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PubMed1986

[Clinical or experimental use of an anticancer drug-oil suspension and its characteristics].

The anticancer agent, Nimustine, which is a derivative of Nimustine hydrochloride (Sankyo CC, Ltd), was suspended in an oil, Lipiodol, using an ultrasonic suspender and used in experimental animals and human subjects with malignant tumor. The use of Lipiodol facilitates the fluoroscopic demonstration of the site into which the suspension has been injected. The Nimustine-Lipiodol suspension was almost stable in room air over 7 days and diffusion of suspended Nimustine into saline in vitro was still noted 4 weeks later. Remarkable regression of tumor size was observed when the Nimustine-Lipiodol suspension was locally injected into the lesion of Lewis lung cancer subcutaneously inoculated into mice. Moreover, a marked regression of tumor size and improvement of CEA level in serum were also obtained when arterial injection of the Nimustine-Lipiodol suspension was carried out in patients with metastatic liver cancer. Therefore, local or arterial injection of Nimustine-Lipiodol suspension is considered to be effective as a method of cancer targeting therapy.

Animals↗
PubMedDate not supplied

[Effect of initiated spores on the resistance of nongerminated resting forms of Bacillus cereus remaining in the suspension to the action of damaging agents].

The elevated resistance of a Bacillus cereus spore suspension against the action of UV was found to depend on the quantity of resting forms initiated in the suspension prior to an irradiation. The resistance against UV increased 80-50 times if 60-90% of spores were initiated in the suspension as compared to that of the original resting forms. When suspensions containing 40% of non-germinated B. cereus spores were kept at 4 degrees C for 14 days, the latter became 10 and 14 times more resistant to elevated temperature (90 degrees C) and chloramine (2.5%), respectively, as compared to control intact spores. The higher resistance of non-germinated spores against the action of physical and chemical damaging agents was registered within the entire period of experiments (over three months). This phenomenon was not observed if ca. 100% of spores were initiated in a suspension. The resistance of initiated spores against the action of UV was 40 times lower than that of B. cereus resting forms.

Bacillus cereus↗
PubMed1978

Canine kidney cells. II. Neutral lipids, phospholipids and fatty acids of Madin-Darby canine kidney cells in suspension and monolayer culture.

Differences in lipid composition and the effects of monolayer and suspension culture were studied in Madin-Darby canine kidney cells and their plasma membranes isolated by the Warren fluorescein-mercuric acetate technique. Unesterified cholesterol was the major neutral lipid extracted from the whole cells and plasma membranes of cultures except for suspension-grown whole cells which had triglyceride as their major neutral lipid. Triglyceride increased about 7- to 20-fold and glycerol ethers increased about 3- to 20-fold in suspension grown whole cells and their plasma membranes compared to those from monolayer cultures. Total quantities of phospholipids are similar in whole cells of both cultures. Plasma membranes from monolayer cultures have about 1.4-fold more total phospholipids than those from suspension cultures. The distribution of fatty acids in the plasma membranes and whole cells generally follow the composition of calf serum used in the culture medium. However, the phospholipids of plasma membranes from monolayer cultures had substantially higher values for C18 unsaturated fatty acids and somewhat lower values for palmitoleic acid than the values for the fatty acids in calf serum. Also, the phospholipids of suspension-grown whole cells had substantially higher values for lauric acid and lower values for C18 unsaturated fatty acids when compared to calf serum.

Animals↗
PubMed1985

[Determination of the number of pathogens in bacterial suspensions using laser nephelometry in comparison to the photometry and plate counting method].

We determined the number of bacteria in suspensions of three bacterial species (S. aureus ATCC 25923, E. coli ATCC 25922, P. aeruginosa ATCC 27853) in liquid medium using two optical methods - laser-nephelometry and photometry. These results were compared with the CFU/ml determined by the agar plate test in each suspension. Further we defined the applicable range of measurement of both optical methods. The calculated factor of correlation (r = 0.99) attested the very good conformity of the results obtained by both optical methods. The determination of the number of bacteria in suspensions by laser-nephelometry is a simple though very sensitive method. The results can well be reproduced. A further advantage of this method is the immediate information about the number of bacteria in suspension. All these facts recommend laser-nephelometry as a method useful in any bacteriological routine laboratory for determination of the number of bacteria in suspensions.

Bacteriological Techniques↗
PubMed1985

Rapid changes in surface antigen expression by blood monocytes cultured in suspension or adherent to plastic.

