RESUMEN
In this manuscript we aimed at the simultaneous separation and quantification of Gemcitabine and Irinotecan hydrochloride (injected both as single components and in combination) from Sprague Dawley rat plasma by using a validated method obtained through the use of a High Performance Liquid Chromatography (HPLC)-diode array detector (DAD). Gemcitabine and Irinotecan hydrochloride were detected and quantified using a Zorbax Extend C-18 column (250â¯mmâ¯×â¯4.6â¯mm; 5⯵m particle size) in gradient elution mode. The chromatographic analyses were carried out in 15â¯min. The analytical mode was calibrated and validated in the concentration range from 0.1 to 18⯵g/mL both for Gemcitabine and Irinotecan hydrochloride. Sprague Dawley rat plasma was used to perform the analysis. 3-methylxanthine was the internal standard. The weighted-matrix matched standard curves of Gemcitabine and Irinotecan hydrochloride showed a good linearity up to 18⯵g/mL. Parallelism tests were also performed to evaluate whether the over-range samples could be analyzed after dilution without affecting the analytical performance. The intra- and inter-day precision (RSD%) values of Gemcitabine and Irinotecan hydrochloride were ≤7.14% and ≤11.5%, respectively. The intra- and inter-day trueness (Bias%) values were in the range from -11.5% to 1.70% for both drugs. The analytical mode performance was further tested after collecting Sprague Dawley rat plasma following a single-dose administration of chemotherapeutics or their association. The validated HPLC-DAD method allowed the simultaneous quantification of Gemcitabine and Irinotecan hydrochloride in the rat plasma, besides the evaluation of the pharmacokinetic parameters and drug delivery.
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Antimetabolitos Antineoplásicos/sangre , Antineoplásicos Fitogénicos/sangre , Camptotecina/análogos & derivados , Técnicas de Química Analítica/métodos , Desoxicitidina/análogos & derivados , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/sangre , Cromatografía Líquida de Alta Presión/métodos , Desoxicitidina/administración & dosificación , Desoxicitidina/sangre , Inyecciones Intravenosas , Irinotecán , Ratas , Ratas Sprague-Dawley , GemcitabinaRESUMEN
The aim of this study was the quality of service evaluation of two different organizational ways in delivering infant vaccination according to a Regional Vaccination Plan. Eleven vaccination centres were selected in two Local Health Units (ASLs) belonging to the Regional Health Service of the Lazio Region, Italy. The services offering paediatric vaccinations for children under three years of age, delivered without an appointment (VACP) or with the need for an appointment (VACL), were investigated. The quality aspects under evaluation were communicational efficiency, organisational efficiency and comfort. Subjective data were collected from different stakeholders and involve the elicitation of best and worst feasible performance conditions for the ASLs when delivering VACP/VACL services. Objective data consists in the observation of current performances of the selected vaccination centres. Quality scorecards were obtained from the combination of all data. Benchmarking between VACP and VACL, i.e., two different organisational ways in delivering infant vaccination, can be performed as a result of the probabilistic meaning of the evaluated scores. An expert of vaccination services, i.e., a virtual combination of patients, doctors and nurses, claims the quality of service delivery of the ASLs under investigation with probability 78.03% and 69.67% for VACP and VACL, respectively. In other words, for short, the quality scores of the ASLs were 78.03% for VACP and 69.67% for VACL. Furthermore our results show how to practically improve the current service delivery. The QuaVaTAR approach can result in improvements of the quality of the ASLs for the two different ways of delivering paediatric vaccinations in a simple and intuitive way.
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Benchmarking , Programas de Inmunización , Vacunación/normas , Preescolar , Comunicación , Humanos , Lactante , ItaliaRESUMEN
In the present paper physical gels, prepared with two polysaccharides, Xanthan and Locust Bean Gum, and loaded with non-ionic surfactant vesicles, are described. The vesicles, composed by Tween20 and cholesterol or by Tween85 and Span20, were loaded with Monoammonium glycyrrhizinate for release experiments. Size and zeta (ζ)-potential of the vesicles were evaluated and the new systems were characterized by rheological and dynamo-mechanical measurements. For an appropriate comparison, a Carbopol gel and a commercial gel for topical applications were also tested. The new formulations showed mechanical properties comparable with those of the commercial product indicating their suitability for topical applications. In vitro release experiments showed that the polysaccharide network protects the integrity of the vesicles and leads to their slow release without disruption of the aggregated structures. Furthermore, being the vesicles composed of molecules possessing enhancing properties, the permeation of the loaded drugs topically delivered can be improved. Thus, the new systems combine the advantages of matrices for a modified release (polymeric component) and those of an easier permeability across the skin (vesicle components). Finally, shelf live experiments indicated that the tested gel/vesicle formulations were stable over 1 year with no need of preservatives.
