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PubMed1996

Platelet-dependent thrombin generation in patients with diabetes mellitus: effects of glycemic control on coagulability in diabetes.

OBJECTIVES: This study sought to assess the usefulness of platelet-dependent thrombin generation as an index of coagulability in diabetes and to determine the effect of glycemic control on coagulability in diabetes. BACKGROUND: It is important to investigate the interaction of platelets and the coagulation factors to clarify the processes of the coagulation system in detail. METHODS: Platelet-rich plasma (150 X 10(9)/liter), 0.5 ml, was prepared, and 40 mmol/liter of calcium chloride was added to initiate clotting. S-2238 was added to each sample in a microtiter plate every 10 min, and the absorbance of the released color product at 2 min was measured spectrophotometrically at a wavelength of 405 nm using a microtiter plate reader as thrombin generation. We measured the platelet-independent thrombin generation in patients with non-insulin-dependent diabetes mellitus grouped according to glycemic control. RESULTS: Platelet-dependent thrombin generation at 30 min after calcium chloride addition was significantly higher in 23 patients with poorly glycemic-controlled non-insulin-dependent diabetes mellitus without complications, such as diabetic retinopathy, nephropathy and neuropathy (hemoglobin [Hb] A1c >/= 9.0%) than in 46 healthy normal subjects (448 +/- 75 vs. 165 +/- 28 mU/min, p < 0.001). Thrombin generation in 31 well controlled diabetic patients without complications (Hb A1c < 9.0%) was intermediate (240 +/- 72 mU/min) between those of the poorly controlled group and healthy normal subjects. Platelet-poor plasma from diabetic patients increased platelet-dependent thrombin generation in normal subjects. CONCLUSIONS: Coagulability is evidently enhanced in patients with non-insulin-dependent diabetes mellitus compared with that in healthy normal subjects on the basis of assessments of the platelet-dependent thrombin generation, and good glycemic control may help to correct a hypercoagulable state in diabetic patients.

Adolescent↗
PubMed1986

Determination of oxalate in urine by flow injection analysis.

A method is described for the determination of oxalate in urine using flow injection analysis and fluorimetry. Oxalate is precipitated with calcium chloride at pH 4.5, redissolved in H2SO4 and measured by flow injection analysis. The minimum detection limit is 6 mumol/l. The coefficient of variation is 7%. Results are in good accordance with normal values found with traditional oxalate analysis.

Adult↗
PubMedDate not supplied

Risk of aluminum accumulation in patients with burns and ways to reduce it.

Severely burned patients experience a bone lesion consisting of markedly reduced bone formation and evidence of decreased resportion. The cause of the lesion may be multifactorial, but aluminum loading, which also occurs in patients with burns, has been documented to produce this type of injury in both humans and animals. To assess the risk of aluminum loading with patients with burns, we analyzed fluids, creams, and medication used in the management of acute burn injury for aluminum content. These substances were classified according to route of administration: cutaneous, enteral, or parenteral, to assess the risk of aluminum loading. Cutaneous exposure to aluminum is greatest from baths, which may provide up to 8 mg aluminum. However, the dynamics of aluminum entry into the blood via a damaged skin barrier are unclear. Enteral exposure to aluminum is no greater than daily dietary exposure. Parenteral sources of aluminum, especially 25% human serum albumin and calcium gluconate, provide the most significant risk of loading because of direct introduction of aluminum into the circulation. Substitution with a different brand of albumin and calcium chloride can reduce the parenteral aluminum load by as much as 95% and minimize any role aluminum may play in the pathogenesis of this bone lesion.

Administration, Topical↗
PubMed1999

Matrix tablets of carrageenans. II. Release behavior and effect of added cations.