Cell surface antigens used as markers of in vivo differentiation may not be stable on monocytes maintained under different conditions of in vitro culture. Monocytes were isolated from blood by centrifugation over Percoll or by adherence to plastic dishes, and the cells cultured in suspension or as adherent monolayers. Initially, monocytes obtained by both methods were similar in size, morphology, and surface antigen expression detected with the antimonocyte monoclonal antibodies OKM1, FMC17, PHM2, and PHM3. After culture, cells maintained in suspension were predominantly small, whereas those adherent to plastic rapidly increased in size; however, cytochemical staining for nonspecific esterase and acid phosphatase showed increased enzymic activity by monocytes in both systems, possibly reflecting increased cell maturation. The most striking difference was a substantial loss of FMC17 antigen by most monocytes within four hours in suspension culture, as compared with a qualitative and quantitative increase in expression by plastic adherent cells within two hours. These changes occurred even if the cells were first reacted with lipopolysaccharide. Monocytes taken from suspension culture and allowed to adhere to plastic rapidly synthesized the antigen, a process inhibited by cycloheximide, and conversely, cells removed from plastic progressively displayed decreased FMC17 antigen expression when transferred to suspension culture. No functional role in adherence or phagocytosis has been found for the FMC17 antigen. The results suggest that antigen expression may depend as much on the physical state of the cells as on apparent activation or maturation events.

Acid Phosphatase↗
PubMed1980

Elimination of acute myelogenous leukemic cells from marrow and tumor suspensions in the rat with 4-hydroperoxycyclophosphamide.

Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells survived fatal irradiation induced aplasia. In a dose related manner 4HC was able to "purge" tumor cells from the cell mixtures. Thus, animals given cell suspensions incubated with the lower doses of 4HC showed prolonged survival before death from leukemia and animals given cell suspensions incubated with higher doses of 4HC survival lethal irradiation without the subsequent appearance of leukemia. These studies clearly establish that tumor cells may be eliminated from normal marrow suspensions without completely destroying the pluripotent stem cells.

Animals↗
PubMedDate not supplied

Magnetic suspension controls for a new continuous flow ventricular assist device.

A new continuous flow ventricular assist device (CFVAD III) using a full magnetic suspension has been constructed. The magnetic suspension centers the centrifugal impeller within the clearance passages in the pump, thus avoiding any contact. This noncontact operation gives very high expected mechanical reliability, large clearances, low hemolysis, low thrombosis, and relatively small size compared with current pulsatile devices. A unique configuration of a system of magnetic actuators on the inlet side and exit sides of the impeller gives full five axis control and suspension of the impeller. The bearing system is divided into segments that allow for three displacement axes and two angular control axes. For the first suspension tests, a decentralized set of proportional, derivative, and integral (PID) controllers acting along the modal coordinates are used to suspend the impeller. The controller design takes into account the blood forces acting on the magnetically suspended impeller, the unbalance forces on the impeller and gravitational loads during various body motions. In the final design, the bearing control axes will be coupled together through fluidic forces so the electronic feedback controller is a centralized multiple input, multiple output controller. The control system design must be robust against these types of externally imposed loads to keep the impeller centered and avoid blood damage. This article discusses the dynamic model, controller, and controller implementation for the magnetic suspension controller of CFVAD III.

Biomechanical Phenomena↗
PubMed1998

Comparative outcome analysis of laparoscopic colposuspension, abdominal colposuspension and vaginal needle suspension for female urinary incontinence.

PURPOSE: The long-term surgical outcome of abdominal colposuspension, laparoscopic colposuspension and vaginal needle suspension for managing anatomical stress urinary incontinence in women was evaluated. MATERIALS AND METHODS: Three nonrandomized contemporaneous groups of 10 women each with anatomical stress urinary incontinence were treated with abdominal colposuspension, laparoscopic colposuspension or vaginal needle suspension. Immediate postoperative and subsequent outcomes were evaluated using a 10-point questionnaire annually up to 36 months. RESULTS: Immediately after surgery the laparoscopic colposuspension group required less analgesia as well as briefer catheterization and hospital stay. Continence rates 10 months postoperatively were 100% for the abdominal colposuspension group, 90% for the laparoscopic colposuspension group and 100% for the vaginal needle suspension group. At 36 months postoperatively these results had declined to 50, 40 and 20%, and satisfaction with surgical outcome was 60, 90 and 60%, respectively. CONCLUSIONS: Despite initially high success rates of these 3 surgical procedures based on the principle of retropubic suspension of the proximal portion of the urethra, responses to questionnaires given at longer postoperative intervals showed a sharp decline in success. We probably should redirect our treatment strategy for women with anatomical stress incontinence to include urethral coaptation and direct suburethral suspension.

