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[Solubilization and purification of opioid receptor molecules of rat brain].

P2 membrane preparation of rat brain (without cerebellum) was solubilized with CHAPS in Tris containing DTT and trypsin inhibitor. Two opiate ligands, 10b and 10cd, prepared by Liu et al, were applied consecutively in affinity chromatography, from which OPRs were eluted with Nx. The eluate was subsequently passed through a WGA affinity column and the OPR eluted with N-GluNAc. This eluate was further purified and concentrated by preparative granular gel isoelectric focusing on SG200. Two protein peaks appeared separately at pH 5 and pH7.8. The eluates from both peaks were analyzed for protein content by using silver staining method and binding activity was measured by RRA with 3H-etor. The results revealed that both samples contained active OPR purified to over 80,000 fold. The Mr was estimated by gel filtration to be 52 and 42 kD for OPR in the pH 5 and pH 7.8 samples respectively. The OPR in pH 5 sample has been characterized to be of mu-type, by its binding activity with 3H-ohm.

Animals↗

Syncatalytic inactivation of prolyl 4-hydroxylase by synthetic peptides containing the unphysiologic amino acid 5-oxaproline.

Peptides containing the unphysiological amino acid 5-oxaproline (Opr) in the sequence R1-Xaa-Opr-Gly-OR2 were found to inactivate prolyl 4-hydroxylase from chick and human origins. Of the substances investigated, compounds with aromatic substituents R1 and R2 were particularly effective when compared with those with an aliphatic group or without a C-terminal blocking group. Both affinity of the individual peptides for the enzyme and partition ratio contributed to the differences in efficiency. Benzylcarbonyl-Phe-Opr-Gly-benzyl ester was the most effective substance tested, its concentration giving 50% inactivation in 1 h being 0.8 microM. Inactivation was only observed in the presence of 2-oxoglutarate and Fe2+. The Opr peptides enhanced the decarboxylation of 2-oxoglutarate by prolyl 4-hydroxylase, the Vmax values obtained with the individual peptides being positively correlated with their inactivating efficiency. Inactivation was prevented by high concentrations of peptide substrate and ascorbate. Lineweaver-Burk kinetics experiments suggested noncompetitive inhibition with respect to peptide substrate and ascorbate. Lysyl hydroxylase was not affected by Opr peptides in concentrations of up to 1.5 mM in either the presence or absence of prolyl 4-hydroxylase. The results suggest that the oxaproline compounds are specific syncatalytic inactivators of prolyl 4-hydroxylase.

Animals↗

Mechanical loading stimulates the release of transforming growth factor-beta activity by cultured mouse calvariae and periosteal cells.

We have shown earlier that mechanical stimulation by intermittent hydrostatic compression (IHC) inhibits bone resorption and stimulates bone formation in cultured fetal mouse calvariae (Klein-Nulend et al., 1986, Arthritis Rheum., 29: 1002-1009). The production of soluble bone factors by such calvariae is also modified (Klein-Nulend et al., 1993, Cell Tissue Res., 271:513-517). Transforming growth factor-beta (TGF-beta) is an important local regulator of bone metabolism and is produced by osteoblasts. In this study, the release of TGF-beta activity as a result of mechanical stress was examined in organ cultures of neonatal mouse calvariae, in primary cultures of calvariae-derived osteoprogenitor (OPR) cells, and in more differentiated osteoblastic (OB) cells. Whole calvariae and calvariae-derived cells were cultured in the presence or absence of IHC for 1-7 days and medium concentrations of active as well as total TGF-beta were measured using a bioassay. IHC (maximum 13 kPa, maximal pressure rate 32.5 kPa/sec) was generated by intermittently (0.3 Hz) compressing the gas phase above the cultures. We found that mechanical loading by IHC stimulated the release of TGF-beta activity from cultured calvariae by twofold after 1 day. IHC also stimulated the release of TGF-beta activity from calvariae-derived cells after 1 and 3 days. The absolute amounts of TGF-beta activity released were lower in OPR cells than in OB cells, but the stimulatory effect of IHC was greater in OPR cells. Total TGF-beta (active and bound) released into the medium was not affected by IHC. IHC did not change the dry weight of the organ cultures, nor the DNA or protein content of the cell cultures. These data show that mechanical perturbation of bone cells, particularly OPR cells, enhances the activation of released TGF-beta. We conclude that modulation of TGF-beta metabolism may be part of the response of bone tissue to mechanical stress.

