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1.
NeuroRehabilitation ; 46(3): 321-331, 2020.
Article in English | MEDLINE | ID: mdl-32250333

ABSTRACT

BACKGROUND: An intensive task-oriented circuit training (TOCT) provides a valid approach in improving motor function in Multiple Sclerosis (MS). OBJECTIVE: We aimed at testing the efficacy of TOCT on gait kinematics in MS patients with mild-moderate disability. METHODS: Nineteen MS patients able of independent walking performed 3-D Gait Analysis before (T0) and after (T1) a two-week TOCT program. Patients were clustered in two different subgroups, according to clinical neurological impairments assessed with specific functional system of Expanded Disability Status Scale (EDSS): pyramidal (Group 1) and cerebellar (Group 2) subjects. Spatio-temporal and kinematic data were compared before and after the TOCT intervention in the total sample of patients and in the two selected subgroups at two time intervals. RESULTS: Data obtained revealed increased dynamic ROM at knee joint after training in the whole study sample. Of note, knee dynamic excursion improved significantly in Group 1 but not in Group 2 patients after TOCT. Moreover, sagittal plane kinematics revealed significant modifications on knee and ankle biomechanics in Group 1 after rehabilitation. CONCLUSIONS: These data point out the benefits of the task specific training on gait dynamics in mild impaired MS subjects, linking to treatment opportunity in patients with a prevalent pyramidal impairment.


Subject(s)
Circuit-Based Exercise/methods , Exercise Therapy/methods , Gait/physiology , Multiple Sclerosis , Biomechanical Phenomena/physiology , Gait Analysis , Humans , Multiple Sclerosis/physiopathology , Multiple Sclerosis/rehabilitation
5.
Eur Rev Med Pharmacol Sci ; 21(22): 5247-5257, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29228441

ABSTRACT

OBJECTIVE: Hair loss generates severe psychosocial implications. To date, exploring the prognostic factors of possible clinical benefit of autologous blood concentrate platelet rich plasma (PRP) was failed. The aim of our pilot study was to explore the correlation between the individual inflammation genetic profile and PRP efficacy in the treatment of hair follicle regeneration. PATIENTS AND METHODS: 41 volunteers (25 men, 16 women) took part in this retrospective study. All the patients were scheduled for 4 sessions of PRP application with intervals of 40-60 days. All the patients were checked up at 6 weekly intervals for 6 months and, then, at the end of the first year. A panel of 5 polymorphisms on 4 genes (IL-1a, IL-1b, IL-6, and IL-10) implicated in the individual genetic inflammation profile were performed. RESULTS: A significant increase rate in hair density was noticed after the third month of treatment in 32/41 (78%) of the subjects. We found an interesting association between the pro-inflammatory cytokine IL-1α polymorphism C>A (rs17561) and responders to PRP treatment. The cases carrying C/C genotype (coding for Ser114) were 21 (66%) in responders and only 2 (22%) in non-responders (p<0.05). In addition, about IL-1a, the frequency of G/G genotype in responder patients was over two times lower in responder (31%) than in non-responder patients (78%). CONCLUSIONS: Our pilot study demonstrated a correlation between the individual genetic inflammatory profile and the efficacy of the PRP treatment in males. On the contrary, in females, it showed a negative correlation. IL-1a could be used as a prognostic value for PRP efficacy. Also, these results provide preliminary evidence that may encourage the design of controlled clinical trials to properly test this modus operandi on a large number of subjects.


Subject(s)
Hair Follicle/drug effects , Inflammation/genetics , Interleukin-1alpha/genetics , Platelet-Rich Plasma , Adolescent , Adult , Aged , Female , Genotype , Hair/growth & development , Humans , Male , Middle Aged , Pilot Projects , Polymorphism, Single Nucleotide , Prognosis , Regeneration/drug effects , Retrospective Studies , Sex Characteristics , Young Adult
6.
Gait Posture ; 57: 130-135, 2017 09.
Article in English | MEDLINE | ID: mdl-28623760