Abdomen↗
PubMed2000

Interfacial properties of barium sulfate suspensions. Implications in their stability.

A surface characterization of barium sulfate particles in aqueous suspensions was carried out in this work. With the aim of predicting the stability conditions of these widely used suspensions, the electrical surface properties of the particles were first studied by electrophoretic mobility determinations. It was found that both H(+) and OH(-) ions can be considered as potential-determining ions for the barium sulfate/water interface. The same conclusion was reached concerning the lattice ions, Ba(2+) (mainly) and SO(4)(2-). It was also found that increasing the concentration of sodium chloride in the dispersion medium can even change the sign of the zeta (zeta) potential: it is suggested that this behavior is an indirect effect provoked by changes in the solubility of barium sulfate with the ionic strength. To compute the van der Waals (LW) attraction between the particles as well as the acid-base contribution to the total energy of interaction, a thermodynamic characterization of the interface was also carried out by measuring the rate of penetration of selected liquids through plugs of the particles. It was found that barium sulfate particles are essentially monopolar in nature; that is, they show electron-donor character as demonstrated by the essentially zero value of the electron-acceptor component of their surface free energy. Pretreatment of the particles with 10(-2) M solutions of BaCl2 and CaCl2 significantly reduced the electron-donor component, whereas both NaCl and Na(2)SO(4) provoked the opposite effect. This result is explained in terms of the acid-base character of the ions added. These data were used to calculate the interaction energy between the particles. The effect of electrolyte concentration on the stability of the suspensions was analyzed on the basis of the dependence with distance of the interaction energy between the particles. Our results suggest that more stable suspensions of barium sulfate are predicted if moderate amounts of SO(4)(2-) ions are added to the dispersion medium.

Barium Sulfate↗
PubMed2000

Pharmacokinetic assessment of an oral enalapril suspension for use in children.

The angiotensin-converting enzyme (ACE) inhibitor enalapril is commonly used to treat pediatric hypertension. Because some children are unable to swallow tablets or require doses less than the lowest available enalapril tablet, an enalapril suspension was developed. This study examined the relative bioavailability of enalapril suspension (10 mg) (S) compared with 10-mg marketed VASOTEC tablets (T) in 16 healthy adult subjects. The geometric mean ratio (S/T) estimate of urinary recovery of free enalaprilat, the active moiety, was 0.92 (90% confidence interval (CI): 0.80, 1.07). Urinary recovery data indicate that approximately 50% of the dose was absorbed (50% recovered in urine as enalapril plus enalaprilat) with about 30% of the dose recovered as free enalaprilat for both S and T. The geometric mean ratios (S/T) of serum AUC and C(max) were 1.01 (90% CI: 0.90, 1.13) and 0.98 (90% CI: 0.83, 1.16), respectively. Suspension T(max) was slightly shorter (0.5 h) than that for tablet, but this difference is not clinically significant. Both formulations were well tolerated and there were no clinically significant adverse experiences. We conclude that the bioavailability of enalapril oral suspension 10-mg is similar to that of VASOTEC 10-mg tablet. Instructions for compounding enalapril are provided.

Administration, Oral↗
PubMed2006

Bioavailability of an extemporaneous suspension of propafenone made from tablets.

Propafenone is an effective antiarrhythmic agent used in children, while in Mexico no specific formulation for children is available, which causes errors in adequate dosage. The aim of this study was to determine the bioavailability of a suspension prepared extemporaneously using commercial tablets of propafenone. The bioavailability was determined in two groups of rabbits (n = 8): the first group received a single intravenous dose of 2 mg/kg of propafenone; the second was orally administered an extemporaneous suspension of propafenone prepared from commercial tablets. Blood samples were drawn at several times during the next 24 h and analysed by HPLC to determine drug levels. The extemporaneous suspension was tested previously with satisfactory results regarding physicochemical and microbiologic stability. The area under the curve (AUC) for the i.v. route was 5600.6 ng/ml.h and for oral administration the AUC was 3327.6 ng/ml.h. The bioavailability was calculated at 59.41%. These results are consistent with previous reports for solid dosage forms. The propafenone suspension prepared extemporaneously using commercial tablets is bioavailable using an animal model; nevertheless, it is necessary to carry out human studies either in volunteers or in patients to confirm these results.