Carrageenans are hydrocolloids in the rubbery state at standard conditions. They are useful excipients for controlled-release tablets. Three carrageenans, two kappa-carrageenans (Gelcarin GP-812 NF and GP-911 NF) and one iota-carrageenan (Gelcarin GP-379 NF), are analyzed regarding their release behavior in combination with sorption, swelling, and rheology. The iota-carrageenan has a higher substitution by sulfate groups. The kappa-carrageenan Gelcarin GP-812 NF contains a small amount of potassium chloride left over from processing. Water sorption of the pure materials was studied gravimetrically, and the rheology of different solutions (2% and 5% w/w) was studied by cup-cylinder rotation viscosimetry. Swelling was determined as the vertical expansion of the tablets with a specially designed swelling apparatus. Drug release from the tablets was performed by the USP paddle method for 8 hr. The data indicate that drug release increases when water sorption and swelling extent decrease and as viscosity increases. The order of release is nearly zero-order kinetics for theophylline monohydrate, a nonionic drug. Diffusion of the anionic drug diclofenac sodium is anomalous. In addition, the influence of the added salts potassium and calcium chloride on swelling and release was studied. Before tableting, physical mixtures of these salts with and without theophylline monohydrate were prepared. Swelling and release change in the same order, but this is only valid when the ionic interactions responsible for this are strong enough. Besides this, physical mixing of salts with the carrageenans can result in an increased release of drug caused by decreased cohesion of the matrix during drug release, mainly for calcium chloride.

Adsorption↗
PubMed2005

Isolation and in vitro fusion of egg and sperm cells in Oryza sativa.

Protocols for isolation of gametes of Oryza sativa were developed and initial results on in vitro fusion of sperm and egg cells are reported. The best yield of viable sperm cells was obtained when pollen grains were cultured in a medium containing of 1.3 mM boric acid, 3.6 mM calcium chloride, 0.74 mM potassium phosphate, and 438 mM sucrose. Embryo sacs were isolated using cell wall degrading enzyme treatments for 2-5 h followed by mechanical manipulation. The maximum yield (38.2%) of egg cell was achieved when 2% cellulase and 0.55% pectinase were used in the medium. However, the optimum concentration of cellulase and pectinase was found to be 1% and 0.85%, respectively. Fluorescein diacetate (FDA) stain was used to determine the viable sperm and egg cells. The optimal procedures (fusion conditions) for gametes fusion occurred in a medium containing calcium chloride at a concentration of 7 mM (pH 7.5) and the best result obtained (55.5%) in terms of fused gametes, is reported.

Cellulase↗
PubMed1998

Cardiovascular consequences of the concomitant administration of nifedipine and magnesium sulfate in pigs.

There is concern regarding the interaction of magnesium sulfate and nifedipine used concomitantly in obstetrical patients, because both are calcium channel antagonists and may induce myocardial depression as well as peripheral vasodilatation. The objective of this study was to determine the hemodynamic consequences of concomitant administration of nifedipine and magnesium sulfate in anesthetized pigs. Twelve pigs were anesthetized with sodium pentobarbital, intubated mechanically ventilated. Following placement of invasive monitors, baseline hemodynamic measurements were made. Animals were randomized to one of two groups. Group I received nifedipine first, and then magnesium sulfate. Group II received magnesium sulfate first, and then nifedipine. Hemodynamic measurements were recorded. Hypotension was treated with calcium chloride, ephedrine and phenylephrine. Nifedipine alone (Group I) decreased peripheral vascular resistance and mean arterial pressure (MAP) (P<0.05). Magnesium sulfate alone in group II decreased the first derivative of left ventricular pressure (LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP) (P<0.05). Magnesium sulfate also decreased peripheral vascular resistance and MAP The concomitant administration of nifedipine and magnesium sulfate in both groups I and 11 led to a further decrease in myocardial contractility, as evidenced by a decrease in LVdP/dt and increase in LVEDP (P<0.05). Treatment with calcium chloride or ephedrine was only partially successful in improving myocardial contractility. Phenylephrine increased peripheral vascular resistance and MAP, but did not improve myocardial function. In conclusion, the depressive effects of nifedipine and magnesium sulfate on the cardiovascular system are potentiated when administered concomitantly.

Journal Article↗
PubMed1990

Light microscopic autoradiography for study of early changes in the distribution of water-soluble materials.

