RESUMEN
BACKGROUND: Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis. MATERIALS AND METHODS: This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed. RESULTS: Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn's disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis. CONCLUSIONS: Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes.
Asunto(s)
Colitis , Inhibidores de Puntos de Control Inmunológico , Humanos , Masculino , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Colitis/inducido químicamente , Estudios de Seguimiento , Europa (Continente)RESUMEN
BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.
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Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Adulto , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Calidad de Vida , Estudios Prospectivos , Anticuerpos Monoclonales/uso terapéutico , Resultado del Tratamiento , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Índice de Severidad de la EnfermedadAsunto(s)
COVID-19 , Heparina , Anticoagulantes/uso terapéutico , Enoxaparina , Heparina/uso terapéutico , Hospitales , HumanosRESUMEN
BACKGROUND: Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn's disease and ulcerative colitis. METHODS: We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulphate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn's disease and 29 ulcerative colitis patients with active and inactive disease was included. RESULTS: In the acute and chronic dextran sulphate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn's disease (p < 0.05) and ulcerative colitis (p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve [AUC]: 0.81, p = 0.0009) and Crohn's disease (AUC: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (AUC: 0.75, p = 0.0219) and Crohn's disease patients with active disease from those in remission (AUC: 0.68, p = 0.05). CONCLUSION: PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn's disease.
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Colitis Ulcerosa/diagnóstico , Colágeno/sangre , Enfermedad de Crohn/diagnóstico , Mucosa Intestinal/metabolismo , Adulto , Animales , Anticuerpos/sangre , Biomarcadores/sangre , Colitis Ulcerosa/metabolismo , Colágeno/inmunología , Enfermedad de Crohn/metabolismo , Sulfato de Dextran/sangre , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas Sprague-DawleyRESUMEN
Celiac disease (CD) is an enteropathy triggered by the ingestion of gluten proteins in genetically predisposed individuals and characterized by excessive activation of effector immune cells and enhanced production of inflammatory cytokines. However, factors/mechanisms that amplify the ongoing mucosal inflammation in CD are not fully understood. In this study, we assessed whether mammalian target of Rapamycin (mTOR), a pathway that combines intra- and extra-cellular signals and acts as a central regulator for the metabolism, growth, and function of immune and non-immune cells, sustains CD-associated immune response. Our findings indicate that expression of phosphorylated (p)/active form of mTOR is increased in protein lysates of duodenal biopsy samples taken from patients with active CD (ACD) as compared to normal controls. In ACD, activation of mTOR occurs mainly in the epithelial compartment and associates with enhanced expression of p-4EBP, a downstream target of mTOR complex (mTORC)1, while expression of p-Rictor, a component of mTORC2, is not increased. Stimulation of mucosal explants of inactive CD patients with pepsin-trypsin-digested (PT)-gliadin or IFN-γ/IL-21, two cytokines produced in CD by gluten-specific T cells, increases p-4EBP expression. Consistently, blockade of such cytokines in cultures of ACD mucosal explants reduces p-4EBP. Finally, we show that inhibition of mTORC1 with rapamycin in ACD mucosal explants reduces p-4EBP and production of IL-15, a master cytokine produced by epithelial cells in this disorder. Our data suggest that ACD inflammation is marked by activation of mTORC1 in the epithelial compartment.
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Enfermedad Celíaca/inmunología , Duodeno/inmunología , Mucosa Intestinal/inmunología , Serina-Treonina Quinasas TOR/inmunología , Biopsia , Enfermedad Celíaca/patología , Duodeno/patología , Femenino , Gliadina/inmunología , Humanos , Inflamación/inmunología , Inflamación/patología , Interferón gamma/inmunología , Interleucinas/inmunología , Mucosa Intestinal/patología , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/inmunología , Diana Mecanicista del Complejo 2 de la Rapamicina/inmunología , Fosforilación/inmunología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.
