The protective effect of solidagenone from Solidago chilensis Meyen in a mouse model of airway inflammation.

Solidagenone is the main active constituent present in Solidago chilensis Meyen which is used in folk medicine to treat pain and inflammatory diseases. This study aimed to evaluate the anti-inflammatory activity of solidagenone in vitro and in a model of allergic airway inflammation. In vitro studies were performed in activated macrophages and lymphocytes. BALB/c mice were sensitized and challenged with ovalbumin and treated with solidagenone orally (30 or 90 mg/kg body weight) or dexamethasone, as a positive control in our in vivo analysis. Supernatant concentrations of nitrite, TNF and IL-1ß, as well as gene expression of pro-inflammatory mediators in macrophages cultures, were reduced after solidagenone treatment, without affecting macrophages viability. Besides, solidagenone significantly decreased T cell proliferation and secretion of IFNγ and IL-2. Th2 cytokine concentrations and inflammatory cell counts, especially eosinophils, in bronchoalveolar lavage fluid were reduced in mice treated with solidagenone. Histopathological evaluation of lung tissue was performed, and morphometrical analyses demonstrated reduction of cellular infiltration and mucus hypersecretion. Altogether, solidagenone presented anti-inflammatory activity in vitro and in vivo in the OVA-induced airway inflammation model, suggesting its promising pharmacological use as an anti-inflammatory agent for allergic hypersensitivity.

Adolescent Exposure to WIN 55212-2 Render the Nigrostriatal Dopaminergic Pathway Activated During Adulthood.

BACKGROUND: During adolescence, neuronal circuits exhibit plasticity in response to physiological changes and to adapt to environmental events. Nigrostriatal dopaminergic pathways are in constant flux during development. Evidence suggests a relationship between early use of cannabinoids and psychiatric disorders characterized by altered dopaminergic systems, such as schizophrenia and addiction. However, the impact of adolescent exposure to cannabinoids on nigrostriatal dopaminergic pathways in adulthood remains unclear. The aim of this research was to determine the effects of repeated activation of cannabinoid receptors during adolescence on dopaminergic activity of nigrostriatal pathways and the mechanisms underlying this impact during adulthood. METHODS: Male Sprague-Dawley rats were treated with 1.2 mg/kg WIN 55212-2 daily from postnatal day 40 to 65. Then no-net flux microdialysis of dopamine in the dorsolateral striatum, electrophysiological recording of dopaminergic neuronal activity, and microdialysis measures of gamma-aminobutyric acid (GABA) and glutamate in substantia nigra par compacta were carried out during adulthood (postnatal days 72-78). RESULTS: Repeated activation of cannabinoid receptors during adolescence increased the release of dopamine in dorsolateral striatum accompanied by increased population activity of dopamine neurons and decreased extracellular GABA levels in substantia nigra par compacta in adulthood. Furthermore, perfusion of bicuculline, a GABAa antagonist, into the ventral pallidum reversed the increased dopamine neuron population activity in substantia nigra par compacta induced by adolescent cannabinoid exposure. CONCLUSIONS: These results suggest that adolescent exposure to cannabinoid agonists produces disinhibition of nigrostriatal dopamine transmission during adulthood mediated by decreased GABAergic input from the ventral pallidum.

Effects of combined 5-HT2A and cannabinoid receptor modulation on a schizophrenia-related prepulse inhibition deficit in mice.

RATIONALE: Prepulse inhibition of the startle reflex (PPI) is disrupted in several psychiatric disorders including schizophrenia. Understanding PPI pharmacology may help elucidate the pathophysiology of these disorders and lead to better treatments. Given the advantages of multi-target approaches for complex mental illnesses treatment, we have investigated the interaction between receptors known to modulate PPI (5-HT1A and 5-HT2A) and the neuromodulatory endocannabinoid system. OBJECTIVES: To investigate serotonin and cannabinoid receptor (CBR) co-modulation in a model of PPI disruption relevant to schizophrenia METHODS: Male Swiss mice were pretreated with WIN 55,212-2 (CBR agonist), rimonabant (CB1R inverse agonist), 8-OH-DPAT (5-HT1A/7 agonist), and volinanserin (5-HT2A antagonist) or with a combination of a cannabinoid and a serotonergic drug. PPI disruption was induced by acute administration of MK-801. RESULTS: WIN 55,212-2 and rimonabant did not change PPI nor block MK-801-induced deficits. 8-OH-DPAT increased PPI in control mice and, in a higher dose, inhibited MK-801-induced impairments. Volinanserin also increased PPI in control and MK-801-treated mice, presenting an inverted U-shaped dose-response curve. Co-administration of either cannabinoid ligand with 8-OH-DPAT did not change PPI; however, the combination of volinanserin with rimonabant increased PPI in both control and MK-801-exposed mice. CONCLUSIONS: WIN 55,212-2 and rimonabant had similar effects in PPI. Moreover, serotonin and cannabinoid receptors interact to modulate PPI. While co-modulation of CBR and 5-HT1A receptors did not change PPI, a beneficial effect of 5-HT2A and CB1R antagonist combination was detected, possibly mediated through potentiation of 5-HT2A blockade effects by concomitant CB1R blockade.