An approach using autoradiography for the study of early changes in the distribution of water-soluble materials and the chemography involved was investigated. Radioactive calcium chloride (45Ca) was injected into the iliac vein of a rat. Ten seconds after the injection the rat was frozen in hexane (-90 degrees C). The frozen rat was embedded in 5% sodium carboxymethyl cellulose and blocked in the coolant. A sheet of plastic tape coated with a synthetic rubber glue was fastened to the trimmed block surface, and whole-body sections 2-10 microns thick were cut with a disposable microtome knife. Selected sections were freeze-dried and then covered with a dried autoradiographic emulsion film about 1 microns thick. The autoradiograph clearly showed the distribution of radioactive calcium in the calcification zone of long bones. The samples chosen to assess chemographic artifacts showed positive and negative chemographies on most of the tissues when these were kept at 23 degrees C, and although both chemographic effects were significantly reduced when the samples were kept at -20 degrees C, cells in several tissues still exhibited positive and negative chemographies. The technique can be used for the study of any animal whose size is suitable for whole-body freeze-sectioning.

Animals↗
PubMed1971

Purification and properties of an polygalacturonic acid trans-eliminase produced by Bacillus pumilus.

A strain of Bacillus pumilus produced an extracellular pectic enzyme with polygalacturonic acid as the substrate. This enzyme, with optimal activity at pH 8.0 to 8.5, produced reaction products that strongly absorbed light at 232 nm, indicating the presence of a pectic acid trans-eliminase (PATE). Neither pectin esterase nor polygalacturonase was detected in the cell-free culture fluid. Chromatographic examination of the end products revealed the presence of large quantities of unsaturated oligouronides unlike those found with B. polymyxa. It was found that the PATE was produced extracellularly during the negative logarithmic death phase of the organism. The filtrate from sonically treated cells did not show any activity for PATE or hydrolases for lower oligogalacturonides at any time during the growth cycle. The enzyme was inducible. Pectin, National Formulary (NF) was the best inducer, followed by polygalacturonic acid and galacturonic acid. Enzyme activity was markedly stimulated by calcium and other divalent ions. Copper and cobalt ions were inhibitory. The partially purified enzyme showed no significant activity on pectin containing a high methoxyl content (96% esterified). However, pectin NF with a lower methoxyl content (68% esterified) was attacked to a degree by the partially purified and crude enzyme preparations. The initial rate of PATE activity increased up to 60 C, about 16-fold higher than that observed at room temperature. The activation energy was calculated as 12,183 cal/mole. A protective action of calcium chloride against heat inactivation of the PATE was observed. Degradation of polygalacturonic acid by this enzyme produced several unsaturated oligouronides soon after its addition to the substrate. The major endproduct was thought to be different from that of other known PATE enzymes. Paper chromatographic studies and viscosity measurements disclosed the random cleaving nature of the enzyme an endo-PATE.

Ammonium Sulfate↗
PubMed2005

Aqueous corrosion of phosphide minerals from iron meteorites: a highly reactive source of prebiotic phosphorus on the surface of the early Earth.

We present the results of an experimental study of aqueous corrosion of Fe-phosphide under conditions relevant to the early Earth. The results strongly suggest that iron meteorites were an important source of reactive phosphorus (P), a requirement for the formation of P-based life. We further demonstrate that iron meteorites were an abundant source of phosphide minerals early in Earth history. Phosphide corrosion was studied in five different solutions: deionized water, deionized water buffered with sodium bicarbonate, deionized water with dissolved magnesium and calcium chlorides, deionized water containing ethanol and acetic acid, and deionized water containing the chlorides, ethanol, and acetic acid. Experiments were performed in the presence of both air and pure Ar gas to evaluate the effect of atmospheric chemistry. Phosphide corrosion in deionized water results in a metastable mixture of mixed-valence, P-bearing ions including pyrophosphate and triphosphate, key components for metabolism in modern life. In a pH-buffered solution of NaHCO(3), the condensed and reduced species diphosphonate is an abundant corrosion product. Corrosion in ethanol- and acetic acid-containing solutions yields additional P-bearing organic molecules, including acetyl phosphonate and a cyclic triphosphorus molecule. Phosphonate is a major corrosion product of all experiments and is the only P-bearing molecule that persists in solutions with high concentrations of magnesium and calcium chlorides, which suggests that phosphonate may have been a primitive oceanic source of P. The stability and reactivity of phosphonate and hypophosphite in solution were investigated to elucidate reaction mechanisms and the role of mineral catalysts on P-solution chemistry. Phosphonate oxidation is rapid in the presence of Fe metal but negligible in the presence of magnetite and in the control sample. The rate of hypophosphite oxidation is independent of reaction substrate.