ABSTRACT

This is an observational cross-sectional study evaluating gait dynamics in patients with Parkinson's Disease (PD) and severe postural deformities, PD without axial deviations and healthy subjects. Ten PS individuals with Pisa syndrome (PS) and nine subjects with Camptocormia (CC) performed 3-D Gait Analysis and were evaluated with walking and balance scales. Correlations with clinical and functional scales were investigated. Spatio-temporal and kinematic data were compared to ten PD subjects without postural deformities (PP) and ten healthy matched individuals (CG). Data obtained showed decreased walking velocity, stride and step length in PP, PS and CC groups compared to controls. The correlation analysis showed that stride and step length were associated with reduced functional abilities and disease severity in PS and CC groups. Kinematic data revealed marked reduction in range of movements (ROMs) at all lower-extremity joints in PS group. While, in CC group the main differences were pronounced in hip and knee joints. PS and CC groups presented a more pronounced reduction in hip articular excursion compared to PP subjects, revealing an increased hip flexion pattern during gait cycle. Moreover, the increased hip and knee flexion pattern adversely affected functional performance during walking tests. Results obtained provide evidence that step length, along with stride length, can be proposed as simple and clear indicators of disease severity and reduced functional abilities. The reduction of ROMs at hip joint represented an important mechanism contributing to decreased walking velocity, balance impairment and reduced gait performance in PD patients with postural deformities.


Subject(s)
Disability Evaluation , Gait/physiology , Hip Joint/physiopathology , Muscular Atrophy, Spinal/physiopathology , Postural Balance/physiology , Spinal Curvatures/physiopathology , Walking/physiology , Aged , Aged, 80 and over , Biomechanical Phenomena , Cross-Sectional Studies , Disabled Persons/rehabilitation , Female , Humans , Male , Middle Aged , Muscular Atrophy, Spinal/rehabilitation , Parkinson Disease/physiopathology , Parkinson Disease/rehabilitation , Spinal Curvatures/rehabilitation , Syndrome
7.
Eur Rev Med Pharmacol Sci ; 19(22): 4443-54, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26636535

ABSTRACT

OBJECTIVE: Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy. MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1). RESULTS: The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy. CONCLUSIONS: Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Fluorouracil/administration & dosage , Organoplatinum Compounds/administration & dosage , Pharmacogenetics/methods , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Genotype , Humans , Oxaliplatin , Polymorphism, Genetic/genetics , Predictive Value of Tests
8.
Eur Rev Med Pharmacol Sci ; 19(24): 4801-10, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26744872

ABSTRACT

OBJECTIVE: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma (NHL) featured by participation of the lymph nodes, spleen, blood and bone marrow with a short remission period to standard therapies and a median overall survival of 4-5 years. PATIENTS AND METHODS: In this study, we compare the levels of bcl-1/JH fusion products detected by q-PCR in the concurrent peripheral blood (PB) and bone marrow (BM) aspirate samples from 7 patients with MCL. RESULTS: In patients with moderate to high levels of bcl-1/JH copies, the results of q-PCR analysis of PB and BM aspirate samples correlate well. In patients with high levels of bcl-1/JH copies, instead, PB levels are a good indication of tumor burden. Finally, in patients with low levels of bcl-1/JH copies, the t(11;14) may be detected by identification of neoplastic cells. CONCLUSIONS: Our data suggest that PB can be reliably used in place of BM aspirate both for detection of translocation status during minimal residual disease monitoring and for a possible molecular relapse, especially in those patients who have moderate to high levels of bcl-1/JH copies. If these results will be confirmed on a wider number of MCL patients, future study will be required to address the issue.


Subject(s)
Genes, bcl-1 , Lymphoma, Mantle-Cell/genetics , Bone Marrow/pathology , Bone Marrow Cells , Bone Marrow Transplantation , Genes, bcl-1/genetics , Humans , Lymphoma, Mantle-Cell/blood , Neoplasm Recurrence, Local , Real-Time Polymerase Chain Reaction , Remission Induction , Translocation, Genetic
9.
NeuroRehabilitation ; 36(1): 93-9, 2015.
Article in English | MEDLINE | ID: mdl-25547770

ABSTRACT

BACKGROUND: Gait impairment, balance problems and falls have a negative impact on independence in ADL and quality of life of patients affected by Hereditary Spastic Paraplegia (HSP). Since no pharmacological options are available, treatments rely mostly on rehabilitation therapy, although almost no data on this topic exist. Given the demonstrated effectiveness of robotics in improving gait and balance in various neurological diseases, aim of this study is to test the effectiveness of a robotic-aided program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP. METHODS: Thirteen patients affected by uncomplicated HSP were subjected to a six-week robotic-aided gait training protocol. Participants underwent a battery of 3 walking test, 1 balance test and 2 quality of life questionnaires. RESULTS: At the end of the treatment a significant improvement of balance, walking ability and quality of life was observed in almost all the tests. The improvements were maintained over a two-month follow-up period. CONCLUSIONS: Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease.


