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PubMed2000

Comprehensive two-dimensional gas chromatography and chemometrics for the high-speed quantitative analysis of aromatic isomers in a jet fuel using the standard addition method and an objective retention time alignment algorithm

A high-speed quantitative analysis of aromatic isomers in a jet fuel sample is performed using comprehensive two-dimensional gas chromatography (GC x GC) and chemometrics. A GC x GC separation time of 2.8 min is achieved for three aromatic isomers in jet fuel, which is 5 times faster than a reference method in which a singlecolumn separation resolves two of the three isomers of interest. The high-speed GC x GC separation is more than 10 times faster than a recent GC x GC separation that fully resolves the three components of interest in gasoline. The high-speed GC x GC analysis of jet fuel is accomplished through short GC columns, high gas velocities, and partial chromatographic peak resolution followed by chemometric resolution of overlapped peaks. The standard addition method and an objective retention time alignment algorithm are used to correct for retention time variations prior to the chemometric data analysis. The standard addition method corrects for chemical matrix effects that cause analytes in complex samples to have peak shapes, widths, and retention times that differ considerably from those of calibration standards in pure solvents. The retention time alignment algorithm corrects for the relatively small retention time variations caused by fluctuating instrumental parameters such as flow rate and temperature. The use of data point interpolation in the retention time alignment algorithm results in a more accurate retention time correction then previously achieved. The generalized rank annihilation method (GRAM) is the chemometric technique used to resolve the overlapped GC x GC peaks. The correction of retention time variations allows for successful GRAM signal deconvolution. Using the retention time alignment algorithm, GRAM quantification accuracy and precision are improved by a factor of 4. The methodology used in this paper should be applicable to other comprehensive separation methods, such as two-dimensional liquid chromatography, liquid chromatography coupled with capillary electrophoresis, and liquid chromatography coupled with gas chromatography.

Journal Article↗

PubMed2006

Liquid chromatography at critical conditions: comprehensive approach to sequence-dependent retention time prediction.

An approach to sequence-dependent retention time prediction of peptides based on the concept of liquid chromatography at critical conditions (LCCC) is presented. Within the LCCC approach applied to biopolymers (BioLCCC), the specific retention time corresponds to a particular sequence. In combination with mass spectrometry, this approach provides an efficient tool to solve problems wherein the protein sequencing is essential. In this work, we present a theoretical background of the BioLCCC concept and demonstrate experimentally its feasibility for sequence-dependent LC retention time prediction for peptides. BioLCCC model is based on three notions: (a) a random walk model for a macromolecule chain; (b) an entropy and energy compensation for the macromolecules within the adsorbent pore; and (c) a set of phenomenological parameters for the effective interaction energies of interactions between the amino acid residues and the adsorbent surface. In this work, the phenomenological parameters have been obtained for C18 reversed-phase HPLC. Note, that contrary to alternative additive models for retention time prediction based on summation of the so-called "retention coefficients", the BioLCCC approach takes into account the location of amino acids within the primary structure of a peptide and, thus, allows the identification of the peptides having the same composition of amino acids but differing by their arrangement. As a result, this new approach allows prediction of retention time for any possible amino acid sequence in particular HPLC experiments. In addition, the BioLCCC model lacks of main drawbacks of additive approaches that predict retention time for sequences of limited chain lengths and provide information about amino acid composition only. The proposed BioLCCC approach was characterized experimentally using LTQ FT LC-MS and LC-MS/MS data obtained earlier for Escherichia coli. The HPLC system calibration was performed using peptide retention standards. The results received show a linear correlation between predicted and experimental retention times, with a correlation coefficient, R2, of 0.97 for a peptide standard mixture and 0.9 for E. coli data, respectively, with the standard error below 1 min. The work presents the first description of a BioLCCC approach for high-throughput peptide characterization and preliminary results of its feasibility tests.

Adsorption↗

PubMedDate not supplied

Prediction of peptide retention at different HPLC conditions from multiple linear regression models.

