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J R Walters

Publications and source records attributed to J R Walters.

At least 55 records · Page 3Linked to original sources
PubMed1995

Stability of itraconazole in an extemporaneously compounded oral liquid.

The stability of itraconazole in an extemporaneously compounded oral liquid formulation was studied. A suspension was prepared from the beads contained in commercially available 100-mg itraconazole capsules and sufficient Simple Syrup, NF, to make a final volume of 60 mL. The final concentration of itraconazole in the suspension was 40 mg/mL. Three identical volumes of each suspension were prepared and stored in 2-oz capped, amber glass prescription bottles and refrigerated at 4 degrees C (range, 2-6 degrees C). Immediately after preparation and at 7, 14, 21, 28, and 35 days, samples were visually inspected and assayed in duplicate by high-performance liquid chromatography; the pH of the samples was also determined. On day 35, the mean +/- S.D. percentage of initial itraconazole concentration remaining in the three suspensions was 95.3 +/- 2.2%. The color, odor, and pH of the samples did not change appreciably over the study period. Itraconazole 40 mg/mL in an oral liquid compounded from simple syrup and beads from capsules, stored in amber glass bottles, was stable for 35 days at 4 degrees C.

Administration, Oral↗
PubMed1995

In vivo characterization of two cell types in the rat globus pallidus which have opposite responses to dopamine receptor stimulation: comparison of electrophysiological properties and responses to apomorphine, dizocilpine, and ketamine anesthesia.

Extracellular single-unit recording techniques were used to examine the rat globus pallidus (GP). In both locally anesthetized, paralyzed rats and ketamine-anesthetized rats, we observed two distinct biphasic extracellular waveforms, which we have labeled Type I (negative/positive waveform) and Type II (positive/negative waveform). No significant differences were observed in the firing pattern or number of cells per track between these cell types, although the Type II neurons had a faster mean firing rate in the locally anesthetized animals. A portion of both cell types could be antidromically activated from the subthalamic nucleus, although Type II neurons had significantly slower conduction velocities. The most striking pharmacological difference between the two cell types was that Type I GP neurons were inhibited by systemic administration of the dopamine agonist apomorphine; previous studies have repeatedly shown that Type II GP cells are excited by this treatment. Pretreatment with a subthreshold dose of apomorphine reduced the responsiveness of Type I cells to a subsequent high dose of apomorphine, as has been shown for Type II cells. However, pretreatment with the NMDA antagonist dizocilpine (MK801) produced a significant change in the pattern of response to apomorphine for Type II GP neurons only. Relative to observations in locally anesthetized, paralyzed rats, ketamine anesthesia reduced the firing rate of both cell types, but did not significantly alter their direction of response to apomorphine. Thus, this study has confirmed the existence of two GP cell types with distinct extracellular waveforms and different responses to dopamine receptor stimulation. These data may necessitate a reevaluation of general theoretical models of basal ganglia function in order to account for these opposite effects of dopamine receptor stimulation on pallidal output.

Anesthesia↗
PubMed1995

Detection of low bone mineral density by dual energy x ray absorptiometry in unsuspected suboptimally treated coeliac disease.

Patients with coeliac disease may present with calcium malabsorption but it is unclear whether this results in longterm impairment of bone mineralisation. Dual energy x ray absorptiometry (DXA) was used to study bone mineral density in 34 asymptomatic coeliac disease patients, treated with a gluten free diet for at least two years, and also in 10 newly diagnosed or untreated patients. As expected, untreated patients had low bone mineral density in all regions. In the 29 treated female coeliac disease patients, overall mean values for age adjusted bone mineral density expressed as Z scores were normal although there were many patients with low values, particularly of the lumbar spine and total body. Scores in the postmenopausal patients were significantly worse than in the premenopausal patients and low mean Z scores were found in the five treated male patients. The subjects who had reduced bone mineral density could not be predicted clinically but, despite being asymptomatic, were more likely to have subtotal or partial villous atrophy on small intestinal biopsy (p < 0.0275). In conclusion, although many treated coeliac disease patients have normal bone mineral density, suboptimally treated and newly diagnosed or untreated patients have osteopenia. To reduce the risk of osteoporotic fractures, it is recommended that bone mineral density be measured in all treated coeliac disease patients and those with osteopenia have a repeat intestinal biopsy to assess disease activity.