Animals↗

Mechanical stimulation by intermittent hydrostatic compression promotes bone-specific gene expression in vitro.

In a previous study of the cellular mechanism underlaying Wolff's law we showed that mechanical stimulation by intermittent hydrostatic compression (IHC) increases bone formation in cultured fetal mouse calvariae compared to non-stimulated cultures. To test whether mechanical stimuli may modulate bone-specific gene expression, we studied the effect of IHC on alkaline phosphatase (AP) expression and enzyme activity as well as collagen and actin mRNA levels in neonatal mouse calvariae and calvarial bone cells. Two cell populations, one resembling osteoprogenitor (OPR) cells and another resembling osteoblasts (OB) were obtained from calvariae by sequential digestion. IHC was applied by intermittently (0.3 Hz) compressing the gas- phase of a closed culture chamber (peak stress 13kPa, peak stress rate 32.5 kPas-1). In control cultures of calvariae as well as OB and OPR cells, AP activity and AP-, collagen-, and actin-mRNA levels all decreased after one or more days, with the exception of OPR cell collagen expression which increased during culture. IHC treatment upregulated AP, collagen and actin expression and AP activity in calvariae and OB cells, but decreased collagen expression in OPR cells. These results suggest that treatment with IHC promotes the osteoblastic phenotype in bone organ cultures and in osteoblasts. Osteoprogenitor cells seem to react somewhat differently to mechanical stress than osteoblasts. The loss of bone-specific gene expression under control culture conditions, in the absence of mechanical stimuli, suggests that the mechanical environment is important in maintaining the differentiated phenotype of bone cells, and that IHC treatment partially restores this environment in bone cell- and organ cultures.

Actins↗

Antibody response against Pseudomonas aeruginosa membrane proteins in experimentally infected sheep.

Shedded sheep inoculated epicutaneously with P. aeruginosa and then wetted experimentally by a sprinkler system, rapidly develop a green bacterial stain. This was associated with an outpouring of serious exudates onto the skin surface in the fleecerot lesion site. Histopathological analysis of dermatitic lesions revealed an infiltration of polymorphonuclear leucocytes into the dermis and the formation of a mosaic of microabscesses beneath the sloughed sheets of cornified epithelium. P. aeruginosa if present, was always localized as aggregates at the leading front of the seropurulent exudate and was never observed to invade the dermis. Animals that had been inoculated with P. aeruginosa but kept dry, showed no signs of dermatitis or serological reactivity against the inoculated bacterium. In contrast, sheep that had been inoculated and wetted, reacted serologically against P. aeruginosa whole cells in an enzyme-linked immunosorbent assay (ELISA). Eleven of 18 sheep were considered to be high-antibody responders and registered an ELISA ratio > 2.5 at one or more time points over the duration of the experiment (14 weeks). Analysis of ELISA reactivity of fleecerot sheep against fractionated cell envelope proteins of P. aeruginosa showed a preferential antibody response to outer (OMP) rather than inner (IMP) membrane proteins. Immunoblots revealed strong antibody activity against 2 major OMPs-Opr F and Opr H with apparent molecular masses of 39 and 21 kDa respectively. OMPs prepared from sarkosyl-resistant outer membrane vesicles were electrophoretically identical to OMPs prepared by a more rapid and efficient organic phase partitioning procedure (Chin and Dai, 1990). Although two other OMPs-Opr E (44 kDa) and Opr G (25 kDa) were seen in Coomassie blue-stained SDS-PAGE gels of P. aeruginosa OMPs, they were not reactive with sera from fleecerot affected sheep. It is likely that sheep with high levels of circulating serum antibody against major outer membrane proteins of P. aeruginosa may, in the event of a fleecerot episode, exude such antibodies onto the skin surface. This could provide a strategy for the control of ovine fleecerot by vaccination if highly conserved outer membrane proteins of P. aeruginosa were found to be protective.

