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RATIONALE & OBJECTIVE: Fabry disease (FD) is an X-linked genetic disorder that causes lysosomal storage of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its derivative globotriaosylsphingosine (lyso-Gb3), with multiorgan dysfunction including chronic kidney disease. Affected individuals may be carriers of gene variants that are of uncertain significance (GVUS). We describe kidney pathology at the early stages of FD-related kidney disease to gain insights into its association with GVUS and sex. STUDY DESIGN: Single-center, case series. SETTING & PARTICIPANTS: Thirty-five consecutively biopsied patients (aged 48.1±15.4 years, 22 females) from among 64 patients with genetically diagnosed FD. Biopsies were retrospectively screened using the International Study Group of Fabry Nephropathy Scoring System. OBSERVATIONS: Genetic mutation type, p.N215S and D313Y, sex, age, estimated glomerular filtration rate (eGFR), plasma lyso-Gb3 (pLyso-Gb3) levels, and histological parameters, including Gb3 deposits were recorded. Genetic analyses showed mostly missense mutations, p.N215S variant in 15, and the "benign polymorphism" D313Y in 4 of the biopsied patients. Morphological lesions were similar for men and women except for interstitial fibrosis and arteriolar hyalinosis being more common in men. Early in their clinical course, patients with normal/mild albuminuria had podocyte, tubular, and peritubular capillary vacuoles/inclusions, and evidence of chronicity, i.e., glomerulosclerosis, interstitial fibrosis, tubular atrophy. These findings appeared to be associated with pLyso-Gb3, eGFR, and age. LIMITATIONS: Retrospective design and inclusion of outpatients partially based on family pedigree. CONCLUSIONS: In early stages of kidney disease in the setting of FD, numerous histological abnormalities are present. These observations suggest that kidney biopsies early in FD may reveal activity of kidney involvement that may inform clinical management.
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BACKGROUND: Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. AIMS: The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. METHODS: A panel of experts of the Italian Society of Alcohology (SIA) met via "conference calls" during the lockdown period to draft the SIA's criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. RESULTS AND CONCLUSIONS: The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.
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Alcoholismo , COVID-19 , Hepatopatías Alcohólicas , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Alcoholismo/terapia , Control de Enfermedades Transmisibles , Humanos , Hepatopatías Alcohólicas/epidemiología , Hepatopatías Alcohólicas/terapia , PandemiasRESUMEN
Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment.
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Alcoholismo/terapia , COVID-19/prevención & control , Control de Enfermedades Transmisibles , Alcohólicos Anónimos , Alcoholismo/epidemiología , Atención Ambulatoria/organización & administración , COVID-19/epidemiología , Vacunas contra la COVID-19/uso terapéutico , Atención a la Salud/organización & administración , Susceptibilidad a Enfermedades , Interacciones Farmacológicas , Humanos , Terapia de Inmunosupresión/efectos adversos , Italia/epidemiología , Cirrosis Hepática Alcohólica/epidemiología , Cirrosis Hepática Alcohólica/terapia , Trasplante de Hígado , Recurrencia , SARS-CoV-2 , Sociedades Médicas , Telemedicina , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: Alcohol use disorder (AUD) is a complex trait with genetic and environmental influences. Several gene variants have been associated with the risk for AUD, including genes encoding the sub-units of the γ-aminobutyric acid (GABA) receptors. AIM: This study evaluated whether specific single nucleotide polymorphisms (SNPs) in genes encoding GABAB receptor sub-units can be considered as candidates for the risk of AUD. SUBJECTS AND METHODS: Seventy-four AUD subjects and 128 Italian controls were genotyped for 10 SNPs in genes encoding GABA-B1 and GABA-B2 sub-units (GABBR1 and GABBR2). Allele, genotype, and haplotype frequencies were tested for the association with the AUD trait. RESULTS: A significant difference between AUD individuals and controls was observed at genotype level for rs2900512 of GABBR2 gene. The homozygous T/T genotype was not found in the controls, whereas it was over-represented in the AUD individuals. Under the recessive model (T/T vs C/T + C/C) this result was statistically significant, as well as the Odds Ratio for the association with the AUD trait. CONCLUSIONS: The results provide preliminary data on the association between GABAB receptor gene variation and risk of AUD. To confirm this finding, studies with larger samples and additional characterisation of the phenotypic AUD trait are required.
