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K M Sanders

Publications and source records attributed to K M Sanders.

At least 127 records · Page 7Linked to original sources
PubMed1996

Involvement of nitric oxide in inhibitory neuromuscular transmission in equine jejunum.

OBJECTIVES: To evaluate the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a transmitter acting through an apamin-sensitive mechanism in mediating inhibitory transmission in the equine jejunal circular muscle, and to determine the distribution of VIP-and NO-producing nerve fibers in the myenteric plexus and circular muscle. PROCEDURE: Circular muscle strips were suspended in tissue baths containing an oxygenated modified Krebs solution and attached to isometric force transducers. Responses to electrical field stimulation (EFS), tetrodotoxin, the NO antagonists L-N-nitro-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine, apamin, VIP, authentic NO, and the NO donar sodium nitroprusside were tested. Immunostaining for VIP-like and NADPH diaphorase histochemical staining were performed on paraformaldehyde fixed tissue. RESULTS: Subpopulations of myenteric neurons and nerve fibers in the circular muscle were positive for NADPH diaphorase and VIP-like staining. EFS caused a frequency-dependent inhibition of contratile activity. Tetrodotoxin prevented the EFS-induced inhibition of contractions. L-NAME (200 microM) and apamin (0.3 microM) significantly (P < 0.01) reduced EFS-stimulated inhibition of contractile activity at most frequencies tested. The effects of L-NAME and apamin were additive. In their combined presence, EFS induced excitation instead of inhibition (196.7% increase at 5 Hz, n = 28, P < 0.01). Inhibition of contractile activity by EFS was mimicked by sodium nitroprusside. Authentic NO (3-6 microM) abolished contractile activity. VIP induced a dose-dependent inhibition of contractile activity (89.1 +/- 6.3% reduction at approximately 0.3 microM, n = 16). Antagonism of NO synthesis did not alter the response to VIP. CONCLUSION: NO, VIP, and a substance acting through an apamin-sensitive mechanism appear to comediate inhibitory transmission in the equine jejunal circular muscle. CLINICAL RELEVANCE: These findings may suggest new therapeutic targets for motility disorders, such as agents that inhibit the synthesis or actions of NO.

Animals↗
PubMed1996

A comprehensive investigation of inpatient intravenous colchicine use shows more education is needed.

OBJECTIVE: To test the hypothesis that colchicine therapy for patients in whom treatment was guided by rheumatology consultation was more appropriately prescribed than therapy for patients not receiving consultation. METHODS: A retrospective chart review of all inpatients with acute crystal induced arthritis who received intravenous (iv) colchicine was performed to assess iv colchicine prescribing errors and any adverse outcomes of iv colchicine therapy. RESULTS: Errors in the prescribing of iv colchicine occurred in 5 of 19 patients (26%). A rheumatology consultation was not obtained in any of these cases. Overall, there was a significant increase in the prescribing error rate in the no-consultation versus the consultation groups (p = 0.045). These 5 errors did not lead to serious adverse outcomes, but leukopenia occurred in one patient and the white blood cell count decreased from 7.3 to 4.3 cells/mm3 in another patient. Leukopenia also occurred in 3 patients in whom iv colchicine was used appropriately. CONCLUSION: (1) Previously published guidelines for iv colchicine use appeared successful at preventing serious colchicine toxicity. (2) These guidelines do not protect against leukopenia occurring from colchicine use. (3) Rheumatology consultation may help prevent errors in the use of iv colchicine. (4) Further education is needed in the correct use of iv colchicine.

Adult↗
PubMed1995

Nitric oxide activates multiple potassium channels in canine colonic smooth muscle.

1. Nitric oxide (NO), an inhibitory neurotransmitter released from peripheral neurones, hyperpolarizes smooth muscle cells and inhibits contraction. The mechanism of this hyperpolarization is unknown. 2. We have identified three classes of K+ channels activated by NO and NO donors in colonic smooth muscle cells. NO and NO donors increased the open probability of 80 pS channels (KNO1), very small channels (< 4 pS, KNO2), and 270 pS Ca(2+)-activated K+ channels (BK channels) in cell-attached patches. 3. Dibutyryl cGMP and 8-bromo cGMP also increased the open probability of KNO1 and KNO2 in cell-attached patches. 4. In excised patches of membrane, direct application of NO or the NO donor, S-nitroso-N-acetyl penicillamine (SNAP), increased the open probability of KNO1 and KNO2, but cGMP or dibutyryl cGMP had no effect. SNAP had no effect on the open probability of BK channels in excised patches. 5. The reducing agent dithiothreitol and the alkylating agent N-ethylmaleimide blocked NO-induced channel openings. 6. In summary, the hyperpolarization response to NO in smooth muscles may be mediated by multiple K+ channels. At least two of these classes of channels may be activated by dual pathways involving direct activation by NO and cGMP-mediated mechanisms.

