Dietary and pharmacological treatment of abdominal pain in IBS.

This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), µ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity.The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1Classes of pharmacological agents for visceral painAntidepressants (tricyclic agents, selective serotonin reuptake inhibitors)Peppermint oil5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron)Non-absorbed antibiotic (rifaximin)Secretagogues (lubiprostone, linaclotide)µ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline)Histamine H1 receptor antagonist (ebastine)Neurokinin-2 receptor antagonist (ibodutant)GABAergic agents (gabapentin and pregabalin).

New therapies for allergic rhinitis.

Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules.

Preseasonal prophylactic treatment with antihistamines suppresses IL-5 but not IL-33 mRNA expression in the nasal mucosa of patients with seasonal allergic rhinitis caused by Japanese cedar pollen.

CONCLUSIONS: These findings suggest that the down-regulation of interleukin (IL)-5 gene expression in collaboration with the suppression of histamine H(1) receptor (H1R) gene expression in the nasal mucosa provides the basis for better therapeutic effects of preseasonal prophylactic treatment with antihistamines in patients with seasonal allergic rhinitis caused by Japanese cedar pollen. OBJECTIVES: The effects of prophylactic administration of antihistamines on the expression of IL-5 and IL-33 mRNA in the nasal mucosa of the patients with pollinosis were investigated. METHODS: Eight patients had already visited the hospital before the peak pollen period and started preseasonal prophylactic treatment with antihistamines. Seventeen patients who first visited the hospital during the peak pollen period were designated as the no treatment group. After local anesthesia, nasal mucosa was obtained by scraping the inferior concha with a small spatula during the peak pollen period. RESULTS: During the peak pollen period, the expression of IL-5 mRNA, but not that of IL-33 mRNA, in the nasal mucosa of patients receiving preseasonal prophylactic treatment with antihistamines was significantly lower in comparison with that of patients without treatment. Moreover, there was a significant correlation between the expression of IL-5 mRNA and the nasal symptoms or the expression of H1R mRNA.

Update on the management of postoperative nausea and vomiting and postdischarge nausea and vomiting in ambulatory surgery.

Postoperative nausea and vomiting (PONV) continues to be one of the most common complaints following surgery, occurring in more than 30% of surgeries, or as high as 70% to 80% in certain high-risk populations without prophylaxis. The 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonists continue to be the mainstay of antiemetic therapy, but newer approaches, such as neurokinin-1 antagonists, a longer-acting serotonin receptor antagonist, multimodal management, and novel techniques for managing high-risk patients are gaining prominence. The related problem of postdischarge nausea and vomiting (PDNV) has received increasing attention from health care providers. The issues of PONV and PDNV are especially significant in the context of ambulatory surgeries, which comprise more than 60% of the combined 56.4 million ambulatory and inpatient surgery visits in the United States. Because of the relatively brief period that ambulatory patients spend in health care facilities, it is particularly important to prevent and treat PONV and PDNV swiftly and effectively.

[Avene-50 and Ebastine in treatment and prevention of photodermatosis].

The clinical efficacy of antihistaminic preparation "Kestine" (Ebastine) in combined treatment of 50 patients suffering from photo-allergic dermatosis (15 - solar urticaria, 20 - solar erythema and 15 - solar eczema) are evaluated. Kestine in dosage of 10 mg a day was prescribed in duration of 10 days. Itch disappearance was observed in 87% of patients, reduction of itching - in 10% and in 3% of patients an itch was remain. Photo protector Avene-50 as sunburn preparation, assigned for different type of skins, has been used. This preparation fit for different demands (including prevention of both beginnings and exacerbation of photo allergic reactions) of patients. Water- and sweat-resistance of Avene-50 formula has been taken in account. Treatment caused increasing of some indices of non specific reactions (Kavetski skin test) that confirms recovery of conjunctive tissue elements' activity. Efficacy and safety of this combined method of photodermatosis treatment allow us to use it widely in dermatologic clinic.

[Clinical efficacy of Ebastine under placebo-controlled outdoors clinical study on cedar pollinosis].