Absorptiometry, Photon↗
PubMed1995

Cellular and regional expression of transcripts of the plasma membrane calcium pump PMCA1 in rabbit intestine.

The plasma membrane Ca(2+)-pumping adenosinetriphosphatase (PMCA) is the energy-dependent step in the active vitamin D-dependent absorption of dietary Ca2+ by the enterocyte. Studies of the various PMCA genes and splicing variants in humans and rats have indicated that the isoform known as PMCA1b is the predominant form expressed in small intestine. Using an oligonucleotide probe, we have studied the regional and cellular distribution of PMCA1 transcripts in rabbit intestinal tissues by in situ hybridization. On small intestinal RNA blots, this hybridized to species similar in size to those detected by PMCA1-specific cDNA probes; an additional larger transcript was present in rabbit than in rat or human. In situ hybridization signals were principally in the enterocyte population of the mucosa and were maximal in differentiating enterocytes on the lower part of the villus, a pattern similar to that previously demonstrated for other nutrient transporters. Reflecting the capacity of the different small intestinal segments to transport Ca2+, much higher levels of transcript were detected by both methods proximally (in duodenum) than distally (in jejunum and ileum) and were also higher in cecum and ascending colon mucosa than in descending colon. We conclude that as enterocytes differentiate in regions that absorb Ca2+, they express high levels of mRNA for PMCA1. These results confirm the importance of transcriptional regulation of this gene for active Ca2+ absorption.

Animals↗
PubMed1994

A role for non-NMDA excitatory amino acid receptors in regulating the basal activity of rat globus pallidus neurons and their activation by the subthalamic nucleus.

We have investigated the hypothesis that excitatory amino acid (EAA) receptors in the globus pallidus (GP) play a significant role in maintaining the firing rates of GP neurons under basal conditions and following activation of the subthalamic nucleus (STN). Drugs were infused directly into the GP and/or STN while the extracellular single unit activity of Type II GP neurons was recorded in ketamine-anesthetized rats. Local infusions of the EAA agonists NMDA (30-300 pmol/200 nl) or AMPA (0.1-1 pmol/200 nl) elicited increases in the firing rate of GP neurons in a dose-dependent fashion. Infusion of the GABAA receptor antagonist bicuculline methiodide (1-10 pmol/100 nl) into the STN also elicited dose-related increases in the firing rate of GP neurons. Intrapallidal infusion of the non-NMDA (AMPA/kainate) receptor antagonist NBQX (0.1-1.0 nmol) reduced the basal firing rate of GP neurons by 40%. In contrast, the NMDA antagonist MK-801 (0.01-0.1 nmol) produced no significant effect on basal firing rate. Intrapallidal infusion of the non-selective EAA receptor antagonist kynurenic acid or NBQX reversed or blocked the increase in firing rate of GP neurons following bicuculline-induced activation of the STN. Similar treatment with MK-801, however, had no significant effect on this response. These results indicate that tonic stimulation of non-NMDA receptors plays an important role in maintaining the basal activity of GP neurons and in mediating the effects of increased excitatory input from subthalamic afferent neurons.

Animals↗
PubMed1994

Plasma-membrane calcium-pump isoforms in human and rat liver.

Plasma-membrane Ca(2+)-pumping ATPases (PMCAs) extrude Ca2+ from the cytoplasm of all cells. Some previous studies of ATP-dependent Ca2+ transport by liver membranes suggested there exist specific properties of the hepatic PMCA, including regulation by hormones which affect calcium signalling. Multiple PMCA isoforms are now known to result from expression of four different genes (known as PMCA 1-4) and alternative RNA splicing at three possible sites (A, B and C). We investigated which isoforms are expressed in adult human and rat liver RNA using reverse-transcription polymerase chain reaction with mixed primers designed to amplify parts of all the known PMCA transcripts. In human liver, products were identified by sequencing from PMCA1, PMCA2 and PMCA4, but not from PMCA3 or from any new gene. In rat liver, by contrast, only PMCA1 and PMCA2 were detectable, although we confirmed that the primers were able to amplify from rat lung a new sequence which is part of rat PMCA4. Of the alternatively spliced variants, at site A in the PMCA2 sequences, all the exons were included in both adult and fetal human liver. In human liver, the exon at site B was excluded in some products from PMCA1 and PMCA4, and at site C, only PMCA1b and one form of PMCA4 were found. Blots of human liver RNA showed PMCA1 and PMCA4 were abundantly expressed, unlike PMCA2. On blots of rat liver RNA, PMCA1 was more abundant than PMCA2, and purified rat parenchymal cell RNA gave similar findings. In summary, no new hepatic PMCA isoforms have been demonstrated, but differences between the predominant human and rat isoforms may have consequences for Ca2+ signalling or the response to liver cell injury.