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Antiinflamatorios no Esteroideos/química , Galactanos/química , Ácido Glicirrínico/química , Liposomas/química , Mananos/química , Gomas de Plantas/química , Polisacáridos Bacterianos/química , Resinas Acrílicas/química , Administración Tópica , Preparaciones de Acción Retardada , Liberación de Fármacos , Geles , Hexosas/química , Cinética , Polisorbatos/química , Soluciones , Tensoactivos/químicaRESUMEN
UNLABELLED: Moxifloxacin has been used in the first-line treatment of Helicobacter pylori infection. The optimal dosage and duration have not been assessed. AIM: To evaluate the effectiveness of moxifloxacin, amoxicillin and esomeprazole in four regimens, in previously untreated patients infected by H. pylori. METHODS AND PATIENTS: Patients were randomly assigned to: esomeprazole 20 mg b.i.d., amoxicillin 1g b.i.d., and one of each of the four following dosages of moxifloxacin: moxifloxacin 400 mg b.i.d. for 10 days (EAM800x10), moxifloxacin 400 mg b.i.d. for 7 days (EAM800x7), moxifloxacin 400 mg b.i.d. for 5 days (EAM800x5), moxifloxacin 400 mg o.i.d. for 10 days (EAM400x10). Eradication was assessed by the Urea Breath Test (UBT) 2 months following the end of therapy. RESULTS: Ninety-four, 102, 92 and 105 patients were recruited in EAM800x10, EAM800x7, EAM800x5, and EAM400x10 respectively. The eradication rate was for Intention-To-Treat (ITT) and Per Protocol (PP) analyses: EAM800x10 group ITT: 90.4%, PP: 94.4%; EAM800x7 group ITT: 80.3%, PP: 86.3%; EAM800x5 group ITT: 71.4%, PP: 75.2%; EAM400x10 group ITT: 80.0%, PP 84.8%. A statistically significant difference was reached between EAM800x10 vs. EAM800x7 (ITT and PP: P<0.05), and between EAM800x10 vs. EAM800x5 (ITT and PP: P<0.01) and vs. EAM400x10 (ITT: P<0.05; PP: P<0.04). Thirty patients treated unsuccessfully with EAM800x5 and EAM400x10 were re-treated with EAM800x10 with an eradication rate of 86.7% (ITT) and 92.2% (PP). Nineteen patients with positive UBT after EAM800x10 and EAM800x7 underwent a second-line rifabutin-based therapy with an eradication rate of 84.2% (ITT and PP). CONCLUSION: A triple therapy with 800 mg of moxifloxacin a day for 10 days is more effective than the same treatment for 5 or 7 days and a treatment with 400mg of moxifloxacin a day for 10 days for the first-line eradication of H. pylori infection. The high cost of moxifloxacin-based treatment however, may limit its wide use as first-line treatment of H. pylori infection.
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Amoxicilina/administración & dosificación , Antibacterianos/administración & dosificación , Antiulcerosos/administración & dosificación , Compuestos Aza/administración & dosificación , Esomeprazol/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Quinolinas/administración & dosificación , Adulto , Anciano , Pruebas Respiratorias , Esquema de Medicación , Quimioterapia Combinada , Femenino , Fluoroquinolonas , Humanos , Masculino , Persona de Mediana Edad , Moxifloxacino , Urea/análisis , Adulto JovenRESUMEN
Various molecular mechanisms have been suggested to be involved in dexamethasone induced thymocyte apoptosis. In this study we show that pharmacological inhibition of cytoplasmic PLA2 in mouse thymocytes for 18 h with arachidonyl trifluoromethyl ketone (AACOCF3) (10 microM) and palmitoyl trifluoromethyl ketone (PACOCF3) (10 microM) induced a drastic increase of thymocyte apoptosis comparable to that observed following Dex (10(-7) M) treatment, while inhibition of secretory PLA2 with p-bromophenacyl bromide (pBPB) (20 microM) did not. AACOCF3-induced thymocyte apoptosis, similarly to Dex-induced thymocyte apoptosis, was eliminated by cell pre-treatment with the PI-PLCbeta inhibitor, U73122, but not by the PC-PLC inhibitor D609. These observations were corroborated by the ability of AACOCF3, like Dex, to induce a rapid and transient increase in DAG generation. In addition, AACOCF3-induced apoptosis involved the activation of the acidic sphingomyelinase (aSMase) but not of the neutral sphingomyelinase (nSMase), as evaluated by measurements of enzyme activity in cell extracts following thymocyte exposure to AACOCF3 and by the ability of monensin to inhibit AACOCF3-induced thymocyte apoptosis. In addition, the AACOCF3 apoptotic effect resulted in an early increase of ceramide levels. AACOCF3-induced thymocyte apoptosis involved the activation of caspase 3, and cell pre-treatment with a caspase 3 inhibitor prevented AACOCF3-induced apoptosis. These observations suggest that cPLA2 inhibition may have a role in Dex-induced thymocyte apoptosis and highlight the importance of cPLA2 activity in thymocyte survival.
