Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic sodium fluoride has been used in the treatment of osteoporosis. Recent studies have shown that it has a positive risk/benefit ratio for use in increasing spinal trabecular bone density. However, thinning of the cortices of the long bones with a resulting increase in fracture incidence has been observed. This study was designed to determine the response of bone to sodium fluoride released from a biodegradable polymer matrix, a technique which could potentially deliver it locally to a site of need in the skeleton which has a positive response to fluoride. In one group of mature New Zealand white rabbits, cylindrical poly(D,L-lactic acid) (PLA) implants, with or without impregnated sodium fluoride, were implanted into the contralateral femoral trochanters and tibial metaphyses. In a second group, similar implants were placed in adjacent vertebrae. Four weeks postimplantation, the femora, tibiae, and vertebrae were removed, sectioned, cleaned of all but mineralized tissue, and the surfaces of the sections stained. The stained surfaces were imaged and analyzed for morphometric properties of the trabeculae. Comparing contralateral vertebrae, those exposed to sodium fluoride had significantly thickened trabeculae, with decreased spacing between them and a greater bone fraction. A similar increase in trabecular width was found in the subchondral bone of the proximal tibiae exposed to local release fluoride. Femoral sections showed no difference, possibly due to the lack of extensive trabecular bone in the region chosen for study.
 ...
PMID:Effect of controlled local release of sodium fluoride on trabecular bone. 161 33

We compared the diagnostic and prognostic utility of phospholipase A (PLA; EC 3.1.1.4) for acute pancreatitis with that of amylase and lipase by analysis of sera from 151 consecutive patients presenting with abdominal pain in whom assays of serum amylase and (or) lipase had been ordered. We determined the diagnostic accuracy for both the initial and the peak enzyme activities. Maximal diagnostic accuracy obtained for the initial activities of amylase, lipase, and PLA was 0.83, 0.83, and 0.76 at cutoff values of 650, 650, and 41 U/L, respectively. Use of peak enzyme activities showed maximal diagnostic accuracy of 0.85, 0.86, and 0.73 at cutoff values of 650, 1050, and 42 U/L, respectively. Receiver-operator characteristic curve analysis revealed the diagnostic performance of amylase and lipase to be similar, whereas that of PLA was almost random and not incremental. As with amylase and lipase, PLA activities in sera showed no relation to patients' survival; three patients who died after an attack of acute pancreatitis failed to demonstrate the dramatic increases in PLA activity previously described. We conclude that assessing the severity of acute pancreatitis by using enzyme activities still remains problematical. Measurements of amylase or lipase activities provide similar diagnostic discrimination when appropriate cutoff values are used and remain the methods of choice for diagnosis of acute pancreatitis.
 ...
PMID:Diagnostic and prognostic utility of phospholipase A activity in patients with acute pancreatitis: comparison with amylase and lipase. 191 91

The hydrolytic and enzymic degradation of poly(L-lactic acid) (PLA) and poly(gamma-benzyl L-glutamate) (PBGA) films, together with a series of surface treatments, were studied, as a function of exposure time. The degradation of these polymers was monitored by weight loss, contact angle, pH changes and tensile strength studies. Glutaraldehyde treatment retained the maximum strength of PLA in buffer, followed by carbodiimide, compared with control films. On the other hand, plasma glow reversed the effect. The ability of alpha-chymotrypsin, carboxypeptidase, ficin, esterase, bromelain and leucine aminopeptidase to modulate the degradation of PLA and PBGA was also investigated. Addition of these enzymes to the polymer-buffer system reduced the tensile strength of these polymers variably. Among the six enzymes studied, leucine aminopeptidase showed the highest enzymic effect on the degradation of the glutaraldehyde-treated and bare PLA or bare PBGA films. However, glutaraldehyde-cross-linked PLA demonstrated maximum stability in buffers or in all other enzyme systems studied compared with bare PLA. It is conceivable that surface treatments on these polymers might have altered their physical and chemical configuration and the subsequent degradation properties. Surface modifications may provide new ways of controlling the biodegradation of polymers for a variety of biomedical applications.
 ...
PMID:Effect of plasma glow, glutaraldehyde and carbodiimide treatments on the enzymic degradation of poly (L-lactic acid) and poly (gamma-benzyl-L-glutamate) films. 172 Jun 76

The effects of endurance training on the skeletal muscle of rats have been studied at sea level and simulated high altitude (4,000 m). Male Wistar rats were randomly assigned to one of four groups: exercise at sea level, exercise at simulated high altitude, sedentary at sea level, and sedentary at high altitude (n = 8 in each group). Training consisted of swimming for 1 h/day in water at 36 degrees C for 14 wk. Training and exposure to a high-altitude environment produced a decrease in body weight (P less than 0.001). There was a significant linear correlation between muscle mass and body weight in the animals of all groups (r = 0.89, P less than 0.001). High-altitude training enhanced the percentage of type IIa fibers in the extensor digitorum longus muscle (EDL, P less than 0.05) and deep portions of the plantaris muscle (dPLA, P less than 0.01). High-altitude training also increased the percentage of type IIab fibers in fast-twitch muscles. These muscles showed marked metabolic adaptations: training increased the activity levels of enzymes involved in the citric acid cycle (citrate synthase, CS) and the beta-oxidation of fatty acids (3 hydroxyacyl CoA dehydrogenase, HAD). This increase occurred mainly at high altitude (36 and 31% for HAD in EDL and PLA muscles; 24 and 31% for CS in EDL and PLA muscles). Training increased the activity of enzymes involved in glucose phosphorylation (hexokinase). High-altitude training decreased lactate dehydrogenase activity. Endurance training performed at high altitude and sea level increased the isozyme 1-to-total lactate dehydrogenase activity ratio to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Skeletal muscle changes after endurance training at high altitude. 177