Animals↗
PubMed1995

Detection of nitric oxide release from canine enteric neurons.

Previous pharmacological and immunohistochemical studies have suggested that nitric oxide (NO) is a mediator of enteric neuromuscular transmission in the canine proximal colon. The present study demonstrates the release of nitric oxide (NO) and/or its oxidation products (collectively termed NOx) following stimulation of intrinsic neurons with the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). Strips of muscularis externa, including the ganglionated myenteric and submucosal plexuses were suspended under tension in modified Krebs solution. DMPP (1-100 microM) produced concentration-dependent inhibition of circular muscle contractile activity and this effect was antagonized by L-nitroarginine methyl ester or L-nitroarginine (100 microM). Tetrodotoxin (TTX, 1 microM) significantly reduced mechanical responses to DMPP (10 microM) but had no effect on responses to high concentrations of DMPP (100 microM). Aliquots of the bathing medium were assayed for NOx after regeneration of NO from NO2- and/or NO3-. NO was measured as chemiluminescence produced by reaction with ozone. Detection was linear over the range 6-25,000 pmol of added NO2- or NO3-. In the absence of drugs, a basal release of 1113.5 +/- 100.4 pmol NOx/g tissue (n = 27) was detected after a 30-min incubation period. DMPP (1-100 microM) stimulated a concentration-dependent increase in NOx to 5099.9 +/- 430 pmol/g per 30 min (n = 17) at 100 microM. NOx release was inhibited by an inhibitor of nitric oxide synthase activity (N(G)-monomethyl-L-arginine) or by reduction in extracellular Ca2+ concentration. DMPP-stimulated NOx accumulation was significantly reduced, but not abolished by TTX (1 microM). These results provide further evidence that NO is released following stimulation of intrinsic neurons in canine proximal colon and support previous suggestions that nicotinic agonists may directly stimulate terminals of NO-releasing neurons.

Animals↗
PubMed1995

c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract.

In vivo injection of a neutralizing, monoclonal antibody (ACK2) to the receptor tyrosine kinase (c-kit) disrupts the normal motility patterns of the mouse small intestine. Immunohistochemical studies showed that cells expressing c-kit-like immunoreactivity (c-kit-LI) decreased in numbers in response to ACK2, but the identity of these cells is unknown. We investigated the identity and development of the cells that express c-kit-LI in the mouse small intestine and colon. Cells in the region of the myenteric plexus and deep muscular plexus of the small intestine and in the subserosa, in the myenteric plexus region, within the circular and longitudinal muscle layers, and along the submucosal surface of the circular muscle in the colon were labeled with ACK2. The distribution of cells that express c-kit-LI was the same as that of interstitial cells (ICs). In whole-mount preparations cells with c-kit-LI were interconnected, forming a network similar to the network formed by cells that stained with methylene blue, which has been used as a marker for ICs in the mouse gastrointestinal tract. Immunocytochemistry verified that ICs were labeled with ACK2. Multiple injections of animals with ACK2 between days 0 and 8 post partum (pp) caused a dramatic reduction in the number of ICs compared to control animals. From an ultrastructural point of view, the proliferation and development appeared to be suppressed in some classes of ICs, while others displayed an altered course of development. Functional studies showed that the decrease in ICs was accompanied by a loss of electrical rhythmicity in the small intestine and reduced neural responses in the small bowel and colon. Morphological experiments showed that c-kit-positive cells are ICs, and physiological evidence reinforced the concept that ICs are involved in generation of rhythmicity and translation of neural inputs in gastrointestinal smooth muscles. Controlling the development of ICs provides a powerful new tool for the investigation of the physiological role of these cells.

Animals↗
PubMed1995

Recycling of L-citrulline to sustain nitric oxide-dependent enteric neurotransmission.

