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Biomedical subjects

A Bond

Publications and source records attributed to A Bond.

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

Pharmacology of metabotropic glutamate receptor-mediated enhancement of responses to excitatory and inhibitory amino acids on rat spinal neurones in vivo.

Using the technique of microelectrophoresis on spinal neurones in pentobarbitone-anaesthetized rats, (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylate (1S,3R-ACPD) reversibly and dose-dependently enhanced responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), kainate, N-methyl-D-aspartate (NMDA) and L-glutamate to a similar extent. 1S,3R-ACPD also enhanced inhibitory responses to both glycine and gamma-aminobutyrate (GABA). Such results are consistent with a metabotropic glutamate receptor-mediated decrease in membrane conductance. 1S,3R-ACPD was the most active metabotropic agonist tested for these effects; the rank order of activity was: 1S,3R-ACPD > or = (2S,3S,4S)alpha-(carboxycyclopropyl)-glycine(L-CCG-l) > (R, S)-3,5-dihydroxy-phenylglycine (3,5-DHPG) > (S)-homoquisqualate > quisqualate = 1S,3S-ACPD > L-2-amino-4-phosphonobutyrate (L-AP4) > 1R,3S-ACPD. These effects of 1S,3R-ACPD were antagonized by (RS)-alpha-methyl-4-carboxy-phenylglycine (M4CPG) and (S)-4-carboxy-3-hydroxy-phenylglycine (4C3HPG) but not by (S)-4-carboxy-phenylglycine (4CPG) or L-amino-3-phosphono-propionate (L-AP3). The pharmacology of the actions of mGluR agonists and antagonists on rat spinal neurones in vivo does not obviously correlate with the published pharmacology of a single cloned metabotropic glutamate receptor subtype but rather suggests that both Group 1 and 2 receptors contribute to the above effects.

Amino Acids↗
PubMed1995

Changes in neuronal markers in a mononeuropathic rat model relationship between neuropeptide Y, pre-emptive drug treatment and long-term mechanical hyperalgesia.

Using the chronic constriction model (CCI) of Bennett and Xie (1988), changes in the lumbar spinal cord in neuropeptides and lectin IB4 were examined at 28 days post-nerve constriction and were compared with the degree of mechanical hyperalgesia. Animals following nerve ligation were significantly more hyperalgesic than sham-operated animals (P < 0.0001). Lectin IB4, a marker of primary afferent C fibres, showed a qualitative decrease in staining intensity in laminae 1-2 with ligation compared with both the unoperated contralateral side and with sham animals. Using fluorescent immunohistochemistry to quantify changes in neuropeptides in the dorsal horn we found that substance P showed significant decreases with ligation compared to sham operation (P < 0.002). CGRP and galanin showed no significant changes in laminae 1-2 compared to sham-operated animals. Neuropeptide Y (NPY) showed no significant changes in intensity in laminae 1-2; however, in laminae 3-4 there was a significant increase with nerve ligation compared to sham (P < 0.005). We examined how pre-emptive drug treatment affected these neuronal markers at 28 days. We used (1) clonidine, an alpha 2-adrenoreceptor agonist (1 mg/kg, i.p.), (2) morphine, a mu-opioid agonist (5 mg/kg, i.p.) or (3) MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist (0.3 mg/kg, s.c.) administered 30 min prior and 6 h following nerve ligation or sham-operation. Hyperalgesia in the ligated group at 28 days was suppressed by treatment with pre-emptive clonidine (P = 0.003) or MK-801 (P = 0.003) but not morphine. With the exception of NPY there was no effect of pre-emptive drug treatment on any neuronal marker examined. Pre-emptive MK-801 reduced the magnitude of the increase in NPY in laminae 3-4 in the ligated group (P < 0.005) and clonidine showed a similar trend but this did not reach significance. Morphine had no effect on NPY staining. There was a significant correlation between the increase in NPY staining in laminae 3-4 and the degree of hyperalgesia (r = 0.6, P < 0.001). These results suggest that the increased NPY expression in laminae 3-4 of the spinal cord (the territory of the myelinated sensory input) may be crucial to the development of hyperalgesia in this model.

Analgesics↗
PubMed1995

Hysterectomy and psychiatric disorder: are the levels of psychiatric morbidity falling?