Administration, Oral↗
PubMed1993

The hydration of proteins in nearly anhydrous organic solvent suspensions.

Water sorption isotherms at 27 degrees C have been measured for lysozyme and chymotrypsin in suspensions of toluene, di(n-butyl) ether, n-propanol, and a solution of 1M n-propanol in benzene. Sorption isotherms for the different suspensions are compared by converting solvent water content to the thermodynamic activity of water in each solvent. The sorption behavior is also compared to that for the two proteins hydrated from the vapor phase. At low water activities, all sorption isotherms are similar when compared on the basis of water activity. However, at higher activities, water sorption by the proteins in the organic suspensions is suppressed relative to the sorption of water vapor. The greatest suppression is observed for n-propanol, which suggests that the suppression may be due to a competition for water-binding sites on the protein by the organic solvent. Sorption isotherms at low water activities have also been predicted using a thermodynamic model in which it is assumed that water binds selectively to the ionizable residues on the surface of the protein. A comparison of predicted and measured sorption isotherms shows that the model can provide reasonable estimates of water sorption in nonpolar or moderately polar organic solvent suspensions at low levels of hydration.

Proteins↗
PubMed2005

Orbital shaker technology for the cultivation of mammalian cells in suspension.

For large-scale applications in biotechnology, cultivation of mammalian cells in suspension is an essential prerequisite. Typically, suspension cultures are grown in glass spinner flasks filled to less than 50% of the nominal volume. We propose a superior system for suspension cultures of mammalian cells based on orbital shaker technology. We found that "square-shaped" bottles (square bottles) provide an inexpensive but efficient means to grow HEK-293 EBNA and CHO-DG44 cells to high density. Cultures in agitated 1-L square bottles exceeded the performance of cultures in spinner flasks, reaching densities up to 7 x 10(6) cells/mL for HEK-293 EBNA cells and 5 x 10(6) cells/mL for CHO-DG44 cells in comparison to (2.5-4) x 10(6) cells/mL for cultures of the same cells grown in spinner flasks. For 1-L square bottles, optimal cell growth and viability were observed with a filling volume of 30-40% of the nominal volume and an agitation speed of 130 rpm at a rotational diameter of 2.5 cm. Transient reporter gene expression following gene delivery by calcium phosphate-DNA co-precipitation was the same or slightly better for HEK-293 EBNA cells grown in square bottles as compared to spinner flasks. Reductions in cost, simplified handling, and better performance in cell growth and viability make the agitated square bottle a new and very promising tool for the cultivation of mammalian cells in suspension.

Animals↗
PubMed1988

Bioavailability of potassium from three dosage forms: suspension, capsule, and solution.

A crossover study was performed in 28, healthy, male volunteers to determine the bioavailability of potassium from a suspension containing microencapsulated potassium chloride compared with that from a marketed microencapsulated potassium chloride capsule and a marketed potassium chloride solution. The 20-day study consisted of four, five-day periods. In three of the periods, a single, 40-mEq dose of one of the potassium formulations was administered; no drug treatment was given in the remaining period so that the amount of potassium contributed by dietary sources could be determined. Meals were served that provided controlled amounts of potassium and sodium. Bioavailability was represented by cumulative amount of K+ excreted in urine 24 and 48 hours after drug administration. The rate of absorption was calculated from excretion rates during each of the intervals of urine collection on Days 4. The pattern of excretion exhibited by the solution indicated rapid absorption and elimination. The potassium from the suspension and the capsules was excreted more slowly and over a longer period, indicating that the potassium content from these formulations was not being dumped. No statistically significant differences between the suspension and the capsules were found. The extent of absorption of K+ was similar from all three products, and the potassium from the suspension was found to be fully bioavailable when compared with the liquid and the capsule.

Adult↗
PubMed1994

Comparison of the pharmacokinetics of naproxen tablets and suspension in children.