Animals↗

Comparison of the reproductive biology between acaricide-resistant and acaricide-susceptible Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

The reproductive fitness of Rhipicephalus (Boophilus) microplus (Canestrini) strains resistant to organophosphate (OP), pyrethroid (P), or formamidine (F) acaricides was compared to an acaricide-susceptible (SUS) strain to determine whether the acquisition of resistance affected reproductive fitness in the resistant strains. The SUS strain females had a 3.0 days preoviposition period, a 12.1 days oviposition period, a 22.5 days egg incubation period, a mean of 3670 eggs per female, and a mean percentage egg hatch of 78.1%, which were all remarkably similar to these same parameters reported for this species throughout the world. The reproductive biology of the P-resistant strain (PYR) and the F-resistant strain (FOR) were, for the most part, similar to those of the SUS strain. In the few instances where statistical differences did occur there was little evidence that the variation had any biological basis that could be attributed to a reduction in fitness related to resistance to P or F acaricides. Although the comparison of reproductive parameters of the OP-resistant strain (OPR) and the SUS strain identified statistical differences between the mean egg incubation and oviposition periods, the magnitude of the differences was not sufficient to conclude that the OPR strain was biologically less fit than the SUS strain. However, the OPR strain produced 30% fewer eggs (2562 eggs per female) than the SUS strain (3670 eggs per female) indicating the acquisition of resistance placed the OPR at a selective disadvantage relative to the SUS strain. This coupled with a lower, though non-significant, egg hatch was used to predict there would be a reduction of at least 34.1% in larval numbers available to potentially re-infest subsequent cattle than were available from the SUS strain. These data may aid the development of management strategies that can be used to control OP-resistant ticks.

Amidines↗

From clusters to ionic complexes: structurally characterized thallium titanium double alkoxides.

A series of sterically varied titanium alkoxides [[Ti(OR)(4)](n)(), n = 4, OR = OCH(2)CH(3) (OEt); n = 1, OCH(CH(3))(2) (OPr(i)); n = 2, OCH(2)C(CH(3))(3) (ONep); n = 1, OC(6)H(3)(CH(3))(2)-2,6 (DMP)] were reacted with a series of thallium alkoxides [[Tl(OR)](x) (x = 4, OR = OEt, ONep; n = infinity, DMP)]. The resultant products of the [Tl(mu(3)-OEt)](4)-modified [Ti(OR)(4)](n)() (OR = OEt, OPr(i), ONep) were found by X-ray analysis to be Tl(4)Ti(2)(mu-O)(mu(3)-OEt)(8)(OEt)(2) (1), Tl(4)Ti(2)(mu-O)(mu(3)-OPr(i))(5)(mu(3)-OEt)(3)(OEt)(2) (2), and TlTi(2)(mu(3)-OEt)(2)(mu-OEt)(mu-ONep)(2)(ONep)(4) (3), respectively. The reaction of [Tl(mu(3)-OEt)](4), 12HOEt, and 4[Ti(mu-ONep)ONep)(3)](2) to generate 3 in a higher yield resulted in the isolation of TlTi(2)(mu(3)-OEt)(mu(3)-ONep)(mu-OEt)(mu-ONep)(2)(ONep)(4) (4). Compounds 1 and 2 possess an octahedral (Oh) arrangement of two Ti and four Tl metal atoms around a mu-O central oxide atom (the Tl-O distance is too long to be considered a bond). For both compounds, each Ti atom adopts a distorted Oh geometry with one terminal OEt ligand. The Tl atoms are formally 4-coordinated, adopting a distorted pyramidal geometry using four mu(3)-OR (OR = OEt or OPr(i)) ligands to complete their coordination sphere. The Tl atoms reside approximately 1.4 A below the basal plane of oxygens. In contrast to these structures, both 3 and 4 utilize ONep ligands and display reduced oligomerization yielding trinuclear complexes without oxo formation. The two Ti cations are Oh, and the single Tl cation is in a formal distorted pyramidal (PYD) arrangement. If the lone pair of the Tl cations are considered in the geometry, each Tl adopts a square base pyramidal geometry. Two terminal ONep ligands are bound to each Ti with the remainder of the molecule consisting of mu(3)- and mu-ONep ligands. The reaction of [Tl(mu(3)-ONep)](4) with two equivalents of [Ti(mu-ONep)(ONep)(3)](2) also led to the isolation of the homoleptic trinuclear complex TlTi(2)(mu(3)-ONep)(2)(mu-ONep)(3)(ONep)(4) (5) which is analogous in structure to the mixed ligand species of 3 and 4. Each Ti is Oh coordinated with six ONep ligands, and the single Tl is PYD bound by ONep ligands. A further increase in the steric bulk of the pendant ligands, using [Tl(mu-DMP)](infinity) and [Ti(mu-ONep)(ONep)(3)](2), resulted in a further decrease in the nuclearity yielding the dinuclear species TlTi(mu-DMP)(mu-ONep)(DMP)(ONep)(2) (6). For 6, the two metals are bound by a mu-ONep and a mu-DMP ligand. The Tl metal center was solved in a bent geometry while the Ti adopted a distorted trigonal bipyramidal (TBP) geometry using three ONep and two DMP ligands to fill its coordination sphere. Further increasing the steric bulk of the ancillary ligands using Ti(DMP)(4) and [Tl(mu-DMP)](infinity) led to the formation of [Tl(+)][(-)(eta(2-3)-DMP)Ti(DMP)(4)] (7). The Ti metal center is in a TBP geometry, and the "naked" Tl cation resides unencumbered by solvent molecules but was found to have a strong pi-interaction with four DMP ligands of neighboring Ti(DMP)(5)(-) anions. For this novel set of compounds, (205)Tl NMR spectroscopy was used to investigate the solution behavior of these compounds. Multiple (205)Tl resonances were observed for the solution spectra of the crystalline material of 1-6, and a broad singlet was observed for 7. The large number of minor resonances noted for these compounds was attributed to sensitivity of the Tl cation based on small variations due to ligand rearrangement. However, the major resonance noted in the (205)Tl NMR solution spectra of 1-7 are in agreement with their respective solid-state structures.