Efficacy of afoxolaner in the flea control in experimentally infested cats / Eficácia do afoxolaner no controle de pulgas em gatos experimentalmente infestados

Abstract The aim of this study was to evaluate the efficacy of a single dose of oral afoxolaner in controlling fleas in cats. Fourteen cats were used. The cats were given identification numbers, housed individually, artificially infested with Ctenocephalides felis felis, and treated (or not) with afoxolaner. Were divided into a treatment group and a control group (n = 7/group), on the basis of the fleas count hours after an infestation applied on Day (one-by-one allocation after ordering by count). At the start of the experimental protocol (designated day 0), the treated group received afoxolaner in a single dose of 2.5 mg/kg and the control group animals received a placebo. All animals were infested with 100 C. felis felis fleas two days before day 0, as well as on days 5, 12, 19, 26, 33, 40, 47, 54, and 63, parasite loads being evaluated at 48 h after each infestation. The efficacy of afoxolaner was 100% on day 2 and remained above 98% until day 42, decreasing to 95.3% by day 63. The findings confirm that a single dose of oral afoxolaner was effective in controlling C. felis felis in cats, and there were no observed adverse events.

Resumo O objetivo do estudo foi avaliar a eficácia de uma dose única de afoxolaner oral no controle de pulgas em gatos. Foram utilizados 14 gatos. Os animais foram identificados, alojados individualmente, infestados artificialmente com C. felis felis e tratados (ou não) com afoxolaner. Foram divididos em um grupo de tratamento e um grupo controle (n = 7/ grupo), com base na contagem de pulgas, horas após a infestação aplicada no dia (alocação de um por um após o período por contagem). No início do protocolo experimental (dia 0), o grupo tratado recebeu afoxolaner em dose inicial de 2,5 mg / kg e os animais do grupo controle receberam um placebo. Todos os animais foram infestados com 100 pulgas C. felis felis dois dias antes do dia 0, assim como nos dias 5, 12, 19, 26, 33, 40, 47, 54 e 63, sendo avaliadas as cargas parasitárias às 48 h após cada infestação. A eficácia do afoxolaner foi de 100% no dia 2 e permaneceu acima de 98% até o dia 42, diminuindo para 95,3% no dia 63. Os resultados confirmam que uma dose única de afoxolaner oral foi eficaz no controle de C. felis felis em gatos, e não houve eventos adversos observados.

Efficacy of afoxolaner in the flea control in experimentally infested cats.

The aim of this study was to evaluate the efficacy of a single dose of oral afoxolaner in controlling fleas in cats. Fourteen cats were used. The cats were given identification numbers, housed individually, artificially infested with Ctenocephalides felis felis, and treated (or not) with afoxolaner. Were divided into a treatment group and a control group (n = 7/group), on the basis of the fleas count hours after an infestation applied on Day (one-by-one allocation after ordering by count). At the start of the experimental protocol (designated day 0), the treated group received afoxolaner in a single dose of 2.5 mg/kg and the control group animals received a placebo. All animals were infested with 100 C. felis felis fleas two days before day 0, as well as on days 5, 12, 19, 26, 33, 40, 47, 54, and 63, parasite loads being evaluated at 48 h after each infestation. The efficacy of afoxolaner was 100% on day 2 and remained above 98% until day 42, decreasing to 95.3% by day 63. The findings confirm that a single dose of oral afoxolaner was effective in controlling C. felis felis in cats, and there were no observed adverse events.