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Trastornos Relacionados con Alcohol/genética , Frecuencia de los Genes , Polimorfismo de Nucleótido Simple , Receptores de GABA-B/genética , Adulto , Anciano , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Receptores de GABA-B/metabolismoRESUMEN
OBJECTIVE: Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. DESIGN: We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800â mg, or placebo, three times daily for 12â weeks, and were followed for additional 12â weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. RESULTS: A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. CONCLUSIONS: Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. TRIAL REGISTRATION NUMBER: ClincialTrials.gov number, NCT00626288.
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Antiinflamatorios no Esteroideos/uso terapéutico , Síndrome del Colon Irritable/tratamiento farmacológico , Mesalamina/uso terapéutico , Adulto , Anciano , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Alcoholic liver disease (ALD) is currently, worldwide, the second most common cause of human fatalities every year. Alcohol use disorders (AUDs) lead to 80% of hepatotoxic deaths, and about 40% of cases of cirrhosis are alcohol-related. An acceptable daily intake (ADI) of ethanol is hard to establish and studies somewhat controversially recommend a variety of dosages of ADI, whilst others regard any intake as dangerous. Steatohepatitis should be viewed as "the rate limiting step": generally, it can be overcome by abstinence, although in some patients, abstinence has little effect, with the risk of fibrosis, leading in some cases to hepatocellular carcinoma (HCC). Chronic alcoholism can also cause hypercortisolism, specifically pseudo-Cushing Syndrome, whose diagnosis is challenging. If fibrosis is spotted early, patients may be enrolled in detoxification programs to achieve abstinence. Treatment drugs include silybin, metadoxine and adenosyl methionine. Nutrition and the proper use of micronutrients are important, albeit often overlooked in ALD treatment. Other drugs, with promising antifibrotic effects, are now being studied. This review deals with the clinical and pathogenetic aspects of alcohol-related liver fibrosis and suggests possible future strategies to prevent cirrhosis.
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Alcoholismo , Humanos , Alcoholismo/complicaciones , Cirrosis Hepática/etiología , Cirrosis Hepática Alcohólica/complicaciones , Cirrosis Hepática Alcohólica/etiología , Hepatopatías Alcohólicas/etiología , Hepatopatías Alcohólicas/complicacionesRESUMEN
BACKGROUND: Alcohol withdrawal syndrome (AWS) is characterized by different phases (acute, early and protracted). Protracted alcohol withdrawal (PAW) presents some symptoms, which may persist for several weeks, months or even years after drinking cessation. METHODS: We conducted a systematic review of the literature in major scientific databases on selected AWS symptoms (craving, sleep disorders, and anhedonia) in patients with alcohol use disorder. RESULTS: Of the 102 eligible publications (70 RCTs and 32 cohort studies), 88 provided data on craving, 21 on sleep disorders, and 1 on anhedonia. Overall, 37 studies assessed craving using the Obsessive Compulsive Drinking Scale (OCDS). Pooled OCDS decreased from 24.2 at baseline to 18.8 at 1 week, 10.3 at 1 month and 9.7 at 3 months. The corresponding estimates for treated individuals were 23.9, 18.8, 8.7, and 8.8, and for non-treated subjects, they were 25.3, 13.9, 13.2, and 11.4, respectively. In 4 studies assessing sleep disorders using the Epworth Sleeping Scale (ESS), the scale remained stable in time, i.e., 7.3 at baseline, 7.3 at 1 week, 7.2 at 1 month, and 7.1 at 3 months. CONCLUSION: This study confirms the presence of PAW after the resolution of the acute phase of AWS. The pharmacological approach to managing PAW may ensure a more rapid reduction of symptoms in three weeks. We highlight the importance of studying PAW and the ability of pharmacological treatment to reduce its symptoms. This review protocol is registered in Prospero (registration number: CRD42020211265). SUMMARY: This systematic review summarizes literature on major symptoms of protracted alcohol withdrawal in patients with alcohol use disorder. The pharmacological approach to manage protracted alcohol withdrawal ensures a more rapid reduction of symptoms (craving in particular), achieving in three weeks similar results obtained only after almost 6 months without treatment.
