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1.
Front Immunol ; 12: 642383, 2021.
Article in English | MEDLINE | ID: mdl-34135888

ABSTRACT

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor.


Subject(s)
Artificial Intelligence , Drug Discovery/methods , Schistosoma/drug effects , Schistosomiasis/drug therapy , Schistosomicides , Animals , Humans
2.
Eur J Obstet Gynecol Reprod Biol ; 235: 97-101, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30287097

ABSTRACT

OBJECTIVE: to compare carbon dioxide and saline solution distension in diagnostic hysteroscopies with regards to patient discomfort and procedural time and in accordance with the instrument diameter (5 mm vs 3.5 mm). The secondary outcome was to evaluate the role of the patient age and the obstetrical history on perception of pain and procedural time. STUDY DESIGN: This is a prospective multicenter randomized study including 1982 patients that underwent office diagnostic hysteroscopy in: Policlinico Abano Terme, Università Cattolica del Sacro Cuore in Rome and Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli" in Acquaviva delle Fonti. They were firstly randomized according to distension medium and secondly according to instrument diameter. Pain perception after the procedure was assessed by VAS (Visual Analogue Scale) score and procedural time was registered. Mann-Whitney U test was used to compare data. RESULTS: Lower pain score and procedural time were recorded with the employment of Carbon Dioxide (p < 001). Patient discomfort and procedural time were significantly influenced by the instrument diameter independent of the distension medium used, though in the subgroup where gas was employed VAS score after 1 min (VAS1) resulted lower compared to saline solution in both the traditional and mini-hysteroscopy procedures (p < 001). CONCLUSION: Carbon dioxide and saline solution are both suitable distension media for outpatient diagnostic hysteroscopy; nonetheless, carbon dioxide confers advantages in terms of pain perception and procedural time.


Subject(s)
Carbon Dioxide/adverse effects , Hysteroscopy/adverse effects , Pain Perception/drug effects , Pain, Procedural/etiology , Saline Solution/adverse effects , Adult , Ambulatory Surgical Procedures/adverse effects , Ambulatory Surgical Procedures/methods , Female , Genital Diseases, Female/diagnosis , Humans , Hysteroscopy/methods , Middle Aged , Operative Time , Pain Measurement , Pain, Procedural/psychology , Patient Satisfaction , Prospective Studies , Time Factors , Treatment Outcome , Young Adult
3.
J Pharm Pharmacol ; 70(8): 1078-1091, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29708588

ABSTRACT

OBJECTIVES: To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. METHODS: Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. KEY FINDINGS: Treatment of CIA mice with HCE 5 mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. CONCLUSIONS: HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/drug therapy , Chenopodium ambrosioides/chemistry , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Bone Density/drug effects , Interleukin-6/blood , Male , Mice, Inbred DBA , Patella/drug effects , Patella/pathology , Plant Extracts/isolation & purification , Tumor Necrosis Factor-alpha/blood
4.
Exp Biol Med (Maywood) ; 242(9): 926-929, 2017 05.
Article in English | MEDLINE | ID: mdl-28440733

ABSTRACT

The aim of this study was to evaluate the effect of intralesional tamoxifen on keloids, particularly on the concentration of fibroblasts, dermal inflammatory infiltrate, and collagen degeneration. A prospective study was carried out to evaluate keloids in 13 patients of both genders pre- and post-treatment with intralesional tamoxifen. Two samples of keloid lesions were obtained by 4-mm punch biopsies during the study: the first at the time of diagnostic confirmation of keloid and the other eight weeks later at the end of intralesional tamoxifen treatment. The biopsy samples were placed in 10% buffered formalin for HE staining and morphological and morphometric study. The degree of collagen fiber reduction and inflammatory infiltration were analyzed. Student's t-test was used for statistical analysis of the mean number of fibroblasts before and following tamoxifen treatment ( P < 0.05). The degree of collagen fiber reduction and inflammatory infiltration were absent before treatment and present in 100% of cases after treatment, while the mean number of fibroblasts was significantly lower after intralesional tamoxifen treatment ( P < 0.0001). We conclude that intralesional administration of tamoxifen promoted an inflammatory stimulus and collagen fiber reduction as well as a significant reduction in the number of fibroblasts that produce collagen. Impact statement Effective treatment of keloid that is a commonly recurrent dermatosis is very difficult, even after standard treatment. Standard treatment consists of partial resection of the lesion (shaving excision), in addition to local corticosteroid injection. Therefore, there is interest in alternative forms of topical treatment, e.g., selective estrogen receptor modulators, particularly tamoxifen has demonstrated in vitro studies to be a promising drug. Nevertheless, there is scarcity of publications on the effects of intralesional tamoxifen on keloids have been found, leading us to the conception of the present study. In this study, tamoxifen has proven to be an interesting alternative drug for the topical treatment of keloid, allowing us to conclude that the intralesional application of tamoxifen in keloids promotes a variable but ever-present inflammatory stimulus, associated with intense reduction of collagen fiber, in addition to a significant decrease in the number of fibroblasts that produce collagen and are involved in disease maintenance.


