Relaxation mechanisms of chloroform root extracts of Prangos heyniae and Prangos uechtritzii on mouse corpus cavernosum.

Erectile dysfunction (ED) is the inability to achieve/maintain an erection. Because of the side effects, interactions, or ineffectiveness of currently used drugs, novel drug discovery studies are ongoing. The roots of Turkish endemic plants Prangos uechtritzii and Prangos heyniae are traditionally used as aphrodisiacs in Anatolia and contain coumarin-like relaxant compounds. This study aims to reveal the relaxant effect mechanisms of chloroform root extracts of P. heyniae (Ph-CE) and P. uechtritzii (Pu-CE). Isolated organ bath experiments were performed on Swiss albino mouse corpus cavernosum by DMT strip myograph. Relaxant responses to extract (10-7 -10-4  g/ml) were obtained in the presence/absence of NO and H2 S synthesis inhibitors nitro-l-arginine methyl ester (l-NAME, 100 µM) and aminooxyacetic acid (AOAA, 10 mM) respectively. Sodium nitroprusside (SNP, 10-9 to 10-4  M) and Na2 S (10-6 to 3 × 10-3  M)-induced relaxations and CaCl2 (10-6 to 10-4  M), KCl (10-2.1 to 10-0.9  M) and phenylephrine (3 × 10-8 to 3 × 10-5  M)-induced contractions were taken in the presence/absence of the extracts (10-4  g/ml). Relaxations induced by Ph-CE but not by Pu-CE were inhibited in the presence of l-NAME and AOAA. Ph-CE increased Na2 S- and SNP-induced relaxations. Ph-CE and Pu-CE decreased the contractions of KCl, phenylephrine, and CaCl2 . It was concluded that NO and H2 S synthesis/downstream mechanisms play roles in relaxations of Ph-CE but not in Pu-CE-induced relaxations. Inhibition of calcium influx appears to be involved in the relaxant effect of Ph-CE and Pu-CE. Since the extracts act directly by relaxing smooth muscle or through H2 S as well as NO, they may be a potential therapeutic agent in diseases such as ED where the bioavailability of NO is impaired.

Abalone-Inspired Adhesive and Photo-Responsive Microparticle Delivery Systems for Periodontal Drug Therapy.

Antibiotics provide promising strategies for treating periodontitis, while their delivery and controllable release with desired oral retention remain challenging. Here, inspired by the unique suction-cup structures of abalones, a novel adhesive and photo-responsive microparticle (MP) delivery system is developed to treat periodontitis through microfluidic electrospray technology. Such MPs are generated by quickly ionic cross-linking of sodium alginate together with photo-curing of poly(ethylene glycol) diacrylate of the distorted microfluidic droplets during their high-speed dropping into calcium chloride solution. Attributing to their unique concave structures, the abalone-inspired MPs exhibit desired underwater adhesion ability and stability under running water. In addition, due to the loading of antibiotics minocycline hydrochloride and near-infrared (NIR)-responsive black phosphorus during their fabrication, the resultant MPs can not only eradicate bacteria directly, but also realize a controllable and effective drug release upon NIR irradiation. Based on these features, it is demonstrated from in vivo periodontitis that the abalone-inspired MPs are firmly adhesive and can controlled-release drugs on the tooth, and thus have outstanding antibacterial efficacy against Porphyromonas gingivalis. These results indicate the particular values of the abalone-inspired MPs for oral-related disease treatment.

Calcium chloride in neonatal parenteral nutrition: A 15 year experience.

