Griffiths and the NHS.
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Community Health Nursing↗
Biomedical subjects
P Strong
Publications and source records attributed to P Strong.
The molecular structure of 16 alpha-iodo-17 beta-estradiol, a high affinity ligand for the estrogen receptor.
16 alpha-Iodoestradiol is an estrogenic steroid with high affinity for the estrogen receptor. When labelled with a gamma emitting isotope, such as 125I, the resulting radioactive steroid is an excellent ligand for the sensitive analysis of the estrogen receptor. The X-ray study of the crystal structure of 16 alpha-iodoestradiol reveals that the bond distances and angles of the iodinated estrogen are similar to those of estradiol and estriol. The substitution of iodine for the 16 alpha-hydroxyl group has little effect on geometric and electronic properties of the molecule and does not interfere with the hydrogen bonding ability of the 17 beta-hydroxyl group. The difference in receptor binding affinity between 16 alpha-estradiol and estriol may be due to competition for intermolecular hydrogen bond formation between the hydroxyls at C(16) and C(17) on estriol. X-Ray data indicate that the 16-hydroxyl can form significantly shorter and presumably stronger hydrogen bonds.
Chemical Phenomena↗
The development of tolerance to antilipolytic agents in rats.
The development of tolerance to the action of certain antilipolytic agents has been investigated in vivo in rats. Tolerance to oral nicotinic acid developed during twice daily dosing for 4 days at 100 and 250 mg/kg but not at 10, 25 or 50 mg/kg. Tolerance induced by high doses of nicotinic acid was no longer detectable after a further week without treatment. Tolerance developed to a dose of 10 mg/kg nicotinic acid when dosing was repeated at hourly intervals for up to 6 hr. Rats made tolerant to nicotinic acid also became tolerant to both 5-methylpyrazole-3-carboxylic acid and to pyridyl-3-tetrazole and rats made tolerant to these antilipolytic agents were also tolerant to nicotinic acid. Rats made tolerant to nicotinic acid still responded to the antilipolytic activity of the prostaglandin analogue, sulprostone. These results suggest that nicotinic acid, pyridyl-3-tetrazole and 5-methylpyrazole-3-carboxylic acid act through a common mechanism or receptor and that the development of tolerance is associated with this receptor or the mechanism by which it is linked to adenylate cyclase.
Animals↗
The development of tolerance to antilipolytic agents by isolated rat adipocytes.
Using an isolated rat epididymal adipocyte system we have studied the development of tolerance to and cross-tolerance between nicotinic acid, 5-methylpyrazole-3-carboxylic acid and pyridyl-3-tetrazole. Preincubating isolated adipocytes with any one of these compounds results in a reduction of the antilipolytic activity of that compound when the cells are exposed to a subsequent challenge dose. Furthermore, preincubation with nicotinic acid, 5-methylpyrazole-3-carboxylic acid or pyridyl-3-tetrazole results in a reduction of the antilipolytic response to challenge with either of the other two compounds. Preincubation of isolated adipocytes with nicotinic acid does not affect the subsequent antilipolytic activity of the PGE2 analogue, sulprostone. Preincubation with sulprostone does not lead to the development of tolerance to its own antilipolytic actions. The results obtained from these studies suggest that nicotinic acid, 5-methylpyrazole-3-carboxylic acid and pyridyl-3-tetrazole exert their antilipolytic activity via a common biochemical pathway which is distinct from that mediating the antilipolytic activity of prostaglandins. These findings also indicate that the development of tolerance occurs prior to the involvement of adenylate cyclase in lipolysis.
Adipose Tissue↗
Errors arising from the use of [1-14C]pyruvate to measure flux through the liver pyruvate dehydrogenase complex.
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Animals↗
Stimulation of flux through hepatic pyruvate dehydrogenase by 3-mercaptopicolinate.