Subject(s)
Keloid/drug therapy , Keloid/pathology , Selective Estrogen Receptor Modulators/administration & dosage , Tamoxifen/administration & dosage , Biopsy , Collagen/analysis , Female , Fibroblasts/physiology , Humans , Inflammation/pathology , Male , Prospective Studies , Treatment Outcome
5.
J Nurs Care Qual ; 32(2): E11-E19, 2017.
Article in English | MEDLINE | ID: mdl-27270847

ABSTRACT

Hand hygiene has the biggest impact and is the least expensive way to prevent and control health care-associated infections. In this study, we assessed the effectiveness of the multimodal strategy of the World Health Organization to improve health care-associated infection rates, hand hygiene compliance, and the related knowledge of health care professionals in a Brazilian university hospital. We observed the necessity for an alternative approach in hospitals with high staff turnover and low attendance of educational sessions.


Subject(s)
Hand Hygiene/standards , World Health Organization/organization & administration , Academic Medical Centers/standards , Academic Medical Centers/statistics & numerical data , Brazil , Guideline Adherence/standards , Guideline Adherence/statistics & numerical data , Hand Hygiene/statistics & numerical data , Health Personnel/standards , Health Personnel/statistics & numerical data , Humans , Infection Control/standards , Infection Control/statistics & numerical data , Surveys and Questionnaires
6.
Transplant Proc ; 48(2): 380-2, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27109960

ABSTRACT

BACKGROUND: Biliary stones after liver transplantation (LT) rarely occur but a focus on those complications and their treatment is needed. PATIENTS AND METHODS: In total, 390 adult patients who underwent an LT from July 2004 to July 2014 entered the study. Biliary complications and notably biliary stones after LT were identified. RESULTS: In total, 365 LT were analyzed. Biliary stones were identified in 14 patients (3.8%). Predictive factors for the onset of biliary stones after LT were hepatocellular diseases (P = .038; OR = 9.7) and biliary stenosis (P = .000; OR = 11.9). Treatments consisted of percutaneous transhepatic procedures (4 patients), endoscopic retrograde procedures (9 patients), and in open surgery (1 case); in 2 cases, due to a failure of previous treatments, holmium intraductal laser lithotripsy (HILL) was used: the first patient, a 35-year-old woman developed multiple intrahepatic biliary stones after LT. Percutaneous transhepatic cholangiography (PTC) was ineffective and a HILL was performed, clearing the right common bile duct but leaving residual stones in the left duct. The patient underwent a retransplantation due to recurrent hepatitis C virus infection but died 3 months later because of graft failure. The second patient, a 42-year-old 14 years after retransplantation, developed biliary sludge and stones; after several attempts with PTC and endoscopic retrograde cholangiopancreatography, a HILL was performed. All stones except one big one were treated. The patient is alive and well. CONCLUSIONS: When usual treatments are unsuccessful and biliary stones are large, their fragmentation and treatment could be done with HILL, a promising procedure after LT.