To quantitatively characterize the structure of a peptide and to predict its gradient retention time at given HPLC conditions three structural descriptors are used: (i) logarithm of the sum of retention times of the amino acids composing the peptide, log SumAA, (ii) logarithm of the van der Waals volume of the peptide, log VDW(Vol), (iii) and the logarithm of the peptide's calculated n-octanol-water partition coefficient, clog P. The log SumAA descriptor is obtained from empirical data for 20 natural amino acids, determined in a given HPLC system. The two other descriptors are calculated from the peptides' structural formulas using molecular modeling methods. The quantitative structure-retention relationships (QSRR), build by multiple linear regression, describe HPLC retention of peptide on a given chromatographic system on which the retention of the 20 amino acids was predetermined. A structurally diversified series of 98 peptides was employed. The predicted gradient retention times on several chromatographic systems were in good agreement with the experimental data. The QSRR equations, derived for a given system operated at variable gradient times and temperatures allowed for the prediction of peptide retention in that system. Matching the experimental HPLC retention to the theoretically predicted for a presumed peptide could facilitate original protein identification in proteomics. In conjunction with MS data, prediction of the retention time for a given peptide might be used to improve the confidence of peptide identifications and to increase the number of correctly identified peptides.

Amino Acid Sequence↗

PubMed1979

Immune retention: immunological requirements for maintaining an easily degradable antigen in vivo.

Radioactive human serum albumin (125I-HSA) was injected into the hind foot pads of unimmunized mice, actively immunized mice and mice passively immunized with mouse or rabbit anti-HSA serum. Eleven days later the unimmunized mice had cleared most of the 125I-HSA. In contrast, a high concentration of 125I-HSA was retained in the feet and draining lymph nodes and, to a lesser extent, in the spleen of the actively or passively immunized mice. Although immune retention required specific antibody, it appeared to be independent of T-cells or T-cell factors, since passively immunized nude mice retained antigen as well as actively or passively immunized normal mice. Depletion of the complement system with cobra venom factor (CVF) increased antigen retention in the feet but decreased retention in the spleen. Treatment with CVF did not decrease antigen retention in lymph nodes of actively immunized mice. Such treatment did, however, decrease retention in lymph nodes of passively immunized mice although not to the same extent as in the spleen. Retention of antigen in the feet was not only complement-independent but was also Fc independent, since F(ab')2 fragments of IgG could mediate immune retention. Antigen dose response studies indicated that immune retention in lymph nodes occurred optimally with minute amounts of antigen, whereas optimal retention in the feet required much higher concentrations of antigen. Foot pad injections of non-radiolabelled HSA eliminated 60% of the radioactivity retained in the foot pads of immunized mice. In contrast, non-radioactive egg albumin (EA) had almost no effect on retained HSA. However, if the mice were immunized to both EA and HSA, an injection of EA would displace a significant amount of retained HSA. Complexes of one specificity can apparently displace some retained antigen of a differing specificity.

Animals↗

PubMed1994

A retention index for micellar electrokinetic chromatography.

A retention index system has been developed for micellar electrokinetic chromatography (MEKC). Three homologous series: alkyl aryl ketones (phenones), 1-nitroalkanes, and alkylbenzenes were studied for use as retention index standards. Micellar systems consisting of sodium dodecyl sulfate (SDS), SDS/Brij 35 (polyoxyethylene lauryl ether), and SDS/SB-12 (N-dodecyl-N, N-dimethylammonium-3-propane-1-sulfonic acid) were used as pseudostationary phases. In addition, three organic modifiers: acetonitrile, methanol, and 1-propanol were used with SDS to evaluate their effect on the retention indices calculated for a set of neutral compounds. Retention indices for the neutral compounds did not vary significantly over the range of surfactant concentrations employed for each of the micellar systems (RSD < 2.0% for non-extrapolated retention indices). However, in the systems where an organic modifier was employed, the calculated retention indices showed some variation (RSD < 3.0%) at different SDS concentrations. The 1-nitroalkanes were found to be the most suitable for use as retention index standards. Alkyl aryl ketones were found to be effective retention index standards for more hydrophobic solutes, but they were not effective for very hydrophilic solutes even with a large amount of organic modifier added to the operating buffer. The alkylbenzenes were too hydrophobic (highly retained) than the alkyl aryl ketones and, therefore, cannot be recommended for use as retention index standards in MEKC.