Isolated hepatocytes from 24-h-starved rats were used to assess the possible effect of the hypoglycaemic agent 3-mercaptopicolinate on flux through the hepatic pyruvate dehydrogenase complex. Increasing the extracellular pyruvate concentration from 1 mM to 2 mM or 5 mM resulted in an increase in flux through pyruvate dehydrogenase and the tricarboxylic acid cycle as measured by 14CO2 evolution from [1-14C]pyruvate and [3-14C]pyruvate. Gluconeogenesis was inhibited by 3-mercaptopicolinate from both 1 mM and 2 mM pyruvate, but significant increases in malate and citrate concentrations only occurred in cells incubated with 1 mM pyruvate. Flux through pyruvate dehydrogenase was stimulated by 3-mercaptopicolinate with 1 mM pyruvate but was unaltered with 2 mM pyruvate. Dichloroacetate stimulated flux through pyruvate dehydrogenase with no effect on gluconeogenesis in the presence of 1 mM pyruvate. There was no effect of 3-mercaptopicolinate, administered in vivo, to 24-h-starved rats on the activity of pyruvate dehydrogenase in freeze-clamped heart or liver tissue, although the drug did decrease blood glucose concentration and increase the blood concentrations of lactate and alanine. Dichloroacetate, administered in vivo to 24-h-starved rats, increased the activity of pyruvate dehydrogenase in freeze-clamped heart and liver, and caused decreases in the blood concentrations of glucose, lactate, and alanine. The results suggest that 3-mercaptopicolinate increases flux through hepatocyte pyruvate dehydrogenase by an indirect mechanism.
Animals↗
Quieting response training: predictors of long-term outcome.
Extensive personality, demographic, and symptom-related information from a heterogeneous group of more than 300 patients was examined for patterns that would discriminate between successful and unsuccessful outcomes in patients undergoing Quieting Response (QR) training, an 8-week program that integrated EMG and thermal biofeedback with a variety of relaxation exercises. Follow-up evaluations were at 3, 6, 12 and 24 months. Agreement between expected (from stepwise discriminant analyses) and observed outcomes was 65% (whole sample), 62% (headache only), and 70% (Raynaud's only). Unimproved patient MMPI scales D, Sc, F, Hy, and Pt were significantly elevated. A variety of additional measures used indicated elevated levels of psychological stress among unsuccessful patients. While stereotypical descriptions of successful and unsuccessful patients are proposed, patterns from outcome groups were more similar than dissimilar, and no combination of factors was identified that had sufficient predictive power for use with future patients. No statistical grounds for exclusion were found among patterns of responses to the measures employed. Factors contributing to the inaccuracy of outcome prediction are discussed.
Biofeedback, Psychology↗
Quieting response training: long-term evaluation of a clinical biofeedback practice.
Clinical evidence for the long-term effectiveness of biofeedback related relaxation training is accumulating. The purpose of this report is to describe the population, self-regulation procedure, outcome criteria, and final outcome for patients who received Quieting Response (QR) training. Data from 340 patients who completed at least the first follow-up at 3 months is presented. Primary presenting symptoms were headaches, 72%; primary and secondary Raynaud's, 14%; hypertension, 4%; irritable colon, 4%; and miscellaneous, 6%. QR training integrated EMG and thermal feedback with deep breathing, progressive relaxation, and autogenic exercises presented on cassette tapes. Eight 1-hour weekly sessions were given, with emphasis on daily home exercises. Follow-up evaluations were at 3 months, 6 months, 1 year, and 2 years. Outcome was based on change in frequency, severity, and duration of symptoms; changes in medication; and secondary benefits. Quieting Response training was found to be most beneficial for patients with primary Raynaud's disease (18 of 23 patients, or 78% successful), classic migraines (9 of 13, or 69%), and common migraines (20 of 32, or 62%), followed by mixed headaches (79 of 131, or 60%), Raynaud's plus other symptoms (9 of 15, or 60%), and the irritable colon syndrome (7 of 13, or 54%). Less successful were patients with headaches plus other symptoms (16 of 37, or 43%), muscle contraction headaches (13 of 33, or 39%), secondary Raynaud's phenomenon (4 of 10, or 40%), and essential hypertension (5 of 15, or 33%). Speculations about the differing outcomes across symptom groups were made.
