Use of proposed systolic and myocardial performance indices derived from simultaneous ECG and PCG recordings to assess cardiac function in healthy Beagles.

Background and Aim: Cardiac time intervals (CTIs) can provide important information on the electrical and mechanical properties of the heart. We hypothesized that cardiac function can be described using the combined power of electrocardiography (ECG) and phonocardiography (PCG) signals. This study aimed to (1) validate a novel custom device in measuring CTI parameters; (2) compare CTI parameters with a commercially available device and standard transthoracic echocardiography (STE); and (3) compare calculated systolic performance index (SPI) and myocardial performance index (MPI) with Tei index from the STE. Materials and Methods: This study determined CTIs based on simultaneous ECG and PCG recordings in 14 healthy Beagle dogs using the custom-built device. These CTI parameters were compared with a commercially available device (Eko DUO ECG + Digital Stethoscope; Eko DUO) and the STE. Agreement of CTI parameters between the custom device and the commercially available device or STE was evaluated. Calculated SPI and MPI based on Wigger's diagram were proposed, compared with SPI and Tei index, and correlated with STE parameters. Results: We found that the ECG and PCG parameters measured from the custom-built device did not differ from the commercially available device and the STE. By combining ECG and PCG signals, we established CTI parameters in healthy dogs including indices for systolic function (SPI: QS1/S1S2) and global cardiac function {F1 ([QS1+S2]/S1S2), F2 ([RS1+S2]/S1S2), and F3 (RS1 + [QS2-QT]/S1S2)}. The SPI, F2, and F3 were comparable with echocardiographic parameters describing systolic (Pre-ejection period/left ventricular ejection time [LVET]) and Tei index ([MCOdur-LVET]/LVET), respectively. Only SPI and F3 were correlated significantly with MCOdur and heart rate, respectively. Conclusion: We have validated the use of the custom-built device to describe CTIs that are comparable to the commercially available device and STE in healthy Beagles. The proposed SPI and MPI derived from CTI parameters can be useful in clinical practice to describe the cardiac function, especially in areas where access to STE is constrained.

Novel Approach to Assess Cardiac Function Using Systolic Performance and Myocardial Performance Indices From Simultaneous Electrocardiography and Phonocardiography Recordings in Dogs With Various Stages of Myxomatous Mitral Valve Disease.

Background and Objective: Myxomatous mitral valve disease (MMVD) progression entails changes in the structural and functional properties of the heart affecting cardiac timings and intervals within the cardiac cycle. Conventionally, echocardiography is used to determine the cardiac time intervals (CTIs) including systolic and myocardial performance indices (SPI and MPI) in evaluating cardiac function. Alternatively, these CTIs can also be measured using simultaneous recordings of electrocardiography (ECG) and phonocardiography (PCG), but their values in different MMVD stages remain to be established. This study aimed to establish and prove the use of derived SPI and MPI from a dedicated device as a novel approach to assess cardiac function in different stages of MMVD dogs. Materials and Methods: A prospective study in 52 dogs with different MMVD stages measured the CTIs using a novel device. These were compared and correlated with standard echocardiographic parameters. The predictive value of SPI and three new proposed formulas to estimate MPI (i.e., F1, F2, and F3) in association with asymptomatic from symptomatic MMVD dogs were investigated. Results: Our findings revealed that CTI parameters measured from a novel device including QS1, QS2, S1S2, MPI-F1, and MPI-F2 were altered at different stages of MMVD. The SPI and all proposed MPI formulas were comparable with the systolic time interval and Tei index from echocardiography. In addition, the SPI, MPI-F1, and MPI-F2 were significantly correlated with the Tei index. However, the SPI was not able to differentiate the various stages of MMVD. Conversely, only the MPI-F1 (i.e., (QS1 + S2)/S1S2) demonstrated good predictive accuracy when compared between asymptomatic and symptomatic MMVD dogs similar to the Tei index. Moreover, this formula was able to differentiate stages B1 and C with remarkable predictive accuracy, higher sensitivity, and high specificity when compared with the Tei index. Conclusion: We have successfully described the CTI parameters in different MMVD stages using simultaneous ECG and PCG recordings in dogs. Furthermore, we have proven that the concept of using the newly proposed parameters from a novel device is equivalent to the Tei index. Thus, we established a novel approach to evaluate cardiac function and its supportive use in the diagnosis of MMVD patients.