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Apoptosis/efectos de los fármacos , Citoplasma/enzimología , Dexametasona/farmacología , Inhibidores de Fosfolipasa A2 , Linfocitos T/efectos de los fármacos , Animales , Ácido Araquidónico/metabolismo , Ácidos Araquidónicos/farmacología , Caspasa 3/metabolismo , Ceramidas/metabolismo , Masculino , Ratones , Ratones Endogámicos C3H , Mifepristona/farmacología , Fosfoinositido Fosfolipasa C/metabolismo , Fosfolipasas A2/fisiologíaRESUMEN
Phospholipid and non-phospholipid vesicles are extensively studied as drug delivery systems to modify pharmacokinetics of drugs and to improve their action in target cells. It is believed that the major barrier to efficient drug delivery is entrapment of drugs in the endosomal compartment, since this eventually leads to its degradation in lysosomes. For these reasons, the knowledge of internalization pathway plays a fundamental role in optimizing drug targeting. The aim of this work is to characterize pH-sensitive Tween 20 vesicles, their interaction with macrophage-like cells and their comparison with pH-sensitive liposomes. The effect of different amounts of cholesteryl hemissucinate on surfactant vesicle formation and pH-sensitivity was studied. To evaluate the initial mode of internalization in Raw 264.7 and the intracellular fate of neutral and pH-sensitive formulations, flow cytometry in presence and in absence of selected inhibitors and fluorescence microscopy in absence and presence of specific fluorescent endocytotic markers were used. The obtained results showed that the surfactant vesicle pH-sensitivity was about two or three fold higher than that obtained with pH-sensitive liposomes in the presence of serum in vitro. The uptake mechanism of surfactant vesicles, after incubation with macrophage-like cells, is comparable to that of liposomes (clathrin-mediated endocytosis).
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Endocitosis/fisiología , Macrófagos/metabolismo , Fosfolípidos/farmacocinética , Polisorbatos/farmacocinética , Tensoactivos/farmacocinética , Animales , Transporte Biológico/efectos de los fármacos , Fenómenos Biofísicos , Línea Celular , Vesículas Citoplasmáticas/química , Vesículas Citoplasmáticas/metabolismo , Endocitosis/efectos de los fármacos , Fluoresceínas/metabolismo , Colorantes Fluorescentes/metabolismo , Concentración de Iones de Hidrógeno , Liposomas/química , Liposomas/metabolismo , Liposomas/farmacocinética , Ratones , Microscopía Fluorescente , Fosfolípidos/química , Fosfolípidos/metabolismo , Polisorbatos/metabolismo , Polisorbatos/farmacología , Tensoactivos/metabolismo , Tensoactivos/farmacologíaRESUMEN
Little is known about prolonged effect of baclofen on oesophageal and lower oesophageal sphincter (LOS) motility. We aimed at investigating the oesophageal motility in gastro-oesophageal reflux disease (GORD) patients 24 h before and after the administration of multiple doses of baclofen. Twenty-one GORD patients underwent a 48-h manometry recording the swallows, the oesophageal and the LOS motility. During the second 24-h period, patients received baclofen 10 mg or placebo four times per day in a double-blind randomized fashion. Baclofen increased the LOS basal tone in comparison with baseline (P = 0.02), with a concomitant reduction in the number of transient LOS relaxations (TLOSRs) (P = 0.01). Moreover, baclofen induced a decrease of the swallows (P = 0.02) and of primary oesophageal body waves (P = 0.04) with no changes in the amplitude. Multiple doses of baclofen determine a reduction in the number of TLOSRs and an increase in the LOS tone throughout the 24 h. The concomitant decreased number of swallows and of primary peristalsis could depend on the well-known lower amount of reflux episodes induced by the drug. The potential therapeutic effect of baclofen could be expressed not only postprandially, but also in the fasting state when reflux episodes are present as well.