Neurons that synthesize nitric oxide from arginine produce stoichiometric amounts of citrulline. We investigated whether nitric oxide-releasing enteric neurons have the capacity to recycle citrulline to arginine and thereby sustain nitrergic neurotransmission. Argininosuccinate synthetase-like immunoreactivity and argininosuccinate lyase-like immunoreactivity, enzymes capable of citrulline to arginine conversion, were both localized in discrete populations of myenteric and submucosal neurons in the canine proximal colon. Argininosuccinate synthetase-like immunoreactivity and argininosuccinate lyase-like immunoreactivity co-localized with neuronal beta-nicotinamide adenine dinucleotide phosphate diaphorase staining, a marker for nitric oxide synthase. The functional significance of argininosuccinate synthetase-like immunoreactivity and argininosuccinate lyase-like immunoreactivity was shown by testing the effects of exogenous citrulline on responses to enteric inhibitory nerve stimulation, which were assessed by measuring contractions, inhibitory junction potentials and electrical slow waves. As shown previously, arginine analogues (L-nitroarginine methyl ester or L-nitroarginine; 100 microM) inhibited nitric oxide-dependent responses, and excess L-arginine restored inhibitory responses. Citrulline alone (0.1-2 mM) had no effect on nitrergic transmission under control conditions, but in the presence of L-nitroarginine methyl ester or L-nitroarginine, citrulline (0.1-2 mM) restored nitrergic transmission in a concentration-dependent manner. Other neutral amino acids (L-serine, L-leucine) did not mimic the effects of citrulline. Taken together, these data suggest that enteric nitrergic neurons have the enzymatic apparatus and functional capability of recycling citrulline to arginine.

Animals↗
PubMed1995

Role of Ca(2+)-activated K+ channels in electrical activity of longitudinal and circular muscle layers of canine colon.

The role of Ca(2+)-activated K+ channels (BK channels) in the canine colon was evaluated by testing the effects of charybdotoxin (ChTX) and tetraethylammonium on K+ currents of isolated myocytes and on electrical and mechanical activity of tissue strips. ChTX blocked Ca(2+)-activated outward current [IK(Ca)] in a dose- and voltage-dependent manner. No significant differences in IK(Ca) density, ChTX block, or Ca2+ sensitivity of BK channels were observed between circular and longitudinal myocytes. ChTX (100 nM) blocked 60% of current at +80 mV. Delayed rectifier current was not inhibited by 100 nM ChTX. In the absence of agonists, ChTX did not affect electrical or mechanical activity of circular muscle strips. In the presence of 10(-6) M BAY K 8644 or 10(-6) M acetylcholine, ChTX increased slow-wave duration and amplitude, induced membrane potential oscillations, and potentiated contraction. In unstimulated longitudinal muscle strips, ChTX depolarized the tissue, increased burst duration and spiking frequency, and resulted in an increase in contractions. These results indicate that BK channels are important regulators of colonic motility. In the longitudinal layer, BK channels are involved in setting membrane potential and determine excitability. In the circular layer, ChTX-sensitive channels do not participate in the in vitro basal electrical activity but limit the responses to excitatory agonists.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Tachykinins activate nonselective cation currents in canine colonic myocytes.

The mechanism of tachykinin-induced excitation was studied in isolated colonic muscle cells and intact muscle strips. In whole cell voltage-clamp studies performed at 33 degrees C, neurokinin A (NKA) and substance P (SP) reduced L-type Ca2+ current. NKA and SP activated a cationic current that reversed near 0 mV. This current (INKA or ISP, respectively) had properties similar to the acetylcholine (ACh)-activated nonselective cation conductance (IACh), activated by muscarinic stimulation in other gastrointestinal smooth muscle cells. INKA and ISP were decreased when external Na+ was reduced. In contrast to IACh, INKA and ISP were not facilitated by increases in internal Ca2+, but little or no current was activated by these peptides when extracellular Ca2+ was low. INKA (10(-7) M) and ISP (10(-5) M) were blocked by Cd2+ (5 x 10(-4) M), quinine (10(-3) M), and the tachykinin-receptor antagonist [D-Pro2,D-Trp7,9]SP (10(-5) M). Current clamp recordings and intracellular recordings of intact tissues showed that NKA and SP depolarized the cell membrane, which is consistent with the activation of a nonselective cation conductance. These data suggest that a primary mechanism of the tachykinins is to activate a nonselective cation conductance that leads to depolarization. The increase in Ca2+ entry due to tachykinin stimulation appears to be secondary to the activation of the nonselective cation conductance.