Subject(s)
Cholangiography/methods , Cholangiopancreatography, Endoscopic Retrograde/methods , Gallstones/therapy , Lithotripsy, Laser/methods , Liver Transplantation , Adult , Bile Ducts, Intrahepatic , Common Bile Duct , Female , Humans , Lasers, Solid-State , Liver , Male , Reoperation
7.
Curr Med Chem ; 22(33): 3765-88, 2015.
Article in English | MEDLINE | ID: mdl-26264924

ABSTRACT

Senescence is a phenomenon characterized by a progressive decline of body homeostasis. Premature senescence acts when the cellular system is not able to adequately respond to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a state of accelerating aging. Moreover, SGK-1-sensitive ion channels participate in the regulation of renal Na(+)/K(+) regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently, we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia. Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases, and cardiovascular disease, among other age-related diseases. However, to date, the data available on SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target to counteract and prevent aging.


Subject(s)
Aging , Cardiovascular Diseases/enzymology , Immediate-Early Proteins/metabolism , Molecular Targeted Therapy , Neoplasms/enzymology , Neurocognitive Disorders/enzymology , Protein Serine-Threonine Kinases/metabolism , Animals , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Neurocognitive Disorders/drug therapy , Neurocognitive Disorders/metabolism
8.
Cell Death Dis ; 5: e1029, 2014 Jan 30.
Article in English | MEDLINE | ID: mdl-24481443

ABSTRACT

Endothelial dysfunction and impaired autophagic activity have a crucial role in aging-related diseases such as cardiovascular dysfunction and atherosclerosis. We have identified miR-216a as a microRNA that is induced during endothelial aging and, according to the computational analysis, among its targets includes two autophagy-related genes, Beclin1 (BECN1) and ATG5. Therefore, we have evaluated the role of miR-216a as a molecular component involved in the loss of autophagic function during endothelial aging. The inverse correlation between miR-216a and autophagic genes was conserved during human umbilical vein endothelial cells (HUVECs) aging and in vivo models of human atherosclerosis and heart failure. Luciferase experiments indicated BECN1, but not ATG5 as a direct target of miR-216a. HUVECs were transfected in order to modulate miR-216a expression and stimulated with 100 µg/ml oxidized low-density lipoprotein (ox-LDL) to induce a stress repairing autophagic process. We found that in young HUVECs, miR-216a overexpression repressed BECN1 and ATG5 expression and the ox-LDL induced autophagy, as evaluated by microtubule-associated protein 1 light chain 3 (LC3B) analysis and cytofluorimetric assay. Moreover, miR-216a stimulated ox-LDL accumulation and monocyte adhesion in HUVECs. Conversely, inhibition of miR-216a in old HUVECs rescued the ability to induce a protective autophagy in response to ox-LDL stimulus. In conclusion, mir-216a controls ox-LDL induced autophagy in HUVECs by regulating intracellular levels of BECN1 and may have a relevant role in the pathogenesis of cardiovascular disorders and atherosclerosis.


Subject(s)
Atherosclerosis/metabolism , Autophagy , Heart Failure/metabolism , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/metabolism , MicroRNAs/metabolism , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Atherosclerosis/genetics , Atherosclerosis/physiopathology , Autophagy-Related Protein 5 , Beclin-1 , Heart Failure/genetics , Heart Failure/physiopathology , Humans , Lipoproteins, LDL/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , MicroRNAs/genetics , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism
9.
Article in English | WPRIM (Western Pacific) | ID: wpr-626433

ABSTRACT

This study investigated the correlation of 8 domains of psychosocial factors with functional outcome one year after hip fracture surgery. A prospective cohort study of patients who had unilateral hip fracture surgery was included. A total of 89 subjects were interviewed between 3rd to 7th day after the hip surgery using the short length Multi-level Assessment Instrument and followed up after 1 year. The functional outcomes were measured through the Harris Hip Score. All of the psychosocial factors have little to no correlation on the functional recovery of the patient but the cognitive domain had a fair correlation in Harris Hip Score (r=0.46) and is significant (p-value<0.0001). The study did not find strong correlation between psychosocial factors and functional outcome one year after unilateral hip surgery. Although statistics have shown little effect on psychosocial factors to functional outcome, it may still be prudent to consider every aspect that may contribute to the whole wellbeing of our patients, which includes their psychosocial background.