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Baclofeno/uso terapéutico , Esfínter Esofágico Inferior/efectos de los fármacos , Reflujo Gastroesofágico/tratamiento farmacológico , Relajantes Musculares Centrales/uso terapéutico , Relajación Muscular/efectos de los fármacos , Peristaltismo/efectos de los fármacos , Adulto , Baclofeno/farmacología , Deglución/fisiología , Método Doble Ciego , Esfínter Esofágico Inferior/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relajantes Musculares Centrales/farmacología , Peristaltismo/fisiología , PlacebosRESUMEN
Several studies have demonstrated that ceramides play an essential role in both the barrier and water-holding functions of healthy stratum corneum, suggesting that the dysfunction of the stratum corneum associated with ageing as well that observed in patients with several skin diseases could result from a ceramide deficiency. In a previous study our group reported a significant increase in skin ceramide levels in healthy subjects after treatment in vivo with a cream containing a preparation of Streptococcus thermophilus. The presence of high levels of neutral sphingomyelinase activity in this organism was responsible for the observed increase of stratum corneum ceramide levels, thus leading to an improvement in barrier function and maintenance of stratum corneum flexibility. The aim of the present work is to investigate the effects of the topical treatment of a Streptococcus thermophilus-containing cream on ceramide levels of stratum corneum of healthy elderly women. The ceramide levels, transepidermal water loss and capacitance were evaluated on stratum corneum sheets from the forearms of 20 healthy female subjects treated with a base cream or the same cream containing a sonicated preparation of the lactic acid bacterium Streptococcus thermophilus. A 2-week topical application of a sonicated Streptococcus thermophilus preparation led to significant and relevant increase of stratum corneum ceramide levels. Moreover, the hydration values of the treated forearm of each subject was significantly higher than control sites. These results suggest that the experimental cream was able to improve the lipid barrier and to increase a resistance against ageing-associated xerosis.
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Ceramidas/análisis , Envejecimiento de la Piel/efectos de los fármacos , Piel/química , Esfingomielina Fosfodiesterasa/administración & dosificación , Streptococcus/enzimología , Administración Tópica , Anciano , Femenino , HumanosRESUMEN
BACKGROUND: Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase. OBJECTIVE: To determine the effect of VSL#3 probiotic therapy on mucosal levels of alkaline sphingomyelinase, both in a mouse model of colitis and in patients with ulcerative colitis. METHODS: Interleukin-10 gene-deficient (IL10KO) and wild type control mice were treated with VSL#3 (10(9) colony-forming units per day) for three weeks, after which alkaline sphingomyelinase activity was measured in ileal and colonic tissue. As well, 15 patients with ulcerative colitis were treated with VSL#3 (900 billion bacteria two times per day for five weeks). Alkaline sphingomyelinase activity was measured through biopsies and comparison of ulcerative colitis disease activity index scores obtained before and after treatment. RESULTS: Lowered alkaline sphingomyelinase levels were seen in the colon (P=0.02) and ileum (P=0.04) of IL10KO mice, as compared with controls. Treatment of these mice with VSL#3 resulted in upregulation of mucosal alkaline sphingomyelinase activity in both the colon (P=0.04) and the ileum (P=0.01). VSL#3 treatment of human patients who had ulcerative colitis decreased mean (+/- SEM) ulcerative colitis disease activity index scores from 5.3+/-1.8946 to 0.70+/-0.34 (P=0.02) and increased mucosal alkaline sphingomyelinase activity. CONCLUSION: Mucosal alkaline sphingomyelinase activity is reduced in the intestine of IL10KO mice with colitis and in humans with ulcerative colitis. VSL#3 probiotic therapy upregulates mucosal alkaline sphingomyelinase activity.
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Colitis Ulcerosa/metabolismo , Mucosa Intestinal/metabolismo , Probióticos/farmacología , Esfingomielina Fosfodiesterasa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Adulto , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colon/enzimología , Modelos Animales de Enfermedad , Femenino , Humanos , Íleon/enzimología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Persona de Mediana EdadRESUMEN
Polyhydric alcohol derivatives of the anticancer agent lonidamine (LND) have been synthesized. The increased water solubility showed by prodrugs 4, 7, and 25 together with their logP values (2.19, 2.55, and 2.54, respectively) and chemical stability might be beneficial for prodrugs absorption after oral administration. Moreover, the new prodrugs undergo enzymatic hydrolysis in plasma and release LND demonstrating that they are promising candidates for in vivo investigations.