Adult↗
Quieting response training: treatment of psychophysiological disorders in psychiatric inpatients.
Self-regulation methods incorporating biofeedback are known to be useful in the treatment of psychophysiological disorders in psychologically normal patients. In this study, the effectiveness of Quieting Response (QR) training for the treatment of secondary psychophysiological complaints in psychiatric inpatients was assessed. Ten male and 27 female inpatients with a variety of secondary psychophysiological diagnoses were accepted into the study. Severely disturbed, confused, or depressed patients were excluded. All patients received QR training, which integrated EMG (electromyogram) and thermal feedback with breathing, progressive relaxation, and autogenic exercises. Daily practice of a 15-minute sequence of exercises was encouraged, and a 6-second reinforcement exercise was presented for use whenever an annoyance was encountered. No other therapeutic modalities were employed. Patients were followed for up to 2 years, and outcome was assessed with a multifactor quartile system. Rate of success at final follow-up for the inpatients (51%) was found to be equivalent to that of outpatients coming to the clinic with primary psychophysiological diagnoses (55%) and was not related to psychiatric diagnosis or nature of presenting complaint. Stepwise discriminant analysis indicated that older, less depressed individuals were more successful. Inpatients differed from nonpsychiatric patients only in the number of additional sessions received. Only one minor incident of increased psychopathology was observed. It was concluded that QR training was as effective for treating secondary psychophysiological disorders in all but the most severely disturbed inpatients as it was for the outpatient clinic population.
Adult↗
The recruitment and training of volunteers for emergency relief work.
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Africa↗
Aerobic lactate synthesis by cardiac muscle.
Cardiac lactate production under aerobic conditions is absolutely dependent upon the availability of extracellular pyruvate. In the steady state, aerobic lactate output is largely independent of cardiac work load, but increases slightly when octanoate is included in addition to pyruvate in the perfusion fluid. Transient episodes of supra-normal lactate production are seen after sudden increases in cardiac work output, and also after transitions from octanoate to pyruvate in the perfusion media. These pulses of lactate production are invariably associated with the slow activation of pyruvate dehydrogenase in response to a sudden change in cardiac metabolic state, and they are abolished by pre-perfusion with dichloracetate, which converts pyruvate dehydrogenase into the fully active form. A second, additional component of the lactate pulses is sensitive to pre-perfusion with the transaminase inhibitor aminooxyacetate. The size of the second component is markedly dependent upon the precise protocol adopted for the experiment, and these variations suggest that the second component is associated with a major redistribution of cardiac Krebs' cycle intermediates and amino acids following the initial exposure to pyruvate-containing media. Steadystate aerobic lactate production is insensitive to both dichloroacetate and aminooxyacetate, and is thought to result from a direct exchange of malate for oxaloacetate across the heart mitochondrial membranes.
Aerobiosis↗
Aerobic lactate synthesis by rat cardiac muscle [proceedings].
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Aerobiosis↗
Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.
Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10-7 cm2/hr to 120 x 10-7 cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphene sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.
Animals↗
Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.
Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10(-7) cm2/hr to 120 x 10(-7) cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphine sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.
Animals↗
Structure determination of 3 beta, 17-dihydroxy-17 alpha-pregn-5-ene-20-one.
The title compound was synthesized as part of an effort to determine the identity of an abnormal steroid metabolite present in the urine of a patient exhibiting pronounced gynecomastia. The X-ray investigation of the synthesized compound showed that the 20-carbonyl of the 17 alpha oriented side chain lies under the D ring, and does not participate in hydrogen bonding in the crystal lattice. This conformation appears to be stable and sufficiently shielded that it is unlikely to make a major contribution to possible protein interactions.
17-alpha-Hydroxypregnenolone↗