Subject(s)
Psychology
10.
Transplant Proc ; 45(7): 2689-91, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24034025

ABSTRACT

Liver transplantation (LT) in patients with hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber, disease is a problematic procedure. In patients with hepatic involvement due to clinically significant arterovenous malformations, there is high risk of intraoperative bleeding and intra- or perioperative complications. Some surgical corrections have been proposed for venous problems, concerning the vena caval anastomosis. A common finding in HHT is arterial enlargement of the celiac trunk and of the common hepatic artery. We report 2 cases of LT in HHT where the arterial anastomosis was successfully performed using the splenic artery of the recipient, which shows less tendency for enlargement than the celiac trunk.


Subject(s)
Anastomosis, Surgical , Arteries/surgery , Liver Transplantation , Telangiectasia, Hereditary Hemorrhagic/surgery , Adult , Female , Humans , Middle Aged , Tomography, X-Ray Computed
11.
Oncogene ; 32(35): 4110-9, 2013 Aug 29.
Article in English | MEDLINE | ID: mdl-23027131

ABSTRACT

Aberrant motility and invasive ability are relevant hallmarks of malignant tumor cells. Pathways regulating the movement of cancer cells from the site of primary tumor toward adjacent and/or distant tissues are not entirely defined. By using a model of malignant transformation induced by Ras, we identified Wnt4 as an early target of Ras oncogenic signaling. Here we show that Wnt4 is repressed by Ras and that forced Wnt4 expression inhibits Ras-induced cell motility. Accordingly, we found that Wnt4 is downregulated in human anaplastic thyroid carcinomas, the most malignant and metastatic thyroid cancer histotype. Wnt4 interferes with Ras-induced actin cytoskeleton reorganization through non-canonical pathways, by altering the balance between the activation of different Rho-family small guanosine triphosphatases (GTPases). Finally, we demonstrate that Wnt4 is post-transcriptionally repressed by miR-24, a Ras-induced micro RNA (miRNA) targeting the 3'-untranslated region (UTR) of Wnt4. Taken together our data highlight a novel Ras-regulated miRNA-dependent circuitry regulating the motile phenotype of cancer cells.


Subject(s)
Cell Movement , Cell Transformation, Neoplastic , Genes, ras , Thyroid Gland/pathology , Wnt4 Protein/physiology , Animals , Cytoskeleton/chemistry , Humans , Phosphatidylinositol 3-Kinases/physiology , Rats , Thyroid Neoplasms/pathology
12.
Malays Orthop J ; 7(2): 29-33, 2013 Jul.
Article in English | MEDLINE | ID: mdl-25722823

ABSTRACT

BACKGROUND: Vacuum Assisted Closure (VAC) is an established method that can be used in order to cover for soft tissue defects. This study focuses on the use of a modified suction machine in the form of an aquarium pump as an economical substitute for the VAC dressing. The improvised suction apparatus was a regular aquarium pump, which was altered in order to draw air in instead of expelling it. The patients were followed-up for a period of three weeks in the wards. METHODS: VAC was applied over the soft tissue defects. Sterilized foam was used and attached to a French 16 suction tube. A tight seal was ensured using a sterile adhesive covering. The tube was then attached to the modified vacuum machine, which maintained the negative pressure. Case Studies : Three cases are presented in this study. The first and second cases involved pediatric patients who sustained degloving injuries of the foot. The third case involved a 23 year-old male who sustained an open patellar fracture due to a motorcycle accident. The dressing was changed every five days and the progress was documented using photographs. The patients were placed on VAC dressing for a period of two weeks. On the 14th day, good granulation was evident on the soft tissue defects hence; the patients were scheduled and subsequently underwent splitthickness skin grafting. Discussion : The modified suction pump is an effective and economical alternative to the VAC machine for the purpose of providing constant negative pressure to promote tissue granulation and healing for large tissue defects. However, in order to establish the efficacy of the proposed intervention, the modified suction pump should be tested on more cases. KEY WORDS: Vacuum-assisted Closure (VAC) System, modified VAC, aquarium pump, soft tissue defect coverage, alternative negative pressure source.