Chromatography↗

PubMed2002

Multiple determinants in voltage-dependent P/Q calcium channels control their retention in the endoplasmic reticulum.

Surface expression level of voltage-dependent calcium channels is tightly controlled in neurons to avoid the resulting cell toxicity generally associated with excessive calcium entry. Cell surface expression of high voltage-activated calcium channels requires the association of the pore-forming subunit, Cavalpha, with the auxiliary subunit, Cavbeta. In the absence of this auxiliary subunit, Cavalpha is retained in the endoplasmic reticulum (ER) through mechanisms that are still poorly understood. Here, we have investigated, by a quantitative method based on the use of CD8 alpha chimeras, the molecular determinants of Cavalpha2.1 that are responsible for the retention, in the absence of auxiliary subunits, of P/Q calcium channels in the ER (referred to here as 'ER retention'). This study demonstrates that the I-II loop of Cavalpha2.1 contains multiple ER-retention determinants beside the beta subunit association domain. In addition, the I-II loop is not the sole domain of calcium channel retention as two regions identified for their ability to interact with the I-II loop, the N- and C-termini of Cavalpha2.1, also produce ER retention. It is also not an obligatory determinant as, similarly to low-threshold calcium channels, the I-II loop of Cavalpha1.1 does not produce ER retention in COS7 cells. The data presented here suggests that ER retention is suppressed by sequential molecular events that include: (i). a correct folding of Cavalpha in order to mask several internal ER-retention determinants and (ii). the association of other proteins, including the Cavbeta subunit, to suppress the remaining ER-retention determinants.

Animals↗

PubMed1997

Calcium retention in relation to calcium intake and postmenarcheal age in adolescent females.

Achievement of maximal calcium retention during adolescence may influence the magnitude of peak bone mass and subsequently lower the risk of osteoporosis. Calcium retention is generally considered to reach a plateau at a certain calcium intake. To test this hypothesis, calcium balance was measured in 35 females with a mean (+/-SD) age of 12.7 +/- 1.2 y (range: 12-15 y) who consumed from 841 +/- 153 to 2173 +/- 149 mg Ca/d. Subjects ate a basal diet that included a fortified beverage containing different amounts of calcium citrate malate. Twenty-one subjects were studied at two dietary calcium intakes with use of a crossover design. Results from a previous study in 14 subjects who were studied at only one calcium intake were included in the data analysis. Calcium retention was modeled as a nonlinear function of calcium intake that included a parameter representing mean maximal retention. Mean maximal calcium retention was 473 mg/d (95% CI: 245, 701 mg Ca/d). At higher postmenarcheal ages, maximal calcium retention was lower but the intake required to achieve this was not affected. Calcium intake explained 79% and 6%, respectively, of the variation in fecal and urinary calcium excretion. Intake of 1200 mg Ca/d, the recommended dietary allowance for calcium published in 1989, resulted in a mean calcium retention that was 57% of the maximal value (95% CI: 25%, 89%). Intake of 1300 mg Ca/d was the smallest intake that allowed some adolescent females to achieve 100% of maximal calcium retention (95% CI: 26%, 100%). These data support the idea that calcium retention plateaus at a certain calcium intake although it continues to increase at intakes > 2 g/d.

Adolescent↗

PubMed2004

Recovery of renal retention function by differentiating the Patlak-Rutland plot.

INTRODUCTION: It has been suggested that renal retention function can be estimated by differentiation of the Patlak-Rutland plot. AIM: To evaluate the error resulting from this method. METHODS: A total of 5800 renograms were generated by convolving real input functions with artificial retention functions. Ten bi-exponential plasma disappearance curves of Tc mercaptoacetyltriglycine (Tc-MAG3) with varying renal clearances served as input functions and 580 retention functions with mean transit time between 3 and 60 min, and variable ratios of minimal to mean transit time served as original retention functions. The retention function was estimated by differentiation of the Patlak-Rutland plot of each renogram. A variant of this retention function was calculated by setting negative values to zero. RESULTS: Minimal transit time was estimated correctly in all cases but the recovered retention function systematically underestimated the original, and negative values were observed. Mean transit time was underestimated with a difference ranging from -22.05 to -0.06 min. By setting the negative values to zero, a less important underestimation was observed which ranged from -13.37 to 0.00 min. Maximal transit time was underestimated systematically with a difference ranging from -22.05 to 0.00 min. All differences were influenced by mean transit time, renal clearance and ratio of minimal to mean transit time. CONCLUSION: Estimation of the renal retention function by differentiation of the Patlak-Rutland plot results in systematic and sometimes important underestimations. By setting the negative values of the recovered retention function equal to zero, important but still partial improvement can be obtained.

