We report a case of Wells' syndrome (eosinophilic cellulitis) with acute cutaneous swelling followed by indolent infiltration. The histopathology is characterized by a dense infiltrate of eosinophils and "flame figures" in the dermis. The electron microscopic findings are peculiar. This case responded well to oral antihistamines. The skin signs and symptoms disappeared completely two weeks later.
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In rats pretreated with pargyline ip injection of 5-methoxytryptamine (5-MT), but not of 5-HT, produced characteristic head twitches. 5-HT receptor blocking agents (cyproheptadine, methergoline, mianserine, WA-335-BS, and methsergide) reduced the effect of 5-MT. These substances in doses 20-160 times higher than their ED50 in head twitch test did not antagonize the pinna reflex. 5-MT-induced head twitches were also inhibited by imipramine, morphine, phenoxybenzamine and aceperone. However, their ED50 were only 3-8 times below the doses necessary to inhibit the pinna reflex. Reserpine, phentolamine, spiroperidol, pimozide and LiCl did not modify head twitches produced by 5-MT, while PCPA even potentiated them. Our results suggest the 5-MT-induced head twitches are due to the activation of the central 5-HT mechanisms probably as a result of direct stimulation of 5-HT receptors by 5-MT. Antagonism of 5-MT-induced head twitches and the dissociation of doses effective in this test from those inhibiting the pinna reflex may be of value in the prediction of central 5-HT receptor blocking properties.
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The discriminative stimulus properties of the clinically important ergot derivative lisuride hydrogen maleate (LHM) were investigated by training groups of rats (13 per group) to discriminate either of three training doses of LHM (0.02, 0.08 or 0.32 mg/kg) from saline. Dose-response tests showed that the three LHM cues were specific to the dose used during training and the dose-response curve became more steep as the training dose increased. In substitution tests, the direct dopamine (DA) agonists apomorphine and lergotrile substituted for LHM and the potency order of the LHM-like effect (LHM greater than apomorphine greater than lergotrile) corresponded to previous electrophysiological and biochemical results. The indirect DA agonist d-amphetamine did not substitute for LHM. The direct serotonin (5-HT) agonists quipazine, MK-212 and 5-methoxy-N,N-dimethyltryptamine produced dose-dependent, but incomplete, substitution for LHM which covaried with LHM training dose. In antagonism tests, only drug capable of blocking DA receptors, haloperidol and methiothepin, attenuated the LHM cues; the 5-HT antagonists cyproheptadine, BC-105 and xylamidine were ineffective. These data indicate that the primary neuronal action mediating the discriminative stimulus effects of a wide range of LHM doses was direct activation of central DA receptors. The 5-HT agonist actions of LHM proved to be secondary in that 5-HT agonists substituted only partially for LHM and 5-HT antagonists failed to attenuate LHM cues.
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Data were obtained from abstracts and peer-reviewed journals. The pathophysiology of the allergic response has been extensively studied. This paper presents only data from studies that used desloratadine at physiologically relevant concentrations.
Anorexia is a major clinical problem in large number of patients with advanced cancer disease. Serotonergic mechanisms are assumed to play a role in the process of feeding behavior during normal and pathologic circumstances, which may also involve cancer anorexia according to previous experimental and clinical studies.
Triamcinolone is a commonly used synthetic corticosteroid that has recently been tested in a large clinical trial for chronic obstructive pulmonary disease and shown to have some benefits. To our knowledge, there are no reviews of the pharmacotherapy of triamcinolone. This review has a brief overview of the pharmacology of triamcinolone, followed by a discussion of the clinical trials with triamcinolone. Triamcinolone is used in the treatment of respiratory inflammation, rheumatoid arthritis and a variety of other inflammatory conditions.
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This study is a one year investigation that evaluates the important role of leukotriene receptor antagonists on nasal polyposis, with or without association to any allergic disease. Likewise, it compares its use with the conventional therapy used in the above mentioned disease.
Phorbol 12-myristate 13-acetate (PMA) induced a slow and progressive increase in tension of rat thoracic aorta strips in the presence of extracellular Ca2+. Complete relaxation could not be obtained in Ca2+-free buffer containing 1 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) and 10(-7) M PMA. In the absence of extracellular Ca2+, PMA (10(-7) M) induced a small but sustained contraction which was not altered by the addition of another 2 mM EGTA and 3 X 10(-5) M verapamil. Papaverine (10(-4) M) relaxed the PMA-induced contraction to the base line, but phentolamine (10(-5) M), cyproheptadine (10(-5) M), atropine (10(-5) M) and tetrodotoxine (10(-6) M) did not change the contraction. Ca2+-depleted muscle strips, prepared by four repeated applications of 10(-7) M norepinephrine in Ca2+-free buffer, were contracted by 10(-7) M PMA, but at a lower maximum tension than nontreated strips. The action of PMA on rat aorta strips in Ca2+-free buffer did not require the presence of the adventitial layer or endothelial cells. These results suggest that PMA may induce activation of protein kinase C and smooth muscle contraction in the absence of extracellular Ca2+, without an increase in myoplasmic Ca2+.
