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Biomedical subjects

L A Martin

Publications and source records attributed to L A Martin.

50 records · Page 3Linked to original sources
PubMed1993

NPC 16377, a potent and selective sigma-ligand. I. Receptor binding, neurochemical and neuroendocrine profile.

6-[6-(4-Hydroxypiperidinyl)hexyloxy]-3-methylflavone HCI (NPC 16377), a structurally novel compound, was found to be a highly potent and selective ligand for sigma-sites. Although 5-fold less potent than haloperidol and 2-fold less potent than ifenprodil to inhibit 1,3-di-o-tolylguanidine binding, NPC 16377 (IC50 = 36 nM) was more potent than alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl butanol (BMY 14802), rimcazole and the atypical antipsychotic, clozapine. A similar rank order of potency was observed when [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperdine was used as the radioligand. Like BMY, rimcazole and clozapine, NPC 16377 (IC50 = 2671 nM) had low affinity for dopamine type 2 receptors. Additionally, the compound was only weakly active in 35 additional receptor binding assays including those for serotonin2 and serotonin1C receptors. In vivo, NPC 16377 potently inhibited the binding of [3H]-(+)-N-allylnormetazocine to sigma sites after both intraperitoneal and oral administration. At doses 30-fold in excess of the ID50 to inhibit [3H](+)N-allylnormetazocine, NPC 16377 failed to displace [3H]raclopride from dopamine type 2 binding sites. Unlike haloperidol, BMY 14802, ifenprodil and clozapine, behaviorally effective doses of NPC 16377 did not increase dopamine turnover in the frontal cortex, nucleus accumbens or corpus striatum of rats. In contrast, each of these agents increased circulating levels of both adrenocorticotropin and corticosterone, but only NPC 16377 decreased circulating plasma levels of prolactin. The results of the current study are consistent with the notion that NPC 16377 is a potent, selective and orally active sigma site ligand. At behaviorally relevant doses the compound produces neuroendocrine effects both similar to, and different from, neuroleptics, other sigma-ligands and atypical antipsychotics, while having no effect on dopamine turnover. Given these data, NPC 16377 should prove to be a useful compound to explore further the physiological and functional significance of sigma-sites in brain.

Adrenocorticotropic Hormone↗
PubMed1992

Peptidyl fluoromethyl ketones as inhibitors of cathepsin B. Implication for treatment of rheumatoid arthritis.

Peptidyl fluoromethyl ketones (FMKs), with the amino acid sequence Phe-Ala held constant but with variable N-terminal groups, were synthesized and tested for inhibition of the cysteine proteinase cathepsin B. The FMKs were effective in inhibiting cathepsin B activity in vitro. The inhibition was time dependent and was not reversed by dialysis, suggesting covalent modification of the enzyme. Cathepsin B activity present in livers and kidneys of rats treated with FMKs was reduced by 22-91% 4 hr after a single oral dose of 25 mg/kg. The FMKs inhibited the severity of inflammation and the extent of cartilage and bone damage in adjuvant-induced arthritis. These effects were seen during the late-stage of the disease with no effect on onset or incidence of disease. This is consistent with inhibition of protease-mediated damage. These FMKs or derivatives may be of clinical value in the treatment of arthritis.

Animals↗
PubMed1992

A multicenter study to evaluate a novel assay for quantitation of soluble interleukin 2 receptor in renal transplant recipients.

The clinical utility of monitoring soluble interleukin 2 receptor (sIL-2R) as an indicator of immune stimulation in renal transplant patients was evaluated in a retrospective study at 3 centers. Serum samples (n = 2360) were obtained from 86 (17 living related donor, 69 cadaver) transplant recipients. The patients had received either triple therapy (n = 35) or antilymphocyte antibody induction therapy followed by triple therapy (n = 51). The mean period of postoperative observation was 118 days (range, 6-349 days). Serum sIL-2R concentrations were quantitated by an automated microparticle enzyme immunoassay (MEIA) (Abbott Diagnostics) in which sIL-2R was captured by 7G7/B6 monoclonal antibody-coated microparticles and detected by an immunospecific rabbit antihuman sIL-2R-alkaline phosphatase conjugate. A distinct advantage of the technique was rapid turn-around time: 1-24 results were obtained in less than 50 min. Cyclosporine trough concentrations were determined by radioimmunoassay or high-performance liquid chromatography. Diagnosis of rejection was established by clinical and histological criteria. The mean sIL-2R concentration in patients receiving antilymphocyte antibody induction therapy increased from 3486 +/- 1729 U/ml (+/- SD) at the time of transplant to a maximum of 7395 +/- 7101 U/ml on the third day posttransplant; this increase was not observed in patients receiving triple therapy (P less than 0.0001). By the sixth day of posttransplant, there were no differences in sIL-2R levels in the two groups. Fifty rejection episodes were observed in 29 patients on triple therapy. The mean sIL-2R concentration rose from 3022 U/ml at the data point prior to rejection to 3524 U/ml at the time of rejection. Thirty-four rejection episodes were observed in 26 patients receiving induction therapy. The mean sIL-2R concentration was 3015 U/ml at the data point prior to rejection and 4815 U/ml at the time of rejection. The sIL-2R concentrations began increasing earlier and rose higher in rejecting patients who received induction therapy than in those receiving triple therapy. Early posttransplant sIL-2R levels increased significantly more in cadaver recipients than in LRD recipients, reaching a maximum on day 2 posttransplant (P less than 0.001). Prerejection sIL-2R concentrations were significantly lower in LRD recipients than in cadaver recipients (2248 U/ml vs. 4290 U/ml, P less than 0.02), as were sIL-2R levels at the time of diagnosis of rejection (2800 U/ml vs. 4832 U/ml, P = 0.01). The mean sIL-2R level in stable long-term graft recipients was 2110 U/ml, with approximately 90% of values less than 3000 U/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Erythrocyte polyamine levels in human prostatic carcinoma.