Corrosion↗
PubMed2000

Role of cyclic adenosine 3',5'-monophosphate and serum albumin in head-to-head agglutination of boar spermatozoa.

It has previously been shown that when boar spermatozoa are incubated in a modified Krebs-Ringer bicarbonate (mKRB), head-to-head agglutination occurs in many cells. The aim of the present study was to investigate the effects of cyclic adenosine 3',5'-monophosphate (cAMP) and serum albumin on sperm agglutination and to discuss a possible mechanism for sperm agglutination. Spermatozoa were collected from four mature boars, washed and incubated in mKRB. After a 1-h incubation, a sample of each sperm suspension was smeared gently on a separate glass slide, dried and stained in a phosphate-buffered solution of Giemsa to assess the percentage of head-to-head agglutinated cells in each suspension. In the samples incubated in mKRB, approximately 50% of the spermatozoa were agglutinated with one another at the acrosome. However, the percentages of head-to-head agglutinated spermatozoa were greatly reduced by a lack of calcium chloride in mKRB, but were recovered by the addition of dibutyryl cAMP (dbcAMP, a cAMP analogue) in a dose-dependent manner between 1 and 1000 microM. Addition of 3-isobutyl-1-methylxanthine (IBMX, 100 and 500 microM) instead of dbcAMP also significantly increased the percentages of head-to-head agglutinated spermatozoa. Moreover, the effects of adding dbcAMP were attenuated by treatment with Rp-adenosine 3',5'-cyclic monophosphorothioate triethylamine salt (0.25-1.0 mM, a cAMP antagonist) or H-89 (5 microM, a protein kinase-A inhibitor), but were enhanced by treatment with okadaic acid (500 nM) and calyculinA (500 nM) (inhibitors of protein serine/threonine phosphatase). In sperm samples incubated in mKRB containing 0.1% polyvinyl alcohol (mKRB-P) or mKRB-P lacking calcium chloride and supplemented with 1 mM dbcAMP, a lack of bovine serum albumin (BSA) resulted in a significant decrease in the percentages of head-to-head agglutinated spermatozoa. Addition of porcine serum albumin (PSA, 1-4 mg mL(-1)) or methyl-beta-cyclodextrin (MBC, 5-10 mg mL(-1)) instead of BSA was as effective as BSA (4 mg mL(-1)) in enhancing sperm agglutination. However, the effects of BSA (4 mg mL(-1)) or MBC (5 mg mL(-1)) were reduced by pre-mixing these reagents with cholesterol 3-sulfate (a cholesterol analogue, 5 microg mL(-1) for BSA and 375 microg mL(-1) for MBC). In addition, a protein 'anti-agglutinin' inhibiting sperm agglutination, was extracted from spermatozoa incubated with serum albumin or MBC and detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques. The obtained Western blots revealed that sperm-bound anti-agglutinin was detected less in the samples incubated with either BSA (4 mg mL(-1)) or MBC (5-10 mg mL(-1)), compared with control samples. Moreover, pre-mixing MBC (5 mg mL(-1)) with cholesterol 3-sulfate (375 microg mL(-1)) reduced this reagent's effects on the loss of sperm-bound anti-agglutinin. Additionally, the assay of sperm agglutination and a chlortetracycline staining assay revealed that the percentages of head-to-head agglutinated spermatozoa were positively correlated with those of spermatozoa classified into B pattern (capacitated spermatozoa). These results are consistent with the following suggestions: (i) an adenylyl cyclase-cAMP-protein kinase system mediates a signalling pathway leading to head-to-head agglutination; and (ii) loss of anti-agglutinin from the spermatozoa may be modulated by changes in the plasma membrane induced by actions of serum albumin or MBC contained in a medium.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

[The efficacy of using enzymes in treating toxic-allergic reactions after cataract extraction with intraocular lens implantation].

