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Biomedical subjects

R Beresford

Publications and source records attributed to R Beresford.

17 recordsLinked to original sources
PubMed2001

Theoretically-derived molecular descriptors important in human intestinal absorption.

A quantitative structure-human intestinal absorption relationship was developed using artificial neural network (ANN) modeling. A set of 86 drug compounds and their experimentally-derived intestinal absorption values used in this study was gathered from the literature and a total of 57 global molecular descriptors, including constitutional, topological, chemical, geometrical and quantum chemical descriptors, calculated for each compound. A supervised network with radial basis transfer function was used to correlate calculated molecular descriptors with experimentally-derived measures of human intestinal absorption. A genetic algorithm was then used to select important molecular descriptors. Intestinal absorption values (IA%) were used as the ANN's output and calculated molecular descriptors as the inputs. The best genetic neural network (GNN) model with 15 input descriptors was chosen, and the significance of the selected descriptors for intestinal absorption examined. Results obtained with the model that was developed indicate that lipophilicity, conformational stability and inter-molecular interactions (polarity, and hydrogen bonding) have the largest impact on intestinal absorption.

Artificial Intelligence↗
PubMed2001

ANN modeling of the penetration across a polydimethylsiloxane membrane from theoretically derived molecular descriptors.

A quantitative structure-permeability relationship was developed using Artificial Neural Network (ANN) modeling to study penetration across a polydimethylsiloxane membrane. A set of 254 compounds and their experimentally derived maximum steady state flux values used in this study was gathered from the literature. A total of 42 molecular descriptors were calculated for each compound. A genetic algorithm was used to select important molecular descriptors and supervised ANN was used to correlate selected descriptors with the experimentally derived maximum steady-state flux through the polydimethylsiloxane membrane (log J). Calculated molecular descriptors were used as the ANN's inputs and log J as the output. Developed model indicates that molecular shape and size, inter-molecular interactions, hydrogen-bonding capacity of drugs, and conformational stability could be used to predict drug absorption through skin. A 12-descriptor nonlinear computational neural network model has been developed for the estimation of log J values for a data set of 254 drugs. Described model does not require experimental parameters and could potentially provide useful prediction of membrane penetration of new drugs and reduce the need for actual compound synthesis and flux measurements.

Algorithms↗
PubMed2001

Vitamin E correlates inversely with non-transferrin-bound iron in sickle cell disease.

Decreased serum vitamin E levels are found in homozygous sickle cell disease (SCD). Excessive transfusions may lead high non-transferrin-bound iron (NTBI). Hypothesizing a relationship between the two, vitamin E (measured using high performance liquid chromatography) was significantly lower in 30 SCD patients than in 30 age-/sex-matched controls (P < 0.001), but NTBI (bleomycin assay) was higher (P < 0.001). Vitamin E was lower in 10 transfused patients than in 20 non-transfused patients (P < 0.001) with a significant inverse correlation between the NTBI and vitamin E (r = -0.58, P < 0.001). NTBI associated with iron overload in SCD may increase the potential for oxidative damage and low vitamin E activity may compound this effect.

Adult↗
PubMed2000

Basic concepts of artificial neural network (ANN) modeling and its application in pharmaceutical research.