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Consenso , Enfermedad de Crohn/terapia , Testimonio de Experto , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/terapia , Guías de Práctica Clínica como Asunto/normas , Cateterismo/métodos , Cateterismo/normas , Ensayos Clínicos como Asunto/normas , Ensayos Clínicos como Asunto/estadística & datos numéricos , Colon/patología , Colon/cirugía , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , Constricción Patológica/terapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Dilatación/métodos , Dilatación/normas , Endoscopía , Fibrosis/diagnóstico , Fibrosis/etiología , Fibrosis/terapia , Humanos , Obstrucción Intestinal/clasificación , Obstrucción Intestinal/etiología , Intestino Delgado/patología , Intestino Delgado/cirugía , Estándares de ReferenciaRESUMEN
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10% of women of reproductive age. It generally shows with oligo/amenorrhea, anovulatory cycles, clinical o biochemical hirsutism, polycystic ovaries and, in a significant percentage of cases, insulin resistance. PCOS is defined as a multifactorial pathology, determined by the association of many factors: genetic, endocrine and environmental. The first and most effective treatment of PCOS is to change life-style and lose weight. The use of oral contraceptives has been shown effective in reducing acne and hirsutism and regulates the menstrual cycle. For women with severe hirsutism, the addition of antiandrogens to estrogen-progestin therapy has significantly improved the results. In cases of anovulatory infertility, the drug of first choice is clomiphene citrate, followed by low-dose gonadotropins. Recently, insulin-sensitizing drugs have been widely prescribed for PCOS patients. They are particularly effective in reducing insulin resistance and improving ovulatory performance. Besides insulin-sensitizing drugs, natural substances, such as inositol, seems to have good efficacy, similar to metformin with fewer side effects. New substances that could be used include statins and natural statins, such as monakolin, alone or combined with myo-inositol. These substances do not have side effects and greatly reduce the hyperandrogenic component in these patients.
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Infertilidad Femenina/terapia , Enfermedades Metabólicas/terapia , Síndrome del Ovario Poliquístico/complicaciones , Antagonistas de Andrógenos/uso terapéutico , Anovulación/tratamiento farmacológico , Anovulación/etiología , Clomifeno/uso terapéutico , Anticonceptivos Hormonales Orales/uso terapéutico , Femenino , Gonadotropinas/uso terapéutico , Hirsutismo , Humanos , Hiperandrogenismo/tratamiento farmacológico , Infertilidad Femenina/etiología , Inositol/uso terapéutico , Resistencia a la Insulina , Estilo de Vida , Enfermedades Metabólicas/etiología , Metformina/uso terapéutico , Pérdida de PesoRESUMEN
BACKGROUND: In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn's disease (CD). AIM: In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy. METHODS: Patients with steroid-dependent/resistant, active CD were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn's Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C-reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored. RESULTS: Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated. CONCLUSIONS: Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C-reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011-002640-27.).
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Enfermedad de Crohn/tratamiento farmacológico , Oligonucleótidos Antisentido/uso terapéutico , Oligonucleótidos/farmacología , Oligonucleótidos/uso terapéutico , Proteína smad7/uso terapéutico , Adulto , Proteína C-Reactiva/análisis , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oligonucleótidos Antisentido/efectos adversos , Inducción de Remisión , Proteína smad7/efectos adversos , Resultado del TratamientoRESUMEN
AIM: Polycystic ovary syndrome (PCOS) affects 5-10% of women of childbearing age and manifests itself through oligomenorrhea, anovulation, hirsutism, micro-polycystic ovaries. Insulin resistance is a characteristic of PCOS patients and is more pronounced in obese patients. Insulin resistance and consequent hyperinsulinemia are related to many aspects of the syndrome such as hyperandrogenism, reproductive disorders, acne and hirsutism. In the long-term it may increase the risk of cardiovascular disease and negatively affect lipid profile and blood pressure. Changes in lifestyle and diet can partially improve these aspects. The use of insulin-sensitizing drugs such as metformin often normalises the menstrual cycle, improving hyperandrogenism and, subsequently, the response to ovulation induction therapies. New molecules have recently been marketed, that produce the same results, but without the side-effects. One of these is myo-inositol, a new insulin-sensitizing molecule which has been successfully administered to women suffering from PCOS. Associations between inositol and other compounds that can increase the therapeutic effect have been proposed. Of these, we found to be interesting the association with monacolin K, a natural statin that reduces cholesterol levels starting point of the synthesis of steroids, including androgens, and lipoic acid, known for its anti-inflammatory, antioxidant and insulin-sensitizing activity. We decided to assess the efficacy of the product. METHODS: We recruited 30 women aged between 24 and 32 years suffering from PCOS with insulin resistance, HOMA index>2.5 and no other endocrine diseases. The following were assessed: Body Mass Index (BMI), characteristics of menstrual cycles, lipid profile (total cholesterol, and HDL), androgens (total testosterone and androstenedione). The patients were also assessed for the degree of hirsutism using the Ferriman-Gallwey Score>8. The subjects were divided into two groups: Group A, treated with an association of 1 g myo-inositol, 5 mg monacolin K and 400 mg lipoic acid for 6 months; Group B, treated with a double dosage of 2 g myo-inositol, 10 mg monacolin K, 800 mg lipoic acid for 6 months. RESULTS: The results have shown good efficacy of both dosages, although women treated with a double dosage of myo-inositol, monacolin K and lipoic acid showed a significantly greater improvement in terms of lipid parameters and those connected with hyperandrogenism. CONCLUSION: This new myo-inositol, monacolin K and lipoic acid association contains appropriate substances to contrast various etiopathogenic elements responsible for the onset of PCOS and the symptoms of hyperandrogenism and dyslipidemia related to it.
