) compared with that in normal cells. In conclusion, despite all variations in every ion channel conductance, only the CaL channel can play a significant role in extending EMD. In addition, cardiac cells with long EMD tend to have inferior mechanical responses due to a lack of Cai compared with normal conditions, which are highly likely to result in a compromised pump function of the heart.

Effects of Changing Anticoagulation with Unfractionated Heparin into Enoxaparin in Hemodialysis Patients:Prospective Non Randomized Unicentre Study

Background: Maintaining the patency of the extracorporeal circuit (ECC) is required. The cost and long-term effect of anticoagulants on hemodialysis (HD) patients' parameters are still matters of concern. We aimed to study the effect of shifting to enoxaparin instead of unfractionated heparin (UFH) during HD and evaluate its efficacy, safety, and benefits.&#x0D; Design and methodology: This study was conducted at Arar hospital, Kingdom of Saudi Arabia (KSA), and included 86 end-stage renal disease (ESRD) patients on HD for six months starting from October 2017. All patients had been on UFH as an anticoagulant during hemodialysis sessions before they were shifted to equivalent doses of enoxaparin sodium (Clexan®) as a therapeutic upgrade to start with. The patients’ files were examined retrospectively for the period of UFH therapy and then all patients were observed prospectively for at least 6 months while on Clexane. The occurrence of clotting in the dialysis sets were recorded and the need for urgent HD for each patient and the reasons. &#x0D; Results: There was a reduction of filter clots even with the reduction of enoxaparin dose. There was a significant reduction of mean cholesterol, calcium, phosphorus, sodium, chloride, and serum osmolality. We found a significant reduction of pre-dialysis potassium among those who presented with a pre-dialysis potassium of higher than 5.5 mg/dl during the enoxaparin phase. Patients, who had thrombocytopenia while on UFH; showed improvement in platelet count after the shift to enoxaparin. However, patients who had platelet count lowered than 150000/mm3 6 months after having been shifted to enoxaparin; many of them received HD through a permanent catheter. No patients had a three-fold increase of normal values (3ULN) of liver function tests whether being on heparin or enoxaparin.&#x0D; Conclusion: Low molecular weight heparin (LMWH) could be more efficacious and safe than UFH with the improvement of some variables in HD patients.

Screening of biochemical parameters in the orthodontic treatment with the fixed appliances: A follow-up study.

The aim of this study was to assess the changes in vital salivary parameters such as calcium, phosphorous, alkaline phosphatase, buffering capacity, pH, flow-rate and Oral Hygiene Index (OHI) in fixed orthodontic treatment patients during the retention period. In this study, saliva samples were collected from 35 patients before de-bonding (T0) and after 4 to 5 weeks of de-bonding or on retention period (T1). The biochemical parameters such as calcium, phosphorous and alkaline phosphatase levels were measured with saliva samples. Additionally, flow-rate, buffering capacity, pH and OHI levels was also measured. The current study results showed reduction in calcium, alkaline phosphatase, pH, flow-rate and OHI levels during T1 (p < 0.05). However, phosphorous and buffering capacity levels were increased at T1. The phosphorous levels showed non statistically significant difference when compared between T0 and T1 (p = 0.42). The remaining salivary parameters showed statistically significant difference when compared between T0 and T1 (p < 0.05). The present study concludes that there was a statistically significant decrease in the calcium, alkaline phosphatase, pH, flow rate and OHI values a month after de-bonding and increased in the buffering capacity values.

Identification of secondary predictive factors for acute hypocalcemia following thyroidectomy in patients with low postoperative parathyroid hormone levels without overt calcium deficiency: A cohort study

BackgroundThe transient acute hypocalcemia (HypoCa) is the most prevalent complication after total thyroidectomy, detected primarily by subnormal intact parathyroid hormone (iPTH) and calcium levels. However, the need for calcium supplementation is ambiguous in patients who exhibit low iPTH with normal calcium levels. The aim of this study was to evaluate complementary predictors of HypoCa in this scenario. MethodsA retrospective cohort study with of 1597 consecutive patients undergoing total thyroidectomy, with or without neck dissection, from January 2014 to December 2018 at a single institution. Patients with an iPTH <12 pg/mL and a total calcium level ≥8 mg/dL in the first 8 h after surgery were included. Results1597 patients identified with low postoperative iPTH without overt calcium deficiency was diagnosed. The transient HypoCa in that specific subgroup was 509 (31.9%). Multivariate analysis indicated that HYPOCA was associated with bilateral level VI neck dissection and pre- to postoperative calcium reduction >38 pg/mL. To better illustrate the model, we plotted a nomogram with the variables selected for the final model. ConclusionTotal thyroidectomy patients who exhibit low postoperative iPTH levels without overt calcium deficiency should be considered for calcium replacement therapy when they a marked drop in iPTH postoperatively and underwent bilateral level VI neck dissection.