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Alcoholes/química , Antineoplásicos/farmacocinética , Glicósidos/química , Indazoles/farmacocinética , Profármacos/metabolismo , Absorción , Administración Oral , Animales , Antineoplásicos/sangre , Antineoplásicos/síntesis química , Línea Celular Tumoral , Humanos , Hidrólisis , Indazoles/sangre , Indazoles/síntesis química , Modelos Químicos , Profármacos/síntesis química , Ratas , Solubilidad , Relación Estructura-Actividad , Agua/químicaRESUMEN
BACKGROUND: A reduction of gastric accommodation after a meal has been documented in patients with idiopathic dyspepsia. In these patients the administration of a 5-HT3 receptor antagonist may reduce some of the dyspeptic symptoms; it is not clear however, whether these drugs influence gastric adaptation to distension as well. AIM: To evaluate the effects of the 5-HT3 receptor antagonist, ondansetron, on gastric distension after a liquid meal in dyspeptic patients with reduced gastric accommodation. METHODS: Before and after a 500 ml water load, gastric accommodation (area of the proximal and distal stomach) was evaluated using real-time ultrasonography in 21 idiopathic dyspepsia patients and 26 healthy controls. In dyspeptic patients, the test was repeated twice: after the administration of placebo and after ondansetron 8 mg i.v. (in both cases, 15 min prior to the water load). Secondary outcomes were epigastric pain, fullness and nausea as assessed by a visual analogue scale at basal and after ondansetron. RESULTS: Fasting gastric size was similar in dyspeptic and controls. Compared with controls, dyspeptic patients showed a statistically significant smaller area of the proximal stomach (14.7+/-1.2 cm(2) vs. 18.6+/-1.4 cm(2), respectively; p=0.0247). In dyspeptic patients, gastric proximal and distal size did not change significantly following placebo, whereas after the administration of ondansetron the mean area of the proximal and distal stomach significantly increased (proximal stomach: 14.6+/-1.6 cm(2) placebo, 20.4+/-1.9 cm(2) ondansetron, p=0.0095; distal stomach: 8.9+/-0.9 placebo, 11.4+/-1.2cm(2) ondansetron, p=0.0409). Of the symptoms, only nausea was significantly reduced after ondansetron. CONCLUSION: In dyspeptic patients with impaired gastric accommodation, ondansetron reverts gastric accommodation to within the range of controls.
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Dispepsia/tratamiento farmacológico , Vaciamiento Gástrico/fisiología , Ondansetrón/uso terapéutico , Tamaño de los Órganos/efectos de los fármacos , Antagonistas del Receptor de Serotonina 5-HT3 , Antagonistas de la Serotonina/uso terapéutico , Estómago/fisiopatología , Adulto , Dispepsia/diagnóstico por imagen , Dispepsia/fisiopatología , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Humanos , Masculino , Estómago/diagnóstico por imagen , Estómago/efectos de los fármacos , Resultado del Tratamiento , UltrasonografíaRESUMEN
INTRODUCTION: The use of peppermint oil in treating the irritable bowel syndrome has been studied with variable results probably due to the presence of patients affected by small intestinal bacterial overgrowth, lactose intolerance or celiac disease that may have symptoms similar to irritable bowel syndrome. AIM: The aim of the study was to test the effectiveness of enteric-coated peppermint oil in patients with irritable bowel syndrome in whom small intestinal bacterial overgrowth, lactose intolerance and celiac disease were excluded. METHODS: Fifty-seven patients with irritable bowel syndrome according to the Rome II criteria, with normal lactose and lactulose breath tests and negative antibody screening for celiac disease, were treated with peppermint oil (two enteric-coated capsules twice per day or placebo) for 4 weeks in a double blind study. The symptoms were assessed before therapy (T(0)), after the first 4 weeks of therapy (T(4)) and 4 weeks after the end of therapy (T(8)). The symptoms evaluated were: abdominal bloating, abdominal pain or discomfort, diarrhoea, constipation, feeling of incomplete evacuation, pain at defecation, passage of gas or mucus and urgency at defecation. For each symptom intensity and frequency from 0 to 4 were scored. The total irritable bowel syndrome symptoms score was also calculated as the mean value of the sum of the average of the intensity and frequency scores of each symptom. RESULTS: At T(4), 75% of the patients in the peppermint oil group showed a >50% reduction of basal (T(0)) total irritable bowel syndrome symptoms score compared with 38% in the placebo group (P<0.009). With peppermint oil at T(4) and at T(8) compared with T(0) a statistically significant reduction of the total irritable bowel syndrome symptoms score was found (T(0): 2.19+/-0.13, T(4): 1.07+/-0.10*, T(8): 1.60+/-0.10*, *P<0.01 compared with T(0), mean+/-S.E.M.), while no change was found with the placebo. CONCLUSION: A 4 weeks treatment with peppermint oil improves abdominal symptoms in patients with irritable bowel syndrome.
