479 research outputs found
The P2X7 Receptor and NLRP3 Axis in Non-Alcoholic Fatty Liver Disease: A Brief Review
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and its prevalence is reaching epidemic characteristics both in adults and in children. The increase of NAFLD prevalence parallels that of obesity, now representing the major cause of liver inflammation, increasing the risk of cirrhosis and hepatocarcinoma. Furthermore, NAFLD is a risk factor for cardiovascular diseases and type 2 diabetes, two of the major leading causes of morbidity and mortality in western countries. Thus a significant amount of studies have dealt with the evaluation of the possible molecular mechanisms leading to NAFLD and its inflammatory consequences within the liver, the non-alcoholic steatohepatitis, and cirrhosis. The inflammasome is a key player in the inflammation and fibrogenic responses in many different tissues, including the liver. The activation of the NLRP3 inflammasome requires the activation by extracellular adenosine tri-phosphate (ATP) of a specific purinergic receptor named P2X7 located in the target cells, although other pathways have been described. To this regard, extracellular ATP acts as an internal danger signal coming from damaged cells participating in the activation of the inflammatory process, a signaling pathway common to many different tissues. Here, we briefly review the involvement of the P2X7 receptor/inflammasome NLRP3 axis in the pathophysiological events leading to NAFLD and its inflammatory and fibrotic evolutions, reporting the possible therapeutical strategies targeting the P2X7 receptor/NLRP3 inflammasome
Lipedema: A Call to Action!
Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage
Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle
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Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster-Randomized FADOI TIAMO Study.
Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP).
Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission).
Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse.
Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality.
Clinical trial registration: ClinicalTrials.gov, identifier NCT05314790
Degeneration and Plasticity of the Optic Pathway in Alström Syndrome.
BACKGROUND AND PURPOSE: Alstrom syndrome is a rare inherited ciliopathy in which early progressive cone-rod dystrophy leads to childhood blindness. We investigated functional and structural changes of the optic pathway in Alstrom syndrome by using MR imaging to provide insight into the underlying pathogenic mechanisms. MATERIALS AND METHODS: Eleven patients with genetically proved Alstrom syndrome (mean age, 23 years; range, 6–45 years; 5 females) and 19 age- and sex-matched controls underwent brain MR imaging. The study protocol included conventional sequences, resting-state functional MR imaging, and diffusion tensor imaging. RESULTS: In patients with Alstrom syndrome, the evaluation of the occipital regions showed the following: 1) diffuse white matter volume decrease while gray matter volume decrease spared the occipital poles (voxel-based morphometry), 2) diffuse fractional anisotropy decrease and radial diffusivity increase while mean and axial diffusivities were normal (tract-based spatial statistics), and 3) reduced connectivity in the medial visual network strikingly sparing the occipital poles (independent component analysis). After we placed seeds in both occipital poles, the seed-based analysis revealed significantly increased connectivity in patients with Alstrom syndrome toward the left frontal operculum, inferior and middle frontal gyri, and the medial portion of both thalami (left seed) and toward the anterior portion of the left insula (right and left seeds). CONCLUSIONS: The protean occipital brain changes in patients with Alstrom syndrome likely reflect the coexistence of diffuse primary myelin derangement, anterograde trans-synaptic degeneration, and complex cortical reorganization affecting the anterior and posterior visual cortex to different degrees
The effect of timing and composition of gestational weight gain in obese pregnant women on infant birth weight: A prospective cohort study.
Introduction: CK2 is a protein kinase implicated in several essential cellular
processes, over-expressed in cancer and described to regulate insulin
signaling cascade. Recently CK2 has been described to negatively regulate
thermogenesis (Shinoda K et al, 2015, Cell Metabolism) and to inhibit
insulin release (Rossi M et al, 2015, PNAS). Nevertheless, the role of CK2
in adipose tissue (AT) and its involvement in human obesity development
and therapy has been poorly investigated.
Methods: Our multi-disciplinary team performed biochemical analysis of
signaling pathways by WB and in vitro kinase activity assays, and glucose
handling studies using glucose uptake assay and IF in adipocyte cultures
and glucose and insulin tolerance test in mice. Moreover we quantify CK2
expression/activity in human AT specimens of 27 obese patients, clinically
characterized, in 12 obese patients underwent relevant weight loss and 11
normal-weight controls.
Results: We proved that CK2 amount and activity were not influenced
by insulin stimulation and that CK2 activity was efficiently inhibited by
specific inhibitors, structurally unrelated. We worked with CX-4945, a
CK2 inhibitor currently used in cancer clinical trials, using the minimal
concentration (2.5 \u192
dM) and pre-treatment time (1hr) able to efficiently
inhibit CK2 activity, avoiding any cytotoxic effect. Pharmacological
inhibition of CK2 did not significantly affect in vitro adipogenic differentiation
or expression profiling of mature adipocytes. Conversely, we
showed that in human and murine adipocytes CK2-inhibition decreases
the insulin-induced glucose uptake by counteracting Akt-signaling and
GLUT4-translocation to the plasma membrane. We compared CK2 expression
and activity in different mouse tissues highlighted that white
skeletal muscle fibres and liver contained the highest quantity of this kinase.
CK2 was expressed more in brown AT than in white AT depots. We
show that CK2 promotes insulin-signaling in mouse AT, liver and skeletal
muscle and that in vivo acute treatment with CX-4945 impairs glucose-
tolerance in mice. Studies in tissues of ob/ob and db/db mice highlights
an up-regulation of CK2 expression and activity only in WAT. CK2
hyper-activation is strongly evident also in SAT and VAT of obese patients
and weight loss obtained by bariatric surgery or hypocaloric diet reverts
CK2 up-regulation to normal level.
Conclusion: We show that CK2 is involved in insulin sensitivity, glucose
handling and remodeling of WAT. Moreover we identify CK2 hyper-activation
as a hallmark of human obesity, suggesting a new potential therapeutic
target for metabolic diseases
The progression from obesity to type 2 diabetes in Alström syndrome.
Rapporten är en studie av åtgärder mot kemiska hälsorisker inom kemisk industri.Rapporten är en studie av åtgärder mot kemiska hälsorisker inom kemisk industri
Minutes to hours after a nuclear event: available radiation poisoning antidotes and practical considerations on possible urgent approaches
The endocanabinnoid system and diabetes - critical analyses of studies conducted with rimonabant
Rimonabant is the first CB1 receptor inhibitor available in the Brazilian market. This new drug has been approved for the treatment of obese or overweight patients associated with cardiovascular risk factors. In this article it is compared the effects of rimonabant treatment in obese patients with cardiovascular risk factors to usual obesity pharmacological treatment
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