Placebo-controlled outdoors clinical study was performed at the Utsunomiya City Forest Park surrounded by many cryptomerias on March 5, 2000, at the season of most cedar pollens, to evaluate the efficacy and its timing and duration of Ebastine. It was a fine weather on the day of the study, and so much cedar pollens as 235 pollens/cm2 were spreading at the park when it was measured at the park. In particular, the amount of cedar pollen for 2 hours from 10:00 a.m. when Ebastine was administered exceeded 50 pollens/cm2 per hour. The nasal symptoms of the placebo-treated subjects promptly aggravated during the time, while the symptoms of the subjects who received oral Ebastine showed the tendency to improve from 2 hours after oral administration under exposure of a large amount of cedar pollens, and the efficacy maintained until 10:00 a.m. at the next morning that passed 24 hours after administration. The results suggest that Ebastine promptly inhibited the symptom induced by the exposure of a large amount of pollens at the season of most cedar pollens and that once daily oral administration of Ebastine maintained the efficacy at least for 24 hours. It was also suggested that outdoors comparative clinical study at the season of cedar pollen was effective to observe and evaluate the natural clinical course of a patient's symptom and was useful for evaluation of clinical efficacy of anti-pollinosis drugs of various types, including an anti-allergic reagent.

[Comparative antihistamine and anti-allergic effects of various antihistamine preparations]. / Sravnitel'noe izuchenie antigistaminnoi i antiallergicheskoi aktivnosti nekotorykh protivogistaminnykh preparatov.

AIM: To compare antihistaminic and antiallergic activity of antihistaminic drugs of the latest generation (ebastin, cetirisine, fexofenadine, loratadine) and antihistaminic drugs of the first generation (clemastin) in the same patients with pollenosis. MATERIAL AND METHODS: Skin prick-titration with 10-dilution histamine and specific allergen, provocative nasal titration with 2-dilution histamine and allergen before and after a single intake of H1-antagonists were made in 30 patients in stable clinical remission of pollenosis during maximal antihistamine activity of the above drugs. RESULTS: Systemic administration of the known H1-antagonists suppresses histamine sensitivity of both skin and nasal mucosa in the same degree. Drugs with more potent antihistaminic activity (fexofenadin and cetirisin) inhibited allergen-induced reactions more effectively. The order of the tested drugs by suppression of allergen-provoked skin and nasal reactions (by lowering antiallergic activity) is the following: fexofenadin and cetirisin > ebastin and loratadin > clemastin. CONCLUSION: The above drugs of the latest generation seem to posses antiallergic activity not only due to antihistaminic effect but also due to other mechanisms. Different suppressive action of H1-antagonists reflects also individual sensitivity to different drugs. The factor of individual sensitivity of the patients to a pharmacological action of the drug may be crucial in the selection of the most effective medicine for each patient. This is confirmed by the data of individual sensitivity of the patient to antihistaminic and antiallergic action of H1-antagonists. The illustrated method may be helpful for individual selection of H1-antagonists for treatment of patients with allergic diseases.

Anti-tumor promoting activity of Dryopteris phlorophenone derivatives.

As a part of screening studies for cancer chemopreventive agents (anti-tumor promoters) 33 Dryopteris phlorophenone derivatives have been evaluated. The compounds tested comprised of monomeric acylphloroglucinols (e.g. desaspidinol, aspidinol) as well as dimeric (e.g. aspidin, desaspidin), trimeric (e.g. filixic acids), and tetrameric (e.g. dryocrassin) phlorophenone, wherein hexacyclic rings are bound together by a methylene bridge. These compounds were examined for their in vitro anti-tumor promoting effect on Epstein-Barr virus antigen activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The two dimeric compounds aspidin and desaspidin, which were found to be the most active among the tested phlorophenones, were also examined in vivo on two stage mouse skin carcinogenesis, and found to show significant inhibitory effect on 7,12-dimethylbenz[alpha]anthracene (DMBA)-TPA tumor promotion.

Overview of allergic mechanisms. Ebastine has more than an antihistamine effect.

Histamine antagonists together with topical steroids are the treatment of choice in allergic rhinitis. Many of these histamine antagonists exhibit effects in addition to blockade of the histamine receptor. In this study we have investigated the effects of ebastine and carebastine on the release of eicosanoids and cytokines from human dispersed polyp cells and the effect of these compounds on the release of inflammatory mediators into nasal lavage fluid after allergen challenge. Ebastine was shown to block the release of anti-IgE-induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp cells (IC30 values of 2.57 and 9.6 mumol/L, respectively) and to inhibit the release of cytokines. Carebastine inhibited the release of PGD2 (IC30 8.14 mumol/L) but had little effect on cytokine release. When patients underwent nasal provocation tests with allergen, ebastine significantly increased the mean number of pollen grains required to induce an allergic response. In addition, the drug inhibited the release of granulocyte-macrophage colony-stimulating factor but had no effect on any other mediators measured.