Algorithms↗

PubMed1992

The carboxylesterase family exhibits C-terminal sequence diversity reflecting the presence or absence of endoplasmic-reticulum-retention sequences.

Resident proteins of the endoplasmic reticulum lumen are continuously retrieved from an early Golgi compartment by a receptor-mediated mechanism. The sorting or retention sequence on the endoplasmic reticulum proteins is located at the C-terminus and was initially shown to be the tetrapeptide KDEL in mammalian cells and HDEL in Saccharomyces cerevisiae. The carboxylesterases are a large family of enzymes primarily localized to the lumen of the endoplasmic reticulum. Retention sequences in these proteins have been difficult to identify due to atypical and heterogeneous C-terminal sequences. Utilizing the polymerase chain reaction with degenerate primers, we have identified and characterized the C-termini of four members of the carboxylesterase family from rat liver. Three of the carboxylesterases sequences contained C-terminal sequences (HVEL, HNEL or HTEL) resembling the yeast sorting signal which were reported to be non-functional in mammalian cells. A fourth carboxylesterase contained a distinct C-terminal sequence, TEHT. A full-length esterase cDNA clone, terminating in the sequence HVEL, was isolated and was used to assess the retention capabilities of the various esterase C-terminal sequences. This esterase was retained in COS-1 cells, but was secreted when its C-terminal tetrapeptide, HVEL, was deleted. Addition of C-terminal sequences containing HNEL and HTEL resulted in efficient retention. However, the C-terminal sequence containing TEHT was not a functional retention signal. Both HDEL, the authentic yeast retention signal, and KDEL were efficient retention sequences for the esterase. These studies show that some members of the rat liver carboxylesterase family contain novel C-terminal retention sequences that resemble the yeast signal. At least one member of the family does not contain a C-terminal retention signal and probably represents a secretory form.

Amino Acid Sequence↗

PubMed1982

Some observations on urinary retention and deep hip sepsis following total hip replacement.

A follow-up study was made of 256 hip replacements, performed at Dunedin Hospital by three orthopaedic surgeons in males aged 45 years and over for the six year period beginning 1975 through to the end of 1980. One surgeon (A) had an elaborate management policy designed to reduce postoperative urinary retention and his cases are compared with Surgeon B's whose methods of avoiding urinary retention would be more representative of the majority of orthopaedic surgeons. Analysis was performed of the 20 cases of urinary retention pooled from all three participating surgeons. Also analysed were the 24 cases of epidural anaesthetics in the entire series. Surgeon A had a significantly (P=.045) lower postoperative urinary retention rate of 3.23% compared to surgeon B (12.07%). Analysis of the 20 cases of urinary retention revealed that cases having retention after previous operations and having nothing done about it invariably went into retention again. The retention rate after the 24 epidural anaesthetics was 16.7% and the retention rate after the 232 general anaesthetic cases was 6.9%. This difference was not statistically significant (p=0.10).

Aged↗

PubMed2006

Improving patient retention after botulinum toxin type A treatment.