Sustained Reduction of Intracellular Calcium Is Important to Maximise GA101-Mediated Direct Cell Death in B-Cell Lymphomas

For over a decade, anti-CD20 monoclonal antibodies (mAbs) have successfully been used in the therapy of B-cell malignancies. Obinutuzumab (GA101), a type-II glycoengineered anti-CD20 mAb approved for treatment of Chronic Lymphocytic Leukaemia (CLL) and Follicular Lymphoma, was designed to have enhanced antibody-dependant cellular cytotoxicity compared with Rituximab. Pre-clinical data showed that in addition, GA101 also exhibited significantly enhanced direct cell death. The complete mechanism of increased direct cell death is still unknown.The biological role of CD20 remains unclear but it has been shown to act as part of an ion channel complex, a component of the store operated calcium (Ca2+) entry system. Numerous studies have investigated the immediate impact of anti-CD20 mAbs on intracellular Ca2+. Yet to date, none have assessed intracellular Ca2+ over a longer period.To investigate the effect of anti-CD20 mAbs on intracellular Ca2+, we initially used 4 B-cell lymphoma cell lines to assess Ca2+ flux immediately after treatment with either Rituximab or GA101. Cells were first stained with a fluorescent calcium indicator and baseline measurements recorded by flow cytometry. Cells were then treated with each antibody and fluorescence measurements were recorded for a further 5-10 minutes. Next, we conducted a time course experiment to visualise the kinetics of intracellular Ca2+ after 1, 2, 4, 8, and 24 hour treatments with either Rituximab or GA101; Trastuzumab was used as an isotype control. After treatment, samples were stained with a labelled calcium indicator before quantifying intracellular Ca2+ using imaging flow cytometry. We validated our findings in primary CLL samples using the same method. We conducted liquid chromatography tandem mass spectrometry based label-free phosphoproteomics on SUDHL4 cells in biological triplicates after 1 and 24 hour treatments with GA101 and Rituximab. Expression levels of >8500 phosphorylation sites were measured across treatments to establish changes in intracellular signalling and kinase activity.In line with published data, we observed an influx of Ca2+ when cells were treated with Rituximab but intracellular Ca2+ was not significantly altered for any of the extended treatments. In contrast, GA101 treatment did not induce an immediate influx of Ca2+,and a reduction in intracellular Ca2+ was observed after 1 hour treatment which was sustained across all extended treatment periods. This difference in kinetics was validated in primary CLL samples. Global phosphoproteomic analysis found that the activity of Polo-Like Kinase 2 (PLK2) was significantly increased following treatment with GA101. The increase in the activity of this kinase was specific to GA101 and was unchanged following treatment with Rituximab. Simultaneously there was a significant increase in the phosphorylation of Calumenin at Ser44, a known binding site of PLK2. Samples treated with GA101 for 24 hours exhibited a larger downregulation of pathways associated with calcium signalling compared to Rituximab-treated and control samples.Calumenin, a member of the CREC family, is able to bind 7 Ca2+ ions. It can be localised in the cytosol, in compartments of the secretory pathway, on the plasma membrane or in the extracellular space. We hypothesise that once phosphorylated, this protein bound with Ca2+ is secreted extracellularly, resulting in reduced intracellular Ca2+.In summary we report for the first time that intracellular Ca2+ is significantly decreased as a result of GA101 treatment in cell lines and primary samples. Using a global unbiased approach we have identified a significant increase in PLK2 activity and we observed a large increase in phosphorylation of Calumenin. Our data suggests that these proteins may contribute to the increased direct cell death observed as a result of GA101 treatment. We believe that expression and activity of these proteins are crucial in order to maximise GA101-mediated direct cell death. Ongoing studies are examining the functional roles of PLK2 and Calumenin in the reduction of intracellular Ca2+, comparing Ca2+ levels in response to antibody treatment in primary samples from different CLL subtypes, and assessing and comparing levels of apoptosis following antibody treatment to see whether there is a correlation with reduced intracellular Ca2+. DisclosuresGribben:Celgene: Honoraria; TG Therapeutics: Honoraria; Genentech/Roche: Honoraria; Karyopharm: Honoraria; Kite: Honoraria; Abbvie: Honoraria; Pharmacyclics: Honoraria; Janssen: Honoraria; Acerta: Honoraria.