Adult↗
PubMed1994

Intracellularly recorded response of rat striatal neurons in vitro to fenoldopam and SKF 38393 following lesions of midbrain dopamine cells.

The effect of long-term (6-19 weeks) 6-hydroxydopamine-induced (6-OHDA) lesions of midbrain dopamine cells on dopamine D1-like agonist-induced changes in the excitability of rat striatal neurons was investigated in vitro using tissue slices and intracellular recording techniques. Fenoldopam and (+/-)-SKF 38393 predominantly decreased excitability in control preparations including striatal neurons located contralateral to 6-OHDA injection sites and neurons obtained from rats receiving sham injections or no treatment. Fenoldopam also inhibited neurons ipsilateral to lesions of midbrain dopamine cells. (+/-)-SKF 38393, unlike fenoldopam, produced predominantly increases in the excitability of ipsilateral striatal neurons. Superfusion of the D1 receptor antagonist, SCH 23390, blocked fenoldopam-induced decreases in excitability but not the (+/-)-SKF 38393-induced excitation of neurons ipsilateral to the lesion. Sequential application of fenoldopam and quinpirole, a D2/D3 receptor agonist, produced responses to both drugs in a majority of neurons. The results demonstrate that inhibitory responses to fenoldopam are mediated by D1 receptors, while excitatory effects of (+/-)-SKF 38393 in the striatum ipsilateral to the lesion are apparently not dependent on D1 receptor activation. These findings also suggest that dopamine D1 and D2/D3 receptors are able to concurrently influence the excitability of striatal neurons in the dopamine deafferentated striatum. Similar regulation of striatal neurons in vivo may contribute to dopaminergic regulation of basal ganglia output and the ability of dopaminomimetic agents to ameliorate symptoms of dopaminergic deficiency in Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Electrophysiological effects of SKF 38393 in rats with reserpine treatment and 6-hydroxydopamine-induced nigrostriatal lesions reveal two types of plasticity in D1 dopamine receptor modulation of basal ganglia output.

To examine the role of D1 dopamine receptors in modulating basal ganglia output and how this role may be altered by changes in dopaminergic transmission, the effects of a D1 dopamine agonist on firing rates of substantia nigra pars reticulata (SNpr) neurons were determined in reserpine-treated rats and compared with effects observed in nigrostriatal-lesioned and normal rats. It was confirmed that systemic administration of the D1 dopamine agonist SKF 38393 (10 mg/kg i.v.) induces a small (averaging 20% above base line) increase in firing rates of SNpr neurons in normal rats and significantly inhibits SNpr single unit activity in rats studied 6 to 26 weeks after 6-hydroxydopamine (6-OHDA)-induced substantia nigra dopamine cell lesion. In contrast to results obtained after 6-OHDA lesions, SKF 38393 administration consistently and significantly increased the firing rates of SNpr neurons in rats treated for 6 days with reserpine (1 mg/kg/day s.c.); increases averaged 88% above base line. Five days after the 6-day reserpine treatment was discontinued, administration of SKF 38393 still induced a pronounced increase in SNpr activity. These increases were reversed by the administration of the D1 dopamine antagonist SCH 23390. SKF 38393 also significantly increased the firing rates of a subpopulation of SNpr neurons in rats treated with only a single dose of reserpine (10 mg/kg s.c. 4-7 hr). The difference between responses in reserpine and 6-OHDA-treated rats was not due to the shorter time course of the reserpine treatments, as SKF 38393 did not consistently affect the activity of SNpr neurons 7 days after 6-OHDA nigral dopamine cell lesion. When the subchronic reserpine treatment was administered to rats lesioned previously with 6-OHDA, D1 dopamine agonist-mediated inhibition of SNpr neuronal activity was obtained. The results show that SNpr responses to D1 dopamine agonist administration after reserpine treatment are enhanced ("supersensitive") relative to normal, whereas SNpr responses to D1 dopamine agonists in animals with 6-OHDA-induced dopamine cell degeneration are opposite to those observed in normal and in reserpinized animals. Current models of basal ganglia function predict that D1 dopamine agonists should reduce activity in the SNpr, because D1 dopamine receptors on striatonigral neurons are thought to stimulate striatonigral firing rates and to enhance the release of tau-aminobutyric acid in the SNpr. The present results call for modification of these concepts.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Electrophysiological characterization of rat striatal neurons in vitro following a unilateral lesion of dopamine cells.