BACKGROUND: Botulinum toxin treatments have been associated with consistently high patient satisfaction rates, but calculation of patient retention rates is not routinely performed. Retention measurements serve as critical indicators of clinical performance and can be optimized by evaluation of current office policies and implementation of strategies to improve patient retention. PURPOSE: To investigate the reasons patients discontinue botulinum toxin treatments and to evaluate the effect of a single intervention intended to improve patient retention. METHODS: A retrospective chart review was performed of all patients who received botulinum toxin injections in a private cosmetic dermatology practice over a 2-year time period to determine the patient retention rate. Patients who had discontinued botulinum toxin treatment after a single session were surveyed to discern their reasons for terminating treatment. A change in office policy was instituted wherein all patients who received their first botulinum toxin treatment were required to undergo a 2-week post-treatment evaluation to determine treatment effect and to receive touch-up treatment as necessary. Retention rates were calculated over the 1-year period immediately after initiation of the new policy. RESULTS: The initial patient retention rate was 55%. The most common reasons cited for discontinuance of botulinum toxin treatments were procedural cost, patient failure to re-schedule, perceived lack of product longevity, and clinical effect falling short of expectations. After initiation of the mandatory 2-week post-treatment office evaluation, a 67% patient retention rate was achieved. CONCLUSIONS: Managing patient expectations of botulinum toxin treatments and mandatory post-treatment appointments for evaluation of the initial procedure increase the patient retention rate.

Appointments and Schedules↗

PubMed1996

Rural physician satisfaction: its sources and relationship to retention.

This study uses survey data to identify areas of satisfaction and dissatisfaction for primary care physicians working in rural areas across the country. It also identifies the specific areas of satisfaction associated with longer retention within a given rural practice, as well as the characteristics of individuals, practices, jobs, and communities associated with the areas of satisfaction that predict retention. Study subjects comprised a sample of 1,600 primary care physicians who moved to nonmetropolitan counties nationwide during the years 1987 through 1990, with oversampling of those who moved to federally designated health professional shortage areas (HPSAs). Physicians serving in the National Health Service Corps (NHSC) were excluded. Sixty-nine percent of the eligible subjects returned completed mail questionnaires in 1991. Analyses for this study were limited to the 620 primary care physicians who worked more than 20 hours per week in towns of fewer than 35,000 population; who were neither in the military nor the NHSC; and who were not in urgent care, emergency room, or full-time teaching positions. Analyses revealed that the areas of rural physicians' greatest satisfaction were their relationships with patients, clinical autonomy, the care they provided to medically needy patients, and life in small communities. Physicians were least satisfied with their access to urban amenities and the amount of time they spent away from their practices. Retention was independently associated only with physicians' satisfaction with their communities and their opportunities to achieve professional goals. Retention was also marginally related to physicians' satisfaction with their earnings. Among the areas of satisfaction not related to retention were satisfaction with autonomy, access to medical information and consultants, and the quality of doctor-patient relationships. In a subsequent series of analyses of the factors that predict the three areas of satisfaction that were associated with retention (satisfaction with the community, professional goal attainment, and earnings), a variety of physician, work, and community factors were identified. These findings reveal that specific features of rural physicians, their work, and their communities predict each of the various aspects of satisfaction and that only certain aspects of satisfaction predict rural physicians' retention. There are no magic bullets to make rural physicians satisfied in all ways. Nevertheless, there are identified approaches to elevate the specific aspects of rural physicians' satisfaction important to their retention. Programs to improve the satisfaction of rural physicians should focus on those areas of satisfaction that predict longer retention and other important outcomes.

Data Collection↗

PubMed2003

Predictive accuracy of rural physicians' stated retention plans.

CONTEXT: The retention of rural physicians is a difficult phenomenon to study because job changes--the outcome of interest--take years to unfold. One common way to study retention is to ask rural practitioners through surveys how much longer they expect to remain in their current positions and use these statements of "anticipated retention" as an expedient proxy measure of actual retention. PURPOSE: To test the predictive accuracy of rural physicians' stated retention plans and test the hypotheses that predictions are more accurate for certain physicians, such as those with more experience, more control of their work situations, and at less risk for job burnout. METHODS: A 1991 mail survey (national stratified random sample) prospectively queried rural physicians' retention plans, and a follow-up survey 5 to 6 years later determined if and when respondents (N = 405, 67.5% combined response rate) had moved. FINDINGS: Retention predictions for the entire cohort corresponded remarkably well to the group's actual retention, with the proportion remaining each year deviating by only a few percentage points from what the group collectively expected. Predictions for individuals were also moderately accurate: 4 of 5 physicians who predicted remaining at least 5 years did so; 2 of 3 who predicted remaining less than 5 years indeed left before 5 years. Predictions of job changes in less than 2 years tended to be more accurate than predictions of 2 to 5 years. Physicians' predictions were more accurate when they worked in practices they owned (greater control) and were on-call 2 or fewer times each week (lower burnout risk). Accuracy was not greater with any of 5 measures of experience. CONCLUSIONS: Rural generalist physicians are moderately accurate when reporting how much longer they will remain in their jobs, validating the use of anticipated retention in rural health workforce studies.

