The treatment of ulcerative colitis (UC) is based on conventional therapies (aminosalicylates, corticosteroids, and immunosuppressants) and when these are ineffective, biologic drugs. However, in a ...substantial portion of patients undergoing treatment with biologic agents there is primary or secondary loss of response. Thus, new therapeutic options are been actively explored; among these, there is interest in the Janus kinase (JAK) inhibitors, small molecules that can be administered orally.
We carried out an extensive literature search concerning the effects of JAK inhibitors for the treatment of patients with UC.
Tofacitinib is the drug more extensively studied in this setting, and it was recently approved in Europe for the treatment of moderate to severe UC. The available data suggest that this drug can be effective in obtaining clinical and endoscopic remission in UC patients unresponsive to other treatments, even in those previously treated with biologic drugs. In addition, the drug was able to improve significantly the quality of life of these patients. There are still few data available for the treatment of UC with other JAK inhibitors.
The JAK inhibitors, in particular tofacitinib, are a new class of orally administered drugs effective for the treatment of UC. However, more studies are needed to ascertain the safety of tofacitinib in the long term and whether other compounds of this class may be equally effective.
In this session different problems regarding the pathogenesis of diverticular disease were considered, including “Genetics”, “Neuromuscular function abnormalities”, “Patterns of mucosa inflammation”, ...and “Impact of lifestyle”. The patients affected by diverticular disease have clear genetic pattern, that might predispose to the occurrence of the disease as well as to its complications. Neuromuscular abnormalities may be recognized already at the stage of diverticulosis, and inflammation may explain symptoms occurrence in symptomatic uncomplicated diverticular disease (SUDD) or symptoms persistence after an episode of acute diverticulitis. Finally, lifestyle might also have an impact on symptoms’ occurrence. Specifically smoking, but also obesity seem to play an important role, while the role of low-fiber diet and constipation is now under debate.
Mood disorders and non-celiac gluten sensitivity Casella, Giovanni; Pozzi, Roberta; Cigognetti, Marta ...
Minerva gastroenterologica e dietologica,
03/2017, Letnik:
63, Številka:
1
Journal Article
Recenzirano
The association between gluten related disorders and psychiatric diseases has been firmly demonstrated. Non-celiac gluten sensitivity (NCGS) is a syndrome diagnosed in patients responsive to ...gluten-free diet after ruling out celiac disease and wheat allergy. The pathogenesis of neuro-psychiatric disorders in NCGS is unclear. An association between gluten and schizophrenia was described for the first time in 1950 by Bender et al. In the 1950's, Dicke noted that gluten-free diet improved mood in celiac patients. In 1970, Goldberg et al., in a study of 80 celiac patients, found that 34% of them showed minor affective disorders. Bipolar disorder patients show an increase of blood anti gliadin deamidated antibodies (IgG). The effect of diet and nutrition on autistic spectrum disorders has been investigated in the last two decades, particularly focusing on the symptoms of hyperactivity and attention. Toxoplasma gondii and other neurotropic pathogens as Influenzavirus and Coronavirus may be associated with mood disorders, probably secondary to an increased intestinal permeability. Abnormalities of host-microbiota interactions or of gut-microbiota composition have been associated with central nervous system disorders, such as autism, anxiety, depression and the integrity of intestinal microbiota may be considered a potential therapeutic goal to treat these conditions.
The aerial parts of Micromeria madagascariensis Baker and M. flagellaris Baker are used by the population of the Vakinankaratra and Itasy regions (Madagascar) to treat breathing difficulty, fever ...and/or headache, wounds, and sores.
This work aimed to characterise plant materials from M. madagascariensis and M. flagellaris to report i) chemical composition, ii) antimicrobial properties, and iii) antioxidant capacity of the essential oils extracted from the aerial parts of these species.
The essential oils from M. madagascariensis (MMO) and M. flagellaris (MFO) were obtained by hydrodistillation. Their chemical composition was quantified using gas chromatography coupled with mass spectrometry (GC-MS). MMO and MFO were also tested against 7 microbial strains using the disk diffusion method and their antioxidant capacity was assessed using the DPPH scavenging assay.
Hydrodistillation yielded 0.26% MMO and 0.29% MFO (w/w) in relation to the fresh weight. Twenty-seven compounds were identified by GC-MS in MMO extract against 36 in MFO one. The main compounds in MMO were pulegone (24.67%), trans-menthone (24.67%), eucalyptol (8.12%), β-caryophyllene (4.98%), α-guanene (4.47), iso-menthone (3.85%), iso-pulegone (3.34%), azulene (3.28%) and 2-isopropyl-5-methylcyclohexenone (2.82%). The main compounds in the MFO were eudesma-4,11-dien-2-ol (13.88%), δ-guanene (6.62%), pulegone (6.40%), cyperone (5.56%), 4-epi-dehydrobietinol acetate (5.39%), eucalyptol (5.12%), trans-menthone (4.67%), limonene (3.77%) and sabinene (2.29%). Regarding the chemotaxonomy, M. flagellaris was very different from M. madagascariensis and both species also differed from the other Micromeria species, as confirmed by multivariate statistical analysis. Both MMO and MFO exerted activities against a large microbial spectrum; the antimicrobial activity of MMO was higher than MFO one against S. pneumoniae and C. albicans due to the presence of pulegone as the main component. MFO showed an excellent scavenging capacity with an SC50 value of 2.17 ± 0.03 μg/mL.