Subject(s)
Exercise Therapy/methods , Gait/physiology , Motor Skills/physiology , Postural Balance/physiology , Quality of Life , Robotics/instrumentation , Spastic Paraplegia, Hereditary/rehabilitation , Walking/physiology , Adult , Exercise Therapy/instrumentation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Treatment Outcome
10.
Cell Death Dis ; 5: e1223, 2014 May 08.
Article in English | MEDLINE | ID: mdl-24810059

ABSTRACT

Glioblastoma (GBM) is the most common and deadly adult brain tumor. Despite aggressive surgery, radiation, and chemotherapy, the life expectancy of patients diagnosed with GBM is ∼14 months. The extremely aggressive nature of GBM results from glioblastoma stem-like cells (GSCs) that sustain GBM growth, survive intensive chemotherapy, and give rise to tumor recurrence. There is accumulating evidence revealing that GSC resilience is because of concomitant activation of multiple survival pathways. In order to decode the signal transduction networks responsible for the malignant properties of GSCs, we analyzed a collection of GSC lines using a dual, but complementary, experimental approach, that is, reverse-phase protein microarrays (RPPMs) and kinase inhibitor library screening. We treated GSCs in vitro with clinically relevant concentrations of temozolomide (TMZ) and performed RPPM to detect changes in phosphorylation patterns that could be associated with resistance. In addition, we screened GSCs in vitro with a library of protein and lipid kinase inhibitors to identify specific targets involved in GSC survival and proliferation. We show that GSCs are relatively insensitive to TMZ treatment in terms of pathway activation and, although displaying heterogeneous individual phospho-proteomic profiles, most GSCs are resistant to specific inhibition of the major signaling pathways involved in cell survival and proliferation. However, simultaneous multipathway inhibition by the staurosporin derivative UCN-01 results in remarkable inhibition of GSC growth in vitro. The activity of UCN-01 on GSCs was confirmed in two in vivo models of GBM growth. Finally, we used RPPM to study the molecular and functional effects of UCN-01 and demonstrated that the sensitivity to UCN-01 correlates with activation of survival signals mediated by PDK1 and the DNA damage response initiated by CHK1. Taken together, our results suggest that a combined inhibition of PDK1 and CHK1 represents a potentially effective therapeutic approach to reduce the growth of human GBM.


Subject(s)
Antineoplastic Agents/pharmacology , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Neoplastic Stem Cells/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/antagonists & inhibitors , Animals , Brain Neoplasms/enzymology , Brain Neoplasms/pathology , Cell Death/drug effects , Cell Line, Tumor , Checkpoint Kinase 1 , Dacarbazine/analogs & derivatives , Dacarbazine/pharmacology , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Glioblastoma/enzymology , Glioblastoma/pathology , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Molecular Targeted Therapy , Neoplastic Stem Cells/enzymology , Neoplastic Stem Cells/pathology , Protein Array Analysis , Protein Serine-Threonine Kinases/metabolism , Proteomics/methods , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Signal Transduction/drug effects , Small Molecule Libraries , Staurosporine/analogs & derivatives , Staurosporine/pharmacology , Temozolomide , Time Factors , Tumor Burden/drug effects , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
11.
Oncogene ; 32(40): 4806-13, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23128394