OBJECTIVE: The objective of this study was to determine if outcomes at our neonatal intensive care units (NICUs) since we began using calcium chloride (CaCl2) as our preferred calcium additive in order to reduce aluminum (Al) exposure are within expected outcome ranges for NICUs in the U.S. where calcium gluconate in glass vials (CaGlu-Gl) has been the preferred additive. STUDY DESIGN: A retrospective study of very low birth weight infants born between January 1, 2000 and December 31, 2014. Outcomes in two intensive care units (NICUs) using CaCl2 were compared to all U.S. NICUs in the Vermont Oxford Network. Primary outcomes were chronic lung disease (CLD), percent requiring supplemental oxygen at 28 days, and mortality excluding early deaths (MEED). The incidence of IV infiltrates of all admissions to the study NICUs in 2013-2014 was compared to the literature. RESULTS: The incidence of CLD and those requiring oxygen at 28 days were 24.0% vs 28.6% and 46.2% vs 51.8% for the study NICUs compared to all U.S. NICUs, respectively (both p < 0.0001). The MEED was 8.7% vs 10.3% (p < 0.002). All major morbidities were lower at the study NICUs. The incidence of infiltrates was lower than that in the literature. CONCLUSION: The use of CaCl2 was not associated with any detectable adverse effects. Calcium chloride appears to be a safe alternative to the use of CaGlu-Gl based upon studies of clinical outcomes.

[CORRECTION OF HEMOSTASIS DISORDER IN HEMORRHAGIC SHOCK].

It is a clinical case of successful correction of hemostasis disorder in hemorrhagic shock. This case demonstrates the need to perform advanced tests that assess hemostatic system in patients with ongoing bleeding. Using of thromboelastography helped us to make a comprehensive assessment of hemostatic system that allowed to detect the point of application of drugs and substitution therapy. Coagulation disorder was treated by intravenous injection of Ca2+. In this case the cause of hypocalcemia was combination offactors such as electrolytes losing during massive bleeding and progressing metabolic acidosis. Therefore, monitoring the level of ionized calcium is especially important in patients undergoing massive blood loss and receiving large doses of donor blood components.

Novel method to dissociate platelet clumps in EDTA-dependent pseudothrombocytopenia based on the pathophysiological mechanism.

BACKGROUND: EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is an in vitro phenomenon of platelet clumping that leads to spuriously low platelet counts by automatic hematology analyzers. The mechanism is not clearly defined, but is known as an immunologically mediated phenomenon due to the presence of EDTA-dependent antiplatelet auto-antibodies that induce platelet clumping. The purpose of this study was to identify antiplatelet antibodies in EDTA-PTCP samples and to design a method to dissociate platelet clumps based on the pathophysiological mechanism. METHODS: The antiplatelet antibody was investigated using direct and indirect immunofluorescent flow cytometric methods in 23 EDTA-anticoagulated whole blood (WB) samples and 12 serum samples of EDTA-PTCP patients, respectively. A novel mixture containing 9 mmol/L CaCl(2) and 0.1 unit/L sodium heparin, that provides calcium replacement while curbing coagulation, was designed to dissociate platelet clumps. The effect on dissociation was demonstrated in 26 samples of EDTA-PTCP and compared with the established method of kanamycin supplementation. RESULTS: The direct test was positive for IgM and IgG antiplatelet antibody in 60.9% and 4.4% of patients, respectively [mean median fluorescence intensity (MFI) of 223.9 and 128.4, respectively]. The indirect test was positive for IgM antiplatelet antibody in 58.3% of patients (mean MFI of 123.4). The novel method dissociated the platelet clumps with a mean increased platelet count of 242.3% and was equivalent in efficiency to kanamycin supplementation. CONCLUSIONS: The novel method is an easily applicable and efficient measure that allows dissociation of platelet clumps, based on the pathophysiological mechanism of EDTA-PTCP.

Concomitant ceftriaxone and high-concentration intravenous calcium therapy in adult critical care patients: a matched cohort study.