Melittin, an activator of phospholipase (PL) A-2, increased the outputs of prostaglandin (PG) F-2 alpha and 6-keto-PGF-1 alpha, but not of PGE-2, from Day-7 guinea-pig uterus superfused in vitro. Reducing the extracellular calcium concentration (by omitting calcium chloride from the superfusing fluid) partially inhibited the stimulatory effect of melittin on uterine PG production. TMB-8 (an intracellular calcium antagonist) completely prevented the stimulation of PGF-2 alpha and 6-keto-PGF-1 alpha output by melittin, although the production of both PGs tended to increase after stopping the melittin and TMB-8 treatments. TMB-8 also inhibited the increases in outputs of PGF-2 alpha, 6-keto-PGF-1 alpha and PGE-2 and prevented contraction of the uterus induced by exogenous PLA-2. Trifluoperazine (a calmodulin antagonist) had no inhibitory effect on the increases in outputs of PGF-2 alpha and 6-keto-PGF-1 alpha produced by melittin; it potentiated the stimulatory effect of melittin on 6-keto-PGF-1 alpha output and allowed melittin to increase PGE-2 output. When melittin was applied twice to the superfused uterus with an interval of 1 h between each treatment, partial refractoriness of the responses to melittin was seen: the magnitudes of the increases in PGF-2 alpha and 6-keto-PGF-1 alpha outputs were 40-50% less after the second treatment than after the first treatment. These results show that melittin stimulates the synthesis of PGF-2 alpha and PGI-2 (measured as 6-keto-PGF-1 alpha) in guinea-pig uterus by mechanisms which are calcium dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of melittin on prostaglandin production by guinea-pig uterus. 178 78

Poly(DL-lactic acid) (PLA), poly(epsilon-caprolactone) (PCL), and their copolymers (PLA-CL) with various monomer compositions were synthesized, and their properties as matrix for the sustained release of drugs were evaluated. The copolymerization technique produced very soft films which incorporated the drugs without deterioration of the elastic properties. Cisplatin and MD-805 were loaded in the films by casting the polymer solution containing the drugs. Fractions of the drugs released from the PLA-CL films were governed by the initial loading, the film thickness, and the polymer molecular weight. The drug release profiles obeyed the classical Fickian diffusion equation at least in the early stage, but significant hydrolytic degradation of the matrix polymers occurred in the later stage, influencing the kinetics of drug release. The monomer composition of copolymer affected the release profile more strongly than the initial molecular weight of the copolymer.
 ...
PMID:In vitro evaluation of sustained drug release from biodegradable elastomer. 179 48

Poly(L-lactic acid) (L-PLA) microspheres containing 5-fluoro-2'-deoxyuridine (FUdR) or its ester prodrugs with saturated aliphatic acids (FUdR-Cn, n = 2, 3, 4, 5, 6, 8, 10 and 12) were prepared. The physicochemical and biological properties and antitumor activity of the L-PLA microspheres were studied. The lipophilicity of FUdR-Cn was increased by prolonging its acyl-promoieties. FUdR-C5, FUdR-C6, FUdR-C8, FUdR-C10 and FUdR-C12 showed almost complete incorporation into the microspheres, while incorporation of hydrophilic FUdR and FUdR-C2 was poor. The sustained release of FUdR from the microspheres containing FUdR-C4, FUdR-C5 and FUdR-C6 was obtained in the presence of esterase, and higher antitumor activity against P388 leukemia was observed in vivo. On the other hand, the release rates of FUdR from the microspheres containing FUdR-C10 and FUdR-C12 were very small, and their antitumor activity was much smaller than that of the free prodrug suspension. Effects of the susceptibility to enzymatic hydrolysis and the physiocochemical properties of prodrugs on the release profiles of FUdR from spheres were discussed.
 ...
PMID:Controlled release of 5-fluoro-2'-deoxyuridine by the combination of prodrug and polymer matrix. 182 27

LN distribution in clone C and clone D cells of the PLA-801 (pulmonary giant cell carcinoma) cell line was studied with immunocytochemical staining. There were less LN and LN receptors found in clone C cells, which were from a low metastatic cell line, but much more LN and LNR were obtained in the highly metastatic clone D cells. The in vitro migration rates of these 2 clones were measured with agarose migratory analysis. The rate of clone D was much greater than that of clone C. With the presence of exgenous LN, clone C cells became activated with a higher migration rate and the migration rate of clone D was greatly reduced when cells were pretreated with anti-LN antibody. These results indicated that LN and LNR may play a vital role in the migration and metastasis of tumor cells.
 ...
PMID:[Laminin distribution in the clonal cells of PLA-801 (pulmonary giant cell carcinoma) cell line and its effect on tumor cell migration]. 183 80

The HPA-1 platelet antigenic system (PLA/Zw) is involved in most cases of antiplatelet alloimmunization. The two alleles HPA-1a and HPA-1b are likely to differ only at the amino acid position 33. This difference is probably due to a unique mutation at base pair position 196 on the glycoprotein IIIa gene which encoded this antigen. Anti HPA-1a alloimmunization is responsible for neonatal thrombocytopenia and post-transfusion purpura. Most immunized women belong to the HLA DR3, DRw52a phenotype, suggesting that this class II molecule may play a role in the presentation of HPA-1a peptide to specific helper T cells.
 ...
PMID:[Anti PLA or anti HPA-1 platelet allo-immunization]. 183 35

Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants.
 ...
PMID:Experimental studies and preliminary clinical trial of vinorelbine-loaded polymeric bioresorbable implants for the local treatment of solid tumors. 191 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>