Journal Article↗

12-Oxophytodienoate-10,11-reductase: occurrence of two isoenzymes of different specificity against stereoisomers of 12-oxophytodienoic acid

The reduction of 12-oxophytodienoic acid (OPDA) to 3-oxo-2(2'[Z]-pentenyl)-cyclopentane-1-octanoic acid is catalyzed by 12-oxophytodienoate-10,11-reductase (OPR). Analysis of the isomer preference of OPR has indicated that the activity is composed of two isoenzymes exhibiting different stereoselectivities. The two isoforms of OPR have been separated, using protein extracts of Rock Harlequin (Corydalis sempervirens) as the starting material. OPRI, the enzyme reported earlier from the same species and corresponding to the cloned OPR from Arabidopsis, utilized 9R,13R-OPDA >> 9S, 13R-OPDA but not the 13S-configured isomers, whereas the new activity, OPRII, effectively reduced all four OPDA isomers, including the natural 9S,13S-OPDA (cis-[+]-OPDA). OPRII activity is characterized in detail. The enzyme's enzymatic, biochemical, and immunological properties prove that it is a close relative of OPRI. The roles of OPRI and OPRII in octadecanoid biology are discussed.

Journal Article↗

Cardiac rehabilitation in patients with rate responsive pacemakers.

This study investigated the suitability of our oxygen pulse reserve (OPR) method for tailoring parameters of rate responsive pacemakers and planning aerobic rehabilitation programs. We selected 11 patients, NYHA Classes I-III (7 males and 4 females; mean age 60 years, range 18-83), with rate responsive pacemakers implanted for high degree AV block and chronotropic incompetence. Five pacemakers had activity sensors, 4 had temperature sensors, and 2 had dual sensors. All patients underwent a cardiopulmonary stress test (CPX). We determined anaerobic threshold time (ATT), VO2/AT, total exercise time (TET), VO2 Max, and VO2 AT/VO2 Max. OPR (mL-O2/beat) was calculated for each patient using the formula OPR = (VO2 Max - VO2 resting)/(HR Max - HR resting). During CPX, this slope was used as the rate response tailoring guideline by comparing the mL-O2/beat equation and the pacing rate. Rate response settings were modified until the optimal relationship between theoretical and paced rate was obtained. The work protocol yielded rate response settings capable of providing pacing rates within +/- 10 beats of the theoretical values. Data relating to theoretical and measured rates have been analyzed statistically. Patients underwent an aerobic rehabilitation program that followed the American College of Sports Medicine guidelines. Pacing rate at the anaerobic threshold was considered the border for an aerobic workload. After 2-7 months, all patients showed an evident improvement in ATT (92%), VO2/AT (48%), TET (49%), VO2 Max (23%), and VO2 AT/VO2 (21%). Particularly, two patients improved from Weber Class C to A, and three improved from C to B. At each CPX step, the mean values of pacing rate and theoretical rate almost overlap, and the relevant coefficients suggest an excellent correlation (P < 0.001). Our OPR method for tailoring rate response provides the basis for an effective rehabilitation program with functional advantages for patients.

