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PubMed1996

Changes in serum concentrations of calcium and its regulating hormones during tail suspension in rats.

To study the effects of mechanical unloading on systemic calcium homeostasis, we determined the changes in serum concentration of calcium, 1,25-dihydroxyvitamin D3 and parathyroid hormone (PTH) during tail-suspension experiments in rats. The serum concentration of ionized calcium significantly increased during the 14 days of the suspension, reflecting increased bone resorption in the hind limbs. This hypercalcemic condition should cause suppression in PTH secretion. Indeed, serum PTH levels decreased on Day 3 of the suspension. This decrease was associated with lower serum levels of 1,25-dihydroxyvitamin [correction of dihyroxyvitamin] D3 probably due to a decrease in the activity of 1 alpha-hydroxylase in the kidneys resulting from a decrease in PTH secretion. Since it is known that 1,25-dihydroxyvitamin D3 stimulates osteoblastic function, it is suggested that endocrine responses evoked by tail suspension aggravate disuse atrophy of the hind limbs.

Amino Acids↗
PubMed1992

Lymph nodal vital staining with newer carbon particle suspensions compared with India ink: experimental and clinical observations.

CH40 and CH1500AA are newly prepared carbon suspensions which were examined as vital staining dyes for their usefulness in visualizing lymphatics at operation and to blacken lymph nodes. In mice, these carbon suspensions at 0.001 ml/g of body weight and India ink were injected subcutaneously into the footpad of the right hindpaw. Regional lymph nodes were visualized and were examined stereomicroscopically to determine how intensely these nodes blackened with carbon suspensions. Compared with India ink, CH40 and CH1500AA blackened the regional lymph nodes much faster and more vividly (1-8 min. after subcutaneous injection). As analyzed by centrifugal particle size distribution, CH40 and CH1500AA are narrowly distributed with a small particle size (150 and 167 nm, respectively, in mean diameter). By contrast, India ink is comprised of widely distributed and relatively large particles in suspension (mean diameter--254 nm). In 10 patients undergoing radical gastrectomy for treatment of stomach cancer, CH40 blackened 69% of regional lymph nodes with metastases (38 of 55) and 76% of those nodes without metastases (387 of 512).

Animals↗
PubMed2003

Changes of bone morphology in response to hindlimb suspension of rats.

Effects of chronic hindlimb suspension or exposure to 2-G from postnatal day 4 to month 3 followed by ambulation recovery on the floor on the morphology of hindlimb bones were investigated in rats. The dorsi-flexion of the ankle was inhibited in the suspended group and such phenomena were not recovered at all. The mean weight and length of femur, tibia, and fibula were less than the cage controls at the end of suspension, but gradually increased during recovery. However, they were still less than those of the age-matched controls even after 3-month recovery. External bending of shaft and rotation of distal end of tibia were observed in the suspended group and these phenomena were not recovered at all. These morphological changes caused the inhibition of dorsi-flexion of ankle joints. The electromyogram activities of ankle plantar-flexors, soleus, plantaris, lateral gastrocnemius, were inhibited and those of dorsi-flexor, tibialis anterior, were increased during suspension. Typical changes in bone morphology were not induced by exposure to 2-G. It was suggested that gravitational unloading during developing period causes irreversible inhibition of normal bone growth. It was also indicated that the suspension-related changes in bone morphology may be caused by abnormal mechanical stress due to the altered mobilization of hindlimb muscles.

Animals↗
PubMed2005

Comparison of tail-suspension and sciatic nerve crush on the musculoskeletal system in young-adult mice.