This paper compares the findings of three studies carried out at intervals over the years 1975-1990. The three studies were concerned with different issues, but each study examined psychiatric morbidity among women undergoing hysterectomy for menorrhagia of benign origin. In all three studies levels of psychiatric morbidity were measured before the operation and 6 months after the operation. Psychiatric morbidity was measured with the Present State Examination (PSE) (Wing et al. 1974), and with established self-report questionnaires. Levels of psychiatric morbidity fell significantly across the three studies. In Study 1, the proportions of psychiatric cases were 58% before hysterectomy and 26% after; in Study 2, 28% before and 7% after; and in Study 3, 9% before and 4% after. The decline in psychiatric morbidity was not associated with demographic and social characteristics, previous psychiatric history, family psychiatric history, the nature of the women's menstrual complaints, or the women's understanding and expectations of the operation. In Study 3 anti-menorrhagic drugs were prescribed twice as frequently as in the two previous studies; while the prescribing of psychotropic medication was significantly higher in Study 1 than in Study 2 or Study 3. The implications of these findings are discussed.

Adaptation, Psychological↗
PubMed1994

Memory functions, alprazolam and exposure therapy: a controlled longitudinal study of agoraphobia with panic disorder.

Benzodiazepines (BZs) produce transient anterograde amnesia when given to normal subjects. The present longitudinal study assessed whether BZs impair memory functions in a clinically anxious group. Eighty-two agoraphobics with panic disorder were randomly allocated to one of four treatment groups resulting from a combination of two drug treatments (alprazolam or placebo) and two psychological treatments (exposure or relaxation). Of these, 38 subjects were assessed on a range of objective and subjective indices of memory and mood at three time points: before treatment, after 8 weeks of treatment and again at 24 weeks when patients had been free of medication from 5-8 weeks. Alprazolam produced pronounced impairments on a word recall task. At the 24-week medication-free follow-up, alprazolam patients were still impaired on the task compared with placebo patients. Alprazolam did not impair performance on an implicit memory task and did not affect digit span. Differences between psychological treatments emerged mainly in subjective memory effects. Findings are discussed in terms of the specificity of BZ-induced amnesia and differential tolerance to the varying effects of BZs. Implications are drawn out for the patient's ability to function optimally in daily life while taking alprazolam.

Adult↗
PubMed1994

Cancer and noncancer risk to women in agriculture and pest control: the Agricultural Health Study.

The Agricultural Health Study is a collaborative effort involving the National Cancer Institute, the US Environmental Protection Agency, and the National Institute of Environmental Health Sciences. A goal of this investigation is to establish a large cohort of men and women that can be followed prospectively for 10 years or more to evaluate the role of agricultural exposures in the development of cancer, neurologic disease, reproductive difficulties, childhood developmental problems, and other chronic diseases. The study also will provide an opportunity to assess the role that diet, cooking methods, and other lifestyle factors have on the cause of cancer and other diseases. The cohort will be composed of approximately 112,000 adult study subjects, including 42,000 women, making this one of the largest cohorts of women ever assembled for an epidemiologic investigation of environmental and occupational exposures. Children of farm families also will be enrolled. The study will be conducted in Iowa and North Carolina. Enrollment will begin in December 1993 and continue for 3 years.

Adult↗
PubMed1994

Systemic absorption and abuse liability of snorted flunitrazepam.

Benzodiazepine hypnotics are widely abused as part of a polydrug misuse culture. This study set out to investigate some pharmacokinetic and pharmacodynamic characteristics of a novel method of abuse, snorting, of flunitrazepam. Twenty healthy volunteers took part: three took 0.5 mg, three took 1 mg, three took 1.5 mg, six took 2 mg and five took placebo. Blood was sampled and ratings of mood, bodily symptoms, strength and liking of drug effect were completed pre- and at 5, 15, 30, 60, 90, 120 and 240 minutes and at 24 hours post-drug. It was found that flunitrazepam could be detected in venous blood 5 minutes after intake. As the dose increased, the peak plasma concentration was higher but also occurred progressively later, the levels reached being comparable to oral or intramuscular administration at 110 minutes. Subjects reported sedation but complained of few side-effects. They liked the drug effects and subjective ratings of strength were correlated with liking and with plasma drug levels.

Administration, Inhalation↗
PubMed1994

The binding of synovial tissue-derived human monoclonal immunoglobulin M rheumatoid factor to immunoglobulin G preparations of differing galactose content.

There are several sites on IgG Fc that have been reported to be the epitopes for binding rheumatoid factors (RF). It is now established that there are alterations in the oligosaccharides on IgG from patients with rheumatoid arthritis and it has been suggested that these changes may enhance immune complex and cryoglobulin formation. We have used a series of IgG preparations differing in their content of oligosaccharide chains lacking galactose from 18 to 86% to determine whether changes in sugar content affect the binding of rheumatoid factor. Five of 16 monoclonal rheumatoid factors prepared from synovial tissue, from patients with juvenile or adult rheumatoid arthritis, bound better to IgG which was deficient in galactose. Six of the 16 rheumatoid factors from the same patients bound independently of the galactose content. Four of the 16 rheumatoid factors could not be absolutely grouped in this manner but seemed to demonstrate a preference for agalactosyl IgG. One rheumatoid factor bound better to fully galactosylated IgG. There was an association between enhanced binding to galactose-deficient IgG and monoreactivity and a very strong association between the functional affinity of the rheumatoid factors and the dependent binding.

