Didona Ungureanu

Measuring fatigue as a symptom in COPD From descriptors and questionnaires to the importance of the problem

Fatigue is a symptom commonly diagnosed in cancers and in many other chronic debilitating diseases and is one of the main therapeutic targets for various pharmacologic and non-pharmacologic interventions. However, in chronic obstructive pulmonary disease (COPD), this symptom, which can be considered as the main extrapulmonary clinical feature of the disease, can impact significantly on the health-related quality of life of the patients. The aims of this review are to discuss the issues related to fatigue assessment in COPD and to highlight the importance of this symptom in this setting based on the data retrieved from articles published between 1987 through August 2014 available on MEDLINE database. Fatigue can be measured by various scales or questionnaires that are designed for generic purposes or for COPD-related purposes but is still underdiagnosed and undertreated. This is due to the fact that its clinical and prognostic relevance are not appropriately acknowledged. The early identification of fatigue clinical descriptors from patients’ reports could help with better management of this symptom.

Cardiac Troponin T and NT-proBNP as Biomarkers of Early Myocardial Damage in Amitriptyline-Induced Cardiovascular Toxicity in Rats:

The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex (P < .0001) and the QT interval (P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.

Immune therapies for malignant mesothelioma.

Malignant mesothelioma (MM) is a rare disease which can develop in pleura, pericardium or peritoneum and in which the therapies available have limited efficacy and are associated with various side effects. Therefore, there is a need for more targeted and more effective therapies which are able to halt the disease progression. Among them immune therapies actively or passively directed against various structures of the MM cells seem to be particularly promising given their inhibitory potential demonstrated in both experimental and early clinical studies. Mesothelin in particular seem to be not only a biomarker of disease activity but also a therapeutic target. This review discusses the immune therapies currently investigated for MM.

Determination of the phosphorylated neurofilament subunit NF-H (pNF-H) in cerebro-spinal fluid as biomarker in acute traumatic spinal cord injuries / Dozarea neurofilamentelor fosforilate (subunitatea pNF-H) ȋn LCR ca biomarker ȋn traumatismul vertebro-medular acut

Abstract Study objective. The objective of this study was to measure the phosphorylated neurofilament subunit NF-H (pNF-H) in cerebro-spinal fluid of patients with spinal cord injury and to determine the correlation between the pNF-H levels and the severity of the injury. Materials and methods. The study included 15 subjects with acute traumatic spinal cord injury: eight patients with complete spinal cord injury (SCI) and seven patients with incomplete SCI. All patients were classified according to the American Spinal Injury Association impairment scale (ASIA) and all patients underwent surgery during the first 24 hours (decompression, stabilization). We measured daily the heavy phosphorylated neurofilament subunit (pNF-H) concentration by sandwich ELISA test in CSF in all patients and we correlated the values of pNF-H with the clinical evolution. Results. For all patients with SCI pNF-H was detectable in CSF samples and the values were different in the cases of complete SCI toward the cases of incomplete SCI and the cerebro-spinal pNF-H level was more elevated in cases of complete SCI. The level of CSF pNF-H was ten to a hundred times higher in complete SCI than the level of CSF pNF-H in cases with incomplete SCI, where the level of this biomarker was close to normal. The patients with a favorable neurological evolution after treatment had a specific pattern of daily values of pNF-H: a sudden increase up to a maximum value then a progressive decrease until normal. The maximum values were different in each case, from 10 times up to 170 times higher than the normal. Conclusion. The phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H) in cerebro-spinal fluid can be a specific biomarker for spinal cord injury and it can distinguish the severity of SCI. pNF-H is a predictive biomarker because of its values pattern can show the reducing or stopping of the secondary lesion and the favorable result. Rezumat Obiectivul studiului. Obiectivul acestui studiu a fost dozarea neurofilamentelor fosforilate (subunitatea pNF-H) în lichidul cefalorahidian al pacienţilor cu leziuni traumatice ale măduvei spinării şi stabilirea unei corelaţii intre valoarea pNF-H şi gravitatea leziunilor medulare. Material şi metode. Studiul a inclus 15 pacienţi cu leziuni traumatice acute medulare: opt pacienţi cu leziuni medulare complete şi şapte pacienţi cu leziuni medulare incomplete. Gravitatea leziunilor medulare a fost apreciată folosind scala ASIA (American Spinal Injury Association scale) şi la toti pacientii s-a aplicat tratamentul chirurgical în primele 24 de ore (decompresiune medulară şi stabilizare vertebrală). S-a facut determinarea zilnică a pNF-H din LCR folosind testul ELISA specific şi am corelat aceste valori cu evoluţia clinică. Rezultate. Subunitatea pNF-H a fost evidenţiată în LCR la toţi pacienţii cu traumatisme acute vertebro-medulare şi valorile au fost diferite în cazurile leziunilor medulare complete faţa de leziunile incomplete. Nivelul pNF-H din LCR a fost de zece până la o sută de ori mai mare în leziunile medulare complete fata de cazurile cu leziuni incomplete, unde nivelul acestui biomarker a fost aproape normal. Pacienţii cu o evoluţie neurologică favorabilă după tratament au avut un model specific al valorilor zilnice de pNF-H: o creştere bruscă până la o valoare maximă apoi o scădere progresivă până la normal. Valorile maxime au fost diferite în fiecare caz, de 10 ori până la 170 de ori mai mari faţă de normal. Concluzii. Forma fosforilată a subunităţii neurofilamentelor cu greutate moleculară mare pNF-H din lichidul cefalorahidian poate fi un biomarker specific pentru leziunile acute traumatice ale măduvei spinării corelat cu severitatea leziunilor medulare. pNF-H pare a fi un biomarker predictiv deoarece modelul evolutiv al valorilor sale arată reducerea sau blocarea leziunilor medulare secundare şi se corelează cu evoluţia favorabilă clinică