The biological properties of the essential oils extracted from the selected species may explain their therapeutic value showing that Malagasy Micromeria species may be very important as new natural sources of bioactive compounds. This study may promote the effectiveness and quality of Malagasy Micromeria species, contributing to sustainable development and commercial valorisation of traditional preparations based on natural local resources.
•First chemical reports on M. flagellaris and M. madagascariesis essential oils.•Major components: Menthone and Pulegone for MMO and Eudesma-4,11-dien-2-ol for MFO.•M. flagellaris and M. madagascariensis belong to two different chemotypes.•PCA showed the differences between both species and the other Micromeria spp.•MFO and MMO showed antimicrobial and antioxidant activities.
Among infectious diseases, zoonoses are increasing in importance worldwide, especially in the Mediterranean region. We report herein some clinical cases from a third-level hospital in Calabria region ...(Southern Italy) and provide a narrative review of the most relevant features of these diseases from epidemiological and clinical perspectives. Further, the pathogenic mechanisms involved in zoonotic diseases are reviewed, focusing on the mechanisms used by pathogens to elude the immune system of the host. These topics are of particular concern for individuals with primary or acquired immunodeficiency (e.g., people living with HIV, transplant recipients, patients taking immunosuppressive drugs). From the present review, it appears that diagnostic innovations and the availability of more accurate methods, together with better monitoring of the incidence and prevalence of these infections, are urgently needed to improve interventions for better preparedness and response.
Synonymous variants have been shown to alter the correct splicing of pre‐mRNAs and generate disease‐causing transcripts. These variants are not an uncommon etiology of genetic disease; however, they ...are frequently overlooked during genetic testing in the absence of functional and clinical data. Here, we describe the occurrence of a synonymous variant NM_005422.4 (TECTA):c.327C>T, p.(Gly109=) in seven individuals with hearing loss from six unrelated families. The variant is not located near exonic/intronic boundaries but is predicted to impact splicing by activating a cryptic splicing donor site in exon 4 of TECTA. In vitro minigene assays show that the variant disrupts the reading frame of the canonical transcript, which is predicted to cause a premature termination codon 48 amino acids downstream of the variant, leading to nonsense‐mediated decay. The variant is present in population databases, predominantly in Latinos of African ancestry, but is rare in other ethnic groups. Our findings suggest that this synonymous variant is likely pathogenic for TECTA‐associated autosomal recessive hearing loss and seems to have arisen as a founder variant in this specific Latino subpopulation. This study demonstrates that synonymous variants need careful splicing assessment and support from additional testing methodologies to determine their clinical impact.
Notch signaling is an established developmental pathway for brain morphogenesis. Given that Delta-like 1 (DLL1) is a ligand for the Notch receptor and that a few individuals with developmental delay, ...intellectual disability, and brain malformations have microdeletions encompassing DLL1, we hypothesized that insufficiency of DLL1 causes a human neurodevelopmental disorder. We performed exome sequencing in individuals with neurodevelopmental disorders. The cohort was identified using known Matchmaker Exchange nodes such as GeneMatcher. This method identified 15 individuals from 12 unrelated families with heterozygous pathogenic DLL1 variants (nonsense, missense, splice site, and one whole gene deletion). The most common features in our cohort were intellectual disability, autism spectrum disorder, seizures, variable brain malformations, muscular hypotonia, and scoliosis. We did not identify an obvious genotype-phenotype correlation. Analysis of one splice site variant showed an in-frame insertion of 12 bp. In conclusion, heterozygous DLL1 pathogenic variants cause a variable neurodevelopmental phenotype and multi-systemic features. The clinical and molecular data support haploinsufficiency as a mechanism for the pathogenesis of this DLL1-related disorder and affirm the importance of DLL1 in human brain development.
Characterized by one of the highest rates of endemism and biodiversity in the world, Madagascar provides a wide variety of medicinal plants, that could represent a potential source of new drugs. The ...main aim of this study was to investigate the potential medicinal properties of the plant species used by indigenous people in Maromizaha forest and to provide the first ethnobotanical inventory of the area.
Data were collected through open semi-structured interviews with local informants, the reported plants were collected and identified to create a specimen herbarium. Informant Consensus Factor (ICF) was calculated for each ailment category mentioned in the use-reports. A selection of seven medicinal plants was submitted to phytochemical and antimicrobial analysis. The results were discussed and compared with those described in ethnobotanical and pharmacological literature.
One hundred and three villagers were interviewed and a total of 509 use-reports were recorded. Information on 117 plant species belonging to 57 botanical families were provided. 12 categories of indigenous uses were recognized, among them the higher ICF values were recorded for cardiovascular complaints (0.75), general and unspecific diseases (0.74), digestive disorders (0.69), and diseases of the skin (0.55). The traditional medicinal uses of 18 species (15 endemic) were described for the first time. In total, 22 different bioactive compounds were identified; polyphenols, monoterpenes, organic acids, and vitamin C were observed in the chemical composition of all the analyzed samples. Macaranga perrieri showed the highest values of both total polyphenolic compounds and antioxidant activity. Antimicrobial activity was observed in leaf and bark extracts of Dilobeia thouarsii.
These results confirmed the importance of investigating the traditional use of plant species, suggesting the crucial role of ethnobotanical studies for rural development, biodiversity conservation, and the sustainable use of plant resources in the studied area.
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