Twenty-three children, aged 8 to 14 years, with postoperative pain, were randomly assigned to receive a fixed 250-mg dose (4.66-7.58 mg/kg) of naproxen as either a liquid suspension or tablet. After an overnight fast, the serum concentrations were measured before and at 0.5, 1, 2, 3, 4, 8, 12, 18, and 24 hours after administration of naproxen. The concentration versus time data were best fit to a one-compartment open model. The area under the concentration versus time curve, apparent volume of distribution (VDss/F), and elimination parameters (CL/F, Ke, elimination half-life) were similar in children who received suspension or tablets. Although the apparent maximum peak plasma concentration (Cmax) was greater in children who received tablets compared with those who received the suspension, Cmax/area under the curve (AUC), apparent time to maximum peak concentration (tmax), Ka, and estimated time to 10%, 50%, and 90% absorption (T10, T50, T90) were not different. The dose range was relatively narrow; hence, direct relationships between dose and elimination parameters, VDss/F, apparent tmax, Ka, T10, T50 or T90 were not observed. Neither VDss/F or CL/F were age related over the relatively narrow range of ages that were studied. Elimination of naproxen in our patients was more rapid than has previously been reported in children or adults, however. From a practical standpoint, naproxen tablets and suspension seem to be bioequivalent in fasting children ages 8 to 14 years.

Administration, Oral↗
PubMed1979

Bioavailability and dissolution behavior of trisulfapyrimidine suspensions.

The bioavailability of seven commercial trisulfapyrimidine suspensions was studied in 14 adult male volunteers. Fifteen blood samples were collected over a 48-hr period following administration of a 1-g dose of each suspension. Serum was assayed for each component (sulfadiazine, sulfamerazine, and sulfamethazine) by high-pressure liquid chromatography. Analysis of variance indicated several significant differences among the seven commercial preparations with respect to Cmax Tmax, and AUC for sulfadiazine, sulfamerazine, and sulfamethazine, The in vitro behavior of each suspension was then studied by the paddle method of the Food and Drug Administration. A 0.5-ml sample was introduced into 900 ml of hydrochloric acid (2.2 x 10(-4) M) at 37 degree and dissolved using a paddle speed of 25 rpm. Samples withdrawn at 15 and 30 min were analyzed by high-pressure liquid chromatography, and the percent of sulfadiazine, sulfamerazine, and sulfamethazine was calculated. Significant correlation was obtained between an in vivo parameter (Cmax for sulfadiazine) and an in vitro parameter (percent sulfadiazine dissolved in 30 min). Results indicate that this method is suitable for the in vitro screening of trisulapyrimidine suspensions.

Adult↗
PubMed1980

Flocculation effect of xanthan gum in pharmaceutical suspensions.

The particulate structure in suspensions of magnesium carbonate, aluminum hydroxide, calcium carbonate, and zinc oxide was assessed by sedimentation volume studies, measurement of particle size by an electronic particle sizer, and visualization by microscopy. The results of the particle-size measruement did not always agree with results from the other techniques. magnesium carbonate, aluminum hydroxide, and zinc oxide were flocculated in water. The addition of xanthan gum increased flocculation of magnesium carbonate and aluminum hydroxide and apparently caused partial deflocculation of zinc oxide suspensions. Calcium carbonate suspensions were deflocculated in water, and xanthan gum did not significantly change the properties. Studies with sodium chloride showed that flocculation cannot be attributed to changes in double-layer repulsion. Flocculation in the suspensions studied appeared to be consistent with a bridging mechanism.

Aluminum Hydroxide↗
PubMed1982

Drug stability in liposomal suspensions: hydrolysis of indomethacin, cyclocytidine, and p-nitrophenyl acetate.

First-order rate constants (kL) for hydrolysis of p-nitrophenyl acetate, cationic cyclocytidine, and anionic indomethacin in the presence of buffered liposomal suspensions of positive, negative, and neutral charge were compared to those determined in the corresponding buffers (kB) using the ratio, Rk = kL/kB. Association between the reactants and the liposomes was evaluated by comparing assays for concentration in the filtrates (CF) with the total concentration in the liposomal suspension (CT) using RC = CF/CT. Liposomes did not influence cyclocytidine hydrolysis rates and no association was observed (Rk congruent to RC congruent to 1). In contrast, indomethacin showed approximately 80% reduction in hydrolysis rate and approximately 80% liposome association value (Rk congruent to 0.2 congruent to RC). In neutral and negatively charged liposomal suspensions, p-nitrophenyl acetate displayed approximately 30% decrease in kB (Rk congruent to 0.7) together with approximately 90% liposomal association (RC congruent to 0.1). However, hydrolysis was greatly accelerated in positively charged liposomal suspensions. Loss was described by a biexponential equation where alpha is the fast and beta is the slow pre-exponential coefficient and alpha/beta/kB = 39:6:1. The observed relationships between hydrolysis rates and reactant-liposome associations are reconciled in terms of the hydrophilicity of the reactants and the potential influence of the liposomes on the expected transition states for the hydrolysis reactions.

Ancitabine↗