BACKGROUND: Based on case reports in infants, the safety of concomitant use of ceftriaxone and intravenous calcium in all ages has recently come under challenge. Systematic population-based data to guide clinicians with respect to this risk are, however, lacking. OBJECTIVE: To determine whether concomitant administration of ceftriaxone and intravenous calcium was associated with the occurrence of severe cardiorespiratory events or death in critically ill adults. METHODS: We performed a matched-cohort study from retrospective data of adults admitted to intensive care units (ICUs) in Calgary, Canada, who were provided continuous high-dose intravenous calcium. Those who received ceftriaxone while on continuous renal replacement therapy were considered exposed. Up to 3 unexposed patients were selected by matching on a number of prognostic factors from the remaining subjects not concurrently exposed to ceftriaxone and calcium. Univariate methods and multivariate conditional logistic regression were used for statistical analysis. RESULTS: We identified 142 patients exposed to the implicated combination who could be matched to at least one unexposed patient. Hospital mortality was 66% in the exposed versus 63% in unexposed patients (p = 0.442). ICU length of stay, ICU mortality, hospital length of stay, and the frequency of acute oxygenation events were all similar by univariate analysis. Multivariate conditional logistic regression modeling failed to find a significant association between exposure and hospital mortality (adjusted OR 1.15, 95% CI 0.65 to 2.04) or other relevant outcomes. CONCLUSIONS: In this high-risk group, administration of high concentrations of calcium and concurrent ceftriaxone was not significantly associated with greater mortality or adverse outcomes compared to matched unexposed patients. Although this was an underpowered study and rare adverse effects from the interaction of these 2 compounds cannot be completely excluded, these data provide overall reassurance of the safety of this combination in the majority of critically ill adults.

Calcium channel blocker toxicity.

Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.

Plaque fluoride concentrations in a community without water fluoridation: effects of calcium and use of a fluoride or placebo dentifrice.

The results of a recent study by Whitford et al. [Caries Res 2002;36:256-265] with subjects whose drinking water was fluoridated led to two major conclusions: (1) Compared to the use of a placebo dentifrice, plaque fluoride concentrations ([F]) throughout much of the day are not significantly increased by the use of an F dentifrice but (2) they are positively related to plaque [Ca] (p = 0.0001). The present double-blind, double-crossover study with 16 subjects used the same protocol and was done to: (1) determine the effects of the use of an F dentifrice on salivary and plaque [F] in a community without water fluoridation and (2) further examine the relationship between plaque [Ca] and [F]. Following the use of an F dentifrice or placebo for one week, whole saliva and plaque were collected 1.0 and 12 h after the last use of the products. The study was repeated to include rinsing with a 20 mmol/l CaCl(2) solution immediately before the use of the dentifrices. The CaCl(2) rinse had only minor effects on salivary [Ca] and [F] and none on the plaque concentrations. Unlike the results found in the fluoridated community, all salivary and plaque [F] associated with the use of the F dentifrice were significantly higher than those associated with the use of the placebo. The results suggest that the cariostatic effectiveness of an F dentifrice should be greater in areas without water fluoridation. As noted previously, plaque [F] were positively related to plaque [Ca] (p = 0.0001).

Severe hyperphosphatemia and hypocalcemia following the rectal administration of a phosphate-containing Fleet pediatric enema.

BACKGROUND: Toxicity secondary to rectally administered hypertonic phosphate solution in patients with normal renal function is rarely reported in the literature. We report a case of electrolyte disturbance and seizure secondary to the rectal administration of 2 Fleet pediatric enemas. CASE REPORT: A 4-year-old white female with spinal muscular atrophy and chronic constipation was brought to the emergency department with complaints of lethargy and difficulty breathing following the administration of 2 Fleet pediatric enemas. In the emergency department, physical examination was significant for a depressed level of consciousness and shallow respirations. A basic metabolic profile was significant for a calcium of 3.3 mg/dL, phosphate of 23 mg/dL, and sodium of 153 mEq/L. Arterial blood gases revealed a pH of 7.24, Pco2 of 38 mm Hg, Po2 of 220 mm Hg. Electrocardiogram revealed a prolonged QT interval of 340 milliseconds with a corrected QT interval of 498 milliseconds. Sixteen hours postexposure, she experienced a generalized seizure unresponsive to multiple doses of lorazepam and responsive only to 100 mg of intravenous calcium chloride. Two days after presentation, the patient experienced complete resolution of symptoms. CONCLUSION: Osmotically acting hypertonic phosphate enemas can result in severe toxicity if retained. This is true even in patients without predisposing risk factors.