Acetylcholine↗
PubMed1995

Impaired development of interstitial cells and intestinal electrical rhythmicity in steel mutants.

Electrical rhythmicity in the gastrointestinal tract may originate in interstitial cells of Cajal (IC). Development of IC in the small intestine is linked to signaling via the tyrosine kinase receptor, c-kit. IC express c-kit protein, and disruption of c-kit signaling causes breakdown in IC networks and loss of slow waves. We tested whether mutations in steel factor, the ligand for c-kit, affect the development of IC networks. IC were found in the region of the myenteric plexus (IC-MY) in mice with steel mutations (i.e., Sl/Sld) at 5-10 days postpartum, but these cells formed an abnormal network. IC-MY were not observed in adult Sl/Sld animals. IC in the deep muscular plexus (IC-DMP) appeared normal in Sl/Sld animals. Electrical slow waves, normally present in the small intestine, were absent in Sl/Sld animals (10-30 days postpartum). Neural inputs were intact in Sl/Sld animals. Steel factor appears important for the development of certain classes of IC, and IC-MY appear to be involved in the generation of electrical rhythmicity in the small intestine.

Animals↗
PubMed1995

Changes in enteric neural regulation of smooth muscle in a rabbit model of small intestinal inflammation.

In vitro electrophysiological studies of ileal circular muscle from rabbits with ricin-induced inflammation were performed to investigate whether altered neural control or myogenic activity contributes to previously described changes in in vivo myoelectric activity. Ricin treatment increased mean slow-wave amplitude but not frequency or resting membrane potential. Prolonged electrical field stimulation evoked a hyperpolarization during the stimulus train and a depolarization on cessation of stimulation. In the presence of atropine, the depolarization was larger in ricin-treated tissue than in control tissue, showing that ileitis enhanced noncholinergic excitation. The nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester reduced the hyperpolarization in ricin-treated but not in control tissue, suggesting that inflammation increased nitric oxide-mediated inhibition. Substance P desensitization reduced noncholinergic excitation and mean slow-wave amplitude only in ricin-treated tissue, demonstrating that changes in these parameters during inflammation resulted from increased release of, or sensitivity to, tachykinins. These data suggest that acute ileitis alters tachykinin- and nitric oxide-mediated neurotransmission that may affect the normal pattern of ileal motility and/or sensory reflexes.

Animals↗
PubMed1994

Block by 4-aminopyridine of a Kv1.2 delayed rectifier K+ current expressed in Xenopus oocytes.

1. The blocking action of 4-aminopyridine (4-AP) on a delayed rectifier Kv1.2 K+ channel expressed in oocytes was investigated at room temperature (22 degrees C) and physiological temperature (34 degrees C) using the double-electrode voltage clamp and patch clamp techniques. 2. At room temperature, 4-AP (100 microM) inhibition occurred only after activation of current. The rate of onset of block was dependent upon the length of time current was activated by a depolarizing step. Similarly, removal of block required current activation. The degree of steady-state block by 4-AP was not reduced by increasingly more depolarized step potentials. The degree of steady-state block also did not change over the duration of a 1 s step. 3. When channels were nearly fully inactivated, 4-AP produced no additional block of a subsequent depolarizing step, suggesting that 4-AP did not bind when channels were in the inactivated state. In single channel experiments, 4-AP decreased the mean open time in a dose-dependent manner but did not alter the single-channel current amplitude. 4. At 34 degrees C the I-V relationship and inactivation curve shifted to more negative potentials. Increasing the temperature to 34 degrees C did not alter the degree of block by 4-AP, although the rate of onset of block was greatly enhanced. 5. Results suggest that 4-AP binds to the open state of the Kv1.2 channel and is trapped when the channel closes. 4-AP cannot bind when the channel is closed or inactivated prior to the addition of the drug. C-type inactivation and 4-AP binding to the channel are mutually exclusive. A model for the proposed mechanism of action of 4-AP on the Kv1.2 channel is proposed based on experimental data.

4-Aminopyridine↗
PubMed1994

Sensitization of the contractile system of canine colonic smooth muscle by agonists and phorbol ester.