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Síndrome del Colon Irritable/tratamiento farmacológico , Aceites de Plantas/uso terapéutico , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Mentha piperita , Persona de Mediana Edad , Placebos , Estudios ProspectivosRESUMEN
Current management of atopic dermatitis is mainly directed to the reduction of cutaneous inflammation. Since patients with atopic dermatitis show abnormalities in immunoregulation, a therapy aimed to adjust their immune function could represent an alternative approach, particularly in the severe form of the disease. Indeed, T-lymphocytes constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated T-cell induced keratinocyte apoptosis appears to be an important pathogenetic factor of the eczematous disease. In recent years, attention has been focused on the interaction between host and probiotics which may have anti-inflammatory properties and immunomodulatory activities. The aim of the present work is to investigate the effect of a selected probiotic extract, the Bifidobacterium infantis extract, on a human keratinocyte cell line (HaCaT) abnormal apoptosis induced by activated-T-lymphocyte. An in vitro model of atopic dermatitis was used to assess the ability of the probiotic extract to protect HaCaT from apoptosis induced by soluble factors (IFN-gamma and CD95 ligand) released by human T-lymphocytes in vitro activated with anti-CD3/CD28 mAbs or Phytohemoagglutinin. Evidence is given that the bacterial extract treatment was able to totally prevent T lymphocyte-induced HaCaT cell apoptosis in vitro. The mechanism underlying this inhibitory effect has been suggested to depend on the ability of the bacterial extract to significantly reduce anti-CD3/CD28 mAbs and mitogen-induced T-cell proliferation, IFN-gamma generation and CD95 ligand release. These preliminary results may represent an experimental basis for a potential therapeutic approach mainly targeting the skin disorders-associated immune abnormalities.
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Apoptosis/efectos de los fármacos , Bifidobacterium/fisiología , Dermatitis Atópica/terapia , Interferón gamma/farmacología , Queratinocitos/efectos de los fármacos , Línea Celular Transformada , Dermatitis Atópica/inmunología , HumanosRESUMEN
Ineffective oesophageal motility (IOM) is a functional disorder affecting about 50% of gastro-oesophageal reflux disease (GORD) patients. This disease in a severe form limits the clearing ability of the oesophagus and is considered one of the predictive factors for poorer GORD resolution. Capsaicin, the active compound of red pepper, exerts a prokinetic effect on oesophageal motility in healthy subjects by increasing the amplitude of body waves, even if no evidence exists on its possible role in situations of reduced motility. The aim of the study was to evaluate the effect of an acute administration of capsaicin on the oesophageal motor pattern in a group of GORD patients affected by severe IOM. Twelve GORD patients with severe IOM received an intra-oesophageal administration of 2 mL of a red pepper-olive oil mixture and 2 mL of olive oil alone serving as a control during a stationary manometry. The motor patterns of the oesophageal body and lower oesophageal sphincter (LOS) were analysed at baseline and after the infusion of the two stimuli. The administration of capsaicin induced a significant improvement in oesophageal body contractility when compared with baseline. The velocity of propagation of waves and the LOS basal tone remained unchanged. The motor pattern was unaltered by the administration of olive oil alone. An acute administration of capsaicin seems to improve the motor performance of the oesophageal body in patients with ineffective motility. Whether this could represent the basis for further therapeutic approaches of GORD patients needs further study.