Musculoskeletal unloading and disuse result in significant muscle and bone loss. These phenomena can be modeled using sciatic nerve crush or tail-suspension. Mature animals eliminate the complication of growth superimposed on bone and muscle loss. In the current study, young-adult (12-week old male) C57BL/6J mice were subjected to sciatic nerve crush (NC; n = 9) or tail-suspension (TS; n = 9) for 14 days, with a normal ambulatory control (n = 10). The soleus, gastrocnemius, and EDL muscles were collected and weighed at sacrifice. Femurs were analyzed in three-point bending for stiffness, elastic force and maximum force. Muscle masses in tail suspended mice were reduced by 41.9% (p < 0.001), 17.5% (p < 0.001), and 9.1% (N.S.) for the soleus, gastrocnemius, and EDL, respectively. In NC mice, muscle masses were reduced by 18.6% (p = 0.004), 37.2% (p < 0.001), and 22.5% (p = 0.003). Femur stiffness, elastic and maximum forces were reduced by 20.9% (p = 0.014), 14.7% (N.S.), and 11.6% (N.S.) in TS, compared to NC where masses were reduced by 15.5% (p = 0.022), 0.2% (N.S.) and 11.2% (N.S.) in the crushed leg compared to the contralateral control. NC resulted in a greater reduction of muscle mass in the gastrocnemius and EDL muscle; whereas tail-suspension had a greater effect on the soleus. Tail-suspension had the greatest effect on bone mechanical properties. When comparing these results to actual spaceflight data, it appears as though TS most closely models muscle loss, and NC most closely models changes in bone mechanical properties. These unloading models have tissue-specific effects that impact their applications for musculoskeletal research.

Adaptation, Physiological↗
PubMed1991

Antimicrobial drug suspensions: a blind comparison of taste of fourteen common pediatric drugs.

Children of preschool age most often receive medications in liquid form, and smell and taste are major determinants in achieving compliance. We compared smell, taste and other characteristics of 14 commonly prescribed antimicrobial suspensions in a blind test in 30 adult volunteers to determine whether there was a difference in their acceptability. A significant difference was observed with cephalosporins ranking highest and penicillins ranking lowest. Our findings support anecdotal observations and claims often made by parents that cephalosporin antimicrobial suspensions taste good and are readily accepted by children and that penicillin suspensions have an unpleasant taste and aftertaste and are poorly accepted. Other drugs had intermediate scores. Of the two erythromycin suspensions evaluated, Ilosone tested superior to Erythromycin ES.

Adult↗
PubMed1989

Stability of carbamazepine suspension after repackaging into four types of single-dose containers.

The stability of carbamazepine in commercially available suspension that had been repackaged in various single-dose containers was studied. Carbamazepine suspension was repackaged in 2-mL and 8-mL aliquots in amber glass vials, polypropylene vials, and amber polypropylene syringes and in 2-mL aliquots in amber glass oral syringes. Containers were stored at room temperature and continuously exposed to fluorescent light for up to 12 weeks. Samples from each container type and volume were assayed for carbamazepine content by high-performance liquid chromatography at various intervals during storage. Carbamazepine concentrations in the samples were compared with the carbamazepine concentration in the original manufacturer's container. The pH of the samples was also determined, and the suspensions were inspected for color, odor, and large particles. There was no significant decrease in carbamazepine concentration of more than 10% in samples stored for up to eight weeks. After 12 weeks, significant decreases in concentration were observed in all but one container type. No changes in color, odor, or consistency were observed during the 12 weeks, and there were no significant changes in pH. In commercially available suspension repackaged in volumes corresponding to common pediatric doses, carbamazepine (20 mg/mL) is stable for at least eight weeks when stored at room temperature in the containers tested.

Carbamazepine↗
PubMed1989

[Study on the interactions during storage of compounds of the antacid group. I. Interactions of the components in suspensions].

Twenty antacid mixtures of six quality groups containing Al(OH)3, gel, Mg(OH)2, Mg2Si3O8, CaCO3 and NaAl(OH)2CO3 at different ratios were prepared and stored for 150 days at 20 degrees C in the form of aqueous suspensions. Changes of pH in the suspensions were measured, and the accompanying structural changes were examined by IR spectrometry and X-ray diffraction analysis. Hydrotalcite was found to be formed during storage of aqueous suspensions of mixtures of Al(OH)3 Mg(OH)2; Al(OH)3: Mg(OH)2: CaCO3; Al(OH)3: Mg(OH)2: NaAl(OH)2CO3 and Mg(OH)2: NaAl(OH)2CO3. Initial neutralization activities of the suspensions and those found after the storage were compared.