Household disinfectant exposure during the COVID-19 pandemic: a retrospective study of the data from an Italian poison control center.

OBJECTIVE: Since the beginning of the COVID-19 pandemic it has been recommended that chemical disinfectants are used to protect surfaces. This study aimed to determine whether the number of exposure calls related to household disinfectants (HD) received between January 30, 2020 to May 18, 2020 varied from the same time period in the previous year. MATERIALS AND METHODS: A retrospective review of the poison control center database from the Fondazione Universitario Policlinico Agostino Gemelli IRCCS, Rome, Italy, was conducted. Calls from Italian citizens, hospitals, and general practitioners received during the same time period in 2019 and 2020 were compared. RESULTS: The center received 1972 exposure calls during the study period. A 5% increase in calls regarding exposure to HDs was noted from 2019 to 2020 (9.8% to 15.2%, p<0.001). The majority of enquiries regarded bleach-containing products, hand sanitizers, ethanol, and hydrogen peroxide. Most calls were received from patients in their homes (n, 259; prevalence, 86%; increase, 107%) and concerned accidental exposure (n, 280; prevalence, 93%; increase, 76%), while cases of intentional exposure decreased (n, 14; prevalence, 5%; decrease, 33%). The main route of exposure was ingestion (n, 170; prevalence, 57%; increase, 45%), but the highest increase was observed in inhalation cases (n, 82; prevalence, 27%; increase, 122%). CONCLUSIONS: As the incidence of enquiries regarding products that can represent an important health hazard, when improperly used, increased in 2020 suggests that the COVID-19 public health messaging on the proper use of HDs should be improved.

Investigating Underfloor and Between Floor Deposits in Standing Buildings in Colonial Australia.

Archaeological deposits build up inside standing buildings both under and between floors and these have the potential to provide considerable information about human behavior in the past. Under and between floor spaces provide a unique depositional environment that allow the survival of rare and fragile organic materials that typically do not survive in other archaeological contexts, including paper, cardboard, fabric and other fibres, seeds, leather, and human hair and skin cells. However, they require a clear understanding of depositional processes to allow their interpretation. Experimental archaeology was conducted to understand the process of artifact deposition and the interpretation of underfloor deposits in twelve standing buildings in Western Australia. Floors were built and a range of artifacts swept across them to determine how artifacts travelled across floorboards or fell through gaps between boards. Size, shape, and angularity of artifacts were key determinants of the likelihood of deposition. Sweeping activity makes it more likely that material will be deposited around the margins of rooms, and particularly, to either side of doorways. Underfloor deposits excavated from two specific Western Australian buildings, Ellensbrook Homestead, and the York Residency Museum, are interpreted based on the results of these experiments.

The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients.

Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1ß, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.

Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.

BACKGROUND: Driving pressure (ΔP) represents tidal volume normalised to respiratory system compliance (CRS) and is a novel parameter to target ventilator settings. We conducted a study to determine whether CRS and ΔP reflect aerated lung volume and dynamic strain during general anaesthesia. METHODS: Twenty non-obese patients undergoing open abdominal surgery received three PEEP levels (2, 7, or 12 cm H2O) in random order with constant tidal volume ventilation. Respiratory mechanics, lung volumes, and alveolar recruitment were measured to assess end-expiratory aerated volume, which was compared with the patient's individual predicted functional residual capacity in supine position (FRCp). RESULTS: CRS was linearly related to aerated volume and ΔP to dynamic strain at PEEP of 2 cm H2O (intraoperative FRC) (r=0.72 and r=0.73, both P<0.001). These relationships were maintained with higher PEEP only when aerated volume did not overcome FRCp (r=0.73, P<0.001; r=0.54, P=0.004), with 100 ml lung volume increases accompanied by 1.8 ml cm H2O-1 (95% confidence interval [1.1-2.5]) increases in CRS. When aerated volume was greater or equal to FRCp (35% of patients at PEEP 2 cm H2O, 55% at PEEP 7 cm H2O, and 75% at PEEP 12 cm H2O), CRS and ΔP were independent from aerated volume and dynamic strain, with CRS weakly but significantly inversely related to alveolar dead space fraction (r=-0.47, P=0.001). PEEP-induced alveolar recruitment yielded higher CRS and reduced ΔP only at aerated volumes below FRCp (P=0.015 and 0.008, respectively). CONCLUSIONS: During general anaesthesia, respiratory system compliance and driving pressure reflect aerated lung volume and dynamic strain, respectively, only if aerated volume does not exceed functional residual capacity in supine position, which is a frequent event when PEEP is used in this setting.

