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Biomedical subjects

E Aranda

Publications and source records attributed to E Aranda.

At least 91 records · Page 5Linked to original sources

[Inhibition of macrophage phagocytic activity by selective sensitization to alloantigens of the H-2 system].

The action exerted by selective sensitizations to alloantigens coded by the Major Histocompatibility System of the mouse, H-2, on the phagocytic ability of the mouse peritoneal macrophages has been studied. The results suggest that when immunizations are performed between completely incompatible animals for the H-2k haplotype, after the third immunization the total number of macrophages able to carry out phagocytosis decreases very significantly. When the incompatibilities, however, are due to the left half of the H-2 system or to minor histocompatibility antigens, such an inhibition does not appear.

Animals↗

Increase in density and accumulation of serotonin by human aging platelets.

51Cr-labeled autologous platelets were infused into splenectomized subjects and the specific radioactivities of high-density (HD) and low-density (LD) platelet subpopulations were determined sequentially in postinfusion samples. A rapid decrease in the specific radioactivity of LD cohorts (T1/2 = 2.5 days) was observed, but the specific radioactivity of HD platelets remained constant or increased slightly during the first 4 days and then gradually declined for the next 5 days. No experimental artifacts during the platelet-labeling steps that could account for these results were demonstrated. These findings confirm previous observations in eusplenic individuals and support the hypothesis that human LD platelets are, on the average, younger than HD platelets. LD platelets contain 33.8 +/- 13.5 ng serotonin (5HT)/10(8) platelets and HD platelets 76.8 +/- 9.5 ng 5HT/10(8) platelets (P less than 0.001). Sequential measurements of 5HT in PRP platelets were performed during the recovery phase of thrombocytopenia following splenectomy in patients with idiopathic thrombocytopenic purpura (ITP), a condition associated with aging of platelets in circulation. Presplenectomy platelet 5HT was 17.7 ng/10(8) platelets and on days 1, 6, and 12 after surgery it increased to 18.1, 37.8, and 61.0 ng/10(8) platelets (n = 7). When three healthy volunteers were given aspirin (500 mg/day) for up to 15 days, no significant change in the 5HT content of circulating platelets was observed. If aspirin blocks, at least partially, the secretory process in vivo without interfering the 5HT uptake by the platelets, this finding stands against the possibility that a net depletion of 5HT occurs during the life-span of normal human platelets. The observation that human HD platelets, enriched with older cells, contain more 5HT than LD platelets taken together with the parallel increase in platelet 5HT and age during the recovery from thrombocytopenia in ITP patients and the lack of effect of aspirin on platelet 5HT content, provides initial evidence that human platelets accumulate 5HT during their life-span in circulation.

Adolescent↗

Kinetics of platelet density subpopulations in splenectomized mongrel dogs.

Autologous 51Cr-platelet kinetic studies were performed in splenectomized mongrel dogs. Mean survival time of PRP-platelets was 5.4 +/- 1.5 (SD) days (n = 6). The curves, though slightly curvilinear, showed mostly a linear type of decay, denoting that platelet removal from the circulation is mainly determined by aging of the cells. High-density (HD) and low-density (LD) platelet cohorts were isolated in Stractan gradients from samples drawn daily after infusion of labeled platelets. Specific radioactivity in HD cohorts declined rapidly postinfusion (T1/2 = 1.3 days), but specific radioactivity in LD platelets increased for 2 days and steadily declined for 4 days thereafter (n = 6). Labeled HD platelets, comprising 11.7% of the total population, lived significantly longer in circulation than LD platelets (19.1% of the total population) (n = 3). The patterns of decay of the radioactivity, however, do not have all the characteristics of pure age-cohort survival curves; 3.7 days after the infusion of labeled HD platelets, the specific radioactivity in LD cohorts was six times higher than on day 1, but attained only 20% of the initial specific radioactivity in HD platelets. After the infusion of labeled LD platelets no radioactivity was recovered in circulating HD cohorts. These findings indicate that mongrel dog platelets decrease in density with aging, but also that platelet density heterogeneity is in part determined during the thrombopoietic process. These data are consistent with those of other authors in rabbits and rhesus monkeys, but contrast with the observations that platelets in humans, baboons, and Macaca fascicularis monkeys increase in density with age, suggesting that the displacement of platelets toward compartments of either higher or lower density depends on the species under study.

Animals↗

[Serum factors present in patients with carcinoma of the bladder: effect on cell-mediated immunity].

The effect of the sera from patients with bladder carcinoma upon the blastic transformation of T lymphocytes and the antibody-dependent K cell cytotoxicity is studied. The sera from cancer patients inhibits both the T cell blastic transformation and the antibody-dependent K cell cytotoxicity, the effect is attained by a different mechanism, and the degree of inhibition correlates with the histologic malignancy and infiltration.

Antibody-Dependent Cell Cytotoxicity↗

Effects of diterpene forskolin on the release reaction and protein phosphorylation of human platelets.