Abnormally high red blood cell polyamine levels were found in benign prostatic hyperplasia and in prostatic adenocarcinoma patients. In prostatic adenocarcinoma patients a relationship was noted between the importance of red blood cell spermidine and spermine concentrations, and the clinical stage of the disease (Whitmore classification). Considering prostatic adenocarcinoma patient populations, patients with metastases (groups 3 and 4) statistically differed from those without metastases (group 2). Furthermore, red blood cell polyamine level determination discriminated patients in the hormonal escape group (group 4) from those usually considered as hormone responsive (groups 2 and 3). No statistically significant correlation was observed between red blood cell polyamine levels and usual tumor markers (prostatic acid phosphatase and prostate specific antigen). These results confirmed that red blood cell polyamine levels must be considered as a circulating index of cell proliferation that might be of clinical importance during the long-term followup and treatment of prostatic adenocarcinoma patients.

Adenocarcinoma↗
PubMed1990

Procedural compliance and clinical outcome associated with therapeutic interchange of extended-spectrum penicillins.

The degree of procedural compliance and the clinical outcome associated with a therapeutic interchange of extended-spectrum penicillins were assessed. Pharmacists conducted a concurrent chart review on all patients receiving mezlocillin as a therapeutic alternative for piperacillin or ticarcillin over a five-month period. The pharmacists assessed whether (1) the pharmacy appropriately dispensed mezlocillin when orders were written for piperacillin or ticarcillin, (2) physicians and nurses were properly notified of the therapeutic interchange, and (3) the bacterial isolates were susceptible to mezlocillin. Pharmacists and physicians evaluated clinical outcomes of all patients receiving mezlocillin through a retrospective chart review and classified the responses as "success," "failure," or "indeterminate." Fifty-one orders for piperacillin were written during the study period, and mezlocillin was selected as a therapeutic alternative in all cases. No orders for ticarcillin were written. Proper notification was made to nurses and physicians in 98% and 65% of cases, respectively. No mezlocillin-resistant gram-negative bacteria were found. Eighty-three courses of therapy were reviewed for clinical outcome; 68 were classified as successes, 0 were failures, and 15 were indeterminate. The cost savings after nine months of therapeutic interchange of mezlocillin for piperacillin was $6600. This study indicates that the pharmacy made a proper therapeutic interchange of mezlocillin for piperacillin and followed the correct procedure for notification of the nursing staff. However, more effort is needed to ensure communication with the prescribing physicians.

Bacteria↗
PubMed1989

Antipyrine interferes with chemical determination of bromide in simultaneous estimation of total body water and extracellular water.

Antipyrine and bromide dilution are frequently used to estimate total body water and extracellular water volumes, respectively. We assessed a potential error with the simultaneous use of these methods. In vitro the bromide concentration of solutions measured by the gold chloride or rosaniline methods decreased linearly with increasing concentrations of antipyrine. With the gold chloride method, the "inhibitory" effect of antipyrine was more pronounced for solutions in plasma than in those in water. With the rosaniline method, the "inhibitory" effect was similar for water and plasma. Antipyrine had no effect on bromide concentration measured by fluorescein or fluorescence excitation methods. We conclude that antipyrine potentially affects the measurement of bromide space by certain colorimetric methods. The mean values of previously published data do not appear to have been affected by the technical problems described in this study, although these problems may account, at least in part, for the large variability of the results.

Antipyrine↗
PubMedDate not supplied

Clinical importance of erythrocyte polyamine level determination during bone marrow transplantation in children.

Previous studies have shown that red blood cell (RBC) spermidine (Spd) and spermine (Spm) concentrations appear to be a reliable index of cell proliferation. Our aim was to study the RBC polyamine level evolution (Spd and Spm) in bone marrow (BM) transplanted children. Because of our interest in the finding of an early blood criteria of BM regeneration, our study was based upon the chemotherapy - induced post-transplant aplasia period. After BM transplantation, two main periods were observed: the first (A-period) corresponded to abnormally low Spd levels. This period ended with an increasing amount of Spd reaching normal values and with an inversion in the Spd/Spm ratio which became greater than 1. The second (B) period was usually linked to abnormally high RBC Spd concentrations and a Spd/Spm ratio greater than 1. The end of the B-period was characterized by an increase in the granulocyte count (reaching 0.5 X 10(9) cells/l). Since the A- and B-periods are considered as a post-transplant aplasia period (only according to leukocyte count) and since normal RBC Spd levels occurred 14 days (SD = 4) after BM transplantation and 16 days (SD = 12) before granulocyte rise, these data led us to consider erythrocyte polyamine levels to be an earlier biological criteria of bone marrow engraftment than the number of circulating granulocytes.

Adolescent↗
PubMedDate not supplied

Your PC can enhance staff and patient education.

Obtaining education materials for both staff and patients can be expensive. Tracking staff certification requirements and available references for individual units can be time consuming and awkward. Using a regular home personal computer and inexpensive software applications, the staff nurse, educator, and manager can produce quality education products, maintain records, and graph representation of administrative trends.

Child↗