48 research outputs found
Intima-media thickness in patients with psoriatic arthritis : a case-control study
No full textFil: Perrotta, F. M. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Scarno, A. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Carboni, A. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Cardini, F. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Montepaone, M. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Lubrano, E. Università del Molise. Dipartimento di Medicina e di Scienze per la Salute; ItaliaFil: Spadaro, A. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; Itali
Clinical and ultrasonography assessment of peripheral enthesitis in ankylosing spondylitis
No full textObjective. The aim of this study was to compare clinical examination with power Doppler US (PDUS) in the detection of entheseal abnormalities in patients with AS. Methods. Thirty-six AS patients underwent clinical and PDUS examination of the following bilateral entheseal sites: common extensor tendon at its insertion at the lateral humeral epicondyle; gluteus tendons at their insertion at the greater trochanter; quadriceps tendon at its insertion at the superior pole of the patella; patellar tendon at its proximal insertion at the inferior pole of the patella; patellar tendon at its distal insertion at the tibial tuberosity; Achilles tendon at its insertion at the calcaneus; and plantar aponeuroses at its insertion at the calcaneus. Results. Clinical and PDUS examination revealed at least one abnormal enthesis in 23 (63.9%) and 35 (97.2%) AS patients, respectively. Furthermore, of 432 entheses examined in our 36 AS patients, 64 (14.8%) were considered abnormal by clinical examination and 192 (44.4%) by PDUS. US abnormalities most commonly found were enthesophytes (31.7%), calcifications (33.7%), thickening (29.8%) and hypoechogenicity (26.6%). We found erosions and PD signals in 9.7 and 6% of examined entheseal sites, respectively. The evidence of entheseal abnormalities by clinical examination has a poor likelihood ratio (LR) for the presence of US abnormalities with vascularization (LR = 1.61), without vascularization (LR = 1.24) or erosions (LR = 1.51) at all sites. Conclusions. PDUS permits detection of structural and inflammatory abnormalities of the enthesis in AS and may complement the physical examination in order to better evaluate enthesitis
Smyd3 open & closed lock mechanism for substrate recruitment: The hinge motion of C-terminal domain inferred from μ-second molecular dynamics simulations
No full textBACKGROUND:
The human lysine methyltransferase Smyd3, a member of the SET and MYND domain containing protein family, harbors methylation activity on both histone and non-histone targets in a tightly regulated manner. The mechanism of how Smyd3 dynamically regulates substrate recognition is still not fully unveiled.
METHODS:
Here, we employed molecular dynamics simulations on full length human Smyd3, performed to a total of 1.2 μ-second, in the presence (holo) and absence (apo) of the S-Adenosyl methionine (AdoMet) cofactor. The dynamical features of Smyd3 in apo and holo states have been examined and compared via examining geometrical and electrostatic properties.
RESULTS:
The results show a distinct dynamics of the C-terminal domain (CTD) in the two states. In the apo state, the CTD undergoes a large hinge like motion and samples more opened configurations, thus acting like a loosened clamp and resulting in expanded substrate binding crevice. In the holo state, the CTD exhibits a restricted motion while the overall structure remains compact, mimicking a closed clamp. This leads to a localized increase in the negative potential at the substrate binding cleft. Further, solvent accessibility of critical residues at the target lysine access channel, important for methylation activity, is increased.
CONCLUSIONS:
We postulate that AdoMet cofactor acts like a key and locks Smyd3 in a closed conformation. In effect, the cofactor binding restricts the elasticity of the CTD, presenting a compact substrate binding cleft with high negative potential, which may have implications on substrate recruitment via long range electrostatics.