The effects of diterpene forskolin on the human platelet release reaction and on platelet protein phosphorylation were studied. This drug is shown to have the same effects as other agents which increase cAMP levels, namely, it inhibits the secretory response to diverse agonists and causes changes in the phosphorylation of several specific proteins. An increase of the 32P content is seen in the MW 47 000, 24 000 and 21 000 polypeptides while a decrease is observed in the MW 41 000 and 27 000 and 20 000 species. Forskolin also inhibits the changes in protein phosphorylation pattern induced by the powerful platelet secretagogue, thrombin. Our results relate the effects of antagonists of platelet secretion such as prostaglandins more closely to changes in cAMP levels and in protein phosphorylation than to other possible effects of the receptor-ligand interaction, which is by-passed by the use of forskolin. Our results also provide additional evidence involving these changes in the mechanisms which regulate the secretory process in platelets.

Blood Platelets↗

Garcia's disease. Cyclic thrombocytopenic purpura in a child and abnormal platelet counts in his family.

After a critical study, a splenectomy was performed in a 6-year-old boy with chronic thrombocytopenic purpura. Failure of surgery and immunosuppressive therapy prompted new investigations which led to the discovery of a cyclic thrombocytopenic purpura related to a periodic variation in maturity of megakaryocytes. The patient's platelets were morphologically and functionally normal and it was not possible to demonstrate neither immunological mechanism, nutritional deficiency, influence of the environment nor consumption or excessive destruction of platelets. Cyclic thrombocytopenia was detected in the father and also cyclic variations in platelet counts from normal values to over 1,000 x 10(9)/1 in 4 of 9 siblings. In view of these findings. The abnormal condition in this family was named Garcia's disease.

Blood Cell Count↗

Prevention of highly emetogenic chemotherapy-induced vomiting: a double blind, randomized crossover study to compare pancopride (LAS 30451) and pancopride plus dexamethasone.

AIMS: Pancopride (PNC) is a new 5HT3 receptor antagonist which has demonstrated complete protection from nausea and vomiting in 25-73% of patients treated with highly emetogenic chemotherapy. A double-blind, randomized crossover study was carried out to assess whether the addition of dexamethasone (DXM) to PNC increases the antiemetic efficacy. METHODS: PNC (0.2 mg/kg. i.v. 30 min before chemotherapy) plus placebo (PLC) was compared with PNC (same dose and schedule) plus DXM (20 mg. i.v. immediately before PNC). In the second cycle, patients received the alternative antiemetic treatment. Eighty patients were included in the study (PNC + DXM = 39, PNC + PLC = 41), 29 of whom were women and 51 men. Fifty-four percent of the patients in the PNC + DXM group and 59% of those in the PNC + PLC group received chemotherapy containing cisplatin. Seventy-seven patients completed the first cycle and 70 the second. RESULTS: Complete protection was obtained in 19/16 patients (50/46%) with PNC + PLC and in 32/22 (82/63%) with PNC + DXM (P < 0.001). Latency was significantly longer in the PNC + DXM group. The efficacy of both treatments was unaffected by the order of administration. Side effects were mild in both groups. CONCLUSIONS: The combination of PNC + DXM is more efficacious than PNC + PLC in protection against highly emetogenic chemotherapy-induced vomiting.

Antiemetics↗

Insect growth regulatory activity of some extracts and compounds from Parthenium argentatum on fall armyworm Spodoptera frugiperda.

The methanolic extract from aerial parts of Parthenium argentatum, afforded argentatin A and B. These compounds were evaluated for their effect on the fall armyworm (Spodoptera frugiperda). Toosendanin, a commercial insecticide derived from Melia azedarach was used as positive control. When tested for activity, using neonate larvae into the no-choice artificial diet bioassays, argentatin A, argentatin B and methanol extract caused significant growth inhibitory activity with GC50 of 17.8, 36.1 and 6.4 ppm at 7 days, respectively, and increased the development time of surviving larvae in a concentration-dependent manner with RGI values of 0.40, 0.60 and 0.26, at 25.0, 25.0 and 5.0 ppm, respectively. In addition, it was possible to observe in most of the treated groups a significant delay in the time of pupation, adult emergence and deformities. Acute toxicity against adults of S. frugiperda was also found, MeOH extract had the most potent activity with LD50 value of 3.10 ppm. In addition, MeOH extract and argentatin A caused acetylcholinesterase inhibition of 93.7% and 90.0%, at 5.0 and 50.0 ppm, respectively; whereas argentatin B had only slight inhibitory activity. Therefore, the MeOH extract was identified as insecticidal extract from P. argentatum with activity at concentrations above 15.0 ppm.

Acetylcholinesterase↗

Acetylcholinesterase and insect growth inhibitory activities of Gutierrezia microcephala on fall armyworm Spodoptera frugiperda J.E. Smith.