ABSTRACT

MicroRNAs (miRNAs) from the gene cluster miR-143-145 are diminished in cells of colorectal tumor origin when compared with normal colon epithelia. Until now, no report has addressed the coordinate action of these miRNAs in colorectal cancer (CRC). In this study, we performed a comprehensive molecular and functional analysis of the miRNA cluster regulatory network. First, we evaluated proliferation, migration, anchorage-independent growth and chemoresistance in the colon tumor cell lines after miR-143 and miR-145 restoration. Then, we assessed the contribution of single genes targeted by miR-143 and miR-145 by reinforcing their expression and checking functional recovery. Restoring miR-143 and miR-145 in colon cancer cells decreases proliferation, migration and chemoresistance. We identified cluster of differentiation 44 (CD44), Kruppel-like factor 5 (KLF5), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) as proteins targeted by miR-143 and miR-145. Their re-expression can partially revert a decrease in transformation properties caused by the overexpression of miR-143 and miR-145. In addition, we determined a set of mRNAs that are diminished after reinforcing miR-143 and miR-145 expression. The whole transcriptome analysis ascertained that downregulated transcripts are enriched in predicted target genes in a statistically significant manner. A number of additional genes, whose expression decreases as a direct or indirect consequence of miR-143 and miR-145, reveals a complex regulatory network that affects cell signaling pathways involved in transformation. In conclusion, we identified a coordinated program of gene repression by miR-143 and miR-145, in CRC, where either of the two miRNAs share a target transcript, or where the target transcripts share a common signaling pathway. Major mediators of the oncosuppression by miR-143 and miR-145 are genes belonging to the growth factor receptor-mitogen-activated protein kinase network and to the p53 signaling pathway.


Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/physiology , Oncogenes , Animals , Cell Division/genetics , Cell Line, Tumor , Colorectal Neoplasms/pathology , Gene Regulatory Networks , Humans , Mice , Real-Time Polymerase Chain Reaction , Transcriptome , Xenograft Model Antitumor Assays
12.
Cell Death Differ ; 19(10): 1644-54, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22539003

ABSTRACT

Glioblastoma multiforme (GBM) is among the most aggressive tumor types and is essentially an incurable malignancy characterized by resistance to chemo-, radio-, and immunotherapy. GBM is maintained by a hierarchical cell organization that includes stem-like, precursor, and differentiated cells. Recurrence and maintenance of the tumor is attributed to a small population of undifferentiated tumor-initiating cells, defined as glioblastoma stem-like cells (GSLCs). This cellular hierarchy offers a potential treatment to induce differentiation of GSLCs away from tumor initiation to a more benign phenotype or to a cell type more amenable to standard therapies. Bone morphogenetic proteins (BMPs), members of the TGF-ß superfamily, have numerous biological activities including control of growth and differentiation. In vitro, a BMP7 variant (BMP7v) decreased primary human GSLC proliferation, endothelial cord formation, and stem cell marker expression while enhancing neuronal and astrocyte differentiation marker expression. In subcutaneous and orthotopic GSLC xenografts, which closely reproduce the human disease, BMP7v decreased tumor growth and stem cell marker expression, while enhancing astrocyte and neuronal differentiation compared with control mice. In addition, BMP7v reduced brain invasion, angiogenesis, and associated mortality in the orthotopic model. Inducing differentiation of GSLCs and inhibiting angiogenesis with BMP7v provides a potentially powerful and novel approach to the treatment of GBM.


Subject(s)
Bone Morphogenetic Protein 7/pharmacology , Neoplastic Stem Cells/metabolism , Animals , Bone Morphogenetic Protein 7/genetics , Bone Morphogenetic Protein 7/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cytokines/metabolism , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , HCT116 Cells , Humans , Mice , Neoplastic Stem Cells/drug effects , Neovascularization, Pathologic , Transplantation, Heterologous
13.
Eur J Paediatr Dent ; 9(2): 88-92, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18605891

ABSTRACT

AIM: The aim of the study was to compare two methods of treatment for aggressive periodontitis: traditional surgical and Nd:YAG laser, evaluating their possible objective clinical advantages. MATERIALS AND METHODS: A total of 36 hemiarches of 18 patients were analysed, 10 males and 8 females of average age of 14, selected according to predefined criteria. Overall we examined 70 radicular surfaces (sites) of 50 teeth. Each hemiarch to treat was randomly assigned to one of two treatment groups. RESULTS AND CONCLUSION: The results, analysed using the Friedman's test, showed a clinically appreciable validity both for the surgical and the laser treatment, while the Wilcoxon signed-rank test didn't highlight any statistically significant difference between the two types of treatment. The laser itself appears as a valid alternative to conventional therapy, in relation to the young age of the patients and for individuals at increased anaesthesiological risk and/or with coagulation and platelet function disorders.