Physiotherapy was administered to 84 patients aged 59-78 years with toxic allergic reaction in the eye after extracapsular cataract extraction with implantation of intraocular lenses (IOL). The patients were divided into 4 groups. Group 1 (n = 15) were treated by fibrinolysin magnetophoresis, group 2 (n = 17) lidase magnetophoresis, group 3 (n = 28) lecozyme magnetophoresis, and group 4 (n = 24) collalysin magnetophoresis. Treatment started on days 3-5 after surgery. Magnetophoresis was carried out using Russian Gradient-1 device, generating a low-frequency magnetic field of 10-12 mT, 10-12 min exposure. For patients with pronounced iridocyclitis and uveitis, enzyme magnetophoresis was supplemented with atropine, adrenalin, and calcium chloride electrophoresis (with monitoring the pupil size). Comprehensive treatment resulted in complete resolution of exudation in the anterior and posterior segments of the eye, hypopyon, loosening and resorption of anterior and posterior synechiae, the vitreous body grew more transparent, visual acuity improved in 91.1% patients (coarse dystrophic changes in the central zone of the fundus oculi were detected in 8.9%). Magnetophoresis with fibrinolysin and lidase is most effective in patients with toxic allergic reaction during the early periods after cataract extraction with IOL implantation, while in later periods magnetophoresis with lecozyme and collalysin should be preferred. The efficacy of collalysin is not inferior to that of lecozyme, but its effect is more mild and the drug causes no allergic reactions. Magnetophoresis with mydriatics (with monitoring the pupil size) and calcium chloride is recommended for all cases.

Aged↗
PubMed1986

Inhibition of calcium oxalate monohydrate (COM) crystal growth by pyrophosphate, citrate and rat urine.

An assay system for the measurement of the rate of Calcium Oxalate Monohydrate (COM) seed crystal growth in a metastable solution of calcium chloride and sodium oxalate containing traces of 14C-oxalic acid was used to assess the inhibitory activity of pyrophosphate (10(-5) M-10(-4) M), citrate (10(-4) M-10(-3) M) and urines of normal and pyridoxine deficient rats. Both pyrophosphate and citrate were strong inhibitors of COM crystal growth and caused a 50% decrease in crystal growth rate at 1.50 X 10(-5) M and 2.85 X 10(-4) M respectively. Normal rat urine strongly inhibited the COM crystal growth, while pyridoxine deficient animals showed a significant (p less than 0.01) decrease in mean inhibitory activity as compared to pair-fed controls. A lowered urinary inhibitory potential accompanied with hyperoxaluria and hypercalciuria, which is known to be associated with pyridoxine deficiency, may be a contributory risk of calcium oxalate crystallization and stone formation.

Animals↗
PubMed2005

Papain entrapment in alginate beads for stability improvement and site-specific delivery: physicochemical characterization and factorial optimization using neural network modeling.

This work examines the influence of various process parameters (like sodium alginate concentration, calcium chloride concentration, and hardening time) on papain entrapped in ionotropically cross-linked alginate beads for stability improvement and site-specific delivery to the small intestine using neural network modeling. A 3(3) full-factorial design and feed-forward neural network with multilayer perceptron was used to investigate the effect of process variables on percentage of entrapment, time required for 50% and 90% of the enzyme release, particle size, and angle of repose. Topographical characterization was conducted by scanning electron microscopy, and entrapment was confirmed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Times required for 50% (T(50)) and 90% (T(90)) of enzyme release were increased in all 3 of the process variables. Percentage entrapment and particle size were found to be directly proportional to sodium alginate concentration and inversely proportional to calcium chloride concentration and hardening time, whereas angle of repose and degree of cross-linking showed exactly opposite proportionality. Beads with >90% entrapment and T(50) of <10 minutes could be obtained at the low levels of all 3 of the process variables. The inability of beads to dissolve in acidic environment, with complete dissolution in buffer of pH >or=6.8, showed the suitability of beads to release papain into the small intestine. The shelf-life of the capsules prepared using the papain-loaded alginate beads was found to be 3.60 years compared with 1.01 years of the marketed formulation. It can be inferred from the above results that the proposed methodology can be used to prepare papain-loaded alginate beads for stability improvement and site-specific delivery.

Alginates↗
PubMed2000

Study of resin-bonded calcia investment: Part 1. Setting time and compressive strength.