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The chemical structure of phenothiazine provides a most valuable molecular template for the development of agents able to interact with a wide variety of biological processes. Synthetic phenothiazines (with aliphatic, methylpiperazine, piperazine-ethanol, piperazine-ethyl, or piperidine side-chain) and/or phenothiazine-derived agents e.g., thioxanthenes, benzepines, imonostilbenes, tricyclic antidepressants, dimetothiazine, and cyproheptadine have been effective in the treatment of a number of medical conditions with widely different etiology. These include various currently clinically used drugs for their significant antihistamic, antipsychotic, anticholinergic (antiparkinson), antipruritic, and/or antiemetic properties. They are also employed, although to a minor extent, as antidepressants, antispasmodics, analgesics, and antiarrhythemics. Some of these agents are also useful as anti-inflammatory, coronary vasodilator, radioprotective, sedative, antitussive, and skeletal muscle-relaxing medication. Still, others show different degrees of effectiveness as antibacterials, anthelmintics, antimalarials, or local anesthetics; a few are valuable in the control of acute migraine attacks and intractable hiccough. Adding to the seemingly ever-expanding therapeutic use of phenothiazine derivatives, a number of "old" and newly synthesized compounds e.g., "half-mustard-type" and benzo[alpha]phenothiazines, appear to be helpful as multidrug resistance modifiers, a property of particular importance in cancer chemotherapy. Some phenothiazines inhibit human plasmatic leucine-enkephalin aminopeptidase(s), enzymes known to regulate the turnover rate of a wide range of bioactive substances. These findings could lead to the design of new therapeutic treatment modalities for conditions such as Alzeimer's and Creutzfeldt-Jakob disease. Hopefully, this work will help to the rational design of new and improved pharmacological approaches based on a better understanding of the correlation between chemical structure, pharmacodynamic properties, and pharmacological activity of various phenothiazines and phenothiazine-derived classes of drugs.
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As there have been no previously published studies, this multinational, double-blind, randomized, placebo-controlled, parallel group study compared the efficacy, safety and impact on quality of life (QoL) in seasonal allergic rhinitis patients (SAR) of fexofenadine and loratadine (with placebo), when administered once daily.
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In experiments on vagotomized and intact rats with the use of two models of experimental gastric ulceration (injection of serotonin and stress) it was demonstrated that the inhibitory action of vagotomy on haemorrhagic gastric effectiveness was more pronounced in stress than after serotonin application. Vagotomy decreased stress-induced erosive lesions but increased serotonin-induced erosions that may be a result of the increase of gastric tissue sensitivity to this amine which developed simultaneously with significant decrease of its level in gastric wall after vagotomy. Serotonin-antagonist peritol decreased stress-induced gastric disturbances in vagotomized rats more significantly than in intact rats; this suggested the great role of serotonin in anti-ulcerogenic effect of vagotomy.
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This multicenter, randomized, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of mizolastine in PAR compared with loratadine and placebo.
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Long-term, population-based case-control studies continue to be an effective way to assess exposure-birth defects associations and provide guidance to health care providers. However, investigators examining rare outcomes covering many years of data collection need to be cognizant of time trends in exposures.
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It has been recognized that phospholipase A2 (PLA2) is a crucial component of snake venom, which contributes greatly to snake venom induced inflammation in man. However, the mechanisms through which N49 PLA2 provoke inflammation remain unclear. Recently, a N49 PLA2, TM-N49 from Protobothrops mucrosquamatus crude venom was characterized in our laboratory. Since the purification procedure developed is able to supply us with relatively large quantity of highly purified TM-N49, we investigated the ability of TM-N49 in induction of inflammation.