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review.

Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro, Brazil, is a main endemic area, with a large number of human and animal cases in the last 19 years. This mycosis is more frequently described in cats rather than in dogs. There are a limited number of oral antifungal agents for the treatment of sporotrichosis in animals. In this context, the effectiveness of terbinafine in the treatment of sporotrichosis in humans, as well as the promising results of in vitro susceptibility tests, inspired us to use this drug in the therapy of this mycosis in dogs. We reported for the first time the use of terbinafine in the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis. Moreover, we provided an overview of therapeutic features of canine sporotrichosis cases reported since the 1960s. One of the dogs presented the fixed cutaneous form of the disease, while the other patient presented hyperemia of the nasal mucosa and respiratory signs only. Terbinafine showed high antifungal activity in vitro against the canine Sporothrix isolates. The dogs were successfully treated with terbinafine, with remission of all clinical signs initially presented. The current reports indicate that this drug can emerge as a therapeutic option for canine sporotrichosis.

LASSBio-1829 Hydrochloride: Development of a New Orally Active N-Acylhydrazone IKK2 Inhibitor with Anti-inflammatory Properties.

Inhibitor of nuclear factor κB kinase 2 (IKK2) is suggested to be a potential target for the development of novel anti-inflammatory and anticancer drugs. In this work, we applied structure-based drug design to improve the potency of the inhibitor (E)-N'-(4-nitrobenzylidene)-2-naphthohydrazide (LASSBio-1524, 1 a: IC50 =20 µm). The molecular model built for IKK2 together with the docking methodology employed were able to provide important and consistent information with respect to the structural and chemical inhibitor characteristics that may confer potency to IKK2 inhibitors, providing important guidelines for the development of a new N-acylhydrazone (NAH) derivative. (E)-N'-(4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzylidene)-2-naphthohydrazide hydrochloride (LASSBio-1829 hydrochloride, 10) is a 7-azaindole NAH able to inhibit IKK2 with an IC50 value of 3.8 µm. LASSBio-1829 hydrochloride was found to be active in several pharmacological inflammation tests in vivo, showing its potential as an anti-inflammatory prototype.

A comparison of pre and post-operative vedaprofen with ketoprofen for pain control in dogs.

BACKGROUND: This prospective randomized blinded clinical study aimed to investigate the potential of vedaprofen for preventive analgesia, comparing its analgesic effects with ketoprofen administered post-operatively in dogs undergoing maxillectomy or mandibulectomy. RESULTS: Pain control was effective and rescue analgesia was not necessary in any group. Pain scores were not significantly different between groups. The respiratory rate and rectal temperature were decreased in all groups at extubation until 6 hours post-extubation compared to baseline. Cortisol and epinephrine levels were increased only at 0.5 hours after extubation in all groups compared to baseline. CONCLUSIONS: Vedaprofen did not present any preventive analgesic effect. Pre- and postoperative vedaprofen were as effective as ketoprofen for postoperative pain control.

Tinea nigra presenting speckled or "salt and pepper" pattern.

A 7-year-old Caucasian female resident of the southern coast of Brazil presented dark spots on the left palm that converged to a unique macule with speckled pattern at about 1 month. The mycological exam and the fungi culture were typical of Hortaea werneckii, the agent of the superficial mycosis Tinea nigra. The patient received butenafine hydrochloride 1% for 30 days, resulting in a complete remission of the lesion. At a follow-up visit 12 months after treatment, there was no lesion recurrence. We describe a form of rare geographical Tinea nigra with a speckled pattern. The "salt and pepper" aspect should be taken into consideration when the mycosis was suspected.

Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: the SHR strain.