Comparison of hyperkalemic cardioplegia with altered [CaCl2] and [MgCl2] on [Ca2+]i transients and function after warm global ischemia in isolated hearts.

AIM: [MgCl(2)] and [CaCl(2)] may modify the cardioprotective effects of hyperkalemic cardioplegia (CP). We changed [MgCl(2)] and [CaCl(2)] in a CP solution to examine their effects on [Ca(2+)]i transients and cardiac function before and after global normothermic ischemia. METHODS: After stabilization and loading of indo 1-AM in Kreb's solution (KR), each heart was perfused with either KR or 1 of 4 CP solutions before 37 degrees C, 30 min ischemia followed by reperfusion with KR. The KR solution contained, in mM, 4.5 KCl, 2.4 MgCl(2) and 2.5 CaCl(2); the CP solutions had in addition to 18 KCl: CP 1 (control CP): 2.4 MgCl(2), 2.5 CaCl(2); CP 2: 7.2 MgCl(2), 2.5 CaCl(2); CP 3, 7.2 MgCl(2), 1.25 CaCl(2); CP 4: 2.4 MgCl(2), 1.25 CaCl(2). RESULTS: In the KR group [Ca(2+)]i markedly increased on early reperfusion while functional return (LVP, dLVP/dt((max and min))) was much reduced; each CP group led to reduced [Ca(2+)]i loading and improved function. The rates of cytosolic Ca(2+) fluxes (d[Ca(2+)]/dt(max) and d[Ca(2+)]/dt(min)) increased significantly compared to baseline in the KR group, but were mostly suppressed in the CP groups, and d[Ca(2+)]/dt(min) was lower after CP 4 compared to CP 1 on reperfusion. At 60 min reperfusion, LVP area to [Ca(2+)] area and cardiac efficiency to phasic [Ca(2+)] relationships were shifted after KR, but not after CP 1-4. With similar functional recovery, [Ca(2+)] transient and [Ca(2+)] area were significantly lower after CP 4 than after CP 1. CONCLUSION: Increasing [MgCl(2)] (CP 2 and 3) did not improve cardiac function or reduce Ca(2+) transients on reperfusion better than the other CP groups, but reducing [CaCl(2)] (CP 3 and 4) was more effective in reducing [Ca(2+)] transients on reperfusion after global ischemia.

Development of a novel concept (Calcigard) for activation of calcium absorption capacity and prevention of milk fever.

The background to the development of a novel concept for the prepartal activation of calcium absorption capacity as a means of preventing parturient hypocalcaemia and milk fever in grazing ruminants is described. It was hypothesised that this objective could be achieved by decreasing the bio-availability of calcium from pasture for a 3 week period. Soya bean oil was chosen as a supplement, from a number of potential binding agents, to form poorly digestible calcium soaps in the gastrointestinal tract. 28 mature twin-pregnant ewes in late pregnancy were used as assay animals to test the hypothesis, and they proved to be a sensitive experimental model for dairy cows. Following the treatment period, overnight starvation was used to challenge calcium homeostasis. Calcium absorption capacity was assessed indirectly by measuring strontium concentrations in plasma following oral dosing with strontium chloride. Strong support for the hypothesis was obtained as the 14 Treated ewes were protected from severe fasting-induced hypocalcaemia (P = 0.002), and this was associated with a greatly increased capacity of the ewes to absorb calcium. The feeding strategy developed in this experiment led to the production of a Calcigard concentrate supplement which was subsequently shown to protect cows from hypocalcaemia and milk fever, and stimulate production.