Aluminum Hydroxide↗
PubMed1986

Right-heart echocontrast in the anesthetized dog after i.v. administration of a new standardized sonographic contrast agent. 2nd communication: dependence of the intensity of contrast on the interval between preparation of the suspension and its injection.

The right-ventricular echocontrast provided by 5 different concentrations of the new standardized sonographic contrast agent SH U 454 (100, 150, 200, 300 and 400 mg microparticles/ml), which consists of pure galactose microparticles, was examined in 3 anesthetized female beagle dogs (8.6-9.3 kg) in order to assess the influence of the period of time which elapsed between preparation of the suspension and its injection. Each animal was given 2 ml of an SH U 454 concentration by intravenous injection at a speed of approximately 2 ml/s immediately after preparation of the suspension and 1, 2, 3 and 5 min thereafter. Evaluation of the intensity of contrast was performed blind by two investigators working independently and using a visual scoring system (ratings 0-5) and also by a videodensitometer. The videodensitometer provided a quantitative evaluation of the maximum intensity of contrast, the duration of contrast and the area under the videodensitometer curve. The intensity of the contrast of the prepared suspension subsided at a constant rate over a period of 5 min for all the concentrations tested. However, the difference between the starting value t0min and the terminal value t5min was small. On the whole, very little difference was found over the 5-min period in the intensity of the contrast provided by any of the SH U 454 concentrations examined. Thus, for the injection the examiner has a timeframe of at least 5 min after preparation of the suspension.

Anesthesia↗
PubMed1985

The proliferation in suspension of the progenitors of the blast cells in acute myeloblastic leukemia.

A minority of blast cells in acute myeloblastic leukemia (AML) form colonies in culture in methylcellulose when stimulated by media conditioned by normal leukocytes in the presence of phytohemagglutinin (PHA-LCM). Blast colonies can be replated successfully, either as pooled cells or suspensions from single colonies. However, the plating efficiency declines with repeated passages, and more than four subcultures have not been achieved. In this study, blast populations were cultured in suspension, with fetal calf serum, alpha-minimal essential medium and PHA-LCM. In cells from 17 of 18 patients, exponential growth of clonogenic blast cells was maintained for six to seven days without reculturing. Colonies obtained from progenitors taken from liquid culture and replated in methylcellulose were replated to obtain the secondary plating efficiency (PE2). In 14 cases, this value was maintained or increased. In three instances, PE2 fell following culture in methylcellulose. When cells in suspension were recultured, exponential growth continued. In nine instances, exponential growth was maintained for from seven to 70 days. During this time, PE2 was maintained. Results from experiments using velocity sedimentation separation and analysis of single colonies were consistent with the view that the increase in clonogenic cells in suspension was a manifestation of their self-renewal capacity. The observations also support a model of blast progenitor growth that contains the postulate that these are capable not only of self-renewal but also of determination-like events leading to loss of proliferative capacity.

Adult↗
PubMed1983

[Degree of cell spreading on a substrate as the factor determining the nature of cell microrelief in suspension].

Quantitative ratio of various types of cell surface microrelief was determined in suspensions prepared from mouse monolayer cultures of embryo fibroblasts grown on different solid substrates: with high (Falcon) or low poly(2-hydroxyethylmethacrylate) adhesiveness; with flat or cylindrical (53-mu curvature radius) surfaces (polyvinylchloride). The electron microscopy revealed that poorly spread cells (on low adhesive or cylindrical substrata) in suspensions had the microvillous surface relief much more often than the cells brought to suspension from highly adhesive or flat substrata. Thus, the lower the degree of cell spreading on the substratum, the higher the probability for the cell to acquire the microvillous relief in suspended state. The microvillous relief of transformed cells in suspensions is, probably, due to their poor spreading on substrata in the monolayer cultures.

Animals↗
PubMed1981

Kinetics of cytolytic T lymphocyte binding to target cells in suspension.