Studies have suggested that the endocannabinoid system is implicated in the pathophysiology of schizophrenia. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs display hyperlocomotion - reverted by atypical and typical antipsychotics. These results suggest that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia and the effects of potential drugs with an antipsychotic profile. The aim of this study was to investigate the effects of WIN55-212,2 (CB1/CB2 agonist), ACEA (CB1 agonist), rimonabant (CB1 inverse agonist), AM404 (anandamide uptake/metabolism inhibitor), capsaicin (agonist TRPV1) and capsazepine (antagonist TRPV1) on the social interaction and locomotion of control animals (Wistar rats) and SHRs. The treatment with rimonabant was not able to alter either the social interaction or the locomotion presented by Wistar rats (WR) and SHR at any dose tested. The treatment with WIN55-212,2 decreased locomotion (1mg/kg) and social interaction (0.1 and 0.3mg/kg) of WR, while the dose of 1mg/kg increased social interaction of SHR. The treatment with ACEA increased (0.3mg/kg) and decreased (1mg/kg) locomotion of both strain. The administration of AM404 increased social interaction and decreased locomotion of SHR (5mg/kg), and decreased social interaction and increased locomotion in WR (1mg/kg). The treatment with capsaicin (2.5mg/kg) increased social interaction of both strain and decreased locomotion of SHR (2.5mg/kg) and WR (0.5mg/kg and 2.5mg/kg). In addition, capsazepine (5mg/kg) decreased locomotion of both strains and increased (5mg/kg) and decreased (10mg/kg) social interaction of WR. Our results indicate that the schizophrenia-like behaviors displayed by SHR are differently altered by cannabinoid and vanilloid drugs when compared to control animals and suggest the endocannabinoid and the vanilloid systems as a potential target for the treatment of schizophrenia.

Cannabinoid type-1 receptor ligands, alone or in combination with cocaine, affect vigilance-related behaviors of marmoset monkeys.

Endocannabinoids (eCB) have been functionally linked to cocaine׳s rewarding effects. However, results differ at the behavioral level, with few reports in nonhuman primates (NHPs). Here we analyzed whether repeatedly administered cannabinoid type-1 receptor (CB1r) agonist WIN 55-212,2 (WIN) or antagonist AM 251 (AM) induce effects per se and if concurrent pre-treatments affect cocaine-induced changes in marmoset behavior. Six groups were tested: WIN-saline; WIN-cocaine; AM-saline; AM-cocaine; vehicle-cocaine; and vehicle-saline. Subjects were pre-treated with either WIN (1mg/kg), AM (2mg/kg) or vehicle and then injected with cocaine (5mg/kg) or saline. Six exposures were held at 48 h intervals. Behaviors were scored during 15-min in an open-field on days 1 and 6, as well as a withdrawal (WD) trial. Marmosets became hypervigilant during cocaine exposures, which did not condition to the injection context. CB1r activation induced an equivalent response, whereas AM had no effect on its own. However, when given as a pre-treatment to cocaine, CB1r blockade enhanced the former׳s hypervigilance effect and potentially conditioned this response to the exposure context. Enhancement may have resulted from AM׳s inhibition of eCB-potentiated cocaine-induced anxiogenesis and/or its action independent of the eCB system, or even CB1r-mediated changes in synaptic plasticity involved in cocaine reward-learning. All effects were independent of motor function. Thus, changes in CB1r function - alone and in combination with cocaine - affected stereotyped vigilance-related behaviors in this NHP, further implicating the eCB system in the neurobiological mechanisms of cocaine addiction.

Intermittent therapy with terbinafine and nail abrasion for dermatophyte toe onychomycosis: a pilot study.

Onychomycosis constitutes up to 50% of all nail disorders. Toenails are generally affected, mostly due to dermatophytes. Terbinafine is the most potent antifungal agent in vitro against dermatophytes. There are few randomised controlled trials using a non-continuous dose of terbinafine. The aim of this open-label pilot study was to reduce the total drug amount, the collateral effects and, specially, the costs; albeit maintaining the same efficacy of the standard regimens. Compare the outcomes of two different intermittent regimens with the same total amount of the medication (42 tablets in 6 months). Forty-one patients were divided into the following groups: terbinafine 250 mg day(-1) , for 7 days, monthly or terbinafine 500 mg day(-1) , once daily, for 7 days, every 2 months, both plus nail abrasion during 6 months. The efficacy was evaluated at months 6, 12 and 18 using the disease free nail criteria. Total cure = group I: eight patients (44.4%) and group II: eight patients (44.4%). Partial cure = group I: five patients (27.8%) and group II: four patients (22.2%). Treatment failure = group I: five patients (27.8%) and group II: three patients (16.7%). Recurrence = group I: zero patients (0.0%) and group II: three patients (16.7%). Two intermittent dosing regimens of terbinafine plus nail abrasion proved to be an alternative statistically effective, safe and with reduced drug costs for dermatophytes toenail onychomycosis.

