196,439 research outputs found
The future of pharmacogenetics in the treatment of migraine
No full textMigraine is considered one of the most disabling neurological disorder with a high socioeconomic burden. Pharmacological management includes many classes of drugs which in the most cases, are administrated in polytherapy. The therapeutic scheme of migraineurs is often affected by comorbidities which need concomitant medications, thus increasing the risk of side effects related to drug-drug interactions. Pharmacogenetics is a promising tool to achieve a personalized cure based on individual genetic profile while the availability of free online knowledge bases allows to check the potential DDIs of selected medications. Combining, these approaches may offer to clinicians a useful tool to improve the appropriateness of migraine polytherapy choice, aiming to increase the efficacy and reduce the toxicity of pharmacological treatments
A rare hepatic mass in an Italian resident
No full textBackground: Amebiasis is a rare condition in developed countries but epidemiologically growing. Clinical manifestation may range from asymptomatic to invasive disease, amoebic liver abscess being the most common manifestation. We report a peculiar case of left hepatic amoebic liver abscess in a patient without a well-known source of infection and presenting with left portal vein thrombosis. Case presentation: Patient, working as longshoreman, presented with complaints of remittent-intermittent fever lasting from 2 weeks. Physical examination was normal. Blood tests showed mild anemia, neutrophilic leukocytosis and elevated inflammation markers. Chest x-rays was normal. Abdominal ultrasound showed multiple hypoechoic liver masses. CT-scan of abdomen showed enlarged left liver lobe due to the presence of large abscess cavity along with thrombosis of left portal vein. The indirect hemagglutination test for the detection of antibodies to Entamoeba histolytica (Eh) was positive. Ultrasound-guided percutaneous drainage revealed "anchovy sauce"pus. Metronidazole and a follow up imaging at 3 months showed resolution of abscess cavity. Conclusion: This case shows that amoebic liver abscess is possible even in first world country patients without travel history. Left sided abscess and portal vein thrombosis are rare and hence reported
Hygiene hypothesis and autoimmune diseases: A narrative review of clinical evidences and mechanisms
No full textSince the start of the “modern era”, characterized by the increase in urbanization, a progressive attention to hygiene and autoimmune conditions has considerably grown. Although these diseases are often multifactorial, it was demonstrated that environment factors such as pollution, diet and lifestyles may play a crucial role together with genetic signature. Our research, based on the newest and most significant literature of this topic, highlights that the progressive depletion of microbes and parasites due to increased socioeconomic improvement, may lead to a derangement of immunoregulatory mechanisms. Moreover, special attention was given to the complex interplay between microbial agents, as gut microbiome, diet and vitamin D supplementation with the aim of identifying promising future therapeutic options. In conclusion, autoimmunity cannot be limited to hygiene-hypothesis, but from the point of view of precision medicine, this theory represents a fundamental element together with the study of genomics, the microbiome and proteomics, in order to understand the complex functioning of the immune system
Inter-individual variation in CYP2A6 activity and chronic obstructive pulmonary disease in smokers. Perspectives for an early predictive marker
No full textNo abstract availabl
FLUORIDE KINETICS IN SALIVA, UPTAKE IN ENAMEL AND BIOAVAILABILITY AFTER USING A FLUORIDE CHEWING GUM