Subject(s)
Aggressive Periodontitis/surgery , Lasers, Solid-State/therapeutic use , Oral Surgical Procedures/instrumentation , Acute Disease , Adolescent , Alveolar Bone Loss/surgery , Female , Humans , Male , Periodontal Index , Statistics, Nonparametric
14.
Oral Implantol (Rome) ; 1(1): 43-8, 2008 Apr.
Article in English | MEDLINE | ID: mdl-23285335

ABSTRACT

OBJECTIVES: This study evaluates the in vitro antimicrobial efficacy, of an absorbable suture coated with triclosan (Vicryl Plus(®)) against two bacteria, potential responsible for the development of oral diseases: Pseudomonas aeruginosa and Streptococcus mutans. METHODS: Vicryl Plus 3-0 and Vicryl 3-0 were tested for their efficiency against P. aeruginosa and S. Mutans. 27 segments 10 cm long each, of every suture, have been tested against P. Aeruginosa and S. Mutans respectively. Every sample has been dipped in a broth culture containing pure dried stocks of P. aeruginosa and S. mutans and placed in a Petri dish right after. Four hours later the sutures have been aseptically removed and placed in a selective culture. The incubation time was 18 hours for P. aeruginosa and 43 hours for S. mutans at 37°C. The antimicrobial efficacy of both sutures was performed by measuring the length of the bacteria-free suture segment. RESULTS: A statistically significant difference between Vicryl Plus 3-0 and Vicryl 3-0 has been observed, with an higher bacterial growth on Vicryl 3-0 for both bacteria (P. aeruginosa and S. mutans). CONCLUSIONS: Vicryl Plus presented an antibacterial effectiveness in vitro against both P. aeruginosa and S. mutans.

15.
Eur J Paediatr Dent ; 7(1): 18-22, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16646640

ABSTRACT

AIM: The purpose of this study was to evaluate the activity of Anterior Temporal, Masseter, Sternocleidomastoid and Anterior Digastric muscles in response to changes in visual input in subjects with defective vision by means surface electromyography. METHODS: A total of 20 children, aged between 7 and 13 years, were evaluated. In the study group 10 children with myopic defects were enlisted, selected among patients afferent to the paediatric dentistry clinic. Ten subjects with normal vision, the control group, were chosen through the Pair Matching procedures, so that each myopic child had a matching age case control. Both study group and control group patients maintained mandible at rest with teeth apart and were submitted to a 15-sec electromyography (EMG) recording with closed eyes followed by a 15-sec EMG recording with open eyes. RESULTS/STATISTICS: The Root Mean Square (RMS) values were elaborated to obtain means and standard deviation. Statistical analysis was undertaken using the Student's T-test for independent samples. Analysis of the results demonstrated a marked difference in tonic activity of temporal anterior muscles at open eyes between the myopic and the normal groups. CONCLUSION: The findings suggest that in the evaluation of masticatory muscles tenderness, such as episodic tension type headaches, attention should be paid to vision defects.


Subject(s)
Masticatory Muscles/physiology , Myopia/physiopathology , Neck Muscles/physiology , Visual Perception/physiology , Adolescent , Case-Control Studies , Centric Relation , Child , Electromyography , Humans , Proprioception
16.
Clin Endocrinol (Oxf) ; 60(6): 694-8, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15163332