The effects of a unilateral 6 to 19-week lesion of dopamine cells on the excitability of rat striatal neurons were investigated in vitro using the intracellularly recorded membrane properties of neurons obtained ipsilateral and contralateral to 6-hydroxydopamine (6-OHDA) injection sites. Neurons ipsilateral to the lesion site and in striatal tissue depleted of dopamine exhibited resting membrane potentials and membrane resistances similar to those recorded in contralateral striatal neurons. Denervation appeared to have no appreciable effect on the proportion of neurons exhibiting various patterns of neuronal spiking (repetitive, bursting, or single spike) evoked by depolarizing current pulses. Current-voltage determinations revealed nominal rectification in the majority of neurons and marked nonlinearity consistent with inward rectification at potentials hyperpolarized and depolarized to rest in a large proportion of the remaining neurons. Neurons ipsilateral to 6-OHDA lesion sites exhibited these relationships in the same proportion as contralateral control cells. However, ipsilateral neurons with nominal rectification exhibited an average rate constant for the early onset of small hyperpolarizing membrane transients which was significantly smaller than that of controls. This finding suggests that intrinsic membrane parameters regulating the excitability of certain striatal neurons may be under the influence of dopamine or other factors closely associated with nigrostriatal nerve terminals.

Animals↗
PubMed1993

Calretinin and calbindin-D28k immunoreactivity in the human gastrointestinal tract.

BACKGROUND: Calretinin and calbindin-D28k are similar Ca(2+)-binding proteins previously described in specific central neurons and other cells. METHODS: The immunocytochemical distribution of these two proteins was studied in the human gastrointestinal tract. RESULTS: In gastric and small intestinal endocrine cells, calbindin-D28k immunoreactivity was confirmed, but calretinin immunoreactivity was not found. Nerve cell bodies in both submucous and myenteric ganglia were immunoreactive for calbindin (13% and 38% of total cells, respectively) or calretinin (23% and 21%), some containing both proteins. In nerve processes, calretinin was generally more abundant than calbindin and was found particularly around blood vessels. Calretinin co-localized with immunoreactive vasoactive intestinal peptide, neuropeptide Y, galanin, or substance P in submucous ganglion cells and with substance P in myenteric cells. Calbindin-D28k colocalized with fewer peptides, specifically vasoactive intestinal peptide or galanin in submucous cells. By 8 weeks of fetal development, discrete neuronal localizations for both proteins and for calbindin-D28k in endocrine cells were apparent. CONCLUSIONS: In the enteric neuroendocrine system, calretinin and calbindin-D28k are useful markers that may help elucidate Ca(2+)-mediated functions in health and disease.

Adult↗
PubMed1993

Behavioral and electrophysiological comparison of ketamine with dizocilpine in the rat.

We have compared the effects of MK 801 and ketamine on a measure of anesthesia (loss of righting reflex) and two measures of basal ganglia dopamine (DA) function: apomorphine (APO)-induced stereotypy and APO-induced excitation of type II globus pallidus (GP) neurons. As expected, ketamine induced anesthesia. High-dose MK 801 administered IP induced ataxia, but not anesthesia. When administered i.v., high-dose MK 801 induced anesthesia in only three of five rats. Using a modified stereotypy scale, it was found that pretreatment with MK 801 blocked APO-induced stereotypic sniffing. Intravenous ketamine also blocked APO-induced stereotypy, but IP ketamine did not. Similar results were observed in neurophysiological studies; MK 801 altered the excitation of type II GP neurons by APO. Intravenous ketamine (5 mg/kg) also altered the responsiveness of these cells to APO, but ketamine anesthesia (150 mg/kg, IP) had no effect. These findings suggest that MK 801 is not an effective anesthetic in rats, and the method of administration of ketamine plays a role in its ability to exert NMDA receptor blockade.