1. Sensitization of the contractile system in response to combinations of excitatory agonists acetylcholine (ACh), methacholine, histamine and neurokinin A (NKA) was investigated in colonic circular smooth muscle of dog, NKA (1 nM) potentiated the contractile response to 1 microM ACh, but did not increase the fura-2 fluorescence ratio (R340/380). Contraction in response to low concentrations of either methacholine or histamine was potentiated significantly by 0.1 microM 4-phorbol 12,13-dibutyrate (PDBu), suggesting that activation of protein kinase C can potentiate contraction at threshold concentrations of agonists. 2. Variability in the sensitivity of the contractile system to Ca2+ was demonstrated over a range of agonist concentrations. KCl, ACh, histamine and NKA each produced a concentration-dependent increase in the amplitude of phasic contractions and R340/380. However, ACh, histamine and NKA each induced maximal increases in R340/380 at concentrations less than that needed to induce maximum force. 3. In depolarized muscles, NKA (50 nM) and PDBu (1 microM) each increased the magnitude of tonic contraction with no change or a decrease in both R340/380 and myosin light chain phosphorylation. In alpha-toxin-permeabilized fibres, 0.1 microM PDBu and 1 microM NKA shifted the Ca(2+)-force response to the left. Ca(2+)-induced contractions were also potentiated by 100 microM GTP-gamma-S or 1 microM NKA plus 10 microM GTP. Potentiation of contraction by NKA and GTP was antagonized by 10 microM GDP-beta-S. 4. The results suggest that endogenous agonists acting via G-proteins sensitize the contractile element of colonic smooth muscle in part by activation of protein kinase C. In some cases, sensitization may be secondary to increased myosin phosphorylation (ACh), but in other cases it appears to be independent of increased myosin light chain phosphorylation (NKA and PDBu). Therefore regulatory mechanisms in addition to myosin phosphorylation contribute to the apparent sensitization of the contractile system to Ca2+.

Acetylcholine↗
PubMed1994

Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine.

1. Interstitial cells of Cajal (ICs) have been proposed as pacemakers in the gastrointestinal tract. We studied the characteristics and distribution of ICs and electrical activity of small intestinal muscles from mice with mutations at the dominant-white spotting/c-kit (W) locus because the tyrosine kinase function of c-kit may be important in the development of the IC network. 2. W/WV mutants (days 3-30 postpartum) had few ICs in the myenteric plexus region compared with wild type (+/+) siblings. The few ICs present were associated with neural elements and lay between myenteric ganglia and the longitudinal muscle layer. 3. Electrical recordings from intestinal muscle strips showed that electrical slow waves were always present in muscles of +/+ siblings, but were absent in W/WV mice. 4. Muscles from W/WV mice responded to stimulation of intrinsic nerves. Neural responses, attributed to the release of acetylcholine, nitric oxide and other unidentified transmitters, were recorded. 5. These findings are consistent with the hypothesis that ICs are a critical element in the generation of electrical rhythmicity in intestinal muscles. The data also show that neural regulation of gastrointestinal muscles can develop independently of the IC network. 6. W locus mutants provide a powerful new model for studies of the physiological role of ICs and the significance of electrical rhythmicity to normal gastrointestinal motility.

Animals↗
PubMed1994

Identification and classification of interstitial cells in the canine proximal colon by ultrastructure and immunocytochemistry.

The ultrastructure and immunocytochemistry of interstitial cells (ICs) in the canine proximal colon were investigated. Three types of ICs were found within the tunica muscularis. (1) ICs were located along the submucosal surface of the circular muscle (IC-SM). These cells shared many features of smooth muscle cells, including myosin thick filaments and immunoreactivity to smooth muscle gamma actin, myosin light chain, and calponin antibodies. IC-SM were clearly different from smooth muscle cells in that contractile filaments were less abundant and intermediate filaments consisted of vimentin instead of desmin. (2) ICs in the region of the myenteric plexus (IC-MY) were similar to IC-SM, but these cells had no thick filaments or immunoreactivity to smooth muscle gamma actin or calponin antibodies. (3) The fine structures and immunoreactivity of ICs within the muscle layers (IC-BU) were similar to IC-MY, but IC-BU lacked a definite basal lamina and membrane caveolae. IC-BU and IC-MY were both immunopositive for vimentin. Since all ICs were immunopositive for vimentin, vimentin antibodies may be a useful tool for distinguishing between ICs and smooth muscle cells. Each class of ICs was closely associated with nerve fibers, made specialized contacts with smooth muscle cells, and formed multicellular networks. A combination of ultrastructural and immunocytochemical techniques helps the identification and classification of ICs by revealing the fine structures and determining the "chemical coding" of each class of ICs.

