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Intestinal motility disorders and some mediators implicated in these disorders were studied in preruminant calves that had been chronically fed a diet containing an antigenic heated soyabean flour (HSF) for 3 months. The calves in the present study had previously been shown to present strong immune reactions against soyabean proteins, as assessed through plasma antibody titres, direct skin tests and in vitro lymphoproliferation. Four of these calves sensitive to soya were fitted with an abomasal catheter and wire electrodes on the jejunum. Myoelectric activity was recorded over 7 h following test meals containing skim milk powder (SMP), HSF or a non-antigenic hydrolysed soya protein isolate (HSPI). The pattern of myoelectric complexes migrating to the jejunum was regular with SMP (mean durations of phases I, II and III: 26, 38 and 5.28 min, respectively). With HSF, diarrhoea appeared, and the total duration of phase I decreased from 149 to 68 min (P < 0.01) while that of phase II increased from 239 to 328 min (P < 0.01). The mean duration of phase III decreased from 5.3 to 3.9 min (P < 0.01). These changes, including diarrhoea, were substantially reversed by feeding HSPI. When promethazine, a H-1 histamine receptor antagonist, was administered i.v. prior to feeding HSF the number of phases I tended to decrease and diarrhoea virtually disappeared. In contrast, indomethacin, a cyclooxygenase inhibitor, had limited effects on motility patterns and diarrhoea. These disorders were partially reproduced by i.p. administration of platelet-activating factor (PAF) prior to feeding with SMP. These findings suggest that calves chronically fed antigenic soya suffer from immune-mediated motility disorders which are linked to histamine action via H-1 receptors, and possibly with PAF. The role of arachidonic acid catabolites of the cyclooxygenase pathway is probably minor.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9559521&dopt=Abstract
Biofizika. 1998 Mar-Apr;43(2):181-5.
[Phenothiazine drugs as photosensitizers and photoprotectors]
[Article in Russian]
Makareeva EN, Lozovskaia EL, Sapezhinskii II.
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia.
The photosensitizing properties of eight N-alkylated phenothiazine neuroleptic drugs were studied. The experiments were carried out in a model system based on photooxidative chemiluminescence of Gly-Trp peptide in aqueous solution. Under irradiation with light longer than 280 nm, all the studied phenothiazine derivatives decrease the chemiluminescence intensity at low concentrations and enhance it at high concentrations. Phenothiazine derivatives is likely to be due to superoxide and/or Gly-Trp free peroxide radicals. Photosensitization begins to dominate over protection at concentrations which are different for various phenothiazine derivatives compounds and lie in the range 10(-6)-10(-5) M. The photosensitizing efficiency decreases in the order: Thioproperazine, Trifluoperazine Hydrochloride, Alimezine, Thioridazine Hydrochloride, Levomepromazine Hydrochloride, Promethazine Hydrochloride, Periciazine, Chlorpromazine Hydrochloride. It was shown that photooxidation of Gly-Trp sensitized by phenothiazine derivatives occurs via singlet oxygen formation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9591093&dopt=Abstract
Am J Trop Med Hyg. 1998 May;58(5):625-9.
In vitro and in vivo reversal of chloroquine resistance in Plasmodium falciparum with promethazine.
Oduola AM, Sowunmi A, Milhous WK, Brewer TG, Kyle DE, Gerena L, Rossan RN, Salako LA, Schuster BG.
Department of Pharmacology and Therapeutics, Postgraduate Institute for Medical Research and Training, College of Medicine, University of Ibadan, Nigeria.
The effect of combining promethazine with chloroquine was examined against Plasmodium falciparum in vitro in the Aotus-P. falciparum model and in bioassays from volunteers given promethazine. The combination of chloroquine plus promethazine (1 x 10(-6) M) reversed chloroquine resistance in standard P. falciparum clones and patient parasite isolates from Nigeria. The combination reduced the 50% inhibitory concentrations (IC50s) for chloroquine against resistant parasites by 32-92%. Coadministration of promethazine with chloroquine also demonstrated a dose-dependent effect in Aotus monkeys infected with chloroquine-resistant P. falciparum. Monkeys were given a chloroquine dose (20 mg/kg of body weight for seven days), which normally has no effect on parasitemia, plus 10, 20, 40, or 80 mg of promethazine/kg of body weight. In one monkey, parasitemia was suppressed at the lowest promethazine dose, but re-treatment with 20 mg/kg resulted in clearance of parasitemia. Initial treatment with chloroquine and 20 or 40 mg/kg of promethazine cleared parasitemia in some animals followed by recrudescence. Re-treatment at higher doses cured one monkey and resulted in initial clearance and delayed recrudescence 28 or 63 days after treatment in two monkeys. Recrudescent parasitemia in the two monkeys was low (10 parasites/microl of blood) and subsequently cleared without re-treatment. An in vitro bioassay model was developed to examine the effects of clinically achievable doses of promethazine on parasites susceptibilities in vitro. Plasma samples taken at hourly intervals from patients given a single oral dose of 25 mg of promethazine decreased the IC50 values for chloroquine by 20-58% with the most significant reductions occurring in plasma obtained from volunteers 3-4 hr after ingestion. Plasma obtained from two volunteers 6 hr after ingestion of the drug demonstrated no effect on chloroquine susceptibility, suggesting that study of the pharmacokinetic disposition and potential interaction is warranted to optimize the dose regimen in patients for antimalarial efficacy. Historic use of this drug combination for treatment or prevention of chloroquine-associated pruritus or as an antiemetic suggest that the combination is safe and effective when used at standard dosages. The results from this study demonstrate that promethazine is a potent modulator of chloroquine resistance. Clinical evaluation of therapeutic regimens is required to validate clinical efficacy of this promising combination for treatment of uncomplicated chloroquine-resistant malaria.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9598452&dopt=Abstract
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