No full textHá um relacionamento direto entre o uso do flúor e a prevenção da dental dentária. Devido ao aumento da fluorose dentária, deve-se dar ênfase ao controle da ingestão diária de flúor, e, mais que isto, à biodisponibilidade do mesmo. Sendo assim, o objetivo deste trabalho, cruzado e duplo-cego, foi analisar a cinética do flúor liberado na saliva total pela goma de mascar Happydent (0,3 mg F como MFP), sua capacidade de incorporação ao esmalte dentário e sua biodisponibilidade através da saliva do ducto da glândula parótida e urina. Na 1ª fase do experimento a saliva de 10 voluntários foi coletada durante 15 min (tempos 0,3,6,9,12 e 15 min) e duas biópsias, uma antes da mastigação (biópsia baseline) e outra após, foram realizadas através da aplicação de 5 µL de HCl a 0,5 M, sobre área delimitada na superfície do incisivo, por 15 seg, seguidas da neutralização da área por aplicação de 5 µL de NaOH a 0,25 N, por 2 vezes. A quantidade de flúor tanto na saliva quanto nas biópsias foi medida com o auxílio de eletrodo íon-específico. As concentrações médias de flúor liberada na saliva total após o uso do Happydent® e Trident® foram de 0,187 e 0,002 mg F, respectivamente. A goma de mascar Happydent® foi capaz de produzir uma incorporação média de flúor ao esmalte dentário correspondente a 1474 ppm. Na 2ª fase, após jejum de 12h, cinco voluntários receberam 3 gomas de Happydent (≈ 1 mg MFP) e foram coletadas amostras de saliva do ducto da glândula parótida: antes do início do experimento (baseline), a cada 3 min durante os 20 min iniciais, a cada 20 min nas primeiras 2 h, a cada 40 min até 4 h e, por fim, em intervalos de 1 h até completarem-se 8 h do início do experimento. Amostras de urina foram coletadas um dia antes e durante o estudo, por 9 h. O F presente na saliva do ducto foi analisado após difusão facilitada por HMDS e o da urina pelo método direto. Os dados obtidos foram analisados estatisticamente através da análise da variância, teste Tukey para comparações múltiplas e teste t, com nível de significância de 5%. Apesar dos altos teores de flúor originados na saliva total, após o uso do Happydent®, terem capacidade de incorporação ao esmalte dentário e serem capazes de produzir um aumento nas concentrações de flúor da saliva do ducto da parótida, tais valores não foram suficientes para serem detectados na urina. Concluiu-se que a alta liberação de flúor proveniente da goma de mascar Happydent representa um fator predisponente para a fluorose dentária, o que inviabiliza a sua utilização por crianças na faixa etária de risco. No entanto, esta goma pode ser útil para auxiliar na prevenção de cáries dentárias em crianças acima da faixa etária de risco para fluorose dentária, o que deveria ser avaliado clinicamente.There is a direct relationship between the use of fluoride and the prevention of dental decay. The purpose of this study was to evaluate the fluoride kinetics in saliva, uptake in enamel and bioavailability after using the chewing gum Happydent® (0.3 mg F as MFP). Methods: In first phase, ten 8-9 year-old children participated in this double-blind crossover study. They received professional prophylaxis and total saliva (baseline) was collected for 3 min. A circular area (0.9 mm diameter) was demarcated on the buccal surface of the maxillary central incisor and an enamel biopsy (baseline) was obtained using 5 µL of 0.5 M HCl. After 15 sec, the acid was removed and added to 50 µL TISAB. Two separate rinses of the biopsy site, each using 5 µL of 0.25 M NaOH was done. The total saliva was colleted for 3 min after 3, 6, 9, 12 and 15 min, while chewing. After the last saliva sample was collected, another acid-etch biopsy was performed on the same tooth. F was analyzed with the ion-specific electrode. Phosphorus in the biopsies was analyzed spectrophotometrically. The mean result of F released in saliva was 0.187 mg/ml and the mean fluoride uptake in enamel after chewing was 1.475 mg/Kg. In second phase, after to fast for 12h, the volunteers chewing 3 gums Happydent® (≅ 1 mg MFP) and samples of duct saliva was collected for 8 hours, in different times. The urine was collected one day before and during the experiment. Fluoride concentrations were analyzed after the electrode following HMDS-facilitated diffusion and the urine by direct method. Conclusions: Data suggest the capacity of fluoride uptake in enamel. However, the high concentration of fluoride in duct saliva after the use of Happydent® have capacity to elevate plasma fluoride levels, but not enough to detect in urine. The conclusion was that children at the age of risk to dental fluorosis should not use the chewing gum Happydent® In addition, the regular use of this gum may be significant in the prevention of dental caries and this should be clinically evaluated
Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in systemic sclerosis