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Alcoholismo , Trastornos del Sueño-Vigilia , Síndrome de Abstinencia a Sustancias , Humanos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Anhedonia , Consumo de Bebidas AlcohólicasRESUMEN
Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. This narrative review aims to resume the current knowledge of female-related features in clinical manifestations, development, and therapy, as well as sexual and psychological implications related to inflammatory bowel disease. The final attempt is to provide gastroenterologists with a roadmap of female-specific differences, to improve patients' diagnosis, management, and treatment.
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Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD.
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Enfermedad Celíaca , Glútenes , Osteoporosis , Enfermedad Celíaca/complicaciones , Osteoporosis/etiología , Densidad Ósea , Enfermedades Óseas Metabólicas , Glútenes/efectos adversos , Vitamina DRESUMEN
BACKGROUND: Life expectancy and the number of ultra-octogenarians increased significantly, thus making crucial the appropriateness of several endoscopic procedures in elderly patients. The aim of our study was to provide a retrospective analysis of the efficacy and safety of capsule endoscopy (CE) in patients aged over 80 years. METHODS: In this single-centre study, 900 patients underwent capsule endoscopy between 2002 and 2015 for different indications; of these 106 patients aged ≥80 years (group A) and 99 patients aged 40-60 years (control group B) were retrospectively selected. RESULTS: Occult gastrointestinal bleeding accounted for 62.1% of all indications for capsule endoscopy in group B, compared to 95.2% in group A (P<0.001). Although not statistically significant, the diagnostic yield was higher in group A (71%) vs. group B (62%). The percentages of reaching the cecum and the median gastric transit time were uniform within the two groups. In contrast, small bowel transit time was longer in group A vs. B. Small bowel preparation was similar in the two groups. The exam was generally well tolerated in both groups, with capsule aspiration being one of the main adverse events, which occurred in two elderly patients. CONCLUSIONS: Our data expand previous findings confirming that capsule endoscopy can be performed safely even in very old patients and show that the diagnostic yield is similar to that of younger patients.
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Endoscopía Capsular , Anciano , Anciano de 80 o más Años , Humanos , Estudios Retrospectivos , Endoscopía Capsular/efectos adversos , Endoscopía Capsular/métodos , Octogenarios , Intestino Delgado , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologíaRESUMEN
BACKGROUND: Current data indicate that infliximab-given immediately after surgery-may be very effective in preventing postsurgical recurrence of Crohn's disease. However, it is unknown whether a similar benefit would result from early diagnosis and treatment, rather than prevention of endoscopic recurrence. AIMS: The primary outcome of this study was to clarify whether infliximab, given after diagnosis of postoperative endoscopic recurrence of Crohn's diseases (Rutgeerts score ≥ 2) can induce endoscopic remission (score <2) at 54 weeks. The secondary outcomes were improvement in the endoscopic score and clinical recurrence at 54 weeks. METHODS: In this prospective open label multicenter pilot study 43 patients with ileocolonic Crohn's disease subjected to curative surgery underwent colonoscopy 6 months after surgery. Patients with endoscopic recurrence (Rutgeerts score ≥2) were treated with either mesalamine 800 mg tid or infliximab 5 mg/kg bw on a maintenance basis. Colonoscopy was performed after 54 weeks of therapy. RESULTS: A total of 24/43 patients were diagnosed with endoscopic recurrence at 6 months. Thirteen were treated with infliximab and 11 with mesalamine. None of the 11 mesalamine-treated patients had endoscopic remission at 54 weeks. Two had clinical recurrence at 8 and 9 months. Fifty-four percent of patients treated with infliximab had endoscopic remission at 54 weeks (P = 0.01) while 69% had an improvement in the endoscopic score. None had clinical recurrence. CONCLUSIONS: Treatment of postsurgical endoscopic lesions by infliximab appears superior to mesalamine. However, a sizeable proportion of patients did not fully benefit from this strategy.
