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Characterization of opioid binding sites in rat spinal cord.

Binding sites were characterized in rat whole spinal cord crude membrane preparations using selective labelling techniques with multiple methods of mathematical analysis of experimental curves. Mathematical analysis of single [3H]-[D-Ala2,MePhe4,Gly-ol5] enkephalin (DAGO) saturation curves suggested binding of the [3H]-ligand at one site, while displacement curves of low concentrations of [3H]-DAGO with selective mu-ligands indicated the presence of high- and low-affinity sites. All the [3H]-DAGO curves processed simultaneously by LIGAND analysis showed the presence of high (27%) and low (73%) affinity components, with a total Bmax of 3.19 pmol/g tissue. Eighty percent of [3H]-[D-Ala2,D-Leu5] enkephalin (DADLE) binding was displaced by DAGO with high affinity, indicating that a high percentage of [3H]-DADLE binding was at mu-sites. Saturation curves of [3H]-DADLE after inhibition of mu-sites by unlabelled DAGO (delta-sites) were monophasic with non-linear fitting analysis and the Bmax was 0.90 pmol/g tissue. Most mathematical analysis of single saturation curves of [3H]-(-)-bremazocine indicated binding at more than one site. DAGO, DADLE, U-69,593 and PD 117302 displaced 0.15 nM of [3H]-(-)-bremazocine biphasically: the percentages of displacement calculated with the non-linear fitting program were respectively 50 (mu-sites), 64 ((mu + delta)-sites), 18 and 25 (kappa-sites). Haloperidol displaced [3H]-(-)-bremazocine only at microM concentrations. suggesting no binding at sigma-sites. In the presence of 225 nM of DAGO, DADLE displaced only 21% of [3H]-(-)-bremazocine 0.15 nM binding (delta-sites). Most mathematical analysis of saturation curves of [3H]-(-)-bremazocine, after inhibition of binding at mu- and delta-sites by DAGO and DADLE, still indicated binding at more than one site and the selective kappa-ligands U-69,593 and PD 117302 displaced [3H]-(-)-bremazocine in these experimental conditions. LIGAND analysis of saturation and inhibition curves of [3H]-(-)-bremazocine by U-69,593 and PD 117302 showed the presence of high (43%) and low (57%) affinity components, with a total Bmax of 2,73 pmol/g tissue. Thus in rat spinal cord there are at least two mu-sites bound by [3H]-DAGO which amount together to approximately 47% of total opioid sites, delta-sites bound by [3H]-DADLE amounting to approximately 13%, kappa-sites and other unknown sites (possibly a kappa-subtype) bound by [3H]-(-)-bremazocine, which together are approximately 40% of total opioid sites.

Animals

Relationships between linear type scores, objective type measures, and indicators of mastitis.

Objectives were to examine the usefulness of objective measures of conformation and linear scores for type for predicting indicators of mastitis. Approximately 300 cows in five herds were scored in the experimental linear classification program of the Holstein-Friesian Association of America, measured objectively for numerous components of conformation, and evaluated for four indicators of mastitis. Indicators of mastitis were average natural logarithm of somatic cell counts during the lactation, percent of samples (taken approximately every 3 mo) infected during a lactation, percent of samples infected with Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, Klebsiella, and percent of samples with signs of mastitic milk. Relationships between conformation and mastitis often were inconsistent because of moderate or low correlations between indicators of mastitis. Indicators of mastitis were predicted from results of multiple regression analyses with subjective scores and objective measures of type as independent variables. Largest differences of predicted indicators of mastitis from variation in any single type trait were sufficient to be important economically, but average differences were much smaller. Selection to reduce frequencies of cows with deep udders, especially low rear udders, widely placed teats, rear teats too far back, and teats that are short and wide, may augment, modestly, efforts to reduce incidence of mastitis through improved sanitation, antibiotic treatment, and proper milking procedures.

Animals

Ownership and organizational performance. A comparison of technical efficiency across hospital types.

Using a national data base of urban hospitals, the effect of ownership (government, nonprofit, and for-profit) on the technical efficiency of hospitals was examined. Efficiency scores were computed using a method called data envelopment analysis. Controlling for environmental and hospital characteristics, for-profit hospitals were found somewhat less frequently and government hospitals consistently more frequently in the efficient category. When examining highly inefficient hospitals as a percentage of those receiving inefficient scores, for-profit hospitals appeared to be highly inefficient relative to the other ownership forms. Government and nonprofit hospitals were somewhat indistinguishable from one another regarding their percentages of highly inefficient scores. For-profit hospitals also tended to use supply and capital asset (hospital size) inputs less efficiently, and service and labor inputs more efficiently than hospitals in the other ownership categories.

Efficiency

[SCAN program for structural analysis of linear polysaccharides based on 13C-NMR spectral data using personal computers].