GENERAL SIGNIFICANCE:
The deletion of the CTD from Smyd3 has been shown to abolish the basal histone methylation activity. Our study highlights the importance of the CTD elasticity in shaping the substrate binding site for recognition and supports the previously proposed role of the CTD in stabilizing the active site for methylation activity
Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up
No full textFinasteride 1 mg is indicated for the treatment of men with androgenetic alopecia (AGA). However, more than 5 years efficacy and safety has not been previously reported. To assess the efficacy over 10 years in different age groups of men with AGA. 118 men, between 20 and 61 years, with AGA receiving finasteride (1 mg/day), were enrolled in this uncontrolled study. Efficacy evaluation was assessed with standardized global photographs at T0, T1, T2, T5, T10. Statistical analysis was made using frequency tables and evaluating the chi-square index with its p-value. Better improvements are observed in patients older than 30 years (42.8% aged between 20 and 30 years did not improve also after 10 years) or with higher AGA grades (58.9% for AGA grade IV and 45.4% for AGA grade V had the first improvement just after 1 year). In 21% of cases, the treatment continuation beyond 5 years provided better results. Side effects were referred by 6% of the patients; nevertheless, some of them went on with treatment because of the great results. In our opinion, the result after the first year can help in predicting the effectiveness of the treatment. Its efficacy was not reduced as time goes on; in fact, a big proportion of subjects unchanged after 1 year, improved later on, maintaining a positive trend
Activation of liver X receptor up-regulates the expression of the NKG2D ligands MICA and MICB in multiple myeloma through different molecular mechanisms
No full textNK cells have an important role in immunosurveillance of multiple myeloma (MM) progression, and their activity is enhanced by combination therapies able to regulate the expression of specific activating ligands. Liver X receptors (LXRs) are nuclear receptors and important regulators of intracellular cholesterol and lipid homeostasis. Moreover, they have regulatory roles in both cancer and immune response. Indeed, they can regulate inflammation and innate and acquired immunity. Furthermore, LXR activation directly acts in cancer cells (e.g., prostate, breast, melanoma, colon cancer, hepatocarcinoma, glioblastoma, and MM) that show an accumulation of cholesterol and alteration of LXR-mediated metabolic pathways. Here, we investigated the role of LXR and cholesterol on the expression of the NK cell-activating ligands major histocompatibility complex class I chain-related molecule A and B (MICA and MICB) in MM cells. The results shown in this work indicate that MM cells are responsive to LXR activation, which induces changes in the intracellular cholesterol content. These changes correlate with an enhanced expression of MICA and MICB in human MM cell lines and in primary malignant plasma cells, 2 ligands of the NK group 2D receptor (NKG2D)/CD314 activating receptor expressed in cytotoxic lymphocytes, rendering MM cells more sensitive to recognition, degranulation, and killing by NK cells. Mechanistically, we observed that LXR activation regulates MICA and MICB expression at different levels: MICA at the transcriptional level, enhancing mica promoter activity, and MICB by inhibiting its degradation in lysosomes. The present study provides evidence that activation of LXR, by enhancing NKG2D ligand expression, can promote NK cell-mediated cytotoxicity and suggests a novel immune-mediated mechanism involving modulation of intracellular cholesterol levels in cancer cells.-Bilotta, M. T., Abruzzese, M. P., Molfetta, R., Scarno, G., Fionda, C., Zingoni, A., Soriani, A., Garofalo, T., Petrucci, M. T., Ricciardi, M. R., Paolini, R., Santoni, A., Cippitelli, M. Activation of liver X receptor up-regulates the expression of the NKG2D ligands MICA and MICB in multiple myeloma through different molecular mechanisms
Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations with disease activity indices
No full textThe aim of the study was to evaluate atherosclerosis in ankylosing spondylitis (AS) through the assessment of morphological and functional measures of subclinical atherosclerosis. Twenty patients [M/F=12/8, age (median/range) 43.5/28-69 years; disease duration (median/range) 9.7/1-36) years] with AS classified according to modified New York criteria and twenty age and sex related healthy controls with negative past medical history for cardiovascular events were enrolled in the study. In all patients and controls, the intima-media thickness (IMT) of common carotid artery, carotid bulb and internal carotid artery, and the flow-mediated dilatation (FMD) of non-dominant arm brachial artery were determined, using a sonographic probe Esaote GPX (Genoa, Italy). Furthermore, we assess the main disease activity and disability indices [bath ankylosing spondylitis disease activity index, ankylosing spondylitis disease activity score-eritrosedimentation rate (ASDAS-ESR), ASDAS-C-reactive protein (CRP), bath ankylosing spondylitis metrology index, bath ankylosing spondylitis functional index) and acute phase reactants. Plasmatic values of total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and homocysteine were carried out in all twenty patients. IMT at carotid bulb was significant higher in patients than in controls (0.67 mm vs 0.54 mm; P=0.03). FMD did not statistically differ between patients and controls (12.5% vs 15%; P>0.05). We found a correlation between IMT at carotid bulb and ESR (rho 0.43; P=0.04). No correlation was found between FMD and disease activity and disability indices. This study showed that in AS patients, without risk factors for cardiovascular disease, carotid bulb IMT, morphological index of subclinical atherosclerosis, is higher than in controls
Changes, functional disorders, and diseases in the gastrointestinal tract of elderly Cambios, dolencias funcionales y enfermedades en el sistema gastrointestinal en personas mayores