Adolescent↗

Predominance of delta-opioid-binding sites in the porcine enteric nervous system.

The antidiarrheal and constipating actions of opioids are mediated in part by enteric neurons, which lie within the wall of the small intestine and colon, but the differential expression of specific, high-affinity opioid-binding sites in ganglionated plexuses within functionally distinct intestinal segments has not been examined. We determined the saturation binding characteristics under Na+-free conditions of the nonselective opioid receptor (OPR) ligand [3H][(5alpha,7alpha)-17-(cyclopropylmethyl)-4,5-epoxy-18,19-dihydro-3-hydroxy-6-methoxy-alpha, alpha-dimethyl-6,14-ethenomorphinan-7-methanol] (diprenorphine) and the respective delta-, kappa-, and mu-OPR ligands [3H]naltrindole, D-(5alpha,7alpha,8beta)-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxoaspiro-(4,5)dec-8-yl]benzeneacetamide ([3H]U-69,593), and [3H][D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) in neuronal membranes isolated from myenteric and submucosal plexuses of porcine small intestine and colon. Naloxone-displaceable [3H]diprenorphine-binding sites (KD values ranging from 0.2-0.5 nM and Bmax = 50-95 fmol/mg of protein) were found in both subregions from all gut segments examined. High-affinity [3H]naltrindole sites (KD = 60-140 pmol) were at highest densities (approximately 60 fmol/mg of protein) in submucosal plexus of the ileum and distal colon myenteric plexus and were at lowest densities (8-9 fmol/mg of protein) in the submucosal plexuses of cecum and distal colon. [3H]U-69,593 sites (KD = 0.3-4 nM) were present only in the myenteric plexuses of all segments examined, with highest densities in cecum and proximal colon (44-47 fmol/mg of protein). [3H]DAMGO-binding sites were expressed at relatively low densities in the enteric plexuses of all gut regions. These results indicate that delta-OPRs predominate in the porcine enteric nervous system with a more circumscribed expression of kappa- and mu-OPRs.

Animals↗

Protection of immunocompromised mice against lethal infection with Pseudomonas aeruginosa by active or passive immunization with recombinant P. aeruginosa outer membrane protein F and outer membrane protein I fusion proteins.

Recombinant outer membrane proteins (Oprs) of Pseudomonas aeruginosa were expressed in Escherichia coli as glutathione S-transferase (GST)-linked fusion proteins. GST-linked Oprs F and I (GST-OprF190-350 [GST linked to OprF spanning amino acids 190 to 350] and GST-OprI21-83, respectively) and recombinant hybrid Oprs (GST-OprF190-342-OprI21-83 and GST-OprI21-83-OprF190-350) were isolated and tested for their efficacy as vaccines in immunodeficient mice. GST-OprF-OprI protected the mice against a 975-fold 50% lethal dose of P. aeruginosa. Expression of GST-unfused OprF-OprI failed in E. coli, although this hybrid protein has been expressed without a fusion part in Saccharomyces cerevisiae and used for immunizing rabbits. The immune rabbit sera protected severe combined deficient (SCID) mice against a 1,000-fold 50% lethal dose of P. aeruginosa. Evidence is provided to show that the most C-terminal part of OprF (i.e., amino acids 332 to 350) carries an important protective epitope. Opr-based hybrid proteins may have implications for a clinical vaccine against P. aeruginosa.

Animals↗

Geographic boundaries in breast, lung and colorectal cancers in relation to exposure to air toxics in Long Island, New York.