Cytolytic T lymphocytes (CTL) were able to specifically bind and lyse allogeneic P815 tumor cells and LPS blast cells in suspension. An assay was developed to measure the rate of target cell binding in suspension independent of the rate of lysis. Target cell binding was found to plateau within 3 hr in suspension. The presence of free, functional CTL and targets at these plateaus was demonstrated, indicating that target cell binding was an equilibrium process. Scatchard plots were used to derive values for Kd (apparent affinity) and bmax (maximum binding). Target cell binding in suspension could not be blocked by purified plasma membranes. Target cell binding was compared for CTL generated by secondary in vitro stimulation with intact cells or with purified membranes. These 2 CTL populations yielded distinct values for Kd and bmax. Implications of this kinetic difference for CTL recognition of purified plasma membranes are discussed.

Animals↗
PubMedDate not supplied

[The effect of the level of lipid peroxidation and the pH value of a liposomal suspension on its antibacterial activity].

Multilamellar phosphatidylcholine liposomes have been shown to possess antibacterial activity with respect to Pseudomonas aeruginosa and Staphylococcus aureus. An increase in the level of lipid peroxidation products in liposomal suspension as the consequence of the earlier oxidation of liposomal lipid leads to a considerable increase in the antibacterial activity of liposomes. The pH of the liposomal suspension has also an essential influence on its activity. If the pH of the suspension has acidic values, its antibacterial activity increases. The bactericidal action of liposomal suspension is more pronounced with respect to S. aureus, than to P. aeruginosa.

Drug Carriers↗
PubMed1994

[Testing the acid-binding capacity of Tisacid suspension and tablets by intragastric pH determination in patients with hyperacidity].

The effect of a Hungarian Al-Mg-containing drug, called Tisacid was studied using of 2.0, 1.0 and 0.5 gram doses. Two administration forms, suspension and tablet were compared. Ten informed, adult hyperacid volunteers were included into the program and three times 5-hour intragastric pH-metry was carried out in a randomized, self-controlled open clinical study (Control, after administration of tablet or suspension). Both forms were found effective in gastric acid reduction at doses of 2.0 and 1.0 g. Tisacid suspension revealed a more pronounced efficacy at the dose of 2.0 g in comparison to the same dose of tablet form. The 0.5 g dose seemed insufficient in reduction of gastric acidity in hyperacid patients applied in tablet or suspension forms. The authors emphasize the role of continuous intragastric pH-metry in clinical practice and investigation of antacids and antisecretory drugs.

Adult↗
PubMed1994

Preparation and properties of buserelin suspensions.

Obtaining and some properties of suspensions with buserelin-there were obtained buserelin suspensions with zinc ions with pH 7.2-7.5 and hormone: zinc molar ratio from 1:2.5 to 1:500. The obtained buserelin suspensions show moderated hormone release in vitro and prolonged action in vivo. The pulsating buserelin release from suspensions has been found in vitro and in vivo.

Animals↗
PubMed1993

[Clinical evaluation of betaxolol in ophthalmic suspension with or without preservative agent in patients with glaucoma or ocular hypertension].

A prospective, randomized, cross-over, double-blind trial was designed to compare the safety and intraocular pressure (IOP) lowering effect of betaxolol 0.25% ophthalmic suspension with and without preservative (benzalkonium chloride). Twenty-seven patients with primary open angle glaucoma or with ocular hypertension were assigned randomly to receive either the preserved or the unpreserved unit dose betaxolol suspension first, followed by the second medication after a 7-10 day washout period. Both test medications significantly reduced IOP from baseline (p < 0.01) twelve hours after dosing at each observation times. IOP was reduced from a mean of 26.1 mmHg at baseline to 21.6 mmHg (preserved formulation) and from a mean of 25.7 mmHg at baseline to 22.3 mmHg (unpreserved formulation) on day 7. There were no significant differences between treatments, nor was there any evidence of any order effect. Adverse events possibly associated with study drugs included transient headache following instillation in one patient on both preserved and unpreserved formulations. It is concluded from this study that inclusion of a preservative in the betaxolol suspension formulation has no effect on the IOP control afforded by betaxolol, and that both preserved and unpreserved suspensions were safe for use in treatment of glaucoma and ocular hypertension.