Artificial neural networks (ANNs) are biologically inspired computer programs designed to simulate the way in which the human brain processes information. ANNs gather their knowledge by detecting the patterns and relationships in data and learn (or are trained) through experience, not from programming. An ANN is formed from hundreds of single units, artificial neurons or processing elements (PE), connected with coefficients (weights), which constitute the neural structure and are organised in layers. The power of neural computations comes from connecting neurons in a network. Each PE has weighted inputs, transfer function and one output. The behavior of a neural network is determined by the transfer functions of its neurons, by the learning rule, and by the architecture itself. The weights are the adjustable parameters and, in that sense, a neural network is a parameterized system. The weighed sum of the inputs constitutes the activation of the neuron. The activation signal is passed through transfer function to produce a single output of the neuron. Transfer function introduces non-linearity to the network. During training, the inter-unit connections are optimized until the error in predictions is minimized and the network reaches the specified level of accuracy. Once the network is trained and tested it can be given new input information to predict the output. Many types of neural networks have been designed already and new ones are invented every week but all can be described by the transfer functions of their neurons, by the learning rule, and by the connection formula. ANN represents a promising modeling technique, especially for data sets having non-linear relationships which are frequently encountered in pharmaceutical processes. In terms of model specification, artificial neural networks require no knowledge of the data source but, since they often contain many weights that must be estimated, they require large training sets. In addition, ANNs can combine and incorporate both literature-based and experimental data to solve problems. The various applications of ANNs can be summarised into classification or pattern recognition, prediction and modeling. Supervised 'associating networks can be applied in pharmaceutical fields as an alternative to conventional response surface methodology. Unsupervised feature-extracting networks represent an alternative to principal component analysis. Non-adaptive unsupervised networks are able to reconstruct their patterns when presented with noisy samples and can be used for image recognition. The potential applications of ANN methodology in the pharmaceutical sciences range from interpretation of analytical data, drug and dosage form design through biopharmacy to clinical pharmacy.

Algorithms↗
PubMed1989

Relation of personality and attentional factors to cognitive deficits in human immunodeficiency virus-infected subjects.

In view of the evidence that patients with human immunodeficiency virus infection experience reactive depression and anxiety, it is important to determine whether these factors might account for some of the cognitive deficiencies observed in this group, as is often the case in psychiatric populations. An extensive battery of cognitive, personality, and attention tests was administered to 26 patients who tested positive for the human immunodeficiency virus. In this group were patients who demonstrated no symptoms, patients who had acquired immunodeficiency syndrome-related complex, and patients who had acquired immunodeficiency syndrome. Pearson Product Moment correlations were computed between scores on the three types of measures. The results of this correlational study suggest that cognitive decline in patients infected with human immunodeficiency virus is independent of mood and attentional changes.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Sufentanil. A review of its pharmacological properties and therapeutic use.

Sufentanil, an opioid analgesic, is an analogue of fentanyl, and has been used for the induction and maintenance of anaesthesia, and for postsurgical analgesia. It has shorter distribution and elimination half-lives, and is a more potent analgesic than fentanyl. In clinical practice, however, intravenously administered sufentanil produces essentially equivalent anaesthesia to fentanyl and is a better anaesthetic than morphine or pethidine (meperidine) for major surgery. It would appear to maintain haemodynamic stability during surgery better than other opioids or inhalational anaesthetics. Postoperative respiratory depression has been reported in a few patients. For outpatient surgery, intravenous sufentanil produces equivalent anaesthesia to isoflurane or fentanyl. Recovery tends to be more rapid after sufentanil and the requirement for postoperative analgesia is less. Initial clinical trials with sufentanil administered epidurally to relieve pain during labour have produced encouraging results, but further studies are required to establish the drug's role in this indication. Epidural sufentanil produces a more rapid onset and better initial quality of analgesia than morphine, buprenorphine or hydromorphine when administered postoperatively, but the duration of analgesia is shorter. Thus, sufentanil's primary place in therapy at this time would appear to be as high dose anaesthesia for major surgery such as cardiac surgery, and as low dose supplement to balanced anaesthesia in general surgery. In addition, low doses administered epidurally seem to have a potential role for analgesia during labour or after surgery although further studies are required to clarify this situation.

Analgesics, Opioid↗
PubMed1987

Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis.