Onychomycosis due to Neoscytalidium treated with oral terbinafine, ciclopirox nail lacquer and nail abrasion: a pilot study of 25 patients.

BACKGROUND: Onychomycosis by Neoscytalidium constitutes chronic infection of the nails, and its frequency has increased in recent decades. Currently, no effective standard treatment exists and literature data remain scarce. This work aimed to conduct a pilot project of combined treatment for this infection. METHODS: Thirty patients were divided into three treatment groups: oral terbinafine plus ciclopirox nail lacquer twice a week; ciclopirox nail lacquer twice a week; and ciclopirox nail lacquer 5 days a week, all associated with nail abrasion when required, for 12 months, with 6 months posttreatment follow-up. Clinical and mycological criteria were used for evaluation. RESULTS: Twenty-five patients completed the study. Significant clinical lesion reduction in disease occurred in all three treatment groups: 21 patients (84%) entered the study with more than 50% of diseased nail plate, at the end of treatment, and at 6-month follow-up, 84 and 96%, respectively, presented less than 25% nail lesion. Negative microscopy was observed in 36% of the patients at the end of treatment and in 24% of the patients at 6-month follow-up. At treatment completion (12 months), culture was negative in 21 patients (84%) and in 18 (72%) at follow-up. It was not possible to establish any clinical or mycological statistical differences between groups (p > 0.05). Global medical evaluation upon treatment completion revealed that one patient (4%) presented complete cure, 8 (32%) presented partial cure, 16 (64%) presented therapeutic failure. At the end of follow-up period, 6 patients (24%) were considered to have recurrence/reinfection. CONCLUSIONS: The results obtained at the 6-month period of follow-up showed marked improvement (96% of clinical improvement and 72% of negative culture) of the patients treated for onychomycosis caused by Neoscytalidium in the three tested groups with no statistical differences between them. Multicentric studies with greater number of patients enrolled are necessary to confirm these results.

The marine sponge toxin agelasine B increases the intracellular Ca(2+) concentration and induces apoptosis in human breast cancer cells (MCF-7).

PURPOSE: In search for new drugs derived from natural products for the possible treatment of cancer, we studied the action of agelasine B, a compound purified from a marine sponge Agelas clathrodes. METHODS: Agelasine B was purified from a marine sponge Agelas clathrodes and assayed for cytotoxicity by MTT on two human breast cancer cells (MCF-7 and SKBr3), on a prostate cancer cells (PC-3) and on human fibroblasts. Changes in the intracellular Ca(2+) concentrations were assessed with FURA 2 and by confocal microscopy. Determination of Ca(2+)-ATPase activity was followed by Pi measurements. Changes in the mitochondria electrochemical potential was followed with Rhodamine 123. Apoptosis and DNA fragmentation were determined by TUNEL experiments. RESULTS: Upon agelasine B treatment, cell viability of both human breast cancer cell lines was one order of magnitude lower as compared with fibroblasts (IC(50) for MCF-7 = 2.99 µM; SKBr3: IC(50) = 3.22 µM vs. fibroblasts: IC(50) = 32.91 µM), while the IC(50) for PC-3 IC(50) = 6.86 µM. Agelasine B induced a large increase in the intracellular Ca(2+) concentration in MCF-7, SKBr3, and PC-3 cells. By the use of confocal microscopy coupled to a perfusion system, we could observe that this toxin releases Ca(2+) from the endoplasmic reticulum (ER). We also demonstrated that agelasine B produces a potent inhibition of the ER Ca(2+)-ATPase (SERCA), and that this compound induced the fragmentation of DNA. Accordingly, agelasine B reduced the expression of the anti-apoptotic protein Bcl-2 and was able to activate caspase 8, without affecting the activity of caspase 7. CONCLUSIONS: Agelasine B in MCF-7 cells induce the activation of apoptosis in response to a sustained increase in the [Ca(2+)]( i ) after blocking the SERCA activity. The reproduction of the effects of agelasine B on cell viability and on the [Ca(2+)]( I ) obtained on SKBr3 and PC-3 cancer cells strongly suggests the generality of the mechanism of action of this toxin.

Clinical efficacy of adapalene (differin(®)) 0.3% gel in Chilean women with cutaneous photoaging.