Reversal of atrial mechanical stunning after cardioversion of atrial arrhythmias: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy.

BACKGROUND: Atrial mechanical stunning develops on termination of chronic atrial arrhythmias and is implicated in the genesis of thromboembolic complications after cardioversion. The mechanisms responsible for atrial mechanical stunning are unknown. The effects of atrial rate, isoproterenol, and calcium on atrial mechanical function in patients with atrial stunning have not been evaluated, and it is not known if atrial stunning can be reversed. METHODS AND RESULTS: Thirty-five patients with chronic atrial flutter (AFL) undergoing radiofrequency ablation were studied. Fifteen patients in sinus rhythm undergoing ablation for paroxysmal AFL were studied as control for effects of the procedure. Left atrial appendage emptying velocities (LAAEVs) and spontaneous echocardiographic contrast (LASEC) were assessed by transesophageal echocardiography during AFL, after reversion to sinus rhythm, during atrial pacing at cycle lengths of 750 to 250 ms, after a postpacing pause, and with isoproterenol or calcium. With termination of AFL, LAAEV decreased from 59.0+/-3.7 cm/s to 18.8+/-1.4 cm/s (P<0.0001) and LASEC grade increased from 0.9+/-0.1 to 2.2+/-0.2 (P<0.0001). Pacing increased LAAEV to a maximum of 38.4+/-3.2 cm/s (P<0.0001) and reduced LASEC grade to 1.9+/-0.2 (P=0.005). Isoproterenol and calcium reversed atrial mechanical stunning with LAAEV increasing to 89.3+/-12.6 cm/s (P=0.0007) and 50.2+/-10.5 cm/s (P=0.005), respectively, and LASEC grade decreasing to 0.2+/-0.1 (P=0.001) and 1.4+/-0.2 (P=0.01), respectively. The postpacing pause increased LAAEV to 69.3+/-3.7 cm/s (P<0.0001). No change in LAAEV was observed in the paroxysmal AFL group. CONCLUSION: Atrial mechanical stunning can be reversed by pacing at increased rates and through the administration of isoproterenol or calcium. These findings suggest a functional contractile apparatus in the mechanically remodeled atrium as a result of chronic atrial flutter.

[Efficacy of treating denture-induced stomatitis by electrically activated aqueous solutions]. / Effektivnost' lecheniia "proteznogo stomatita" élektroaktivirovannymi vodnymi rastvorami.

The authors investigated the oral mucosa in 35 patients, who were divided into four groups: Group 1 (n = 17) received traditional treatment, Group 1 (n = 18) had the similar treatment supplemented by electrically activated aqueous calcium chloride solutions. The findings have shown that the use of electrically activated aqueous calcium chloride solutions in the complex treatment of orthopaedic stomatitis exert more marked clinical and immunological effects than the traditional treatment (p < 0.001-0.01).

The use of plasma-rich growth factors (PRGF) in oral surgery.

The therapeutic objective of utilizing growth factors in oral surgery is to improve upon the body's regenerative capacity. In many situations, the unaided regeneration process is insufficient to allow complete repair of both bone and soft tissues. This article presents two clinical cases that describe different applications of growth-factor preparation applied at the surgical site in order to stimulate regeneration of osseous and epithelial tissues. Both clinical cases demonstrate the therapeutic effectiveness of utilizing the described technique for the incorporation of plasma-rich growth factors as an adjuvant in regenerative procedure.

Cardiogenic shock triggered by verapamil and atenolol: a case report of therapeutic experience with intravenous calcium.

Cardiogenic shock developed in a 72-year-old Japanese woman during combination therapy with verapamil and atenolol for recurrent supraventricular arrhythmia. She had coronary atherosclerosis, liver cirrhosis and bradycardia-tachycardia syndrome. Despite of the high-dose catecholamines and counterpulsation, she progressively deteriorated. Bolus administration of intravenous calcium chloride (CaCl2) immediately resolved her hemodynamic collapse.