A programme SCAN was elaborated for the 13C NMR--based structural analysis of regular polysaccharides, which represents our earlier programme (Lipkind G.M. et al. Carbohydr. Res. 1988. V. 175. No 1. P. 59-75) modified for IBM-PC-compatible personal computers. SCAN was successfully applied for the structural elucidation of 24 polysaccharides of bacterial origin. Optimal combinations of the computer-assisted method with other approaches for analysis of carbohydrates and scopes of application of the programme are discussed.

Carbohydrate Conformation

Metabolism of carbamazepine: evidence of autoinduction in Chinese.

To investigate the autoinduction of carbamazepine (CBZ) metabolism in Chinese, eleven healthy male volunteers joined in this study. There were two phases of drug administration with a wash-out interval of one month, 400 mg CBZ was taken orally in single-dose phase, and 200 mg three times per day were given for seven days in multiple-dose phase. Plasma samples were obtained in series of time after the last dose of drug in each phase. CBZ concentrations were determined by a high pressure liquid chromatography method. A non-linear regression program was applied in a personal computer to estimate the pharmacokinetic parameters. The average CBZ half-lives in single- and multiple-dose phases were 50.1 +/- 12.1 (mean +/- SD) hours and 26.1 +/- 4.2 hours and the clearances were 16.4 +/- 3.3 ml/kg/h and 45.3 +/- 23.4 ml/kg/h respectively, both with significant differences (p less than 0.005). There is evidence to support the presumption of autoinduction in Chinese.

Adult

Open-loop feedback control of serum bentazepam concentrations and Bayesian estimation in multiple dosage regimens in patients.

The time course of serum levels of bentazepam was studied in 10 patients receiving anxiolytic agent orally at a dose of 25 mg on multiple dosage regimens with dosage intervals of 8 and 12 h. Using the methods of "open-loop feedback control", no linear regression programs and Bayesian estimation, it was possible to establish the best estimates of the pharmacokinetic parameters corresponding to the single-compartment model for each patient from all their data relating to the serum levels obtained after the first dose and after multiple dosing with different regimens. The application of the Kruskal Wallis test showed that there were only statistical differences for the absorption constant, determined with and without Bayesian estimation. However, no statistically significant differences were found on comparing the experimentally obtained serum levels with the corresponding theoretical values calculated independently for each patient from the parameters established with and without Bayesian estimation. As population pharmacokinetic parameters of bentazepam, the following were established: Ka = 2.330 +/- 0.665 l/h; Vd = 1.209 +/- 0.546 l/Kg and Ke = 0.160 +/- 0.118 l/h, corresponding to a mean value for the elimination half-life of 4.33 h.

Administration, Oral

A heuristic approach to nurse scheduling in hospital units with non-stationary, urgent demand, and a fixed staff size.

We present a practical approach to personnel scheduling problems arising in hospital units with demand that is of an urgent nature, cannot be backlogged, and is highly dependent on the time of day. A simple rounding heuristic is combined with a simulated annealing algorithm to obtain near-optimal solutions to large linear integer programming models of these personnel scheduling problems in a reasonable amount of time on a personal computer. The models are designed to complement the current state-of-the-art of commercially available hospital staff scheduling systems.

Algorithms

[Analysis of the circadian rhythm of pain].

An electronic pulp tester was used to study the stimulus threshold in human teeth of 28 healthy volunteers for 1,5-4 days and the duration of local anaesthesia in 55 patients with caries. Rhythm analysis was performed with a non-linear fitting program on an IBM computer (PHARMFIT); in 21 out of the 28 volunteers significant daily rhythms in stimulus threshold could be detected. In the patients the maximum duration of local anaesthesia was after drug application at 2 p.m.

Adolescent

[Demographic and economic trends in medical schemes--a time series analysis].

A time series analysis was performed on medical scheme statistics with the aim of determining current and future demographic and economic trends. This would enable one to reach a better perspective on the current and future financial dilemma presently experienced by medical schemes. Data for the period 1978-1986 was analysed on a computer, using the Statgraphics program. The linear trend projection method, based on the regression analysis technique was used. Real values were determined by deflating nominal values against the consumer price index with 1980 as base year. There are at present 253 medical schemes in operation. Approximately 16 per cent of the economically active population are members of medical schemes. White members increased by only 3.8 per cent during the period 1978-1986, in comparison to the 87.1 per cent by black members. The beneficiaries represent 19 per cent of the total population; black beneficiaries increased by 422.1 per cent, while Whites increased only fractionally by 0.73 per cent. Membership fees increased by an average of R8.08/member/month or R1.72/member/month in real terms. Ninety five per cent of the income of medical schemes was derived from membership fees. The average real growth rate of income was 8.4 per cent, while net assets increased by only 3 per cent. An average deficit of R11.02 million/year is estimated for the recommended reserve funds in real terms. The greatest proportion of benefits paid was for professional services (47.4 per cent) followed by medicine (26.3 per cent) and hospital services (19.8 per cent). The real growth rate for benefits paid was 8.6 per cent per year.(ABSTRACT TRUNCATED AT 250 WORDS)

Economics