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Hiperandrogenismo/tratamiento farmacológico , Inositol/uso terapéutico , Lovastatina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Adulto , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Dislipidemias/tratamiento farmacológico , Dislipidemias/etiología , Femenino , Hirsutismo/tratamiento farmacológico , Hirsutismo/etiología , Humanos , Hiperandrogenismo/etiología , Inositol/administración & dosificación , Resistencia a la Insulina , Lovastatina/administración & dosificación , Síndrome del Ovario Poliquístico/fisiopatología , Ácido Tióctico/administración & dosificación , Adulto JovenRESUMEN
The onset of vasomotor symptoms in postmenopausal women represents the beginning of a hard period from the emotional point of view which involves some of the most important neurotransmitters. Hot flushes and insomnia associated with a state of anxiety that affect postmenopausal women are included in an index known as the Kupperman Index. The use of nutraceuticals in Italy is increasingly widespread, and only 6-8% of women currently choose to take hormone replacement therapy. The action of these natural supplements primarily depends on the selection of substances and the dose of each single ingredient. Moreover, it also depends on the range of vasomotor symptoms (from mild to moderate/severe). The aim of this study was to test the action of a new product without phytoestrogens containing Cimicifuga racemosa, chasteberry (Vitex agnus-castus), hyaluronic acid, zinc and ginger (ElleN®) in two different groups of women: one with mild and the other with moderate/severe menopausal symptoms. All women received a dose of one tablet per day of ElleN® for three months. Results showed a significant reduction in the Kupperman Index in both groups. The treatment was particularly effective against hot flushes associated with night insomnia and anxiety. The product was well tolerated, did not cause any side effects, and none of the subjects dropped out of the study. In conclusion, it can be stated that the supplement evaluated in the present study is able to reduce moderate/severe menopause symptoms.
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Suplementos Dietéticos , Sofocos/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Posmenopausia , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Anciano , Femenino , Sofocos/etiología , Humanos , Italia , Persona de Mediana Edad , Fitoterapia/métodos , Extractos Vegetales/química , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: The clinical presentation of organic and functional intestinal disorders can overlap and clinicians often rely on invasive and time-consuming procedures to make a final diagnosis. Regenerating islet-derived 3-alpha (Reg3α) is detectable in the circulation of patients with intestinal graft-versus host disease and patients with inflammatory bowel disease (IBD). AIM: To determine whether serum Reg3α testing is useful for discriminating mucosal enteropathies from functional intestinal disorders. METHODS: We prospectively included 47 patients with active coeliac disease (ACD), 13 patients with refractory coeliac disease (RCD), seven patients with common variable immunodeficiency (CVID), 72 patients with active Crohn's disease, 22 patients with active ulcerative colitis (UC) and 28 patients with irritable bowel syndrome (IBS)-related diarrhoea. Sera were also taken from 10 CD patients before and after 6-12 months of a gluten-free diet (GFD) and from 14 patients with IBD before and after induction therapy with Infliximab (IFX). Sera of 119 healthy volunteers were used to determine the cut-off value. Reg3α levels were measured by a commercial ELISA kit. RESULTS: Levels of Reg3α exceeded the cut-off value of the assay in 43/47(91%) ACD patients, 13/13(100%) RCD patients, 7/7(100%) CVID patients, 65/72(90%) Crohn's disease patients, 17/22(77%) UC patients and one patient with IBS(4%). Reg3α levels distinguished mucosal enteropathies from IBS with a sensitivity of 90% and a specificity of 96%. Reg3α levels significantly decreased in CD patients following a GFD and in IBD patients after treatment with IFX. CONCLUSION: Reg3α is a serum biomarker of intestinal damage that, combined with clinical data, identifies patients who should undergo invasive tests for diagnosing enteropathies.