Fifteen-year phenological plant species and meteorological trends in central Italy.

The present study was carried out in a phenological garden in central Italy that contains vegetative clones of shrubs and trees common to several international phenological gardens, such as Cornus sanguinea L.; Corylus avellana L.; Ligustrum vulgare L.; Robinia pseudoacacia L.; Salix acutifolia Willd. and Sambucus nigra L. Vegetative plant growth monitoring was carried out weekly using common international keys: BBCH07, bud break and leaf unfolding; BBCH19, young unfolded leaf; BBCH91, adult leaves; BBCH93, beginning of leaf colouring. The phenological dates thus obtained provide a model of the development for these different species in relation to the 15-year period of observation (1997-2011). From a meteorological point of view, temperature and precipitation trends were studied, with the highest anomalies during the study period recorded during the first 2 months of the year (January, February). There was relative invariance in the manifestation of the open bud phase and the contemporary advance of the young open leaves phase, particularly from 2006. This was accompanied by shortening of the leaf opening period, which appeared due to more rapid spring temperature increases over the last few years. The advance tendency of the BBCH91 phase showed adult leaves from the first summer weeks with fully green foliage monitored for a long time. Generally, the autumn leaf colouring phase tended to remain constant, with the exception of Salix acutifolia and Sambucus nigra, for which, on the other hand, the first leaf development phases appeared to be most likely influenced by the photoperiod.

Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.

BACKGROUND AND PURPOSE: Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors. EXPERIMENTAL APPROACH: The anticonvulsant profiles of two CBDV BDSs (50-422 mg·kg(-1) ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays. KEY RESULTS: CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg(-1) ) and audiogenic seizure models (≥87 mg·kg(-1) ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg(-1) ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ(9) -tetrahydrocannabinol and Δ(9) -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV. CONCLUSIONS AND IMPLICATIONS: CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.

Treatment of vitiligo with a chimeric monoclonal antibody to CD20: a pilot study.

Five patients with active disseminated vitiligo were given 1g of a chimeric (murine/human) monoclonal antibody to CD20 in a single intravenous infusion and followed-up for 6 months. Three of the patients showed an overt clinical and histological improvement of the disease, one presented slight improvement and the remaining patient showed no changes. Improvement was neither associated with changes in laboratory parameters nor to a specific human leucocyte antigen D-related (HLA-DR) phenotype. We believe that these preliminary results are encouraging, and further clinical trials should be undertaken. An important aim should be the finding of a marker with a good response to this therapeutic approach.

[The possible uses of balneotherapy in treating chronic venous insufficiency of lower limbs]. / Possibilità della balneoterapia termale nell'insufficienza venosa cronica degli arti inferiori.

The Chronic Venous Insufficiency (CVI) of inferior limbs is a widespread disease, with an increasing incidence as a consequence of longer life expectance, life-style, obesity, smoking, use of drugs as oestrogens and progestins and working conditions. Medical therapy is still lacking for evidence of efficacy, and compression therapy is useful only in preventing a worsening of this condition. Surgical treatment is the only radical therapy effective for the advanced phases of the disease. In this context spa balneotherapy can be considered as a possible chance to improve some subjective and objective symptoms of CVI of inferior limbs, and to prevent worsening of this condition. The authors performed a review of the relevant scientific literature concerning the treatment of CVI of inferior limbs with mineral water balneotherapy, in order to evaluate its effects on objective and subjective symptoms and its effectiveness to prevent further worsening. We searched the PubMed/Medline, Cochrane Library, Embase, Web of Science databases for articles published between 1990 and 2011 on this topic. To this end, the authors selected few clinical-controlled and case-controlled studies; patients affected from CVI of inferior limbs were treated with balneotherapy at health spas with sulphureous, sulphate, salsojodic or salsobromojodic mineral waters. Baths in mineral waters were often associated with idromassotherapy and vascular pathway. Effects of spa balneotherapy are related to some aspecific properties, like hydrostatic pressure, osmotic pressure and water temperature, partly related with specific chemico-physical properties of the adopted mineral water. The controlled clinical studies on spa therapy showed significant improvement of subjective (such as itch, paresthesias, pain, heaviness) and objective symptoms (namely edema and skin discromias). These studies suggest that spa balneotherapy may give a good chance of secondary prevention and effective therapy of CVI of inferior limbs, but also that it needs of other clinical controlled trials.