Treatment of labor pain with locally applied ketocaine.

Ketocaine, a new local anesthetic drug, was used for treatment of referred pain during labor. In a randomized, double-blind manner, fifty primigravidae received compresses containing either ketocaine in a 10 per cent ethanol solution or compresses with saline (placebo). The compresses were applied to the skin areas where the patient experienced the most intense pain. Nineteen of the 25 patients receiving ketocaine compresses reported good or moderate pain relief for an average of 2.5 h (range 1--5 h). These patients had a mean cervical dilatation of 3 cm (range 2--5 cm). In patients without effect of the compresses, the cervix was dilated to a mean of 6 cm (range 5--8 cm). In patient reporting good effect of the treatment, pains were located mainly to the back. Only six of the 25 patients receiving placebo compresses obtained relief of pain. The effect ceased immediately upon removal of the compresses. There was no relation between pain relief and the degree of cervical dilatation, or localization of the pain. No maternal or fetal side-effects related to the treatment were registered.

[Therapy of childhood schizophrenia]. / Die Therapie der kindlichen Schizophrenie.

Due to the multifacet genesis and variability of clinical phenomenology, the therapy of childhood schizophrenia must be multidimensional. Formerly applied techniques like electroshock- and insulin-therapy are now replaced by pharmaco-therapy, primarily with phenothiazines, butyrophenones and chlorprothixens. The dosage depends on age, body weight or body surface. Because of extrapyramidal motor side effects, combinations with anticholinergic drugs may be necessary. Psychopharmaco-therapy alone, however, is insufficient. High emphasis must be placed on psychotherapy and educational guidance and counselling of the psychotic child. Participation in play groups, sports, muscial activities, arts and crafts, and acting helps make it possible to improve communication behaviour and to transform aggressive anxiety defense into stabilized control of emotions and impulses. In addition to successive integration of the psychotic child into small groups, play therapy with the single child is meaningful. In this case, a constant and confidential relation between therapist and child is extremely important and only possible if the therapist attempts to place himself into the magic-animistic phantasies of the psychotic child. He has first to learn the psychotic language of his patient in order to support more reality-oriented behaviour processes of the child's thinking, preceiving and performing later on. In this manner, the magic-omnipotent phantasies can be dissolved and an increasing orientation of the child toward reality can be encouraged. This involves strengthening and support of non-pathological ego-functions and initiation of a new level of ego-functioning. Such an integrated developmental concept can best be realized through play therapy.

Conceptual issues in the use of drugs for the treatment of aggression in man.

Violence is a symptom of an underlying mental state such as a psychosis, a characterological problem, or brain dysfunction. Thus drugs used to treat aggression in man exert effects by their specific pharmacological actions (e.g., antipsychotic, anticonvulsant). Most literature to date has dealt with animals and human models of aggression and lacks conceptual clarity. Aggression differs from depression, a coherent clinical entity, in its etiological diversity and its paroxysmal or impulsive basis, and this may account for the relationship seen in literature linking violence to epilepsy; yet literature on anticonvulsants is equivocal with regard to beneficial effects on aggression. Lithium has been shown to have positive effects, although its mode of action is unclear. A variety of antipsychotic agents and minor tranquilizers have been mentioned. Central nervous system stimulants have been found useful to treat hyperkinetic syndromes in both children and adults where aggression is a symptom. Hormonal agents are discussed. Drug treatment of aggression should not obscure the need for verbal therapies, and social and environmental factors should always be regarded.

Observations on the psychopharmacology of the aged.

Psychotropic drugs are discussed under the descriptive categories of antipsychotic, antidepressive, antimanic, anti-anxiety, and cognitive acting. In the antipsychotic classification, special attention is given to side effects (extrapyramidal motor signs, tardive dyskinesias, akathisis) and to dosage for the elderly. The section on congenitive acting drugs includes some pertinent observations on cognitive ability in the aging, the importance of correct diagnosis, and therapeutic strategy. The aged are a population at risk for not only disease, but iatrongenic illness due to direct and indirect drug action. Rational therapy involves understanding the underlying dynamics of the disease and thus the selection of the most effective treatment. Psychotropic drugs in an appropriate program are valuable therapeutic assets.