13.
Phys Rev Lett ; 108(5): 057002, 2012 Feb 03.
Article in English | MEDLINE | ID: mdl-22400953

ABSTRACT

We report the characterization of a two-qubit processor implemented with two capacitively coupled tunable superconducting qubits of the transmon type, each qubit having its own nondestructive single-shot readout. The fixed capacitive coupling yields the sqrt[iSWAP] two-qubit gate for a suitable interaction time. We reconstruct by state tomography the coherent dynamics of the two-bit register as a function of the interaction time, observe a violation of the Bell inequality by 22 standard deviations after correcting readout errors, and measure by quantum process tomography a gate fidelity of 90%.

14.
Radiol Med ; 117(3): 426-44, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22228124

ABSTRACT

PURPOSE: This study was done to investigate the efficacy and safety of percutaneous renal denervation with the Symplicity catheter for reducing blood pressure in patients with essential hypertension resistant to medical therapy (systolic blood pressure >160 mmHg despite the use of three or more antihypertensive drugs, including a diuretic). MATERIALS AND METHODS: In September 2010, five patients affected by essential hypertension resistant to medical therapy were treated. All patients were studied by computed tomography angiography (CTA) of the renal arteries before the procedure and underwent follow-up at 30 and 60 days with colour Doppler ultrasound (CDUS) with evaluation of resistive index, glomerular filtration rate (GFR), 24-h blood pressure and serum catecholamine concentration. Student's t test was used to assess the effectiveness of the procedure in lowering blood pressure. RESULTS: In treated patients, mean blood pressure at baseline was 171/100 mmHg [standard deviation (SD) ± 8/10]; mean GFR was 91.6 ml/min/1.73 m(2) (SD ± 15). Blood pressure after the procedure was reduced by -18/-5 and -13/-10 mmHg at 30 and 60 days, respectively, with a mean medication reduction of 3.6. No complications occurred during the intra- or periprocedural period or during short-term follow-up. CONCLUSIONS: The Symplicity system proved to be efficacious and without serious adverse events in reducing blood pressure and antihypertensive medication use in patients affected by essential hypertension resistant to medical therapy. Although encouraging, our data are preliminary and need to be validated by larger prospective randomised studies.


Subject(s)
Catheter Ablation/methods , Denervation/methods , Endovascular Procedures/methods , Hypertension/surgery , Kidney/innervation , Blood Pressure , Drug Resistance , Humans , Hypertension/drug therapy
15.
Nutr Metab Cardiovasc Dis ; 22(7): 561-6, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21944738

ABSTRACT

BACKGROUND AND AIMS: The American Diabetes Association (ADA) has revised criteria for diagnosis of type 2 diabetes recommending an A1C cut point of ≥6.5% in addition to criteria based on glucose levels. We compared A1C, fasting plasma glucose (FPG) or 2-h post-challenge glucose (2-hPG) criteria for the diagnosis of diabetes in a cohort of Italian Caucasians. METHODS AND RESULTS: A total of 1019 individuals without known diabetes completed an oral glucose tolerance test (OGTT) and had A1C measured. Moderate agreement existed for A1C and FPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.522), with 85.5% of individuals classified as not having diabetes by both A1C and FPG criteria, and 5.8% classified as having diabetes by both A1C and FPG criteria. Discordant classifications occurred for 5.5% of individuals who had an A1C ≥ 6.5% and FPG <126 mg dl(-1), and for 3.2% who had an A1C <6.5% and FPG ≥126 mg dl(-1). Modest agreement existed for A1C and 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.427), with 81.8% of individuals classified as not having diabetes by both A1C and 2-hPG criteria, and 6.0% classified as having diabetes by both A1C and 2-hPG criteria. The area under the receiver operating characteristic curve of A1C for identifying subjects with diabetes according to FPG or 2-hPG criteria was 0.856 and 0.794, respectively. Modest agreement existed for A1C and FPG and/or 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.446). CONCLUSIONS: A1C ≥ 6.5% demonstrates a moderate agreement with fasting glucose and 2-hPG for diagnosing diabetes among adult Italian Caucasians subjects.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/diagnosis , Glycated Hemoglobin/analysis , White People , Adult , Chromatography, High Pressure Liquid , Cohort Studies , Diabetes Mellitus, Type 2/blood , Fasting , Female , Glucose Tolerance Test , Humans , Italy/epidemiology , Male , Middle Aged , ROC Curve , Risk Factors
16.
Oncogene ; 30(3): 275-86, 2011 Jan 20.
Article in English | MEDLINE | ID: mdl-20956945