Animals↗
PubMed1993

Human and rat intestinal plasma membrane calcium pump isoforms.

The intestinal basolateral membrane Ca(2+)-transporting adenosinetriphosphatase is the energy-dependent step in the absorption of dietary Ca2+ by the vitamin D-dependent transcellular pathway. Multiple plasma membrane Ca(2+)-pump isoforms are produced from four genes (PMCA1 to 4) and alternative mRNA splicing. We have studied which isoforms are detectable in adult human and rat gastrointestinal tissues by polymerase chain reaction (PCR) amplification, sequencing, and blotting. PMCA1 was the predominant gene product amplified from human small intestinal mucosa, although a minor additional variant lacking the exon at splice site B was detected, which resembled that described for PMCA4. Of the variants described at site C, only the shortest transcript of PMCA1 was amplified; both previously described forms of PMCA4 were found, particularly in colon where PMCA4 predominated. From rat intestinal cDNA, mixed primer PCR amplified PMCA1 and a novel sequence, the rat PMCA4 homologue, which was expressed in many tissues including small intestinal muscle and colon. However, PMCA1 was overwhelmingly predominant in the mucosa of the small intestine, being most abundant in duodenum. These results suggest the involvement of the Ca(2+)-pump isoform PMCA1b in intestinal Ca2+ absorption.

Amino Acid Sequence↗
PubMed1992

Molecular cloning and chromosomal assignment of human calbindin-D9k.

Human calbindin-D9k, the vitamin D-dependent calcium binding protein, has been cloned and sequenced following initial amplification of intestinal cDNA sequences by the polymerase chain reaction using mixed oligonucleotide primers. The derived amino acid sequence of 79 residues has a calculated molecular weight of 9015 and is 89% homologous with the bovine and porcine sequences. Probing DNA from human-rodent somatic cell hybrids mapped human calbindin-D9k to chromosome Xp. A single abundant mRNA transcript was detectable in proximal small intestine but not in kidney, uterus or placenta.

Amino Acid Sequence↗
PubMed1992

Plasma membrane calcium pump expression in human placenta and small intestine.

To identify the forms of the plasma membrane calcium pump present in tissues that transport calcium, cDNA from human placenta and proximal small intestine was amplified by the polymerase chain reaction using a pair of mixed primers based on all the known human and rat plasma membrane calcium pump sequences. Clones were identified from the two human forms HPMCA1 and HPMCA4, but no new sequences were found in either tissue. RNA blots probed with HPMCA1 showed two bands in both tissues; probing with HPMCA4 gave a single, larger species. In placenta, HPMCA4 was the more abundant form and similar expression was found in full-term and second-trimester placentas. In contrast, in the small intestine, HPMCA1 was more abundant, suggesting that calcium absorption is not associated with any one specific isoform in calcium transporting cells.

Amino Acid Sequence↗
PubMed1992

Lichen planus associated with chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution.

A patient who developed lichen planus while receiving chenodeoxycholic acid and ursodeoxycholic acid therapy for gallstones is described. Skin biopsy was performed and histological examination suggested a drug etiology. An association between lichen planus and liver disease is recognized, but this patient exhibited no clinical or biochemical evidence of liver disease and the rash disappeared after cessation of the bile acid therapy. Bile acids may cause lichen planus. The mechanism is unknown.

Aged↗
PubMed1992

Apomorphine-induced changes in striatal and pallidal neuronal activity are modified by NMDA and muscarinic receptor blockade.

Systemic administration of apomorphine decreased the firing rate of caudate Type I neurons and increased the firing rate, presumably via disinhibition (16), of globus pallidus (GP) Type II neurons. In the present study, extracellular single-unit recording techniques were used to demonstrate that systemic administration of the NMDA antagonist dizocilpine (MK801) reduced both the inhibition of caudate neurons by apomorphine as well as the apomorphine-induced excitation of GP neurons. In addition, the muscarinic antagonists atropine and scopolamine had effects similar to dizocilpine. Thus, both glutamate and acetylcholine appear to play a role in dopaminergic modulation of striatal and GP activity.

Acetylcholine↗