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Anticuerpos Monoclonales/administración & dosificación , Colonoscopía/efectos adversos , Enfermedad de Crohn/terapia , Mesalamina/administración & dosificación , Complicaciones Posoperatorias , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Quimioprevención/métodos , Colonoscopía/métodos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/fisiopatología , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control , Periodo Posoperatorio , Prevención Secundaria , Resultado del TratamientoRESUMEN
INTRODUCTION: Inflammatory bowel diseases (IBDs) are conditions affecting the gut at different levels characterized by an abnormal activation of the intestinal immune system. In this narrative review, we will provide the reader with an update on the efficacy and safety of new pharmacological strategies to treat IBD patients. EVIDENCE ACQUISITION: We performed a thorough literature review via PubMed, EMBASE, MEDLINE and Science Direct databases addressing studies reporting on new therapies for IBD management published in the last ten years (January 2010-December 2020). Data from pharmaceutical companies and abstracts of conferences/meetings have also been considered. EVIDENCE SYNTHESIS: The discovery of monoclonal antibodies blocking pro-inflammatory cytokines, e.g., tumor necrosis factor-α (TNF-α) radically changed the management of IBDs. Anti-TNF-α agents represent the prototype molecule of "biologics"/"biologicals." These compounds have significantly improved the therapeutic management of IBDs refractory to standard medications as they provide clinical remission, mucosal healing and prevent extra-intestinal manifestations. However, about 50% of patients treated with biologicals experienced drawbacks, including primary failure or loss of response, requiring new effective treatments. Translational studies have identified new strategies, different from the TNF-α blockade, and new molecules, e.g. sphingosine-1-phosphate agonists and the JAK kinase inhibitors, have been proposed as potential therapeutic options for IBDs. CONCLUSIONS: With the availability of novel approaches reviewed in this article, physicians and especially gastroenterologists will increase the therapeutic options to provide a better management of IBD patients, particularly those poorly responsive to biologicals.
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Productos Biológicos , Enfermedades Inflamatorias del Intestino , Anticuerpos Monoclonales/efectos adversos , Productos Biológicos/uso terapéutico , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) which can affect any part of the whole gastrointestinal tract (from mouth to anus). Malnutrition affects 65-75% of CD patients, and it is now well acknowledged that diet is of paramount importance in the management of the disease. In this review, we would like to highlight the most recent findings in the field of nutrition for the treatment of CD. Our analysis will cover a wide range of topics, from the well-established diets to the new nutritional theories, along with the recent progress in emerging research fields, such as nutrigenomics.
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Enfermedad de Crohn/dietoterapia , Terapia Nutricional , Nutrición Enteral , Humanos , Terapia Nutricional/métodos , Nutrición ParenteralRESUMEN
Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder leading to a wide array of clinical manifestations. Among these, gastrointestinal (GI) symptoms such as abdominal pain, bloating, and diarrhea affect about half of the FD adults and more than half of FD children. GI symptoms could be the first manifestation of FD; however, being non-specific, they overlap with the clinical picture of other conditions, such as irritable bowel syndrome and inflammatory bowel disease. This common overlap is the main reason why FD patients are often unrecognized and diagnosis is delayed for many years. The present narrative review is aimed to promote awareness of the GI manifestations of FD amongst general practitioners and specialists and highlight the latest findings of this rare condition including diagnostic tools and therapies. Finally, we will discuss some preliminary data on a patient presenting with GI symptoms who turned to be affected by a variant of uncertain significance of alpha-galactosidase (GLA) gene.
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Enfermedad de Fabry , Enfermedades Gastrointestinales , Síndrome del Colon Irritable , Dolor Abdominal , Adulto , Niño , Diarrea/etiología , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/epidemiología , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Humanos , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/epidemiologíaRESUMEN
Inflammatory bowel diseases such as ulcerative colitis (UC) may be complicated by several extraintestinal manifestations. These involve joints, skin, eyes and less commonly lungs and heart. Myocarditis may result from the toxic effect of drugs (ie, mesalazine) commonly used for the treatment of UC or due to infections (eg, Coxsackieviruses, enteroviruses, adenovirus). Here, we report a case of a 26-year old man affected by UC and complicated by two episodes of myocarditis. Both episodes occurred during two severe exacerbations of UC. However, in both cases the aetiology of myocarditis remains uncertain being ascribable to extraintestinal manifestation, drug toxicity or both.