Haloperidol decanoate is a depot preparation of haloperidol, a commonly used butyrophenone derivative with antipsychotic activity. Haloperidol decanoate has no intrinsic activity: its pharmacodynamic actions are those of haloperidol--primarily that of central antidopamine activity. The monthly administered depot formulation has several clinical and practical advantages over oral haloperidol: better compliance and more predictable absorption; more controlled plasma concentrations; fewer extrapyramidal side effects; less frequent reminders of condition; and reduced medical workload. In open and controlled studies, haloperidol decanoate has produced adequate maintenance or improvement of the condition of patients with psychoses (mainly schizophrenia) when an abrupt change from orally administered haloperidol or other antipsychotic drugs has been instituted. Limited comparative studies indicate that the depot and oral forms of haloperidol are equally effective, and that haloperidol decanoate is at least as effective as depot forms of fluphenazine, pipothiazine, flupenthixol and perphenazine in controlling the symptoms of psychosis. Extrapyramidal side effects and the need for concomitant anti-Parkinsonian drugs may be a problem, but may be less frequent than with oral haloperidol or other depot antipsychotics. Thus, haloperidol decanoate offers a useful alternative in the treatment of psychoses to orally administered haloperidol or to other depot antipsychotic drugs.

Haloperidol↗
PubMed1987

Proquazone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in rheumatic diseases and pain states.

Proquazone is a non-steroidal anti-inflammatory agent (NSAID) which, unlike most other NSAIDs, does not have a free acid group in its structure. It is advocated for use in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, musculoskeletal disorders, acute inflammatory conditions and acute pain states such as dysmenorrhoea, postoperative pain and headache. Published data in small groups of patients indicate that proquazone 300 to 900 mg/day in 3 divided doses is a possible alternative to aspirin, ibuprofen, indomethacin, and naproxen in rheumatoid arthritis, and to indomethacin and ibuprofen in ankylosing spondylitis. Similarly, proquazone 300 to 900 mg/day is as effective as aspirin, diclofenac, ibuprofen, indomethacin and naproxen in patients with osteoarthritis. Preliminary studies have confirmed the efficacy of proquazone in acute inflammatory disorders, and shown that it provides useful analgesic relief in acute pain states such as dysmenorrhoea, headache and after minor surgery. Evidence from small groups of patients with rheumatoid arthritis treated for a year or more suggests that proquazone may inhibit or arrest progression of bone erosions. However, these encouraging findings clearly need confirmation in a larger number of patients studied under well-controlled conditions. The overall impression from clinical trials to date is that proquazone at dosages of greater than or equal to 900 mg/day produces a high incidence of gastrointestinal symptoms such as diarrhoea (in approximately 30% of patients). However, these effects were usually of mild to moderate severity and transient in nature and in most comparative studies the overall tolerability of proquazone was assessed as being comparable to that of other NSAIDs tested. Similarly, withdrawal from therapy due to side effects was no greater with proquazone than with other NSAIDs evaluated. Initial experience with lower dosages of proquazone (300 to 450 mg/day) suggest that efficacy is maintained and tolerability markedly improved. Thus, at present, proquazone would seem to be as effective as other NSAIDs used in the management of rheumatoid arthritis and osteoarthritis. However, further studies are needed to fully evaluate the efficacy and tolerability of this agent, especially at the lower daily dosages currently recommended, and to clarify whether it does have significant 'disease modifying' potential.

Analgesics↗
PubMed1986

Betaxolol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension.

Betaxolol is a relatively cardioselective beta-adrenoceptor blocking drug, with no partial agonist (intrinsic sympathomimetic) activity and weak membrane-stabilising (local anaesthetic) activity. Its pharmacokinetic properties of most interest include high bioavailability after oral administration, and a long elimination half-life. It has a narrow dose-response range, which obviates the need for dose titration, with 10 to 20 mg once daily being the usual dosage. This dose reduces systolic and diastolic blood pressures by about 15 mm Hg in most patients with mild to moderate hypertension. In a few comparative studies betaxolol 20 mg daily was as effective as atenolol and moderate doses of propranolol, and more effective than acebutolol, in reducing blood pressure in such patients. Betaxolol has been well tolerated in most patients. Thus, betaxolol is an effective alternative to other beta-blocking drugs in patients with essential hypertension, with properties that may offer advantages in some patients.

