Changes in neurokinin A (NKA) airway responsiveness with inhaled frusemide in asthma

BACKGROUND: Inhaled frusemide exerts a protective effect against bronchoconstriction induced by several indirect stimuli in asthma which could be due to interference of airway nerves. A randomised, double blind, placebo controlled study was performed to investigate the effect of the potent loop diuretic, frusemide, administered by inhalation on the bronchoconstrictor response to neurokinin A (NKA) and histamine in 11 asthmatic subjects. METHODS: Subjects attended the laboratory on four separate occasions to receive nebulised frusemide (40 mg) or matched placebo 10 minutes prior to bronchial challenge with NKA and histamine in a randomised, double blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and responsiveness to the agonists was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). RESULTS: Compared with placebo, inhaled frusemide reduced the airway responsiveness to NKA in all the subjects studied, the geometric mean (range) values for PC20NKA increasing significantly (p < 0.001) from 130.3 (35.8-378.8) to 419.9 (126.5-1000) micrograms/ml after placebo and frusemide, respectively. Moreover, a small but significant change in airway responsiveness to histamine was recorded after frusemide, their geometric mean (range) PC20 values being 0.58 (0.12-3.80) and 1.04 (0.28-4.33) mg/ml after placebo and frusemide, respectively. CONCLUSIONS: The decrease in airway responsiveness to NKA after administration of frusemide by inhalation suggests that this drug may interfere with the activation of neurotransmission in human asthma.




     

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

Clinical course of central nervous system demyelinating neurological adverse events associated with anti-TNF therapy

Journal of Neurology - Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight...     

Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit “Regina Elena” National Cancer Institute

Neurological Sciences - The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and...     

Effect of salbutamol on nasal symptoms and mast cell degranulation induced by adenosine 5'' monophosphate nasal challenge

BACKGROUND: In addition to its well-known functional agonism at the level of beta(2) adrenergic receptors on airways smooth muscle cells, salbutamol appears to have additional protective effects, possibly through an inhibition of mast cell activation. OBJECTIVE: The aim of this study is to provide the first evidence in vivo of inhibition of human mast cell activation by salbutamol. METHODS: Nine atopic subjects received placebo and salbutamol (5 mg/mL) 15 min before an adenosine 5' monophosphate (AMP) nasal provocation in a double-blind crossover study design. The nasal lavage was collected from these subjects prior to or 3, 5, 15 or 30 min after the AMP nasal challenge, and concentrations of histamine and tryptase in the nasal lavage were measured. RESULTS: AMP nasal provocation produced considerable sneezing and induced a transient increase in histamine and tryptase release with peak values achieved at 3 min after the challenge in all the subjects studied. Compared with placebo, salbutamol significantly attenuated the release of histamine and tryptase induced by AMP challenge (P=0.048 and 0.020, respectively). Moreover, the AMP-induced sneezing was also inhibited by pre-treatment with salbutamol (P=0.004). CONCLUSIONS: Intranasal salbutamol attenuates nasal symptoms and inhibits histamine and tryptase release caused by AMP nasal provocation thus supporting the hypothesis that salbutamol may play an additional protective role in the airways by inhibiting mast cell activation.     

Study of the cytotoxic activity of beauvericin and fusaproliferin and bioavailability in vitro on Caco-2 cells

Beauvericin (BEA) is a cyclohexadepsipeptide mycotoxin which has insecticidal properties and produces cytotoxic effects in mammalian cells. Fusaproliferin (FUS) is a mycotoxin that has toxic activity against brine shrimp, insect cells, and teratogenic effects on chicken embryos. The aim of this study was to determine the cytotoxicity of BEA and FUS in human epithelial colorectal adenocarcinoma HT-29 and Caco-2 cells, the transepithelial transport and the bioavailability using Caco-2 cells as a simulated in vitro gastrointestinal model of the human intestinal epithelium. The inhibitory concentration (IC₅₀) evidenced by BEA in the Caco-2 cells was 24.6 and 12.7 μM at 24 and 48 h exposure, respectively, whereas the IC₅₀ values evidenced in HT-29 cells were 15.0 and 9.7 μM, respectively. FUS was cytotoxic, but no IC₅₀ data were observed in the range of concentration tested. BEA bioavailability was variable from 50.1% to 54.3%, whereas FUS presented a bioavailability variable from 80.2% to 83.2%. Results obtained demonstrated a potential risk for human health.     

Primary headache and multiple sclerosis: preliminary results of a prospective study

The aim of this study was to explore the association between different types of headache (HA) and the clinical features of multiple sclerosis (MS). The relationship between HA and MS-specific therapies was also analysed. A total of 102 MS patients were recruited at the MS Centre of S. Andrea Hospital in Rome. According to International Headache Society criteria, the lifetime prevalence of primary HA was 61.8%. Migraine was observed more often in young relapsing-remitting MS patients, whilst tension-type HA was associated with older age, male gender and a secondary progressive course. Sixty-four patients had a history of ongoing or past interferon beta (IFNb) exposure. Of these, 17 subjects did not have a history of HA, while 24 complained of an increase in frequency of migraine attacks and 7 reported an IFNb-induced HA. Investigating and treating HA in MS patients starting IFNb therapy may improve MS-specific medication compliance.