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Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Miocarditis , Adulto , Colitis Ulcerosa/complicaciones , Humanos , Masculino , Mesalamina/efectos adversos , Miocarditis/inducido químicamenteRESUMEN
In the course of heart failure, plasmatic levels of Tumor Necrosis Factor-alpha (TNF-alpha) are high and are related to prognosis and mortality. Infliximab, a recombinant chimeric antibody anti-TNF-alpha, was used in heart failure with disappointing results, similar to those obtained with other biological drugs.The aim of this study was the echocardiographic evaluation of infliximab infusion in nine patients without cardiac pathologies. The findings demonstrate a reduction of sistolic function and a modification of diastolic function after infliximab infusion in patients without cardiopathy. This study confirms the protective role played by TNFalpha on the myocardium, as suggested by previous experimental studies.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Ecocardiografía , Fármacos Gastrointestinales/uso terapéutico , Insuficiencia Cardíaca , Adulto , Animales , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Diástole/fisiología , Modelos Animales de Enfermedad , Ecocardiografía Doppler , Femenino , Fármacos Gastrointestinales/administración & dosificación , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Infliximab , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Sístole/fisiología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
About 50% of persons with an alcohol use disorder may have symptoms of alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption. Protracted alcohol withdrawal (PAW), an underestimated and not yet clearly defined clinical condition that follows the acute stage of AWS, is characterized by the presence of substance-specific signs and symptoms (i.e. anxiety, irritability, mood instability, insomnia, craving) common to acute AWS, but persisting beyond the generally expected acute AWS time frames. Considering that PAW symptoms are mainly related to the neuro-adaptive changes of gamma-aminobutyric acid (GABA) and N-methyl-d-aspartate (NMDA) systems, naltrexone, nalmefene, and disulfiram may not be able to suppress the symptoms of PAW. After treatment of the acute phase of AWS, a more specifically pharmacological therapy able to suppress PAW symptoms could perhaps be used earlier and may be more helpful in preventing the risk of alcohol relapse, which remains higher during the first months of treatment. In light of this, medications acting on GABA and NMDA neurotransmitter systems to counterbalance the up-regulation of NMDA and the down-regulation of GABA could be employed in combination and started as soon as possible.
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Alcoholismo/tratamiento farmacológico , Antagonistas de Aminoácidos Excitadores/farmacología , Agonistas del GABA/farmacología , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/fisiopatología , Alcoholismo/complicaciones , Humanos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Síndrome de Abstinencia a Sustancias/etiología , Factores de TiempoRESUMEN
Coeliac disease is a chronic and systemic autoimmune condition triggered by gluten ingestion in genetically predisposed subjects. Currently, the only effective treatment available is a strict, lifelong gluten-free diet. However, patients perceive gluten withdrawal as an unsustainable burden in their life and some of them can exhibit persistent symptoms despite a strict diet. Thus, gluten-free diet represents a challenge, leading scientists to look for alternative or complementary treatments. This review will focus on non-dietary therapies for coeliac disease highlighting six therapeutic strategies: (1) decreasing gluten immunogenic content before it reaches the intestine; (2) sequestering gluten in the gut lumen before absorption; (3) blocking the passage of gluten through a leaky intestinal barrier; (4) preventing the enhancement of immune response against gliadin; (5) dampening the downstream immune activation; (6) inducing immune tolerance to gluten. Most developing therapies are only in the pre-clinical phase with only a few being tested in phase 2b or 3 trials. Although new approaches raise the hope for coeliacs giving them a chance to come back to gluten, for the time being a cautionary appraisal of new therapies suggests that they may have a complementary role to gluten withdrawal, mainly to prevent inadvertent gluten contamination.