ABSTRACT

miR-21 is a microRNA (miRNA) frequently overexpressed in human cancers. Here we show that miR-21 is upregulated both in vitro and in vivo by oncogenic Ras, thus linking this miRNA to one of the most frequently activated oncogenes in human cancers. Ras regulation of miR-21 occurs with a delayed kinetic and requires at least two Ras downstream pathways. A screen of human thyroid cancers and non-small-cell lung cancers for the expression of miR-21 reveals that it is overexpressed mainly in anaplastic thyroid carcinomas, the most aggressive form of thyroid cancer, whereas in lung its overexpression appears to be inversely correlated with tumor progression. We also show that a LNA directed against miR-21 slows down tumor growth in mice. Consistently, a search for mRNAs downregulated by miR-21 shows an enrichment for mRNAs encoding cell cycle checkpoints regulators, suggesting an important role for miR-21 in oncogenic Ras-induced cell proliferation.


Subject(s)
Cell Division/physiology , MicroRNAs/physiology , Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/physiology , Up-Regulation/physiology , Animals , Cell Line, Tumor , Cell Transformation, Neoplastic , DNA Damage , Gene Knockdown Techniques , Humans , Mice , MicroRNAs/genetics
17.
Transplant Proc ; 42(4): 1240-3, 2010 May.
Article in English | MEDLINE | ID: mdl-20534271

ABSTRACT

To expand the donor pool, split-liver transplantation has been implemented in recent years. In the classic technique, the arterial axis with the artery for segment 4 (S4) coming from the left hepatic artery (HA) is included with the right graft. To give a surgical advantage to pediatric recipients in our center, the left HA, the common HA, and the celiac trunk are generally retained with the left liver. Thus the artery for S4 is sacrificed. We compared the outcomes of S4 in 290 whole grafts (WG; group A) with 28 right in situ split-liver grafts (SSLG; group B), which were transplanted over the past 10 years (January 1999-December 2009). The rates of major biliary and of hemorrhagic complications were similar. In most of cases (16/24, 66%) S4, on computerized tomographic scan appeared to show signs of hypoperfusion, sometimes with a peripheral aspect of hyperperfusion in the arterial phase. S1 showed signs of hypoperfusion in only 2 cases. A biliary collection near the resection line present in 8 cases was treated in 6 of them with percutaneous drainage and in 2 with laparotomy. These complications did not influence graft or patient survival. Graft survivals at 1, 5, and 10 years for WG and SSLG were not different among the groups: 85%, 74%, and 66% vs 89%, 79%, and 63%, respectively (P = .8). Although our technique cannot be considered to be anatomically correct, the ischemia of S4 did not influence the outcome. The rate of retransplantations for hepatic artery thrombosis was 17.9% in RSSG and 3.4% in WG (P = .001), which was probably due at least in part to the insertion of interposition grafts.


Subject(s)
Hepatectomy/methods , Liver Transplantation/physiology , Liver/anatomy & histology , Adult , Aged , Female , Graft Survival , Hepatic Artery/pathology , Hepatic Artery/transplantation , Humans , Intraoperative Complications/epidemiology , Liver/blood supply , Liver Transplantation/methods , Liver Transplantation/mortality , Liver Transplantation/pathology , Magnetic Resonance Spectroscopy , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Survival Rate , Survivors , Tissue Donors , Tomography, X-Ray Computed , Treatment Outcome
18.
Transplant Proc ; 42(4): 1369-74, 2010 May.
Article in English | MEDLINE | ID: mdl-20534305