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Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Enfermedad Celíaca/sangre , Colitis Ulcerosa/sangre , Inmunodeficiencia Variable Común/sangre , Enfermedad de Crohn/sangre , Síndrome del Colon Irritable/sangre , Lectinas Tipo C/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedad Celíaca/diagnóstico , Colitis Ulcerosa/diagnóstico , Inmunodeficiencia Variable Común/diagnóstico , Enfermedad de Crohn/diagnóstico , Femenino , Humanos , Síndrome del Colon Irritable/diagnóstico , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Pancreatitis , Adulto JovenRESUMEN
AIM: Polycystic ovary syndrome (PCOS) is a multifactorial pathology affecting 7-10% of the female population. Usually occurs with oligo/amenorrhea, anovulation, hirsutism, polycystic ovaries. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome. It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients. METHODS: Original association between myo-inositol and alpha-lipoic acid, has recently been successfully administered in women with PCOS. The α-lipoic acid is a powerful natural antioxidant and an enzyme cofactor of the mitochondrial respiratory chain, is found to be a substance capable of improving glycemic control in patients with type II diabetes. In our study we compared two groups: group A, treated with metformin (3 g) and group B treated with metformin (1.7 g), myo-inositol and alpha-lipoic acid. RESULTS: The results of this study demonstrated a good efficacy of both treatments, although in the group treated with the combination of metformin/myo-inositol/alpha-lipoic acid improvement in hyperandrogenism, BMI and HOMA index were significantly better. CONCLUSION: Thus, the association metformin/myo-inositol/alpha-lipoic acid represents an excellent therapy choice to suggest to those obese women affected by PCOS who do not want to take hormones and neither to have any severe side effect.
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Antioxidantes/uso terapéutico , Metformina/uso terapéutico , Obesidad/tratamiento farmacológico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Adulto , Antioxidantes/administración & dosificación , Glucemia/análisis , Índice de Masa Corporal , Quimioterapia Combinada , Transporte de Electrón/efectos de los fármacos , Femenino , Hormonas Esteroides Gonadales/sangre , Homeostasis , Humanos , Inositol/administración & dosificación , Inositol/uso terapéutico , Resistencia a la Insulina , Metformina/administración & dosificación , Obesidad/sangre , Obesidad/complicaciones , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Índice de Severidad de la Enfermedad , Ácido Tióctico/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: Polycystic ovary syndrome (PCOS) is a multifactorial pathology affecting 5-10% of the female population. Usually occurs with oligo/amenorrhea, anovulation, hirsutism, polycystic ovaries. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome. It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients. METHODS: A new molecule with insulin-sensitizing properties, myo-inositol, has recently been successfully administered in women with PCOS. New associations between natural substances like myo-inositol and other components have been proposed to improve the therapeutical efficacy. Among these substances, the monacolin K, a natural statin appeared to have important actions in cholesterol synthesis. In this article we study the effect of inositol alone and the association between myo-inositol and monacolinin K in the treatment of PCOS with insulin resistance, menstrual irregularities and hirsutism. RESULTS AND CONCLUSION: The results of this study demonstrated a good efficacy of both treatments, although in the group treated with the combination of myo-inositol/monacolin K improvement in lipids and hyperandrogenism were significantly better.
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Hiperandrogenismo/complicaciones , Hiperandrogenismo/tratamiento farmacológico , Inositol/uso terapéutico , Metabolismo de los Lípidos , Lovastatina/uso terapéutico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Quimioterapia Combinada , Femenino , Humanos , Adulto JovenRESUMEN
Celiac disease (CD)-associated inflammation is characterized by high interleukin- 21 (IL-21), but the mechanisms that control IL-21 production are not fully understood. Here we analyzed IL-21 cell sources and examined how IL-21 production is regulated in CD. Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs), isolated from CD patients and non-CD controls, were analyzed for cell markers, cytokines, and transcription factors by flow cytometry. IL-21 was highly produced by CD4+ and CD4+/CD8+ IELs and LPLs in active CD. IL-21-producing cells coexpressed interferon-γ (IFN-γ) and to a lesser extent T helper type 17 (Th17) cytokines. Treatment of control LPLs with IL-15, a cytokine overproduced in CD, activated Akt and STAT3 (signal transducer and activator of transcription 3), thus enhancing IL-21 synthesis. Active CD biopsies contained elevated levels of Akt, and blockade of IL-15 in those samples reduced IL-21. Similarly, neutralization of IL-15 in biopsies of inactive CD patients inhibited peptic-tryptic digest of gliadin-induced IL-21 expression. These findings indicate that in CD, IL-15 positively regulates IL-21 production.