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Capsaicina/administración & dosificación , Trastornos de la Motilidad Esofágica/fisiopatología , Esófago/efectos de los fármacos , Reflujo Gastroesofágico/fisiopatología , Adulto , Esfínter Esofágico Inferior/efectos de los fármacos , Femenino , Humanos , Masculino , Manometría , Persona de Mediana EdadRESUMEN
In this work, we report the preparation, the characterization and interaction with cells of novel pH-sensitive non-phospholipid vesicle formulations, from a non-ionic surfactant mixed with cholesterol (CHOL) and his derivative cholesteryl hemisuccinate (CHEMS), as pH-sensitive molecule. This molecule, can destabilize the vesicle lipid bilayer when exposed to an acidic environment, with a subsequent release of vesicular content, enhancing the cytoplasmatic delivery of drugs to target cells. Vesicles were characterized by static and dynamic light scattering, in order to evaluate their dimensions, bilayer thickness and vesicle stability. Membrane permeability changes were determined by the release of entrapped hydroxypyrene-1,3,6-trisulfonic acid (HPTS). Also diphenylhesatriene (DPH) fluorescence anisotropy and zeta potential measurements were used to evidence the pH sensitivity. Furthermore vesicles were characterized by means of electronic microscopy after freeze-fracture. The interaction of non-lipid vesicles containing different fluorescent dyes with Raw 264.7, mouse monocite macrophage, were analyzed by flow cytometric analysis. The obtained results indicate that the pH-sensitive vesicular structures show good plasma stability and relevant pH-sensitivity. Moreover this formulation was able to interact with target membranes (i.e. plasma or endosomal membrane) and to release the encapsulated material into the cytoplasm.
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Colesterol/química , Concentración de Iones de Hidrógeno , Macrófagos/citología , Tensoactivos/química , Animales , Línea Celular , Colesterol/metabolismo , Endocitosis , Colorantes Fluorescentes/química , Técnica de Fractura por Congelación , Ratones , Microscopía Electrónica de Transmisión , Permeabilidad , Fosfolípidos/química , Fosfolípidos/metabolismo , Plasma , Tensoactivos/metabolismoRESUMEN
Propolis and Zingiber officinale have been shown to be specifically targeted against Helicobacter pylori strains, to possess antiinflammatory, antioxidant and antitumoral activity and to be used in traditional medicine for the treatment of gastrointestinal ailments. Considering that these natural products could potentially serve as novel therapeutic tools also in combination with an antibiotic, the aim of this work was to evaluate their effect when combined with clarithromycin on clinical H. pylori isolates (n = 25), characterized in respect to both clarithromycin susceptibility and the presence of the cagA gene. The results showed that the combinations of propolis extract + clarithromycin and Z. officinale extract + clarithromycin exhibited improved inhibition of H. pylori with synergistic or additive activity. Interestingly, the susceptibility to combinations was significantly independent of the microbial clarithromycin susceptibility status. Only one H. pylori strain showed antagonism towards the Z. officinale extract + clarithromycin combination. The data demonstrate that combinations of propolis extract + clarithromycin and Z. officinale extract + clarithromycin have the potential to help control H. pylori-associated gastroduodenal disease.
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Antibacterianos/farmacología , Claritromicina/farmacología , Helicobacter pylori/efectos de los fármacos , Extractos Vegetales/farmacología , Própolis/farmacología , Zingiber officinale/química , Adulto , Análisis de Varianza , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Combinación de Medicamentos , Sinergismo Farmacológico , Etanol/química , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/clasificación , Helicobacter pylori/genética , Humanos , Masculino , Medicina Tradicional , Pruebas de Sensibilidad Microbiana , Própolis/químicaRESUMEN
The aim of this work was to evaluate the antibacterial effect of plant extracts as alternative and[sol ]or as active agents supporting antibiotics for treating Helicobacter pylori infection. The effect of either, ethanolic or aqueous extracts from 17 plant materials were studied against one H. pylori standard strain and 11 clinical isolates using a disc diffusion test and by evaluating the minimum inhibitory concentration (MIC) on solid media. An inhibitory activity against H. pylori strains was recorded in a large percentage of tested plants. MIC values of ethanolic extracts were from two to four concentration steps lower than the aqueous ones. In particular, ethanolic extracts of Cuminum cyminum L. and Propolis expressed MIC90 values of 0.075 mg/mL. The results show a significant in vitro effect of plant extracts against H. pylori that could be considered a valuable support in the treatment of the infection and may contribute to the development of new and safe agents for inclusion in anti-H. pylori regimens.