No full textSystemic sclerosis (SSc) is a complex disease characterized by immune dysregulation, extensive vascular damage and widespread fibrosis. Human leucocyte antigen-G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by complex immunomodulating properties. HLA-G is expressed on the membrane of different cell lineages in both physiological and pathological conditions. HLA-G is also detectable in soluble form (sHLA-G) deriving from the shedding of surface isoforms (sHLA-G1) or the secretion of soluble isoforms (HLA-G5). Several immunosuppressive functions have been attributed to both membrane-bound and soluble HLA-G molecules. The plasma levels of sHLA-G were higher in SSc patients (444·27 ± 304·84 U/ml) compared to controls (16·74 ± 20·58 U/ml) (P < 0·0001). The plasma levels of transforming growth factor (TGF)-β were higher in SSc patients (18 937 ± 15 217 pg/ml) compared to controls (11 099 ± 6081 pg/ml; P = 0·003), and a significant correlation was found between TGF-β and the plasma levels of total sHLA-G (r = 0·65; P < 0·01), sHLA-G1 (r = 0·60; P = 0·003) and HLA-G5 (r = 0·47; P = 0·02). The percentage of HLA-G-positive monocytes (0·98 ± 1·72), CD4+ (0·37 ± 0·68), CD8+ (2·05 ± 3·74) and CD4+ CD8+ double-positive cells (14·53 ± 16·88) was higher in SSc patients than in controls (0·11 ± 0·08, 0·01 ± 0·01, 0·01 ± 0·01 and 0·39 ± 0·40, respectively) (P < 0·0001). These data indicate that in SSc the secretion and/or shedding of soluble HLA-G molecules and the membrane expression of HLA-G by peripheral blood mononuclear cells (PBMC) is clearly elevated, suggesting an involvement of HLA-G molecules in the immune dysregulation of SSc
Advanced 3D “Modeling” and “Printing” for the Surgical Planning of a Successful Case of Thoraco-Omphalopagus Conjoined Twins Separation
No full textThe surgical separation of two Conjoined Twins is a particularly complex operation. Surgical times are particularly long and post-operative complications are very frequent in this type of procedure. We report a clinical case of surgical separation of two thoraco-omphalopagus conjoined twins in which, thanks to the use of (3D) three dimensional technologies, we were able to significantly reduce operative times and improve clinical outcomes
H2-antagonist in IgE-mediated type I hypersensitivity reactions: what literature says so far?
No full textHistamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons
Optimising migraine treatment. From drug-drug interactions to personalized medicine
No full textMigraine is the most disabling and expensive chronic disorders, the etiology of which is still not fully known. The neuronal systems, (glutammatergic, dopaminergic, serotoninergic and GABA-ergic) whose functionality is partly attributable to genetically determined factors, has been suggested to play an important role. The treatment of acute attacks and the prophylactic management of chronic forms include the use of different category of drugs, and it is demonstrated that not each subject has the same clinical answer to them. The reason of this is to be searched in different functional capacity and quantity of phase I enzymes (such as different isoforms of CYP P450), phase II enzymes (such as UDP-glucuronosyltransferases), receptors (such as OPRM1 for opioids) and transporters (such as ABCB1) involved in the metabolic destiny of each drug, all of these dictated by DNA and RNA variations. The general picture is further exacerbated by the need for polytherapies, often also to treat comorbidities, which may interfere with the pharmacological action of anti-migraine drugs. Personalized medicine has the objective of setting the optimal therapies in the light of the functional biochemical asset and of the comorbidities of the individual patient, in order to obtain the best clinical response. Novel therapeutic perspectives in migraine includes biotechnological drugs directed against molecules (such as CGRP and its receptor) that cause vasodilatation at the peripheral level of the meningeal blood vessels and reflex stimulation of the parasympathetic system. Drug-drug interactions and the possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale. Drug-drug interactions and their possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale
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