Adrenergic beta-Antagonists↗
PubMed1986

Pirprofen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.

Pirprofen is a non-steroidal anti-inflammatory drug, related structurally to drugs such as ibuprofen, ketoprofen and naproxen. Published clinical trials indicate that pirprofen 600 to 1200 mg/day as 2 or 3 divided doses is a suitable alternative to usual therapeutic dosages of aspirin, flurbiprofen, ibuprofen, indomethacin, ketoprofen, naproxen, piroxicam and sulindac in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, musculoskeletal disorders and non-articular rheumatism. More studies are required to evaluate its potential relative to other commonly used drugs in the treatment of gout, juvenile rheumatoid arthritis and dysmenorrhoea. In patients with acute postsurgical, trauma or cancer pain, single oral or intramuscular doses of pirprofen 200 to 400mg provide equivalent analgesic activity to usual therapeutic doses of aspirin, diflunisal, ketoprofen, noramidopyrine, paracetamol and pentazocine. As with other non-steroidal anti-inflammatory drugs, gastrointestinal complaints are the most frequently reported side effects. At equivalent analgesic or anti-inflammatory dosages, pirprofen probably causes fewer side effects than aspirin and appears to be as well tolerated as the other agents with which it has been compared. Long term tolerability, particularly compared with some of the newer, purportedly less gastrotoxic agents or formulations, needs to be investigated further. Pirprofen does not appear likely to offer any particular advantage with respect to efficacy and tolerability over other non-steroidal anti-inflammatory drugs, except aspirin. However, as no one agent is the most suitable drug for all patients requiring such therapy, pirprofen may be considered along with other drugs of this type in the therapy of arthritic conditions and acute pain states.

Animals↗
PubMed1979

Effects of 2,4-dinitrophenol amylobarbitone and certain other drugs on the rate of oxygen consumption and force of contraction of isolated curarized diaphragm muscle of the rat.

1 A technique has been developed for studying over periods of 10 min or longer the effects of drugs on both the force of electrically-induced contractions and the oxygen consumption of an isolated, curarized, mammalian, skeletal muscle preparation.2 The resting oxygen consumption of the muscle was increased substantially by 2,4-dinitrophenol in concentrations (0.02 mM and higher) that eventually produced contracture. Two other uncoupling agents, 4,6-dinitro-o-cresol and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, behaved similarly.3 The oxygen consumption over 10 min of the stimulated muscle was also increased by 2,4-dinitrophenol (0.05 mM), although the strength of the ;maximal' contractions was lessened.4 Amylobarbitone increased the strength of contraction at a concentration (0.2 mM) that did not affect oxygen consumption significantly. Amylobarbitone and pentobarbitone also increased it at a concentration (1 mM) that depressed oxygen consumption. They decreased both strength of contraction and oxygen consumption at a concentration of 5 mM. Phenobarbitone had a weaker action.5 S-n-decyl-thiouronium increased oxygen consumption when given at a concentration (1 mM) that diminished strength of contraction and eventually produced contracture of the muscle.6 Both S-methyl-thiouronium (1 mM) and 4-aminopyridine (0.1 mM and 0.5 mM) increased strength of contraction without increasing oxygen consumption. Neither strength of contraction nor oxygen uptake was affected by ouabain (up to 0.01 mM) or by phenformin (0.1 mM).7 It is concluded that the response to 2,4-dinitrophenol is due mainly, if not wholly, to its known ability to uncouple oxidative phosphorylation; that the response to the barbiturates is due to a combination of a known metabolic action (viz., blocking of the respiratory chain) and a stimulant action on muscle; and the response to S-n-decyl-thiouronium to a disruptive action on cell membranes. The disproportionate actions of 4-aminopyridine and S-methyl-thiouronium on strength of contraction relative to oxygen consumption are also attributed to a non-metabolic action.

Amobarbital↗