No full textThis article describes changes in the basic digestive functions (motility, secretion, intraluminal digestion, absorption) that occur during aging. Elderly individuals frequently have oropharyngeal muscle dysmotility and altered swallowing of food. Reductions in esophageal peristalsis and lower esophageal sphincter (LES) pressures are also more common in the aged and may cause gastroesophageal reflux. Gastric motility and emptying and small bowel motility are generally normal in elderly subjects, although delayed motility and gastric emptying have been reported in some cases. The propulsive motility of the colon is also decreased, and this alteration is associated with neurological and endocrine-paracrine changes in the colonic wall. Decreased gastric secretions (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently described in the elderly and may lead to gastric ulcer. Exocrine pancreatic secretion is often decreased, as is the bile salt content of bile. These changes represent the underlying mechanisms of symptomatic gastrointestinal dysfunctions in the elderly, such as dysphagia, gastroesophageal reflux disease, primary dyspepsia, irritable bowel syndrome, primary constipation, maldigestion, and reduced absorption of nutrients. Therapeutic management of these conditions is also described. The authors also review the gastrointestinal diseases that are more common in the elderly, such as atrophic gastritis, gastric ulcer, colon diverticulosis, malignant tumors, gallstones, chronic hepatitis, liver cirrhosis, Hepato Cellular Carcinoma (HCC), and chronic pancreatitis.Este artículo describe los cambios en las funciones digestivas básicas (motilidad, secreción, digestión intraluminal, absorción) que ocurren en el envejecimiento. Los individuos ancianos a menudo presentan una dismotilidad de la musculatura orofaríngea y una alteración de la deglución de los alimentos. Las reducciones en el peristaltismo esofágico y de las presiones del esfínter esofágico inferior (EEI) también son más frecuentes en las personas mayores y pueden causar un reflujo gastroesofágico. La motilidad y el vaciamiento gástricos así como la motilidad intestinal son, por lo general, normales en los individuos ancianos, si bien se han notificado en algunos casos una motilidad y vaciamiento gástricos retardados. La motilidad propulsora del colon también está disminuida y esta alteración se asocia con cambios neurológicos y endocrinos-paracrinos de la pared colónica. En el anciano se describen frecuentemente disminución de las secreciones gástricas (ácido, pepsina) y alteración de la barrera mucosa-bicarbonato, lo cual puede favorecer la úlcera gástrica. A menudo la secreción pancreática exocrina está disminuida, así como el contenido en sales biliares de la bilis. Estos cambios representan mecanismos subyacentes de las disfunciones gastrointestinales sintomáticas del anciano tales como disfagia, enfermedad por reflujo gastroesofágico, dispepsia primaria, síndrome del intestino irritable, estreñimiento primario, maladigestión y disminución de la absorción de nutrientes. También se describe el manejo terapéutico de estos trastornos. Los autores también revisan las enfermedades gastrointestinales que son más frecuentes en el anciano, tales como las gastritis atrófica, la úlcera gástrica, la diverticulosis colónica, los tumores malignos, los cálculos biliares, la hepatitis crónica, la cirrosis hepática, el carcinoma hepatocelular (CHC) y la pancreatitis crónica
Assessment of aortic stiffness in endurance athletes by strain Doppler echocardiography
No full textPurpose. Our previous reports showed that the decreased vessel wall radial strain measured by Doppler may be an important supplement to the assessment of the elastic properties of thoracic aorta in various cardiovascular diseases. The aim of this study was to assess the long-term effect of intense endurance training on the elastic properties of the large arteries.
Methods. We studied 25 regularly trained endurance athletes (17 males, mean age 23±7yrs) and 25 age- and sex-matched control subjects (17 males, mean age 22±8yrs). Studies were performed at the resting state. Aortic M-mode and TDI parameters were measured 3 cm above the aortic valve. Aortic distensibility (D), pulse wave velocity (PWV), and aortic stiffness index (SI) were calculated using accepted formulae. Maximum velocity of the first and second systolic wall expansion peaks (S, S1,cm/sec), acceleration time (AT, msec), maximum velocity of early (E, cm/sec) and late (L, cm/sec) diastolic retraction velocity peaks of the ascending aorta and wall peak systolic strain (ps-, %) were determined (EchoPAC, version 9.0, GE Ultrasound).
Results. Higher PWV (9.7±1.8m/s vs 6.9±1.7m/s, p<0.05) and SI (6.6±1.1 vs 4.8±0.9, p<0.01) indicated increased aortic stiffness in athletes. Aortic ps- (8.8±2.5% vs 16.3±4.1%, p<0.005) and D (51±13 m2/N vs 68±16 m2/N, p<0.05) were significantly decreased in athletes group compared with the control group. Athletes had significantly higher systolic and diastolic blood pressure (128±11 vs. 119±14, and 81±8 vs.74±11, p<0.05, respectively) and reduced heart rate (59±9 vs.68±6, p<0.05) compared to controls. Multiple stepwise linear regression analysis in the athletes group revealed that aortic S velocity (β=0.34, p=0.006) and ps- (β=0.41, p=0.008) were the main predictors of aortic distensibility (overall R2 = 0.59).
Conclusions. Our data show that aortic wall velocity and strain assessed by TDI are increased in endurance athletes and suggest reduced arterial wall distensibility
Rapid effectiveness of certolizumab pegol in non-radiographic axial spondyloarthritis
No full textIn axial spondyloarthritis (SpA), the efficacy of certolizumab pegol (CZP), a novel pegylated anti-tumor necrosis factor alpha drug has not been investigated. We report that CZP showed a rapid effectiveness, assessed clinically and by magnetic resonance imaging, in a patient with a non-radiographic axial SpA, classified according to Assessment in SpondyloArthritis International Society (ASAS) criteria. This case suggests that CZP could be considered an useful treatment in non-radiographic axial SpA, supporting that an earlier therapeutic approach could play a relevant role in the management of the disease