Adult↗
PubMed1993

High-level expression of secreted proteins from cells adapted to serum-free suspension culture.

We have developed a host cell/vector system based on the use of adenovirus-transformed cells and a promoter, designated GBMT, capable of being activated by the Ela tumor antigen produced in these cells. GBMT-based vectors were constructed with hygromycin phosphotransferase and murine dihydrofolate reductase as selective markers. We demonstrate their utility in two adenovirus-transformed cell lines, human kidney 293 and Syrian hamster AV12-664. Further, we describe methods and conditions for the direct adaptation of isolated recombinant clones to serum-free suspension growth conditions. For exemplary purposes, we describe the generation of stable recombinant 293 cell lines with single-copy integrated vectors secreting the highly complex clotting factor human protein C at levels as high as 20 mg/l in serum-free suspension culture. In addition, using the AV12-664 cell line with GBMT and direct dominant selection of the dhfr gene, we have isolated clones secreting a tissue plasminogen activator derivative at levels of about 40 mg/l under serum-free suspension conditions. The distinct advantages of this vector/host cell system are 1) the direct selection of stable clones expressing relatively high levels of recombinant protein, eliminating the need for the tedious stepwise gene amplification process and 2) the direct adaptation to serum-free suspension culture.

Adaptation, Physiological↗
PubMed1996

A comparison of the performance in vitro of precision cut tissue slices and suspensions of human spleen with special reference to immunoglobulin and cytokine production.

During the past decade our knowledge of the cellular and molecular events associated with key immunological responses has been greatly advanced by the use of isolated subpopulations of immunocompetent cells, cloned cell lines and recombinant derived cytokines. Valuable as these studies have been they do not truly reflect the complex integrative events which take place in both primary and secondary lymphoid tissue both in vivo and in vitro. In order to address this problem we have developed a tissue culture procedure which is a modification of that previously used by others to study T cell maturation in the thymus. This involves culturing precision cut slices of human lymphoid tissue in a sponge culture system. Using this technique we have observed marked differences in both immunoglobulin and cytokine secretion between slices and suspensions of human spleen. In brief, cultured slices (mitogen stimulated or otherwise) consistently secrete higher levels of immunoglobulin, IL-1 beta, IL-6, IL-8 and IL-11 and exhibit much lower proliferation than suspensions of the same tissue. Mitogen stimulated suspensions on the other hand secrete higher levels of IL-2, IL-4, IL-10 and TNF alpha than do slices. These differences are also observed at the intracellular cytokine level. Additional studies reveal that the immunoglobulin and cytokine secretion observed is largely due to the de novo synthesis of these molecules and not as a result of spontaneous secretion of preformed products. Furthermore immunoglobulin secretion in both slices and suspensions can be inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha while IL-6 production can be differentially modulated by a variety of substances. Preliminary studies indicate that close interaction between B cells and stromal cells within explants accounts for some of the observed differences. This review article describes the basic technique, summarises the results we have obtained in this system and outlines the possible basis of the observed differences.

B-Lymphocytes↗
PubMed1997

Differing effects of two-week suspension on male and female mouse bone metabolism.

The effects of suspension on bone histomorphometry during the first and second week of tail suspension are compared for male and female mice of the common inbred strain, the C57BL/6J. In male mice, significant changes in bone formation rate (BFR) were largely confined to the endocortical perimeter. BFR along the endocortical mid-diaphysis in the femora of suspended male mice was reduced 54.1% and 55.6% for the first and second week, respectively. In female mice, however, measured metabolic changes due to suspension occurred along the periosteal perimeter, where there was a decrease in BFR of 58.3% for the first week and 60.9% for the second. The notable difference in the bone perimeter affected by suspension observed in male and female mice indicates a difference in the metabolic control of bone development in male and female C57BL/6J mice. More importantly, this may indicate a sex-based difference in preserving structural properties in the response of the skeleton to unloading.

Animals↗