Effect of oral administration of a calcium chloride gel on blood mineral concentrations, parturient disorders, reproductive performance, and milk production of dairy cows with retained fetal membranes.

OBJECTIVE: To assess the effect of oral administration of CaCl2 gel on blood mineral concentrations, parturient disorders, reproductive performance, and milk production of dairy cows with retained fetal membranes (RFM). DESIGN: Randomized field trial. ANIMALS: 20 cows that calved normally and were not treated with CaCl2 gel (group 1), 20 cows with RFM that were treated with CaCl2 gel (group 2), and 20 cows with RFM that were not treated with CaCl2 gel (group 3). PROCEDURE: Group-2 cows were treated orally with CaCl2 gel (54 g of calcium) 24 and 48 hours after parturition. RESULTS: Administration of CaCl2 gel 24 and 48 hours after parturition did not have a significant effect on serum normalized calcium, total calcium, magnesium, or phosphorus concentrations or on incidence of metritis or left displacement of the abomasum, days to first insemination, pregnancy status after first insemination, or milk production. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of CaCl2 gel 24 and 48 hours after parturition did not have significant effect on blood mineral concentrations, parturient disorders, reproductive performance, and milk production in dairy cows with RFM.

Calcium supplements increase the serum levels of crosslinked N-telopeptides of bone collagen and parathyroid hormone in rachitic Nigerian children.

OBJECTIVES: Biochemical markers of bone turnover were measured in the sera of 16 controls and 10 children with calcium-deficiency rickets, during a 12-week course of calcium supplementation (1 g CaCO3/d) that was effective in healing the bone lesions of the rachitic children. DESIGN AND METHODS: Serum levels of crosslinked N-telopeptides of bone collagen (NTx), parathyroid hormone (PTH), alkaline phosphatase (ALP), and urinary deoxypyridinoline (LP) were assayed at baseline and during the course of calcium therapy and compared with data of the 16 non-rachitic controls. RESULTS: Calcium therapy suppressed serum NTx and PTH levels in the rachitic children within 24 h; however, after the first week, PTH and NTx levels increased to the extent that at 12 weeks both were elevated when compared with controls or to baseline levels. Serum levels of NTx and PTH were correlated in the controls and experimental subjects (r = 0.63, p < 0.001). CONCLUSIONS: The rate of bone resorption, as estimated by serum NTx concentration, is increased during the healing of rachitic lesions.

Cardioprotection by activation of NO/cGMP pathway after cardioplegic arrest and 8-hour storage.

BACKGROUND: We determined whether activation of the nitric oxide/cyclic guanosine monophosphate pathway by sodium nitroprusside (SNP) protects hearts subjected to cardioplegic arrest and prolonged hypothermic storage. METHODS: Isolated rat hearts arrested with St. Thomas' II cardioplegia and stored at 3 degrees +/- 1 degree C for 8 hours were reperfused at 37 degrees C in Langendorff (10 minutes) and working (60 minutes) modes. RESULTS: During reperfusion, left ventricular work was depressed in stored hearts relative to fresh hearts. When present during arrest, storage, and both reperfusion phases, SNP (200 mumol/L) improved work to values close to those in fresh hearts. When added only during the 10-minute period of Langendorff reperfusion, SNP also improved the subsequent recovery of work. This effect was antagonized by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Poststorage coronary perfusion was not increased by SNP. CONCLUSIONS: The ability of SNP to enhance recovery independent of changes in coronary perfusion and in an ODQ-sensitive manner suggests that SNP-induced protection is due to activation of the myocardial nitric oxide/cyclic guanisine monophosphate pathway. These results suggest that supplementing cardioplegic solutions with SNP, administering SNP during early reperfusion, or both may offer additional means to improve donor heart preservation.

Pharmacology of pediatric resuscitation.

The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.