The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis.

BACKGROUND AND PURPOSE: The non-psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin-type1 (TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis. EXPERIMENTAL APPROACH: Murine peritoneal macrophages were activated in vitro by LPS. Nitrite levels were measured using a fluorescent assay; inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2) and cannabinoid (CB1 and CB2 ) receptors were analysed by RT-PCR (and/or Western blot analysis); colitis was induced by dinitrobenzene sulphonic acid (DNBS). Endocannabinoid (anandamide and 2-arachidonoylglycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry. Colonic inflammation was assessed by evaluating the myeloperoxidase activity as well as by histology and immunohistochemistry. KEY RESULTS: LPS caused a significant production of nitrites, associated to up-regulation of anandamide, iNOS, COX-2, CB1 receptors and down-regulation of CB2 receptors mRNA expression. Cannabichromene significantly reduced LPS-stimulated nitrite levels, and its effect was mimicked by cannabinoid receptor and TRPA1 agonists (carvacrol and cinnamaldehyde) and enhanced by CB1 receptor antagonists. LPS-induced anandamide, iNOS, COX-2 and cannabinoid receptor changes were not significantly modified by cannabichromene, which, however, increased oleoylethanolamide levels. In vivo, cannabichromene ameliorated DNBS-induced colonic inflammation, as revealed by histology, immunohistochemistry and myeloperoxidase activity. CONCLUSION AND IMPLICATIONS: Cannabichromene exerts anti-inflammatory actions in activated macrophages - with tonic CB1 cannabinoid signalling being negatively coupled to this effect - and ameliorates experimental murine colitis.

Prokinetic effect of a standardized yarrow (Achillea millefolium) extract and its constituent choline: studies in the mouse and human stomach.

BACKGROUND: Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by alterations in gastric motility. Yarrow (Achillea millefolium L., Fam Asteraceae) preparations are traditional remedies used to treat dyspeptic complaints. Herein, we investigated the effect of a standardized dry water extract obtained from A. millefolium flowering tops (AME) on gastric motility. METHODS: The effect of AME on motility was evaluated on the resting tone of the isolated gastric antrum and on gastric emptying in vivo (phenol red meal method) both in control mice and in the model of cancer chemotherapy (cisplatin)-induced gastric abnormalities. KEY RESULTS: The AME contracted mouse and human gastric strips and this action was unaffected by hexamethonium and tetrodotoxin, but strongly reduced by atropine. Among various chemical ingredients in yarrow, choline, but not the flavonoids rutin and apigenin, mimicked the action of AME. Furthermore, AME deprived of choline did not exert a contractile effect. In vivo, AME stimulated gastric emptying both in control and in cisplatin-treated mice, being more active in pathological states. CONCLUSIONS & INFERENCES: It is concluded that (i) AME exerts a direct spasmogenic effect on gastric antrum; (ii) choline is the chemical ingredient responsible of such effect; (iii) the prokinetic effect of AME observed in vivo could provide the pharmacological basis underlying its traditional use in the treatment of dyspepsia.

Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice.

BACKGROUND: Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice. METHODS: Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin. KEY RESULTS: Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10(-6) mol L(-1) ), protease-activated receptor-2 (PAR-2) antagonist, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol L(-1) ), phospholipase C (PLC) inhibitor, neomycin (3 × 10(-3) mol L(-1) ), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10(-6) mol L(-1) ). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner. CONCLUSIONS & INFERENCES: Our data suggest that BR inhibits intestinal motility - preferentially in pathophysiologic conditions - with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes.

Birth-weight as a risk factor for cancer in adulthood: the stem cell perspective.