Adult↗

PubMed2004

Factors influencing the retention and attrition of community health aides/practitioners in Alaska.

CONTEXT: The Community Health Aide Program (CHAP) is a unique program employing local, indigenous peoples as primary care nonphysician providers in extremely remote frontier, tribal Alaskan communities. With attrition rates up to 20%, recommendations for improving retention are necessary to maintain access to health services for Alaska Natives in these communities. PURPOSE: The purpose of this study was to identify factors contributing to retention in Alaska's CHAP program. METHODS: Key informant interviews were conducted with 41 community health aides/practitioners (CHA/Ps) in 15 villages statewide. Efforts were made to ensure the sample included a mix of villages with high retention of health aides and villages with lower retention. Geographic and ethnic diversity were also considered. Transcripts were coded using NUD*IST software, and data were analyzed for differences between high retention and low retention villages and between more experienced and less experienced CHA/Ps. FINDINGS: Five fundamental needs of health aides were identified as crucial for retention of personnel. These needs include strong co-worker support, access to basic training, a fully staffed clinic, good community support, and supportive families. CONCLUSIONS: For 35 years, the CHAP program has worked to diminish health disparities for Alaska Natives. Though unique challenges associated with the job have factored into low retention of CHA/Ps, improved retention is possible with easier access to basic training, increased support from colleagues and community, enhanced team-building skills, and better on-call schedules.

Adult↗

PubMed2002

Activated polymorphonuclear cells increase sickle red blood cell retention in lung: role of phospholipids.

This study investigates the role of the activated polymorphonuclear cell (APMN) products on sickle red blood cell (SRBC) retention/adherence in the pulmonary circulation. Isolated rat lungs were perfused with (51)Cr-labeled normal RBCs (NRBC) or SRBCs (10% hematocrit) suspensions +/- PMNs. Specific activities of lung and perfusate were measured and retention (the number of SRBC/g lung) was calculated. SRBC retention was 3.5 times greater than NRBC retention. PMN activation was required to increase SRBC retention. Supernatants from APMN increased SRBC retention, which suggested soluble products such as oxidants, PAF, and/or leukotriene (LTB(4)) are involved. Heat inactivation of PMN NADPH oxidase had no effect on retention. Whereas neither platelet-activating factor (PAF) nor LTB(4) (secreted by APMN) increased SRBC retention, PAF+LTB(4) did. The PAF antagonist, WEB-2170, attenuated SRBC retention mediated by PAF+LTB(4) and APMNs. Similarly, zileuton (5-lipoxygenase inhibitor) attenuated APMN-mediated SRBC retention. We conclude the concomitant release of PAF and LTB(4) from APMN is involved in the initiation of microvascular occlusion by SRBCs in the perfused rat lung.

Anemia, Sickle Cell↗

PubMed1994

Effects of environmental parameters and composition of poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymers on the retention of rat lymphocyte subpopulations (B- and T-cells).

