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Biomedical subjects

W Rahman

Publications and source records attributed to W Rahman.

13 recordsLinked to original sources
PubMed2001

Electrophysiological studies on the role of the NMDA receptor in nociception in the developing rat spinal cord.

The present study investigated the effects of spinally applied N-methyl-D-aspartate (NMDA) antagonists 2-amino-5-phosphonovaleric acid (AP5) and ketamine on convergent neurones in the deep dorsal horn of rats, in vivo at different postnatal ages (P) 14, 21, 28, and 56 days. AP5 inhibited the primary afferent fibre input, the C fibre, post-discharge and windup evoked responses in a dose-dependent manner at each age, and was significantly more effective in the pups than adult rats (P<0.03 at 100-microg dose). AP5 100 microg abolished windup almost completely in the pups, whilst the adults required 10-fold higher doses. In contrast there was no difference in ketamine potency between age groups. Windup in the ketamine groups was reduced in a dose-dependent manner equally across all the age groups. The differential inhibitory effects of AP5 and ketamine may be due to postnatal changes in density, localisation and receptor subunit composition, altering receptor affinity and kinetics.

2-Amino-5-phosphonovalerate↗
PubMed1999

Chemoprevention of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine-induced mammary carcinogenesis in rats.

Modifying effects of dietary exposure of diallyl disulfide (DAD), aspirin, DL-alpha-difluoromethylomithine (DFMO), beta-naphthoflavone (beta-NF), alpha-naphthoflavone (alpha-NF), indole-3-carbinol (I3C) and protocatechuic acid (PCA) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examined in two experiments with female rats. For both experiments, PhIP in corn oil at a concentration of 85 mg/kg was given to animals via an intragastric tube for eight doses for an initial 4 weeks, and test chemicals were given in the diet (Experiment 1: DAD, 200 ppm; aspirin, 400 ppm; DFMO, 400 ppm; beta-NF, 1000 ppm; Experiment 2: alpha-NF, 1000 ppm; I3C, 1000 ppm; PCA, 2000 ppm) for an initial 4 weeks. The experiments were terminated after 25 weeks. In Experiment 1, exposure of beta-NF decreased the incidence and multiplicity of total mammary tumors (fibroadenoma, intraductal carcinoma and invasive ductal carcinoma) (P < 0.001 and P < 0.0001), and lowered the incidence of ductal carcinoma (P < 0.0001). DAD lowered the incidence of ductal carcinoma and decreased the multiplicity of the total tumors (P < 0.01 and P < 0.005). Furthermore, aspirin decreased the total tumors (P < 0.05). In Experiment 2, alpha-NF decreased the multiplicity of ductal carcinoma (P < 0.05). These results suggest that alpha-NF, beta-NF, DAD or aspirin could be chemopreventing agents for mammary neoplasia.

Allyl Compounds↗
PubMed1999

Electrophysiological studies on the postnatal development of the spinal antinociceptive effects of the delta opioid receptor agonist DPDPE in the rat.

1. The antinociceptive effects of the delta opioid receptor selective agonist, DPDPE [(D-Pen2,D-Pen5)-enkephalin] was studied in rats aged postnatal day (P) 14, P21, P28 and P56. 2. Antinociceptive effects of DPDPE were measured as percentage inhibition of the C-fibre evoked response and post-discharge of dorsal horn neurones evoked by peripheral electrical stimulation. DPDPE was administered by topical application, akin to intrathecal injection. 3. DPDPE (0.1-100 microg) produced dose-related inhibitions at all ages; these inhibitions were reversed by 5 microg of the opioid antagonist naloxone. 4. The dose-response curves for C-fibre evoked response and post-discharge of the neurones were not different in rats aged P14 and P21. DPDPE was significantly more potent at P14 and P21 compared with its inhibitory effects on these responses at P28 and P56. 5. DPDPE produced minor inhibitions of the A-fibre evoked response of the neurones at P14, P21, P28 and P56, suggesting that the inhibitory effects of DPDPE are mediated via presynaptic receptors on the terminals of C-fibre afferents. 6. Since spinal delta opioid receptor density changes little over this period, the increased antinociceptive potency of DPDPE in the rat pups compared with the adult is likely to be due to post-receptor events, or in developmental changes in the actions of other transmitter/receptor systems within the spinal cord.