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Enfermedad Celíaca/metabolismo , Interleucina-15/metabolismo , Interleucinas/biosíntesis , Mucosa Intestinal/metabolismo , Enfermedad Celíaca/genética , Enfermedad Celíaca/patología , Células Cultivadas , Expresión Génica , Humanos , Interferón gamma/metabolismo , Interleucinas/genética , Mucosa Intestinal/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores CXCR5/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
OBJECTIVES: To prospectively evaluate the safety of metformin administration during pregnancy in a group of PCOS patients by assessing its effect on the prevalence of gestational complications and neonatal outcome. STUDY DESIGN: Our prospective, single centre study included 98 pregnant women with PCOS treated with metformin throughout pregnancy and 110 normal pregnant controls. All PCOS patients were hyperinsulinemic and received metformin (1700-3000 mg/day) before conception and until 37 weeks' gestation. RESULTS: Metformin treatment in the pregnant PCOS patients resulted in significant decrease in miscarriage rate (9.1% vs 20%; p<0.05), gestational diabetes (0 vs 13%; p<0.005), and gestational hypertension (0 vs 11%; p<0.005) and a non-significant decrease in pre-eclampsia (0 vs 3%; p=.24), compared to the control group. Mean neonatal Apgar score, weight and length were comparable between the two groups. CONCLUSIONS: Continuing metformin therapy throughout pregnancy resulted in significant reduction in pregnancy complications with concomitant improved neonatal outcome, with no serious deleterious side effects.
Asunto(s)
Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/prevención & control , Aborto Espontáneo/epidemiología , Aborto Espontáneo/prevención & control , Adulto , Glucemia/análisis , Diabetes Gestacional/epidemiología , Diabetes Gestacional/prevención & control , Femenino , Humanos , Hiperinsulinismo/prevención & control , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/prevención & control , Hipoglucemiantes/efectos adversos , Insulina/sangre , Italia/epidemiología , Metformina/efectos adversos , Síndrome del Ovario Poliquístico/sangre , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo , PrevalenciaRESUMEN
Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.
Asunto(s)
Moduladores de Receptores de Cannabinoides/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/metabolismo , Animales , Ácidos Araquidónicos/farmacología , Citocinas/biosíntesis , Humanos , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/patología , Intestinos/patología , Ratones , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/metabolismo , Factor de Transcripción STAT4/metabolismo , Proteínas de Dominio T Box/metabolismoRESUMEN
An altered balance between effector and regulatory factors is supposed to sustain the tissue-damaging immune response in inflammatory bowel disease (IBD). We have recently shown that in IBD, there is a defective synthesis of the counter-regulatory cytokine, interleukin (IL)-25. In this study we investigated factors that control IL-25 production in the gut. IBD patients produced less IL-25 when compared with normal controls. Stimulation of normal intestinal explants with tumor necrosis factor-α (TNF-α), but not interferon-γ (IFN-γ) or IL-21, reduced IL-25 synthesis. Consistently, IL-25 production was enhanced by anti-TNF-α both in vitro and in vivo. Upregulation of IL-25 was also seen in normal colonic explants stimulated with transforming growth factor-ß1 (TGF-ß1). As in IBD, TGF-ß1 activity is abrogated by Smad7, we next assessed whether inhibition of Smad7 with an antisense oligonucleotide enhanced IL-25 expression. Knockdown of Smad7 was accompanied by an increase in IL-25 production. Data show that IL-25 production is differently regulated by TNF-α and TGF-ß1 in the human gut.
Asunto(s)
Regulación de la Expresión Génica , Interleucina-17/metabolismo , Mucosa Intestinal/inmunología , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedad Celíaca/inmunología , Regulación de la Expresión Génica/inmunología , Técnicas de Silenciamiento del Gen , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Interleucina-17/genética , Proteína smad7/genética , Proteína smad7/metabolismoRESUMEN
AIM: Among the factors contributing to male infertility, asthenospermia constitutes both a health and a social problem frequently associated with alterations in sexual function. Studies have shown that acetyl carnitine and L-arginine improve sperm motility and that ginseng enhances libido and sexual performance. This study examined the effect of treatment with carnitine, acetyl carnitine, L-arginine and ginseng in men with idiopathic asthenospermia and altered sexual function. METHODS: The study population was 180 patients with asthenospermia randomly assigned to two groups: group A (90 men) received treatment and group B (90 men) did not. The sperm count was 16.6 ± 3.2 x 106/mL and the total sperm motility was 26.5 ± 3.4%. RESULTS AND CONCLUSION: Sexual satisfaction was measured using the sexual satisfaction index (SSI). At the end of therapy, a significant improvement was observed in progressive sperm motility on spermiogram evaluation and in SSI scores in the treatment group.