Retention behavior of rat lymphocyte subpopulations (B- and T-cells) was investigated on poly(2-hydroxyethyl methacrylate)-graft-polyamine (HA) copolymers with various copolymer compositions. Separation mechanism of B- and T-cells was then evaluated by focusing on several parameters, such as pH, temperature, and ionic strength. The interaction of lymphocytes with HA surfaces was mainly through the electrostatic force from their retention profile at varying ionic strengths of the medium. Temperature also has a crucial effect on the response of lymphocytes toward pH-induced phase transition of polyamine grafts at the polymer interface with aqueous milieu. At 4 degrees C, both B- and T-cells showed minimal retention on HA surfaces at pH 8. At this pH, polyamine grafts existed in a compact conformation with a low degree of protonation. However, at pHs below 8, at which polyamine grafts existed in extended conformation, the resolution of B- and T-cells was achieved. In contrast, at 23 degrees C, the phase transition of polyamine grafts significantly influenced T-cell retention, resulting in a decrease in the retention of T-cells on HA with polyamine in a compact conformation. Consequently, preferential retention of B-cells was achieved under this condition. The polyamine content was found to be another important factor affecting the retention behavior of lymphocyte subpopulations. On HA copolymers with low polyamine content (HA7, HA10), conformational transition of polyamine grafts showed a significant influence for B-cell retention, although the influence decreased with increasing polyamine content. From the study estimating the effect of neuraminidase treatment of lymphocytes on their retention to HA surfaces, sialic acid residues on the plasma membrane surface of lymphocytes are suggested as feasible anionic sites showing electrostatic interaction with polyamine grafts.

Amines↗

PubMed2002

Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats.

The effect of post-training intrahippocampal injection of gamma-aminobutyric acid (GABA) receptor agonists and antagonists, immediately after a training session on memory retention of passive avoidance learning in rats, was measured in the presence and absence of physostigmine. Post-training treatments were carried out in all the experiments. The different doses of the GABAA receptor agonist muscimol (2, 4 and 6 microg/rat) decreased memory retention in rats dose-dependently. The higher response was obtained with 6 microg/rat of the drug. When the GABAA receptor antagonist bicuculline (0.5, 1, 2 and 4 microg/rat) was administered, only one dose of the drug (1 microg/rat) increased memory retention; however, the antagonist reduced the effect of muscimol. The GABAB receptor agonist, baclofen (0.25, 0.5, 1 and 2 microg/rat) also reduced memory retention in the animals. Intrahippocampal injection of lower doses of the GABAB receptor antagonist CGP35348 (P-[3-aminopropyl]-p-diethoxymethyl-phosphinic acid) (2.5, 5, 10 microg/rat) did not effect memory retention, although the higher doses of the drug (25 and 50 microg/rat) decreased memory retention. The doses of antagonist (2.5, 5 and 10 microg/rat), which did not elicit any response alone, reduced the effect of baclofen. The inhibitory response of CGP35348 was also decreased by bicuculline. In another series of experiments, physostigmine improved memory retention. The GABA receptor agonists, muscimol and baclofen, as well as the GABA receptor antagonists bicuculline and CGP35348, decreased the effect of physostigmine. Atropine decreased memory retention by itself and potentiated the response of muscimol and baclofen. It is concluded that GABAA and GABAB receptor activation may be involved in the impairment of memory retention.

Animals↗

PubMed1984

Effect of age and diet on renal cadmium retention in rats.

The results of our previous and recent work on cadmium metabolism in relation to age and diet are presented. Experiments were performed on albino rats aged 1-26 weeks. In some experiments rats were given different foods (milk, meat, bread) instead of standard rat diet. Some animals received trisodium calcium salt of diethylenetriaminepentaacetate (DTPA) intraperitoneally to decrease cadmium retention. Radioactive cadmium (115mCd) was administered orally and intraperitoneally. Whole body (WB), carcass (C) and organ (kidney, liver and brain) retentions were determined 1 and 2 weeks after a single radioisotope administration. The results are expressed as percentages of the administered dose (% D) and as percentages of whole body (% WB) and carcass (% C) radioactivities. After oral administration whole-body cadmium retention was higher in sucklings than in weaned animals, primarily due to increased gut retention. The kidney retention of orally administered cadmium was about 5-7 times higher in sucklings than in older rats. Cadmium distribution (% C) was similar after oral and intraperitoneal administration. In sucklings, kidney retention made a lower fraction of the carcass radioactivity one week after 115mCd administration but reached adult values a week later. Liver retention in sucklings was a slightly lower fraction of the carcass radioactivity than in older rats at both time intervals. Brain retention (% C) was about 10 times higher in sucklings than in older rats throughout the experiment. Preliminary data on the influence of dietary treatments and treatment with DTPA indicate that some treatments which influence cadmium retention also influence cadmium distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