BACKGROUND: This two-part study employs several statistical techniques to evaluate the geographic distribution of breast cancer in females and colorectal and lung cancers in males and females in Nassau, Queens, and Suffolk counties, New York, USA. In this second paper, we compare patterns in standardized morbidity ratios (SMR values), calculated from New York State Department of Health (NYSDOH) data, to geographic patterns in overall predicted risk (OPR) from air toxics using exposures estimated in the USEPA National Air Toxics Assessment database. RESULTS: We identified significant geographic boundaries in SMR and OPR. We found little or no association between the SMR of colorectal and breast cancers and the OPR for each cancer from exposure to the air toxics. We did find boundaries in male and female lung cancer SMR and boundaries in lung cancer OPR to be closer to one another than expected. CONCLUSION: While consistent with a causal relationship between air toxics and lung cancer incidence, the boundary analysis does not demonstrate the existence of a causal relationship. However, now that the areas of overlap between boundaries in lung cancer incidence and potential airborne exposures have been identified, we can begin to evaluate local- as well as large-scale determinants of lung cancer.

Journal Article↗

Long and short forms of the ovine prolactin receptor: cDNA cloning and genomic analysis reveal that the two forms arise by different alternative splicing mechanisms in ruminants and in rodents.

Prolactin is a pituitary hormone that binds to specific receptors in numerous tissues. Depending on the size of their cytoplasmic domain, long and short prolactin receptors (l-PR, s-PR) have been described. Up to now, s-PR were found in rodents only. We report here the cloning of full-length coding sequences for short and long ovine prolactin receptors (s-oPR, l-oPR). The only difference between s- and l-oPR coding sequences was, respectively, the presence or absence of a 39 base pair insert at the beginning of the cytoplasmic domain, with two contiguous inframe stop codons at its 3' end. Sequence comparison revealed that the alternative splicing producing s- and l-oPR was different from that of rodents, although the resulting proteins were very similar. PCR experiments on ovine genomic DNA showed that the 39 base pair insert was directly linked to the downstream exon, and separated from the upstream exon by an 800 base pair intron. Thus, the alternative splicing used a single intron with one 5' and two 3' sites. The same organization was found in bovine and caprine genomes, suggesting that this feature is general in ruminants and different from rodents, which use mutually exclusive exons to produce s-PR and l-PR.

Alternative Splicing↗

[Goal-oriented outcome measurement in inpatient or day care orthopedic-rheumatologic rehabilitation of patients with back pain].

The comparison of patient characteristics and effectiveness of inpatient rehabilitation (IPR) and outpatient rehabilitation (OPR) is of growing importance in terms of flexible and cost-effective structures in rehabilitation. The effectiveness of the treatment is measured applying a goaloriented approach based on the individual rehabilitation goals and the attainment of these goals at the end of the programme. The frequencies of rehabilitation goals chosen by patients in IPR and OPR are similar. Decrease of pain, improvement of muscular strength and improvement of the range of motion are the main goals of patients in IPR and OPR (92-56%). No relevant differences can be seen considering the effectiveness of IPR and OPR, except for the markedly higher improvement of vitality in IPR. Patients in need of rehabilitation whose primary rehabilitation goal is improvement of vitality should therefore preferentially be referred to an inpatient rehabilitation programme.

Adult↗

[Laparoscopic rectum repair].

A reliable and simple method of allograft fixation in laparoscopic posterior-loop rectopexy (LPR) was developed. The study was carried out on 40 cadavers, peak effort of separation of the net fixed to the sacrum by various methods was evaluated. Effort of separation in fixation of the net by sutures was 10.1 +/- 2.12 kg, in fixation by hernial stapler--1.13 +/- 0.36 kg, stapler "Pro-Tack"--6.38 +/- 1.85 kg, in fixation of the net by the new device--8.9 +/- 0.75 kg. From 1995 till 1999 LPR was performed with the new device in 15 patients, the open posterior-loop rectopexy (OPR) with fixation of the net by non-absorbable sutures--in 16 patients. In LPR intraoperative blood flow was twice as small (146.0 +/- 79.2 ml) as in OPR (275.6 +/- 76.9 ml). Mean time of LPR was 183.1 +/- 69.8 min, OPR--211.3 +/- 57.9 min. Relief of pain after LPR enabled with reduction of narcotic analgetics requirement (58.3 +/- 1.5 mg). Mean dose of narcotic analgetics after OPR was 93.2 +/- 1.4 mg. The proposed method of allograft fixation and device for it realization are effective and meet all requirements.