Actins↗
PubMed1994

Localization of nitric oxide synthase in canine ileocolonic and pyloric sphincters.

The distribution of neurons containing NAD-PH-diaphorase (NADPH-d) activity and nitric oxide synthase-like immunoreactivity (NOS-LI) in the canine pyloric and ileocolonic sphincters was studied. Cells within the myenteric and submucosal ganglia were positive for NADPH-d. These cells generally had the morphology of Dogiel type-I enteric neurons, however, there was some diversity in the morphology of NADPH-d-positive neurons in the myenteric plexus of the pylorus. Intramuscular ganglia were observed in both sphincters, and NADPH-d was found in a sub-population of neurons within these ganglia. Dual staining with an antiserum raised against nitric oxide synthase (NOS) demonstrated that almost all cells with NOS-LI were also NADPH-d positive. Varicose fibers within ganglia and within the circular and longitudinal muscle layers also possed NOS-LI and NADPH-d activity. Dual staining with anti-VIP antibodies showed that some of the NADPH-d-positive cells in the myenteric and submucosal ganglia also contained VIP-LI, but all VIP-LI-positive cells did not express NADPH-d activity. These data are consistent with recent physiological studies suggesting that nitric oxide serves as an inhibitory neurotransmitter in the pyloric and ileocolonic sphincters. The data also suggest that VIP is expressed in a sub-population of NADPH-d-positive neurons and may therefore act as a co-transmitter in enteric inhibitory neurotransmission to these specialized muscular regions.

Amino Acid Oxidoreductases↗
PubMed1994

Excitation-contraction coupling in gastric muscles.

Several mechanisms contribute to the regulation of force generated by gastric muscles. Phasic contractions in the stomach are triggered by the propagation of electrical slow waves. These events are associated with an influx of Ca2+ and an increase in intracellular Ca2+ sufficient to elicit contraction. Entry of Ca2+ may be supplemented by the release of Ca2+ from intracellular stores. Excitatory agonists enhance the amplitude of slow waves, increase the amplitude of Ca2+ transients, and increase the force of phasic contractions. Inhibitory agonists have opposite effects. Excitatory agonists may also enhance release of Ca2+ from stores via the production of IP3. Excitatory and inhibitory agonists may also regulate the sensitivity of the contractile apparatus for Ca2+ and therefore alter the contractile response to a given change in intracellular Ca2+.

Animals↗
PubMed1994

Anti-proliferative effects of deflazacort on Nb2 cells as quantitated by formazan production.

Prolactin and other lactogenic hormones are mitogenic for the rat T-cell lymphoma line, Nb2. Glucocorticoids have antiproliferative effects on these cells. A limiting feature of experiments utilizing the Nb2 line is their labor-intensive nature. We therefore adapted the commonly used MTT dye proliferation assay for the Nb2 cell line. While rPRL, hPRL, oPRL, hGH, bPL, and to a lesser extent bPRL stimulated the Nb2 cells, hormones without lactogenic activity, rGH and oGH did not. Human serum and rat sera from animals bearing a PRL-secreting tumor stimulated the Nb2 cells in parallel to standards. Glucocorticoids had anti-proliferative effects on Nb2 cells in the presence of half-maximal or maximal PRL doses, as measured by the MTT proliferation assay. It has been claimed that an oxazoline steroid, deflazacort, has anti-inflammatory effects in clinical studies with fewer of the deleterious side-effects common to glucocorticoids. We therefore compared the in vitro anti-proliferative effects of deflazacort with other glucocorticoids. Deflazacort's negative effect on Nb2 cell proliferation was similar to that of cortisol and prednisolone and less than that of dexamethasone. We conclude that the MTT proliferation assay can be used to study both mitogenic and anti-proliferative substances in Nb2 cells. In addition we found that deflazacort acts similarly in vitro to other glucocorticoids.

Animals↗