The 'stem cell burden' hypothesis represents a plausible explanation for the association between birth-weight and the risk of breast cancer in adulthood. The size of the overall stem cell pool would be expected to affect organ size and consequently birth-weight, making birth-weight a proxy for the overall number of fetal stem cells. As stem cells are self-renewing, the greater their number is at birth, the higher will be the chance that one of them will undergo carcinogenesis over the years. To investigate the correlation between birth-weight and stem cell burden, we examined the cord blood hematopoietic CD34+ stem cell population as an indicator of the overall fetal stem cell number. We measured both the CD34+ level (by flow cytometry) and the CD34+ proliferative potential (by the GM-CFU culture), in a sample of 1037 healthy newborn cord blood donors. We found that heavier babies had a significantly greater CD34+ stem cell concentration (p<0.001) and a higher GM-CFU number than lighter babies (p<0.001). Thus, a high birth-weight was positively associated with a high concentration of CD34+ stem cells and also with a qualitatively higher "stemness" of this pool. Therefore, our data support the theory that birth-weight reflects the number of fetal stem cells.

Cannabinoids and gastrointestinal motility: animal and human studies.

The plant Cannabis has been known for centuries to be beneficial in a variety of gastrointestinal diseases, including emesis, diarrhea, inflammatory bowel disease and intestinal pain. delta9-tetrahydrocannabinol, the main psychotropic component of Cannabis, acts via at least two types of cannabinoid receptors, named CB1 and CB2 receptors. CB1 receptors are located primarily on central and peripheral neurons (including the enteric nervous system) where they modulate neurotransmitter release, whereas CB2 receptors are concerned with immune function, inflammation and pain. The discovery of endogenous ligands [i.e. anandamide and 2-arachidonoyl glycerol (2-AG)] for these receptors indicates the presence of a functional endogenous cannabinoid system in the gastrointestinal tract. Anatomical and functional evidence suggests the presence of CB1 receptors in the myenteric plexus, which are associated with cholinergic neurons in a variety of species, including in humans. Activation of prejunctional CB1 receptors reduces excitatory enteric transmission (mainly cholinergic transmission) in different regions of the gastrointestinal tract. Consistently, in vivo studies have shown that cannabinoids reduce gastrointestinal transit in rodents through activation of CB1, but not CB2, receptors. However, in pathophysiological states, both CB1 and CB2 receptors could reduce the increase of intestinal motility induced by inflammatory stimuli. Cannabinoids also reduce gastrointestinal motility in randomized clinical trials. Overall, modulation of the gut endogenous cannabinoid system may provide a useful therapeutic target for disorders of gastrointestinal motility.

Correlation between large-scale atmospheric fields and the olive pollen season in Central Italy.

Olives are one of the largest crops in the Mediterranean and in central and southern Italy. This work investigates the correlation of the Olea europaea L. pollen season in Perugia, the capital city of the region of Umbria in central Italy, with atmospheric parameters. The aim of the study is twofold. First, we study the correlation between the pollen season and the surface air temperature of the spring and late spring in Perugia. Second, the correlation between the pollen season and large-scale atmospheric patterns is investigated. The average surface temperature in the spring and late spring has a clear impact on the pollen season in Perugia. Years with higher average temperatures have an earlier onset of the pollen season. In particular, a 1 degrees C higher (lower) average surface temperature corresponds to an earlier (later) start of the pollen season of about 1 week. The correlation between the pollen season and large-scale atmospheric patterns of sea level pressure and 500-hPa geopotential height shows that the cyclonic activity in the Mediterranean is unequivocally tied to the pollen season in Perugia. A larger than average cyclonic activity in the Mediterranean Basin corresponds to a later than average pollen season. Larger than average cyclonic activity in Northern Europe and Siberia corresponds to an earlier than average pollen season. A possible explanation of this correlation, that needs further investigation to be proven, is given. These results can have a practical application by using the seasonal forecast of atmospheric general circulation models.

Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors.