Analgesics, Opioid↗

[Central hemodynamics as dependent on the method of bicycle exercise in sanatorium patients who have had a myocardial infarct].

AIM: To study central hemodynamics response to bicycle exercise with optimal pedalling rate (OPR) and in free-choice regimen of pedalling as regards the initial pedalling rate in postmyocardial infarction (PMI) patients on sanatorium treatment. MATERIALS AND METHODS: Bicycle ergometry and tetrapolar rheography examinations were performed in 124 PMI male patients. Bicycle exercise was carried out in three regimens: a) optimal pedalling rate (1), b) muscular load chosen by the patient at the first training kept further for daily training (2), c) free-choice daily load (3). RESULTS: In OPR 30 and 45 rpm, patients on regimen 3 improved their myocardial contractility both at rest and exercise. In OPR 60 rpm, exercise in regimen 1 was more effective. Regimen 2 was not effective. CONCLUSION: Hemodynamic effects were most pronounced (improved myocardial contractility in more effective cardiac performance) in the regimen of OPR 60 rpm.

Adult↗

Effects of theophylline on respiratory drive in patients with chronic obstructive pulmonary disease.

Effects of theophylline administration on the respiratory drive were studied in seven patients with chronic obstructive pulmonary disease (COPD). End tidal CO2 (PetCO2), minute ventilation (Ve), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), oxygen consumption (VO2), carbon dioxide output (VCO2), serum theophylline level (STL), ventilatory response (VeR), and mouth occlusion pressure response (OPR) to rise in PetCO2 on rebreathing were measured before and at 2-hour intervals after oral administration of 5 mg/kg anydrous theophylline or placebo. Mouth occlusion pressure response and VeR showed c significant increase after theophylline but not after placebo. Significant positive correlation between changes (delta) in STL and OPR (delta OPR = 0.025 + 0.8 delta STL; SEE = 1; r = 0.4; P < 0.005) and between STL and VeR (VeR = 0.82 + 0.055 STL +/- SEE = 0.7; r = 0.46; P < 0.01) and an inverse correlation between delta STL and delta PetCO2 (delta PetCO2 = 13.8 - 0.59 delta STL; SEE = 9.1; r = 0.61; P < 0.001) were noted. There was no correlation between the indices of respiratory drive and FEV1, Ve, VO2, or VCO2. It is concluded that theophylline increases respiratory drive in clinically employed doses independently of its bronchodilator or metabolic effects.

Aged↗

Orthogonal polynomial regression for the detection of response variability in event-related fMRI.

Previous studies using event-related potentials (ERPs) have identified a variety of brain regions that respond to rare nontarget distractor stimuli presented in the visual oddball task. By contrast, event-related functional magnetic resonance imaging (ER-fMRI) studies using similar stimuli have found little or no response in these same regions, suggesting that ER-fMRI may be less sensitive than ERPs for detecting stimulus-evoked activity. It was hypothesized here that variations in ER-fMRI response amplitude evoked by successive stimuli may have reduced detection sensitivity in these previous studies. Multiple regression with orthogonal polynomials (OPR) was used to increase detection sensitivity by employing orthogonal polynomial equations to model such variations in response amplitude. ER-fMRI data was collected from 17 subjects during performance of the visual oddball task, which included frequent nontarget, rare nontarget distractor, and rare target block letter stimuli, to which subjects made a speeded button press response. When compared with multiple regression using main effect regressors alone, OPR identified an increased volume of significant target and distractor evoked main effect response due to reduced error variance. In addition, distractor-evoked activity was found to correlate with orthogonal polynomial regressors but not main effect regressors across a large volume of prefrontal and paralimbic brain regions including dorsal-lateral prefrontal, inferior-lateral prefrontal, and cingulate cortex. These results illustrate that considerable variability is present in ER-fMRI responses evoked by rare distractor stimuli in the oddball task. Such variability can be modeled using OPR, leading to increased detection sensitivity and better anatomical correspondence between the findings of ER-fMRI and ERP studies.

Adult↗