Serum Uric Acid Concentration in Overweight and Obese Women with Polycystic Ovary Syndrome / Nivelul acidului uric la femeile supraponderale și obeze cu sindromul ovarelor polichistice

Abstract Background: Women with polycystic ovary syndrome (PCOS) are at high risk for the development of diabetes mellitus, hypertension and coronary heart disease. Due to the inverse correlation between serum uric acid and insulin sensitivity, the measurement of uric acid may provide a marker of insulin resistance. Objective: To establish the relationship between uric acid and markers of insulin resistance in obese and overweight women with PCOS. Methods: Serum uric acid levels were measured in 38 PCOS obese and overweight patients and 30 controls matched for age and body mass index (BMI). Anthropometric variables, plasma glucose and insulin levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). Results: No statistically significant differences in uric acid levels between PCOS and non-PCOS women were found. Serum uric acid levels were positively correlated with BMI, waist circumference, insulin and HOMA. Following the use of stepwise linear regression analysis, BMI was the only parameter retained by the regression model, responsible for 42.1% of the variability of serum uric acid levels. Conclusions: In PCOS women obesity seems to be the main determinant of plasma uric acid levels. Insulin and HOMA are also involved to a lesser extent, but their role remains to be clarified by further studies. Rezumat Femeile cu sindromul ovarelor polichistice (PCOS) au un risc crescut de a dezvolta diabet zaharat, hipertensiune arterială și afectare coronariană. Datorită corelației negative dintre nivelul seric al acidului uric și sensibilitatea la insulină, determinarea acidului uric ar putea reprezenta un marker al rezistenței la insulină. Obiectiv: Stabilirea relației dintre acidul uric și markeri ai rezistenței la insulină la femeile supraponderale și obeze cu PCOS. Metodă: Nivelul seric al acidului uric a fost măsurat la un lot de 38 de paciente supraponderale și obeze cu PCOS comparativ cu un lot control alcătuit din 30 de femei cu aceeași vârstă și indice de masă corporală (BMI). Au fost evaluați parametri antropometrici, nivelul glicemiei și insulinemiei. Rezistența la insulină a fost apreciată prin calcularea indicelui HOMA (HOmeostasis Model Assessment). Rezultate: Nu au existat diferențe statistic semnificative între nivelurile de acid uric la femeile cu PCOS comparativ cu femeile fără PCOS. Nivelul acidului uric s-a corelat pozitiv cu BMI, circumferința taliei, insulină și HOMA. Aplicând analiza regresiei liniare, am observat că BMI a fost singurul parametru responsabil de 42,1% din variabilitatea nivelului acidului uric. Concluzii: La femeile cu PCOS obezitatea pare principalul determinat al nivelului de acid uric. Insulina și HOMA sunt implicate de asemenea în mai mică măsură, rolul lor urmând a fi clarificat în studii viitoare.