Skin photoaging is a concern for many patients today, and it is important for dermatologists to evaluate new therapeutic approaches. This 6-month open-label study evaluated the effectiveness and safety of adapalene 0.3% gel in 40 Latin American women with signs of facial photoaging. Assessments at baseline, week 12, and week 24 included clinical severity grading, measurement of transepidermal water loss, hydration, and elasticity (Cutometer MPA 850®), evaluation of general skin tone and number of wrinkles (VISIA(®) Complexion Analysis System), and ultrasonography to measure changes in skin thickness. There were significant improvements in clinical grading of wrinkles (p < 0.01) with a reduction in mean severity score of 40% in forehead wrinkles, 52% in periorbital wrinkles, and 29% in perioral wrinkles. Melanin, transepidermal water loss, and hydration were improved, as were general skin tone and the number of wrinkles (p < 0.05). Measurement of skin thickness showed a non-significant improvement in the epidermis and dermis and a significant decrease of the elastosis band (11.6% at week 12 and 15.1% at week 24). Adapalene was well tolerated overall, although three patients discontinued the study due to skin irritation in the first month. We conclude that adapalene 0.3% gel is a new safe and effective approach to photoaging.

A simple HPLC-DAD method for determination of adapalene in topical gel formulation.

A simple stability indicating high-performance liquid chromatography method for the analysis of adapalene in pharmaceutical gel formulation is developed and validated. An isocratic separation is performed using a Merck RP-8 (150 mm × 4.6 mm i.d., particle size 5 m) column and a mixture of acetonitrile water (67:33, v/v, pH adjusted to 2.5 with phosphoric acid) as the mobile phase. The detection is achieved with a photodiode array detector at 321 nm. The specificity of the method is verified by subjecting both the reference substance and the pharmaceutical form to hydrolytic, oxidative, photolytic, and thermal stress conditions. There is no interference from the excipients of the formulation on the determination of adapalene in gel. The response is linear over the concentration range of 8.0-16.0 µg/mL (r > 0.999) with a limit of detection and quantification of 0.04 and 0.14 µg/mL, respectively. The mean recovery is 100.8%. The RSD values for the intra- and inter-day precision studies are < 1.2%. The method is validated by reaching satisfactory results for linearity, selectivity, specificity, precision, accuracy, robustness, and system suitability.

Refinement and initial validation of a multidimensional composite scale for use in assessing acute postoperative pain in cats.

OBJECTIVE: To refine and test construct validity and reliability of a composite pain scale for use in assessing acute postoperative pain in cats undergoing ovariohysterectomy. SAMPLE POPULATION: 40 cats that underwent ovariohysterectomy in a previous study. PROCEDURES: In a previous randomized, double-blind, placebo-controlled study, a composite pain scale was developed to assess postoperative pain in cats that received a placebo or an analgesic (tramadol, vedaprofen, or tramadol-vedaprofen combination). In the present study, the scale was refined via item analysis (distribution frequency and occurrence), a nonparametric ANOVA, and item-to-total score correlation. Construct validity was assessed via factor analysis and known-groups discrimination, and reliability was measured by assessing internal consistency. RESULTS: Respiratory rate and respiratory pattern were rejected after item analysis. Factor analysis resulted in 5 dimensions (F1 [psychomotor change], posture, comfort, activity, mental status, and miscellaneous behaviors; F2 [protection of wound area], reaction to palpation of the surgical wound and palpation of the abdomen and flank; F3 [physiologic variables], systolic arterial blood pressure and appetite; F4 [vocal expression of pain], vocalization; and F5 [heart rate]). Internal consistency was excellent for the overall scale and for F1, F2, and F3; very good for F4; and unacceptable for F5. Except for heart rate, the identified factors and scale total score could be used to detect differences between the analgesic and placebo groups and differences among the analgesic treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results provided initial evidence of construct validity and reliability of a multidimensional composite tool for use in assessing acute postoperative pain in cats undergoing ovariohysterectomy.

Cannabidiol inhibits the hyperphagia induced by cannabinoid-1 or serotonin-1A receptor agonists.