From the aerial parts of Gutierrezia microcephala (Asteraceae), four oxyflavones were isolated, namely 5,7,2'-trihydroxy-3,6,8,4',5'-pentamethoxyflavone (1); 5,7,4'-trihydroxy-3,6,8-trimethoxyflavone (2); 5,7,2',4'-tetrahydroxy-3,6,8,5'-tetramethoxyflavone (3); 5,2'-dihydroxy-3,6,7,8,4',5'-hexamethoxyflavone (4), and an ent-clerodane, bacchabolivic acid (5). Compounds 1-5, the synthetic methyl ester (6), n-hexane and MeOH extracts were evaluated against the fall armyworm (Spodoptera frugiperda). Gedunin, a known insect growth regulator isolated from Cedrela spp. was used as a positive control. When tested for activity on neonate larvae into the no-choice artificial diet bioassay, flavone (1), clerodane (5), its methyl ester (6), MeOH and n-hexane extracts caused significant larval mortality with MC50 of 3.9, 10.7, 3.46, 7.95 and 7.5 ppm at 7 days, respectively, as well as growth reduction. They also increased the development time of surviving larvae and a significant delay in time to pupation and adult emergence. Acute toxicity against adults of S. frugiperda was also found, 5, 6, gedunin and n-hexane extract had the most potent activity with LD50 value of 6.59, 15.05, 10.78, and 12.79 ppm, respectively. In addition, MeOH, n-hexane extracts, 5, 6 and gedunin caused acetylcholinesterase inhibition with 93.7, 100, 90.2, 62.0 and 100% at 50.0 ppm, respectively; whereas 1-4 exhibited only moderate inhibitory activity. Compounds 1, 5 and 6 showed inhibitory activities comparable with gedunin. These compounds could be responsible of the insect growth inhibitory activity of this plant.

Acetylcholinesterase↗

Insect growth regulator and insecticidal activity of beta-dihydroagarofurans from Maytenus spp. (Celastraceae).

From the aerial parts of Maytenus disticha, we have isolated 9beta-benzoyloxy-1alpha,2alpha,6beta,8alpha,15penta-acetoxy-dihydro-beta-agarofuran (1) and from seeds of Maytenus boaria 9beta-furoyloxy-1alpha,6beta,8alpha-triacetoxy-dihydro-beta-agarofuran (2). These compounds and their MeOH and hexane/ethyl acetate (1:1 v/v) extracts were evaluated for their effects on the fall armyworm (Spodoptera frugiperda). Toosendanin, a commercial insecticide derived from Melia azedarach was used as a positive control. When tested for activity using neonate larvae in a nochoice artificial diet bioassays, the agarofurans 1, 2 and toosendanin as well as the MeOH and hexane/EtOAc extracts caused significant growth inhibitory effects with GC50 of 7.55; 3.84; 1.75; 14.0 and 7.3 ppm at 7 days, respectively. Compounds 1 and 2 caused 100% larval mortality at 25 and 15 ppm, respectively. MeOH and hexane/EtOAc extracts caused 100% larval mortality at 25.0 ppm, respectively, they also increased the development time of surviving larvae and a significant delay for the time of pupation and adult emergence. These compounds showed comparable potency of activity with toosendanin. Acute toxicity against adults of S. frugiperda was also found, for hexane/EtOAc extract and 2 had the most potent activity with LD50 value of 4.7 and 1.9 ppm, respectively. MeOH extract, hexane/EtOAc extract, 1 and 2 caused acetylcholinesterase inhibition with 78.0, 89.2, 79.3 and 100% inhibition at 15.0 ppm, respectively. Therefore, the furoyloxy agarofuran may be responsible for the insecticidal activity of these plants.

Animals↗

Retrospective evaluation of toxicity in three different schedules of adjuvant chemotherapy for patients with resected colorectal cancer. TTD Spanish Cooperative Group.

Adjuvant chemotherapy has been established since 1990 as standard treatment for patients with colon cancer stage III (Dukes' C). Chemotherapeutic schemes combining 5-fluorouracil with levamisole or leucovorin have shown significant advantage over surgery alone. Adjuvant trials are being currently implemented to investigate some relevant questions, such as which is the optimal duration of chemotherapy, as well as the possible advantage of levamisol versus leucovorin schedules, and of high-dose versus low-dose leucovorin. While these trials are ongoing, a retrospective evaluation of the toxicity associated with the different chemotherapeutic schemes might be of help when choosing the most appropriate regimen for individual patients not involved in clinical trials. A total of 519 patients subjected to three different schedules of adjuvant chemotherapy between 1993 and 1996, were evaluated for toxicity according to the NCI-CTC criteria. Chemotherapeutic regimens were: 5-fluorouracil plus levamisole (5-Fu+Lev; Moertel schedule), 5-fluorouracil plus low-dose leucovorin (5-Fu+LVLD; NCCTG schedule) and 5-fluorouracil plus high-dose leucovorin (5-Fu+LVHD; IMPACT-modified schedule). 5-Fu+LVLD is significantly more toxic than the other two regimens in terms of neutropenia, mucositis and diarrhea. delay in chemotherapy and dose reduction of 5-fluorouracil were also more frequent in the 5-Fu+LVLD group. However, the percentage of prematurely discontinued treatments was significantly higher in the 5-Fu+Lev group. Information on toxicity of adjuvant chemotherapy for colon cancer may help medical oncologists to choose the most appropriate regimen for individual patients not involved in clinical trials.

Adjuvants, Immunologic↗