Flow Cytometry Analysis of Pparα Receptors in Metabolic Syndrome / Studiul Receptorilor Pparα prin Metoda Citometriei în Flux în Sindromul Metabolic

Abstract Introduction. Metabolic syndrome (MS) is a cluster of distinct metabolic alterations with an increased cardiovascular risk. Peroxisome Proliferator-Activated Receptor - Alpha (PPARα), member of the nuclear receptor superfamily of transcription factors, is critically involved in the management of lipid metabolism during homeostasis or inflammatory stresses in various cell types and represents one of the therapeutic targets in MS. We analysed the PPARα expression in leukocytes of pacients with MS, in order to address PPARα involvement in these group of diseases. Material and method. Our study included 57 adult patients recruited under informed voluntary consent, investigated in order to establish whether they present MS, according to International Diabetes Federation (IDF) European guidelines and grouped in 2 lots: the MS Lot (26 patients) and control group, non-MS Lot (31 subjects). Common clinical and laboratory parameters targeted in MS evaluation were determined for all the studied cases. The expression levels of 2 molecules, PPARα and CD36 were evaluated in various circulating leukocyte populations of these patients by an optimized flow cytometry method. Statistic analysis clarifying the significance of value differences for various parameters measured was performed under SPSS and simple statistical tests (Pearson, t-Student, Chi -test). Results and discussion. The fluorescence staining for PPARα were significantly dimmer when comparing the cellular expression in eosinophils (p<0.05) of MS versus the Control group of subjects. Conclusions: Our study is the first to show that circulating eosinophils display significantly reduced PPARα protein expression in MS patients. The differences in key molecule expression in circulating leukocytes (like PPAR species, CD36, and other) might be evocatory for the endothelial dysfunction and obesity and might be of use in the therapeutic decision. Rezumat Introducere. Sindromul metabolic (SM) reprezintă o asociere de alterări metabolice independente cu risc cardiovascular crescut. Receptorii activați de inductorii proliferării peroxizomilor-alpha (PPARα), membri ai superfamiliei receptorilor nucleari cu rol de factori de transcripţie , sunt implicați în reglarea metabolismului lipidic și inflamație în diferite tipuri de celule și reprezintă una din țintele terapeutice în SM. Am analizat expresia PPARα în leucocitele pacienților cu SM, îndreptându-ne spre implicarea PPARα în această patologie. Material și metoda. Studiul s-a desfășurat pe un număr de 57 pacienți adulți recrutați după semnarea consimțământului informat, investigați pentru evidențierea SM conform criteriilor Federației Internaționale de Diabet (IDF) și care au fost grupați în două loturi: lotul SM (26 pacienți) și lotul de control, fără SM (31 subiecți). Au fost determinați parametrii clinici și de laborator utilizați curent în evaluarea SM. În populațiile de leucocite circulante ale pacienților au fost evaluate nivelurile de expresie a două molecule, PPARα și CD36, printr-o metodă optimizată de citometrie în flux . Semnificația diferențelor dintre valorile parametrilor măsurați a fost stabilită prin analiza statistică, utilizând programul SPSS și teste statistice simple (Pearson, t-Student, Chi-test). Rezultate și discuții. Când am comparat nivelul de expresie a PPARα în eozinofile, am obținut a reducere semnificativă a intensității medie de fluorescență (p<0.05) pentru PPARα în lotul MS versus lotul martor. Concluzii. Studiul nostru este primul care arată că nivelul de expresie a PPARα în eozinofile este diminuat semnificativ la pacienții cu SM. Diferențele de expresie ale acestor molecule cheie în leucocitele circulante (ca diferite specii de PPAR, CD36 și altele) ar putea deveni evocatoare pentru disfuncția endotelială și obezitate și ar putea fi utile în elaborarea unei decizii terapeutice.