BACKGROUND AND PURPOSE: Salvinorin A, the active component of the hallucinogenic herb Salvia divinorum, inhibits intestinal motility through activation of kappa-opioid receptors (KORs). However, this compound may have target(s) other than the KORs in the inflamed gut. Because intestinal inflammation upregulates cannabinoid receptors and endogenous cannabinoids, in the present study we investigated the possible involvement of the endogenous cannabinoid system in salvinorin A-induced delay in motility in the inflamed gut. EXPERIMENTAL APPROACH: Motility in vivo was measured by evaluating the distribution of a fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; direct or indirect activity at cannabinoid receptors was evaluated by means of binding, enzymic and cellular uptake assays. KEY RESULTS: Salvinorin A as well as the KOR agonist U-50488 reduced motility in croton oil treated mice. The inhibitory effect of both salvinorin A and U-50488 was counteracted by the KOR antagonist nor-binaltorphimine and by the cannabinoid CB(1) receptor antagonist rimonabant. Rimonabant, however, did not counteract the inhibitory effect of salvinorin A on motility in control mice. Binding experiments showed very weak affinity of salvinorin A for cannabinoid CB(1) and CB(2) and no inhibitory effect on 2-arachidonoylglycerol and anandamide hydrolysis and cellular uptake. CONCLUSIONS AND IMPLICATIONS: The inhibitory effect of salvinorin A on motility reveals a functional interaction between cannabinoid CB(1) receptors and KORs in the inflamed--but not in the normal--gut in vivo.

Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice.

BACKGROUND AND PURPOSE: Cannabidiol is a Cannabis-derived non-psychotropic compound that exerts a plethora of pharmacological actions, including anti-inflammatory, neuroprotective and antitumour effects, with potential therapeutic interest. However, the actions of cannabidiol in the digestive tract are largely unexplored. In the present study, we investigated the effect of cannabidiol on intestinal motility in normal (control) mice and in mice with intestinal inflammation. EXPERIMENTAL APPROACH: Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with ACh. KEY RESULTS: In vivo, cannabidiol did not affect motility in control mice, but normalized croton oil-induced hypermotility. The inhibitory effect of cannabidiol was counteracted by the cannabinoid CB1 receptor antagonist rimonabant, but not by the cannabinoid CB2 receptor antagonist SR144528 (N-[-1S-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide), by the opioid receptor antagonist naloxone or by the alpha2-adrenergic antagonist yohimbine. Cannabidiol did not reduce motility in animals treated with the fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine, whereas loperamide was still effective. In vitro, cannabidiol inhibited ACh-induced contractions in the isolated ileum from both control and croton oil-treated mice. CONCLUSIONS AND IMPLICATIONS: Cannabidiol selectively reduces croton oil-induced hypermotility in mice in vivo and this effect involves cannabinoid CB1 receptors and FAAH. In view of its low toxicity in humans, cannabidiol may represent a good candidate to normalize motility in patients with inflammatory bowel disease.

The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high-fat diet.

BACKGROUND AND PURPOSE: Endocannabinoids (via cannabinoid CB(1) receptor activation) are physiological regulators of intestinal motility and food intake. However, their role in the regulation of gastric emptying is largely unexplored. The purpose of the present study was to investigate the involvement of the endocannabinoid system in the regulation of gastric emptying in mice fed either a standard diet (STD) or a high-fat diet (HFD) for 14 weeks. EXPERIMENTAL APPROACH: Gastric emptying was evaluated by measuring the amount of phenol red recovered in the stomach after oral challenge; CB(1) expression was analysed by quantitative reverse transcription-PCR; endocannabinoid (anandamide and 2-arachidonoyl glycerol) levels were measured by liquid chromatography-mass spectrometry. KEY RESULTS: Gastric emptying was reduced by anandamide, an effect counteracted by the CB(1) receptor antagonist rimonabant, but not by the CB(2) receptor antagonist SR144528 or by the transient receptor potential vanilloid type 1 (TRPV1) antagonist 5'-iodoresiniferatoxin. The fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine (but not the anandamide uptake inhibitor OMDM-2) reduced gastric emptying in a way partly reduced by rimonabant. Compared to STD mice, HFD mice exhibited significantly higher body weight and fasting glucose levels, delayed gastric emptying and lower anandamide and CB(1) mRNA levels. N-arachidonoylserotonin (but not rimonabant) affected gastric emptying more efficaciously in HFD than STD mice. CONCLUSIONS AND IMPLICATIONS: Gastric emptying is physiologically regulated by the endocannabinoid system, which is downregulated following a HFD leading to overweight.