Afferent Pathways↗
PubMed1998

Postnatal development of multiple opioid receptors in the spinal cord and development of spinal morphine analgesia.

The postnatal ontogeny of mu, delta and kappa opioid receptor binding sites in the spinal cord of rat pups at various postnatal days was determined using in vitro autoradiographical methods. The functional effect of spinal morphine was also assessed using in vivo electrophysiological methods in rats at P14, P21 and adults (P56). Both mu and kappa opioid receptor binding-sites are present from P0 and spread relatively diffusely throughout the spinal cord. Overall binding peaks at P7 and subsequently decreases to adult levels with the mu opioid receptor binding sites regressing to become denser in the superficial dorsal horn. delta Opioid receptor binding was first seen at P7, and no distinction between superficial and deeper laminae was seen. In the adult, the relative proportions of the opiate receptors in the superficial dorsal horn are 63%, 22% and 15%, for mu, delta and kappa receptor binding sites, respectively. C-fibre evoked dorsal horn neuronal responses recorded from anaesthetized rat pups were highly sensitive to spinal morphine at P21, (EC50 0.005 microgram), compared to the adult (EC50 0.9 microgram). However, the EC50 (0.2 microgram) at P14 was greater than at P21 despite the fact that mu receptor binding was greater at P14. Opioid receptor binding is developmentally regulated and undergoes substantial postnatal reorganization. However, the number of mu receptor binding sites appears not to be the only determinant of functional sensitivity to spinal morphine. Other factors, such as coupling of the receptors are likely to be important.

Analgesics↗
PubMed1996

The opioid ketobemidone has a NMDA blocking effect.

There are clinical observations that neurogenic pain can respond well to the opioid ketobemidone, in contrast to pethidine and morphine. This has led us to the hypothesis that the analgesic effect of ketobemidone in neurogenic pain may be due to both opioid as well as additional non-opioid effects. The present study was therefore made to evaluate the effects of ketobemidone. The study consists of two parts. (1) Single unit recordings were made from dorsal horn neurones in the halothane-anaesthetised rat. Neurones were activated by transcutaneous electrical stimulation of their receptive fields at C-fibre strength and their responses quantified. The wind-up of the neurones, due to N-methyl-D-aspartate (NMDA) receptor activation, leading to marked increases in C-fibre responses and an associated post-discharge was also measured. Ketobemidone, applied to the spinal cord, equivalent to an intrathecal injection, dose-dependently and selectively reduced C-fibre evoked responses. Ketobemidone was also found to block wind-up more effectively than morphine at equieffective doses, but unlike morphine in a non-naloxone-reversible manner. (2) In a binding study ketobemidone was shown to inhibit [3H]MK-801 binding with a Ki value of 26 microM. Therefore, ketobemidone appears to possess both mu opioid agonist as well as NMDA blocking effects.

Analgesics, Opioid↗
PubMed1996

Rapid genotypic confirmation of methicillin resistance.

Detection of phenotypic methicillin resistance in Staphylococcus aureus clinical strains by conventional disk diffusion testing is fraught with problems. We used gene amplification of the mecA locus by polymerase chain reaction (PCR), in conjunction with a capillary/air thermal cycler, to overcome both the inaccuracy of phenotypic methods and the lengthy processing times required for previous genotypic methods. The rapid PCR method correctly identified methicillin resistance in a consecutive series of 30 S. aureus isolates when compared with routine and reference phenotypic methods. The shorter processing time and smaller reagent volumes required for the air thermal cycler make same-day determination of methicillin resistance in clinical isolates feasible for diagnostic laboratories.

DNA, Bacterial↗