ABSTRACT

OBJECTIVE: The aim of this study was twofold: first to investigate the presence of extraocular muscle antibodies (EMAb) in sera of Graves' patients with ophthalmopathy characterized by clinical extraocular muscle (EM) involvement; second to evaluate in Graves' patients without ophthalmopathy whether longitudinal variations of EMAb have a predictive role for the development of eye disease. PATIENTS: We evaluated sera of Graves' patients previously tested for G2sAb and FpAb; in particular, sera of 32 patients with moderate or severe ophthalmopathy and EM involvement: 18 with active disease (group 1), 14 with inactive disease (group 2). Moreover, we evaluated longitudinally sera of 19 Graves' patients without ophthalmopathy previously tested for anti-GS2 (G2sAb) and antiflavoprotein antibodies (FpAb; group 3). During the 18-month follow-up, four of them did not develop ophthalmopathy (group 3a), and 15 did: seven developed eye disease (group 3b) with clinical EM involvement. In particular, moderate disease and clinical activity score (CAS) >/= 4 in four of them, severe ophthalmopathy and CAS /= 4 without EM involvement (group 3c). MEASUREMENTS: EMAb were evaluated in all samples by indirect immunofluorescence method. RESULTS: EMAb were detected in 13 out of 18 patients (72.2%) in group 1 (titre 1/32-1/128) and in five out of 14 patients (35.7%) in group 2 (titre 1/2-1/8). As regards to group 3, at the start of the study EMAb were detected in 13 out of 19 patients (72%) at titres 1/2-1/8; during the follow-up they became or persisted negative in all patients in group 3a, while they increased at titres ranging from 1/64 to 1/128 in all patients in group 3b before the onset of ophthalmopathy. Finally, in group 3c, four patients showed a mild increase (1/8-1/16) of EMAb before the onset of eye disease, while four patients were negative during the entire follow-up. CONCLUSIONS: Our results indicate that EMAb are a good marker of ophthalmopathy with EM involvement and their titre is higher in patients with active than in those with inactive disease. Thus, even if our results must be confirmed on a larger cohort of patients, the increase of EMAb in patients with Graves' disease could be considered as a risk factor for the development of ophthalmopathy with subclinical/clinical EM impairment. In this connection we propose the evaluation of EMAb, in Graves' patients with subclinical and clinical ophthalmopathy, as a simple and sensitive marker of the EM inflammatory process.


Subject(s)
Antibodies/blood , Eye Diseases/immunology , Graves Disease/immunology , Oculomotor Muscles/immunology , Acute Disease , Adult , Biomarkers/blood , Disease Progression , Female , Humans , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Statistics, Nonparametric
17.
Int J Artif Organs ; 26(1): 39-45, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12602468

ABSTRACT

This work studies protease concentration decrease in aqueous solutions in contact with a modified polyethersulphone graft membrane onto which antiproteases were immobilized. As a model of protease/antiprotease interaction, elastase and alpha1-antitrypsin were used. Experiments were carried out either under fixed amounts of immobilized antiproteases and variable protease concentration or under fixed protease concentration and variable amounts of immobilized antiproteases. In both cases, active protease concentrations decreased with increase in contact time with the membrane. Experimental conditions under which active elastase concentration becomes zero were also found. Occurrence of the same phenomenology has also been ascertained with protease solutions obtained from human blood neutrophils. The membrane activated with alpha1-antitrypsin showed differential inhibitory power on elastase and cathepsin G. This technology could open new perspectives in manufacturing new membranes to be used in hemodialysis and extracorporeal circulation when elastase is released.


Subject(s)
Extracorporeal Circulation/adverse effects , Inflammation/prevention & control , Neutrophils/metabolism , Pancreatic Elastase/metabolism , Protease Inhibitors/therapeutic use , Renal Dialysis/adverse effects , alpha 1-Antitrypsin/metabolism , Cardiopulmonary Bypass/adverse effects , Computer Simulation , Erythrocytes/metabolism , Humans , Inflammation/etiology
18.
Biotechnol Prog ; 18(5): 975-85, 2002.
Article in English | MEDLINE | ID: mdl-12363348

ABSTRACT

The effect of methanol on the kinetically controlled synthesis of cephalexin by free and immobilized penicillin G acylase (PGA) was investigated. Catalytic and hydrophobic membranes were obtained by chemical grafting, activation, and PGA immobilization on hydrophobic nylon supports. Butyl methacrylate (BMA) was used as graft monomer. Increasing concentrations of methanol were found to cause a greater deleterious effect on the activity of free than on that of the immobilized enzyme. Methanol, however, improved the kinetic stability of cephalexin synthesized by free PGA, resulting in higher maximum yields. By contrast, immobilized PGA reached 100% yields even in the absence of the cosolvent. Cephalexin synthesis by the catalytic membrane was also performed in a non-isothermal bioreactor. Under these conditions, a 94% increase of the synthetic activity and complete conversion of the limiting substrate to cephalexin were obtained. The addition of methanol reduced the non-isothermal activity increase. The physical cause responsible for the non-isothermal behavior of the hydrophobic catalytic membrane was identified in the process of thermodialysis.