Δ9-THC is a component of Cannabis sativa that increases food intake in animals and humans, an effect prevented by selective CB1 receptor antagonists. Cannabidiol (CBD) is another constituent of this plant that promotes several opposite neuropharmacological effects compared to Δ9-THC. CBD mechanisms of action are still not clear, but under specific experimental conditions it can antagonize the effects of cannabinoid agonists, block the reuptake of anandamide and act as an agonist of 5-HT1A receptors. Since both the cannabinoid and serotoninergic systems have been implicated in food intake control, the aim of the present work was to investigate the effects caused by CBD on hyperphagia induced by agonists of CB1 or 5-HT1A receptors. Fed or fasted Wistar rats received intraperitoneal (i.p.) injections of CBD (1, 10 and 20 mg/kg) and food intake was measured 30 min later for 1 h. Moreover, additional fed or fasted groups received, after pretreatment with CBD (20 mg/kg) or vehicle, i.p. administration of vehicle, a CB1 receptor agonist WIN55,212-2 (2 mg/kg) or a 5-HT1A receptor agonist 8-OH-DPAT (1 mg/kg) and were submitted to the food intake test for 1 h. CBD by itself did not change food intake in fed or fasted rats. However, it prevented the hyperphagic effects induced by WIN55,212-2 or 8-OH-DPAT. These results show that CBD can interfere with food intake changes induced by a CB1 or 5-HT1A receptor agonist, suggesting that its role as a possible food intake regulator should be further investigate.

Comparative study of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis.

UNLABELLED: Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250 mg has been successfully applied to the treatment of cutaneous sporotrichosis. OBJECTIVE: To compare the efficacy of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis. MATERIALS AND METHODS: A bidirectional cohort study was conducted on 55 patients receiving 250 mg/day terbinafine and 249 patients receiving 100 mg/day itraconazole. The latter patients were matched for age and clinical form to the terbinafine group at a ratio of 5:1. Sporothrix schenckii was isolated by culture from all patients (age range: 18-70 years), who were submitted to the standard care protocol consisting of clinical and laboratory evaluation and periodic visits. RESULTS: Cure was observed in 51 (92.7%) patients of the terbinafine group and 229 (92%) of the itraconazole group within a similar mean period of time (11.5 and 11.8 weeks, respectively). An increase in the terbinafine dose to 500 mg was necessary in two patients due to the lack of a response, and one patient presented recurrence. In the itraconazole group, two patients required a dose increase and three presented recurrence. Adverse events were equally frequent among patients receiving terbinafine (n = 4, 7.3%) and itraconazole (n = 19, 7.6%) and were generally mild without the need for drug discontinuation, except for two patients of the itraconazole group. CONCLUSION: Terbinafine administered at a daily dose of 250 mg is an effective and well-tolerated option for the treatment of cutaneous sporotrichosis.

Community study of fixed-combination adapalene 0.1% and benzoyl peroxide 2.5% in acne.

A new fixed-dose combination formulation of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% has shown excellent efficacy and safety in registration studies; however, it can be difficult to judge the real-world performance of a product using only the results from controlled clinical trials. This 12-week, open-label, community-based study evaluated adapalene/BPO in 91 patients with mild to moderate acne (20-50 inflammatory lesions and 30-100 noninflammatory lesions) who were treated at dermatology centers throughout Argentina. The study evaluated efficacy, described the most common side effects, determined tolerability, and assessed the level of patient satisfaction with treatment. By week 12, there were statistically significant reductions in both inflammatory and noninflammatory lesions (80.6% and 69.3% from baseline, respectively; P < .001); there were also significant improvements in the Investigator's Global Assessment scores (median score, 2.9 at baseline and 1.0 at week 12; P < .001). By week 12, 67% of patients were rated clear or almost clear by investigators. Local tolerability was good overall. When cutaneous irritation was present, it typically occurred in the first 2 weeks of treatment and improved or resolved with continuing therapy. Patients were highly satisfied with the results of treatment, and 74% of patients felt that they had marked or total improvement by week 12. Patient survey also revealed that 94% rated the efficacy as good or very good and 87.5% rated tolerability as good or very good. A significant majority (81%) felt that the treatment met expectations, and 62% perceived that improvement had been rapid during adapalene/BPO therapy. These results demonstrate that adapalene/BPO has good efficacy and tolerability in routine practice, resulting in continuous reductions in lesion counts throughout the study. Adapalene/BPO therapy is also associated with high patient satisfaction, which is important for therapeutic adherence and satisfaction with the physician's care.