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The multidrug-resistance-associated proteins 1 and 2 (MRP1/MRP2) are transporters responsible for the efflux of drugs and endogenous compounds. Madin Darby canine kidney (MDCK) cells transfected with the human MRP1 or MRP2 genes were used to assess whether several widely used pharmaceuticals are potential substrates by examining their differential toxicity, accumulation and efflux. Loratadine, an antihistamine, was 1.4-fold less toxic to MRP1 cells and its retention was 1.3-fold lower than that from MDCK control cells. Fosinopril, an angiotensin converting enzyme inhibitor, was 2.4-fold less toxic and its retention was 4.5-fold lower in MRP2-transfected cells compared with control cells. To determine whether fosinopril contributed to a drug-drug interaction, fosinopril efflux was examined in vitro in combination with other known or suspected MRP2 substrates over a period of 20 min. When fosinopril was coincubated with desloratadine, loratadine or methotrexate, its retention was increased by 2-, 4.7- and 2-fold, respectively, which likely indicates that a drug-drug interaction is occurring. In vivo studies were conducted, in which FVB wild-type and FVB/Mrp2(-/-) mice were dosed with fosinopril and the known MRP2 substrate methotrexate, and tissues collected after 1 h. In mice lacking Mrp2, drug levels were reduced in the intestine by 1.5-fold, but increased in the liver, serum and kidneys, by 2.1-, 2.9- and 3-fold, respectively. These data suggest that, in the absence of Mrp2, fosinopril alters the retention of a second drug. These findings will help increase our understanding of the role that MRP2 plays in altering the retention and disposition of coadministered pharmaceuticals.
The effect of the H1-antihistamine drug loratadine and its active metabolite descarboxyethoxyloratadine upon histamine release was examined on anti-immunoglobulin E (IgE) triggered human basophils and 2,4-dinitrophenyl (DNP) triggered rat basophilic leukemia (RBL-2H3) cells. In both experimental systems, dose-dependent inhibition of histamine release was observed at descarboxyethoxyloratadine and loratadine doses above 2 and 7 microM, respectively. In the RBL-2H3 experimental system, inhibition by loratadine increased when the concentration of extracellular Ca2+ was reduced from 1.8 to 0.45 mM. We further investigated the effect of loratadine and descarboxyethoxyloratadine on the increase in cytosolic calcium concentration (Ca2+)i, an early step in biochemical events leading to exocytosis. The effect of these two drugs upon (Ca2+)i changes was measured using the fluorescent probe fura-2 loaded into RBL-2H3 cells passively sensitized with DNP-specific IgE. Both drugs inhibited, in a dose-dependent manner (2.5-25 microM), the (Ca2+)i rise induced by DNP-BSA challenge in sensitized RBL cells, a process observed in both the presence and absence of extracellular Ca2+. Loratadine also inhibited the Mn2+ influx into these cells, thus reflecting the Ca2+ influx. These results suggest that loratadine and descarboxyethoxyloratadine impair the increase in (Ca2+)i following cell activation by decreasing both the influx of extracellular Ca2+ and the release of Ca2+ from intracellular stores.
The behavioural effects of beta,beta'-iminodipropionitrile (IDPN) were studied in chicks and adult fowls. Repeated administration of IDPN (75 mg/kg) for 5 days induced behavioural changes in chicks and adult fowls characterized by excitation, choreiform head and neck movements and circling (ECC-syndrome). Both acute and chronic administration of IDPN induced EEG desynchronization, EMG activation and enhancement of photic-evoked response (PER) in the hyperstriatum and pontine reticular formation while a decrease in PER was observed in the optic tectum. d-Amphetamine (2.5-5 mg/kg), apomorphine (0.1-0.25 mg/kg), piribedil (2.5-5 mg/kg), atropine (2.5-5 mg/kg), hyoscine (2.5-5 mg/kg) and cyproheptadine (0.5 mg/kg) potentiated the circling and choreiform head and neck movements. These activities were antagonized by pimozide (1 mg/kg), physostigmine (0.5 mg/kg) and quipazine (2.5-5 mg/kg). The results suggest that dopaminergic, serotoninergic and cholinergic mechanisms may be involved in IDPN-induced behavioural effects in chicks.
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The effects of a variety of substances influencing the initiation of cyclic motor events at the gastroduodenal junction were studied in conscious sheep. A significant and long-lasting decrease in the frequency of cyclic events from approximately 100 min to 30-40 min was elicited by the intraduodenal bulb administration of the lysergic acid derivatives methylergonovine and methysergide. This effect was dose-dependent and occurred with smaller dosages than those effective when administered parenterally or more distal in the jejunum. Intraluminal administration of cyproheptadine, fonazine, and metergoline into the duodenal bulb increased the interval between phase III activity. At higher dosages, however, cyproheptadine and metergoline reduced the spiking activity of the antroduodenal junction, without significantly changing the cycle duration of the migrating myoelectric complex on the duodenal bulb or jejunum. After administration of cyproheptadine, fonazine, and metergoline, the cycling activity of the duodenojejunum was irregular for 1-2 days. These findings are compatible with a resetting of the enteric biological clock at a faster rhythm and suggest a selective action via an enteric serotoninergic mechanism involved in the normal pacing of the cyclic motor events of the gut.
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The clinical efficacy of the H1 receptor blocker loratadine was to be measured upon a wheal response subsequent to an intracutaneous injection of 0.1 ml histamine (0.1%).