This study was carried out to develop a new titanium casting investment consisting of calcia as the refractory material and a cold-curing resin system as the binder. The setting time of the investment was investigated under different N,N-dimethyl-p-toluidine (DMPT) contents in methyl methacrylate monomer (MMA) and benzoyl peroxide (BPO) contents in calcia without any sintering agent. The effects of the sintering agents, which were calcium fluoride (CaF2) and calcium chloride (CaCl2), on the compressive strength of the investments were investigated at room temperature before and after heating to two different temperatures. The shortest setting time (68 minutes) of the investment was obtained at 0.37 DMPT/BPO (1.5 vol% /1.0 mass%) ratio by mass. The highest strength (16.5 MPa) was obtained from the investment which contained 2 mass% CaF2 and was heated to 1,100 degrees C. It was found that the developed calcia investment containing 2 mass% CaF2 has a possibility for use in titanium castings.

Alloys↗
PubMed2000

Effects of micronutrients on growth and starch hydrolysis of Thermococcus guaymasensis and Thermococcus aggregans.

The effects of micronutrients on growth of Thermococcus guaymasensis and Thenrmococcus aggregans in a starch-containing medium were investigated. A trace minerals solution, a vitamins solution and calcium chloride were omitted from the medium or added in different amounts. The growth rates of both species were not affected over a significant range of concentrations of these compounds, but appreciable inhibition of growth was observed after the addition of elemental sulfur to the medium. T. guaymasensis exhibited a significant tolerance to high amounts of trace element and vitamin solutions but growth was inhibited by the omission of these compounds from the medium. Moreover, both amylolytic and pullulytic activities increased in the presence of 6-fold higher amounts of trace element and vitamin solutions, compared to the concentrations used in the usual medium. In T. aggregans, both enzymatic activities were enhanced in the presence of either increased (4-fold) amounts of trace element and vitamin solutions, or after the addition of elemental sulfur to the medium. Furthermore, larger activities of starch-hydrolysing enzymes were detected with a 10-fold higher concentration of calcium chloride, compared to the usual medium, in the absence of trace element and vitamin solutions. When both Thermococcus species were tested for the tolerance to specific cations and oxyanions, T. guaymasensis exhibited higher tolerance compared to T. aggregans, the former strain being capable to grow in the presence of 6 mM Ni2+, 4mM Cu2+, 1.5 mM SeO4(2-), and 1.5 mM MoO4(2-). The content of total cell proteins followed the pattern of starch-hydrolysing enzymes and an over-expression of proteins in the range of 35, 50 and 70 kDa was observed.

Culture Media↗
PubMed1982

Cardiovascular effects of protamine sulfate in man.

Systemic hypotension is commonly observed in association with the administration of protamine after cardiopulmonary bypass. Previous studies have not conclusively demonstrated whether protamine induces its effect by altering myocardial performance or by changing systemic vascular resistance (SVR) or both. To elucidate the hemodynamic effects of protamine sulfate administration (150 mg/m2 body surface area), we studied 22 patients following cardiopulmonary bypass. In Group I (N = 8) protamine was infused over 30 seconds and while in Group II (N = 8), over 60 seconds. Group III (N = 6) received calcium chloride (20 mg/kg) prior to protamine administration. The hemodynamic response was assessed by continuous recording of myocardial contractile element velocity (maximal value-Vpm), aortic blood flow, systemic and pulmonary arterial and right atrial pressures, and electrocardiogram. A significant (p less than 0.05) decrease in the systolic, diastolic and mean blood pressure was observed in all groups. A significant increase in cardiac index and a significant decrease in SVR was observed in all groups. A small depression in Vpm was detected in those patients who experienced a mean blood pressure fall greater than 10 mm Hh. Heart rate and left ventricular end-diastolic pressure (LVEDP) did not change significantly. The response to protamine sulfate among the three groups was similar. These results demonstrate that protamine-induced hypotension is primarily the result of peripheral vasodilatation only partically compensated by an increase in cardiac index. In some patients, these changes were associated with a small decline in myocardial contractile state. Hemodynamic changes were transient (less that 3 to 4 minutes), unrelated to the rate of administration, and not prevented by preinjection of calcium chloride.