ABSTRACT

Portal vein arterialization (PVA) is a salvage procedure for insufficient hepatic arterial or portal vascularization. It plays a role in auxiliary and orthotopic liver transplantation (OLT). In OLT, current indications for PVA include hepatic artery thrombosis (HAT), pre-OLT or post-OLT extended splanchnic vein thrombosis, intraoperative low portal flow, and anatomic variations like the absence of portal and mesenteric veins. Out of the transplantation domain, PVA is used both in extensive surgery for malignancies of the liver, biliary tract, and pancreas and in the treatment of fulminant hepatic failure (FHF) due to intoxications. We describe a case of acute post-OLT HAT successfully treated with PVA as a short bridge to retransplantation. By Doppler ultrasound of clinical PVA we detected an increased intrahepatic portal flow velocity, with disappearance of the arterial spikes, a finding that needs further investigation. PVA represents a rare surgical procedure. In fact, it has been used most of all in urgent conditions or in case of abrupt vascular complications during surgery. According to the literature, PVA emerges as a salvage procedure for poor arterial or portal hepatic flow, both in OLT and in general abdominal surgery. The outcome of this procedure is unpredictable. The aim of the shunt is to gain time, awaiting the onset of collateral arterial vessels or the performance of definitive surgery. Its early thrombosis may be a catastrophic event, due to acute liver ischemia. In contrast, a late occlusion is often well tolerated. Strict surveillance is always useful because sometimes it is mandatory to embolize the arterioportal fistula to treat or to prevent the onset of portal hypertension.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatic Artery/pathology , Liver Neoplasms/surgery , Liver Transplantation/methods , Portal Vein/surgery , Thrombosis/pathology , Blood Flow Velocity , Hepatic Artery/surgery , Humans , Liver Transplantation/adverse effects , Liver Transplantation/diagnostic imaging , Male , Middle Aged , Portal Vein/diagnostic imaging , Reoperation , Treatment Outcome , Ultrasonography
19.
J Thromb Haemost ; 8(4): 828-37, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20088941

ABSTRACT

BACKGROUND: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. OBJECTIVES: To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients. METHODS: Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE). RESULTS: Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001). CONCLUSIONS: Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.


Subject(s)
Acarbose/therapeutic use , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Hyperglycemia/blood , Hyperglycemia/drug therapy , Hypoglycemic Agents/therapeutic use , Platelet Activation/drug effects , Aged , Arginine/analogs & derivatives , Arginine/blood , Biomarkers/blood , Biomarkers/urine , C-Reactive Protein/metabolism , CD40 Ligand/blood , Diabetes Mellitus, Type 2/urine , Dinoprost/analogs & derivatives , Dinoprost/urine , Double-Blind Method , Enzyme Inhibitors/therapeutic use , Female , Glycated Hemoglobin/metabolism , Glycoside Hydrolase Inhibitors , Humans , Hyperglycemia/urine , Italy , Lipid Peroxidation/drug effects , Male , Middle Aged , P-Selectin/blood , Postprandial Period , Thromboxane B2/analogs & derivatives , Thromboxane B2/urine , Time Factors , Treatment Outcome
20.
G Ital Nefrol ; 26 Suppl 46: 71-8, 2009.
Article in Italian | MEDLINE | ID: mdl-19644822

ABSTRACT

Numerous studies have shown a marked increase in the incidence of diabetes mellitus worldwide. Diabetes mellitus is currently considered equivalent to coronary artery disease in terms of prognostic risk stratification, and its high prevalence makes this clinical condition the first cause of end-stage renal disease requiring chronic hemodialysis or kidney transplant. Even if chronic kidney disease remains the ''Cinderella of the cardiovascular profile'', the presence of microalbuminuria is closely related to a high risk of development of coronary artery disease. The same risk factors that impair heart function are also harmful to the kidney, and the common pathophysiological features of the two systems are at the origin of a new subspecialty, cardionephrology. A crucial task of cardiologists and nephrologists is the early identification of high risk patients with concurrent cardiovascular and kidney disease. The utilization of simple screening methods such as assessment of microalbuminuria and glomerular filtration rate by family doctors may help in establishing prevention strategies directed towards cardiovascular risk and progression of kidney disease. In conclusion, early stratification of cardiovascular risk, coupled with primary prevention strategies aimed at the general population, is warranted to obtain a significant reduction of kidney and cardiovascular disease and of the need for chronic hemodialysis treatment. This strategy is safe and cost-effective in comparison with the costs of chronic dialysis of patients affected by chronic kidney disease.


Subject(s)
Cardiovascular Diseases/complications , Diabetes Complications/complications , Kidney Diseases/complications , Albuminuria/complications , Humans , Hyperglycemia/complications , Hyperglycemia/drug therapy , Prognosis , Severity of Illness Index
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