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Antibacterianos/farmacología , Cuminum , Helicobacter pylori/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Própolis , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéuticoRESUMEN
BACKGROUND: Abdominal symptoms linked to lactose malabsorption may be caused by metabolic activity of colonic bacteria. Rifaximin, a non-absorbable rifampycin derivative, is active against colonic bacteria, it may be useful in the treatment of lactose intolerance. AIM: The aim of this study has been to evaluate short-term rifaximin therapy in patients with lactose intolerance. METHODS: Thirty-two patients with lactose intolerance diagnosed using the hydrogen lactose breath test were studied. Fourteen patients received rifaximin 800 mg/day for 10 days, 13 patients followed a diet without milk for 40 days and 5 patients received a placebo for 10 days. Total breath H(2) excretion expressed as area under the curve, and the symptom score were evaluated in all patients at the start, and subsequently after 10 and 40 days. RESULTS: In the 14 patients who received rifaximin for 10 days, area under the curve at day 10 and day 40 was statistically significantly lower than the one computed at basal (P<0.01). Diet reduced area under the curve progressively reaching statistical significance at day 40, while the placebo did not change area under the curve throughout the study. The total symptom score significantly improved after rifaximin and diet. CONCLUSION: In patients with lactose intolerance, a 10-day therapy with rifaximin as well as 40-day diet without lactose reduces the area under the curve and the symptom score.
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Antiinfecciosos/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Intolerancia a la Lactosa/tratamiento farmacológico , Rifamicinas/uso terapéutico , Adulto , Área Bajo la Curva , Femenino , Humanos , Intolerancia a la Lactosa/microbiología , Intolerancia a la Lactosa/fisiopatología , Persona de Mediana Edad , RifaximinaRESUMEN
BACKGROUND: Rifabutin has been empirically used in Helicobacter pylori infections resistant to triple therapy. There are no data on primary and secondary resistance to rifabutin and its use in specific cases. AIM: To analyse the susceptibility and resistance to rifabutin in H. pylori-positive patients with or without previous H. pylori therapy and to test the efficacy of rifabutin in H. pylori resistant to clarithromycin and tinidazole. METHODS: Four hundred and twenty H. pylori-positive patients without previous exposure to triple therapy and 104 patients who had already received one course of triple therapy underwent upper endoscopy for dyspeptic symptoms and H. pylori susceptibility test. Amoxicillin, clarithromycin, tinidazole and rifabutin were evaluated for resistance and susceptibility. Forty patients with primary resistance to both clarithromycin and tinidazole and with susceptibility to amoxicillin and rifabutin, and 65 patients with secondary resistance and susceptibility to the same antibiotics were identified. All these patients received a 10-day triple therapy with pantoprazole amoxicillin and rifabutin. Treatment success was evaluated by the 13C-Urea Breath test. RESULTS: In naive patients 23% of strains were resistant to clarythromycin, 35% to tinidazole, 9% to both antibiotics, and none was resistant to rifabutin In patients already treated the percentages of resistant strains were 76, 64.4, 62.5 and 1%, respectively. With rifabutin based triple therapy eradication rates were (Per Protocol and Intention-to-Treat analysis) 100 and 87.5% in primary resistance to clarithromycin and tinidazole and 82.2 and 78.5% in secondary resistance. CONCLUSION: H. pylori primary and secondary resistances to clarithromycin and tinidazole are high in our geographic area, while resistance to rifabutin is rare. Rifabutin-based triple therapy, can be successfully used in primary and secondary resistance to clarithromycin and tinidazole according to the in vitro susceptibility test.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Rifabutina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antitricomonas/uso terapéutico , Claritromicina/farmacología , Claritromicina/uso terapéutico , Farmacorresistencia Microbiana , Quimioterapia Combinada , Femenino , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tinidazol/farmacología , Tinidazol/uso terapéuticoRESUMEN
BACKGROUND: Antibiotic resistance of Helicobacter pylori is the most common reason for failure in its eradication. AIM: To determine the incidence of primary and secondary resistance to tinidazole, clarithromycin and amoxycillin in Helicobacter pylori isolates from dyspeptic patients in central Italy and to evaluate the modifications of resistance over the period from 1998 to 2002. METHODS: H. pylori strains were isolated from antral biopsies taken during upper endoscopy in 406 dyspeptic patients with no previous therapy against H. pylori, and in 96 patients who had already undergone one or more triple therapies. Antibiotic susceptibility test was performed using the screening agar method and agar dilution method. RESULTS: Overall primary resistance to tinidazole, clarithromycin and amoxycillin was 36.7, 23.4 and 0.2%, respectively. Secondary resistance rates were: tinidazole 69.8%, clarithromycin 82.3% and amoxycillin 1%. Resistance to clarithromycin was often associated with tinidazole resistance and was significantly higher in female patients (p<0.05). Primary and secondary antibiotic resistance did not change during the 4 years of observation. CONCLUSIONS: The dyspeptic population with H. pylori infection in central Italy shows high levels of antibiotic resistance. Primary resistance to clarithromycin is most frequent in female patients. In patients with secondary resistance, dual resistance to clarithromycin and tinidazole is found in the majority of cases.