Subject(s)
Cephalexin/chemical synthesis , Membranes, Artificial , Methanol/chemistry , Penicillin Amidase/chemistry , Temperature , Water/chemistry , Anti-Bacterial Agents/chemical synthesis , Bioreactors , Catalysis , Cephalosporins/chemistry , Enzyme Activation , Enzymes, Immobilized/chemistry , Escherichia coli/enzymology , Hydrophobic and Hydrophilic Interactions , Methacrylates/chemistry , Nylons , Penicillin Amidase/metabolism , Propylene Glycols/chemistry , Sensitivity and Specificity
19.
Radiol Med ; 102(4): 233-7, 2001 Oct.
Article in Italian | MEDLINE | ID: mdl-11740450

ABSTRACT

PURPOSE: The objectives of this study were: 1) to evaluate the role of color-Doppler ultrasonography (CDU) assessment of thyroid vascularity, measuring the peak systolic velocity (PSV) at the level of the inferior thyroid artery, and the intrathyroid vascularization in Graves' diseas; 2) to evaluate the role of contrast agent administration in predicting the relapse of hyperthyroidism or the biological activity of the disease after withdrawal of antithyroid drugs. PATIENTS AND METHOD: The study included 74 Graves' patients (59 F/ 15 M; mean age 45 years; range 23-71). Graves' disease was diagnosed according to the usual clinical and laboratory criteria. On the basis of the clinical and biochemical findings we divided Graves' patients into 4 different groups. Treatment was continued for at least 12 months, CDU examination was carried out after discontinuing therapy. Eight patients showed a relapse of hyperthyroidism within 5 months after suspension of therapy. In all cases the evaluation of intraparenchymal vascularization and PSV at the level of the inferior thyroid artery in basal conditions was followed by administration of contrast agent (Levovist, 300 mg/ml), with slow infusion (<2 ml/min) to avoid blooming artifact. Intraparenchymal vascularization was classified into 4 patterns according to Vitti et al. RESULTS: The value of the peak systolic velocity (PSV) at the level of the inferior thyroid artery was the best predictor of relapse. A value higher than 40 cm/sec was present in all the patients that showed relapse and only in two patients with stable remission. Administration of contrast agent is important to evaluate the biological activity of the disease. In the 5 patients exhibiting slightly increased vascularization after contrast agent administration we could assume the clinico-pathological recovery. CONCLUSIONS: CDU study of thyroid vascularization, based on the measurement of PSV at the level of the inferior thyroid artery and on the response to contrast agent administration is useful to distinguish three groups of patients: A) PSV >40 cm/sec with pattern III for at least 10 minutes from the beginning of the contrast agent administration (High risk of relapse); B) PSV <40 cm/sec with pattern II or III after contrast agent administration (Biological activity of the disease-Thyroiditis); C) PSV <40 cm/sec with Pattern I after contrast agent administration (Poor biological activity of the disease-recovery).


Subject(s)
Graves Disease/diagnostic imaging , Graves Disease/physiopathology , Ultrasonography, Doppler, Color , Adult , Aged , Blood Flow Velocity , Contrast Media , Female , Follow-Up Studies , Humans , Male , Middle Aged , Systole
20.
Enzyme Microb Technol ; 28(9-10): 773-784, 2001 Jun 07.
Article in English | MEDLINE | ID: mdl-11397458

ABSTRACT

The behaviour of five different hydrophobic beta-galactosidase derivatives, obtained by grafting different amount of butylmethacrylate (BMA) on planar nylon membranes, has been studied under isothermal and non-isothermal conditions.Under isothermal conditions the effect of the grafting percentage on the enzyme activity has been studied as a function of pH, temperature and substrate concentration. Independently from the parameters under observation, the yield of the catalytic process reaches the maximum value at a grafting percentage value equal to 21%. The apparent K(m) values result linearly increasing with the increase of the grafting percentage, while the apparent V(max) exhibits a maximum value.Under non-isothermal conditions, a decrease of the apparent K(m) values and increase of the apparent V(max) has been found in respect to the same values obtained under isothermal conditions.The percentage activity increases induced by the presence of a temperature gradient have been found to decrease with the increase of the percentage of graft BMA.A parameter correlating the percentage increase of enzyme activity under non-isothermal conditions with the hydrophobicity of the catalytic membrane has also been identified. This parameter is the ratio between thermoosmotic and hydraulic permeability.Results have been discussed in terms of reduction of diffusion limitations for substrate and products movement towards or away from the catalytic site by the process of thermodialysis.The usefulness of using non-isothermal bioreactors in industrial biotechnological processes has been confirmed.

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