Antibodies, Anti-Idiotypic↗
PubMed1994

Differential B lymphocyte galactosyltransferase activity in the MRL mouse model of rheumatoid arthritis.

Oligosaccharides can be of fundamental importance to glycoprotein function. Glycosylation abnormalities are present in rheumatoid arthritis (RA) and may be associated with disease pathogenesis. To determine whether similar disease mechanisms occur in the MRL-1pr/1pr autoimmune arthritic mouse, studies on B lymphocyte galactosyltransferase (GTase) have been carried out. In MRL mice, a significant reduction in peripheral blood lymphocyte (PBL) GTase activity was found when compared to their paired splenic (SP) GTase activity (-69%, p = 0.002) and histocompatible non-autoimmune control CBA/Ca mice (-67%; p = 0.002). The changes in PBL GTase activity are similar to those found in RA and on further analysis, using mixing experiments in the presence of purified human milk GTase, this reduction was shown not to be due to the presence of a soluble intracellular GTase inhibitor. Furthermore when examining MRL derived hybridoma cells producing IgG, significantly reduced GTase activity was detected in the rheumatoid factor (RF) producing hybridoma cells compared to those secreting an irrelevant antibody (-21%, p < 0.05). Together these findings suggest that the glycosylation changes observed in this study, and those reported previously in RA, are tissue-specific, may result from cells trafficking from centres of disease activity and are not the result of direct enzyme inhibition. It is now important to further understand the mechanisms controlling glycosylation and relate disease associated changes with those occurring as part of normal cellular physiology.

Animals↗
PubMed1993

Human IgG preparations isolated by ion-exchange or protein G affinity chromatography differ in their glycosylation profiles.

IgG from patients with rheumatoid arthritis (RA) is abnormally glycosylated in the Fc region, with sialic acid and galactose levels lower than normal. Protein G and DEAE purify populations which are differentially glycosylated. Significantly increased exposure of sialic acid was detected in normal IgG compared with that of RA IgG when ion exchange was used to prepare samples. However, when the same samples were prepared using protein G, no difference in the detection of sialic acid was seen between the two groups. When examining the heavy chain of IgG, more sialic acid, galactose and N-acetylglucosamine were detected in DEAE purified IgG compared with that prepared by protein G Detection of sialic acid and N-acetylglucosamine was also increased on light chains from IgG prepared by ion exchange chromatography. Since this occurs notably on rheumatoid light chains it would appear that this arrangement would contribute to the overall glycosylation changes in IgG. In the case of molecules lacking galactose the discrimination between the RA and normal IgG is significantly improved when ion exchange chromatography is used. Since differentiation between disease and normal groups relies on the purification technique used, we recommend that more than one method is employed before undertaking an analysis of glycosylation changes.

Arthritis, Rheumatoid↗
PubMed1993

The pharmacology of LY290324 in the guinea-pig: an orally active, potent and selective cysteinyl leukotriene receptor antagonist.

This study describes the evaluation of LY290324 as a leukotriene D4 (LTD4) receptor antagonist in guinea-pigs. In vitro, LY290324 was a potent and persistent antagonist of the contractile responses to LTD4 and LTE4 with pA2 values of 9.1 +/- 0.2 and 8.9 +/- 0.17 respectively. The antagonism appeared competitive and selective for LTD4/E4, as LY290324 (10(-6) M) had no effects on contraction elicited by LTC4, prostaglandin F2 alpha (PGF2 alpha), histamine and acetylcholine. In vivo the compound was highly effective in a dose-dependent manner by the intravenous, oral and inhaled routes in preventing LTD4-induced bronchospasm. Administered i.v. LY290324 prevented the development (ED50 = 3.4 micrograms/kg) of an LTD4-induced bronchospasm and readily reversed an established bronchospasm, but failed to prevent the bronchospasm to either histamine or platelet activating factor (PAF). Oral studies demonstrated efficacy for at least 12 h. Administered orally 6 h previously, LY290324 reduced LTC4, LTD4 and LTE4-induced bronchospasm with ED50s of 0.3, 0.28 and 0.37 mg/kg respectively. Relatively low inhaled levels (2 micrograms/kg) also significantly reduced (72.5%, P < 0.001) LTD4-induced bronchospasm. Finally the compound administered orally was effective in reducing antigen-induced bronchospasm in immunologically sensitised animals.