Blood Pressure↗
PubMed2006

Antibody-conjugated soybean oil-filled calcium phosphate nanoshells for targetted delivery of hydrophobic molecules.

Hollow calcium phosphate nanoparticles capable of encapsulating poorly water-soluble molecules were produced by self-assembly. Previously reported were solid calcium phosphate nanoparticles and water-filled calcium phosphate nanocapsules suited for encapsulating mostly hydrophilic, but not hydrophobic compounds. Here, calcium phosphate was deposited around 100 nm diameter, 1,2-dioleoyl-sn-glycero-3-phosphate stabilized soybean oil nanoemulsions using either calcium chloride or NaOH titrations to achieve shell thickness between 20-70 nm. The surface was functionalized with carboxylic acid via the addition of carboxyethylphosphonic acid to attach Molecular Probes AB-594C antibody using sulpho-n-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with an efficiency of approximately 70%, while retaining near complete antibody function. Hydrophobic pyrene was encapsulated with an efficiency of 95%, at concentrations much higher than its water solubility limit, and exhibited spectral features characteristic of a hydrophobic environment. These materials can be used in the targeted delivery of many useful, yet poorly water-soluble pharmaceutical and nutraceutical compounds.

Antibodies↗
PubMed1995

Beneficial myocardial metabolic effects of insulin during verapamil toxicity in the anesthetized canine.

OBJECTIVE: Myocardial depression from verapamil toxicity may result from alterations in carbohydrate metabolism as well as calcium-channel antagonism. We hypothesized that pharmacologic doses of insulin may be effective in reversing both of these deficits. DESIGN: Randomized, controlled, prospective study. SETTING: Laboratory of an urban hospital. SUBJECTS: Thirty mongrel dogs. INTERVENTIONS: Thirty mongrel canines were anesthetized with alpha-chloralose. Toxicity was induced by the administration of 0.1 mg/kg/min iv of verapamil, until there was a 50% reduction in mean arterial pressure, for 30 mins (titration), followed by a continuous verapamil infusion of 1 mg/kg/hr. Animals (n = 6 per group) were randomized to the control group (saline only) or to one of four treatment protocols: a) calcium chloride (20 mg/kg), then 0.6 mg/kg/hr; b) hyperinsulinemia-euglycemia (4.0 U/min of recombinant insulin, with arterial glucose concentration clamped to +/- 10 mg/dL [+/- 0.5 mmol/L] of the basal value); c) epinephrine, with a starting rate of 1.0 microgram/kg/min, titrated to maintain left ventricular pressure at basal values; or d) glucagon, a 0.2-mg/kg bolus, followed by a 150-microgram/kg/hr infusion. Animals were monitored until death or 240 mins; infusate volumes were held constant for all groups. MEASUREMENTS AND MAIN RESULTS: During verapamil titration, the myocardial respiratory quotient increased from 0.84 +/- 0.05 to 1.07 +/- 0.11 (p < .05, paired t-test) and myocardial glucose uptake doubled, despite a reduction in cardiac work (p < .05, paired t-test). Net myocardial lactate uptake also increased significantly, excluding myocardial ischemia. In controls, this trend continued, indicating preferential carbohydrate metabolism during untreated verapamil toxicity. Despite hyperglycemia, the plasma insulin concentration was not significantly different in controls (basal value 11 +/- 2 vs. 39 +/- 21 microU/mL at 30 mins). Hyperinsulinemia-euglycemia increased both myocardial glucose and lactate uptake five-fold, and significantly increased the ratio of myocardial oxygen delivery/work, along with superior improvements in maximal left ventricular elastance at end systole compared with other treatments (p < .05 vs. other treatments, contrast analysis). CONCLUSIONS: Verapamil toxicity renders the heart dependent on carbohydrate metabolism. Inasmuch as the positive inotropic effects of all treatments were coincident with increased indices of myocardial carbohydrate uptake, adequate treatment of verapamil toxicity appeared to require maximal myocardial carbohydrate utilization. Hyperinsulinemia-euglycemia allows larger increases in myocardial carbohydrate metabolism and myocardial contractility than calcium chloride, epinephrine, or glucagon, resulting in improved survival rates during severe verapamil toxicity.

Anesthesia, Intravenous↗