Administration, Inhalation↗
PubMed1993

Factors affecting general practitioners' recruitment of patients into a prospective study.

Many research projects depend on general practitioners (GPs) to recruit patients into the study. As part of a study of patients' experiences of treatment for menorrhagia, completeness of recruitment and the extent of bias introduced by failure to recruit was assessed. Only 129 (41%) of 315 GPs who had agreed to recruit patients actually did so. A review of notes in six practices revealed that only 40 (20.4%) of 196 eligible patients had been recruited. There was some evidence that the recruited patients had more severe symptoms than those not recruited. There was no difference in recruitment rates between male and female doctors, but those who had received a practice visit from a member of the research team recruited more patients. A survey of participating GPs revealed that forgetfulness and time pressures were the main factors inhibiting recruitment.

Adult↗
PubMed1993

Low serum cholesterol and suicide.

"Primary prevention trials which have shown that the lowering of serum cholesterol concentrations in middle-aged subjects by diet, drugs, or both leads to a decrease in coronary heart disease have also reported an increase in deaths due to suicide or violence. There has been no adequate explanation for this association. I have reviewed the relevant published work and describe a physiological mechanism that might account for this curious finding. One of the functions of serotonin in the central nervous system is the suppression of harmful behaviour impulses. When mouse brain synaptosomal membrane cholesterol is increased there is a pronounced increase in the number of serotonin receptors. Low membrane cholesterol decreases the number of serotonin receptors. Since membrane cholesterol exchanges freely with cholesterol in the surrounding medium, a lowered serum cholesterol concentration may contribute to a decrease in brain serotonin, with poorer suppression of aggressive behaviour".

Brain↗
PubMed1993

Gender differences among adolescent suicide attempters.

When males attempt suicide, they often use more lethal and violent methods than females. However, this article suggests that gender alone is not especially useful in assessing the seriousness of adolescent suicide attempts. In the study discussed here, the sociodemographic and psychological characteristics of female and male suicide attempters seen in a pediatric hospital are compared. There were no sociodemographic differences between the groups. Boys and girls were similar when assessed regarding suicidal ideation, depression, and hopelessness. More males than females were diagnosed with conduct disorders. Some items on the Suicide Intent Scale indicated that boys exhibited more serious intentionality than girls. Division of the sample based on suicide intentionality resulted in differences in the level of reported depression.

Adolescent↗
PubMed1992

The effect of Ca2+ channel modulators on vagally induced bronchoconstriction in the guinea-pig.

The effects of N- and L-type voltage operated calcium channel (VOCC) antagonists were examined on the bronchoconstriction induced by vagal stimulation in artificially respired guinea-pigs. Vagal stimulation produced a reproducible and consistent bronchoconstrictor response which corresponded to an increase in pulmonary inflation pressure equivalent to (10.4 +/- 1.0%) of the maximum. This vagally induced rise in pulmonary inflation pressure was reduced (54% P less than 0.001) by pretreatment with atropine (1 mg/kg i.v.) and almost completely blocked by pretreatment with capsaicin (54.5 mg/kg s.c.) and atropine. omega-Conotoxin GVIA (CgTx) (5-20 micrograms/kg i.v.) caused a dose and time-related inhibition of the vagal response but did not affect either methacholine or substance P (SP)-induced bronchoconstriction. Combination studies with CgTx, atropine and capsaicin pretreatment revealed that CgTx effectively blocked both the atropine-sensitive cholinergic component and the capsaicin-sensitive non-adrenergic non-cholinergic (NANC) component of the vagal response. Selective L-type VOCC antagonists nicardipine, diltiazem and verapamil, at doses which had significant cardiovascular effects, did not reduce the rise in pulmonary inflation pressure to vagal stimulation. This study indicates that N-type VOCCs are important in controlling the release of neurotransmitters from both the cholinergic and NANC neurones within the airways of guinea-pigs.

Animals↗
PubMed1992

The effect of calcium channel modulators on blood pressure and pressor responses to noradrenaline in the guinea-pig.

Selective L-type voltage-operated calcium channel (VOCC) antagonists nicardipine, diltiazem and verapamil all produced pronounced falls in mean arterial blood pressure (MAP) in the anaesthetized artificially ventilated guinea-pig. This fall in MAP was associated with a significant reduction of the pressor response induced by i.v. noradrenaline. omega-Conotoxin GVIA (CgTx) a preferential N-type VOCC antagonist produced a significant time-dependent fall in MAP, similar in magnitude to the L-type VOCC antagonist, but did not affect the noradrenaline-induced pressor responses.

Animals↗