Insulin resistance and adipokine levels correlate with early atherosclerosis – a study in prediabetic patients

Abstract Cardiovascular risk of prediabetes is still subject to controversies. We analyzed the associations between insulin resistance, adipokines and incipient atherosclerosis estimated by intima-media thickness (IMT) in a cross-sectional study on 122 prediabetic subjects without clinical signs of atherosclerotic disease. Homeostasis model assessment of insulin resistance (HOMA-IR, calculated as fasting insulin × fasting plasma glucose / 22.5), adiponectin, leptin, leptin-to-adiponectin ratio, carotid and femoral IMT were evaluated. We also assessed other parameters related to insulin resistance and adipokines (HbA1c, anthropometric and lipid parameters), as they may also influence atherosclerosis. Carotid IMT was correlated to adiponectin and leptin-to-adiponectin ratio (all p < 0.05), but not with HOMA-IR or leptin, while femoral IMT showed no relationship with these factors. After adjusting for leptin, leptin-to-adiponectin ratio, triglycerides, HDL-cholesterol, cholesterol-to-HDL ratio, triglycerides-to-HDL ratio and HbA1c, IMT values became correlated with HOMA-IR. Adjustment for HOMA-IR induced the appearance of new correlations between adipokines and both IMT values. In conclusion, insulin resistance and adipokines seem related to IMT in prediabetic subjects without clinical signs of arterial obstruction.

Molecular markers in cervical screening – a promise for the future

Abstract Cervical cancer is one of the leading cancers in women worldwide. The detection and diagnosis of cervical carcinoma and its precursor lesions, called cervical intraepithelial lesions (CIN), represents the main goal in order to decrease the morbidity and mortality of this disease. In the majority of cases CIN resolve spontaneously. Only a minor part of the lesions develop to high-grade lesions and eventually invasive cancer and it is important to detect those CIN with potential to progress to cervical cancer. For clinical management it is important to distinguish the cervical dysplasia with regression potential in order to avoid unnecessary treatments. Many potential biomarkers have been analyzed for the characterization of cervical cancer and pre-cancer. So far, detection of HPV has been the most promising clinical application. Several new markers have been evaluated intensively and might be used in some clinical settings, mainly p16, MCM5/CDC6 and HPV RNA, integration of HPV DNA into the host genome, chromosomal imbalances. In this article, representative examples of these markers are presented in the context of improved cervical disease detection and progression. Rezumat Cancerul de col uterin reprezintă unul din cele mai frecvente cancere întâlnite la femeie. Elementul cheie pentru scăderea morbiditătii şi mortalităţii în cancerul cervical este diagnosticul acestuia în stadii incipiente precum şi a leziunilor precanceroase numite displazii de col uterin. Displaziile de col uterin pot fi de grad redus sau de grad înalt. Un număr semnificativ dintre displaziile de grad redus regresează spontan şi doar un număr limitat progresează către leziuni de grad înalt şi cancer cervical. Pentru clinician este esenţială identificarea acestora întrucât pot fi astfel evitate tratamente inutile. De-a lungul timpului au fost analizaţi multipli markeri care să identifice displaziile cervicale cu potenţial evolutiv. Momentan cel mai utilizat marker este reprezentat de genotiparea virală. Pe lângă acesta şi alţi markeri şi-au demonstrat utilitatea în încadrarea evolutivă a leziunilor cervicale: p16, MCM5/CDC6, integrarea ADN-ului în genomul celulei gazdă. Articolul trece în revistă cei mai importanţi markeri utilizaţi la ora actuală ilustrând cu cazuistica proprie utilizarea acestora.

Are There Any Substantial Differences in the Anthropometric and Metabolic Profile Between Patients with Impaired Fasting Glycemia and Impaired Glucose Tolerance

Abstract Background and Aims: Prediabetes, a category of incipient hyperglycemia that includes impaired fasting glycemia (IFG) and impaired glucose tolerance (IGT), has an increasing incidence in the modern world. We searched for differences in anthropometric and metabolic characteristics between subjects with isolated IFG and IFG+IGT. Material and Methods: In our cross-sectional study, 154 subjects with IFG and IFG+IGT, without any other major pathologies, were analyzed. Anthropometric data, lipid profile, uric acid, insulin resistance indexes, adiponectin, leptin and leptin-to-adiponectin ratio were compared. Results: Only 122 subjects (64 with isolated IFG and 58 with IFG+IGT), without any other identifiable major disease, were included in the final analysis. Most characteristics of the two groups were similar, only minor differences in anthropometric data, biochemical profile and insulin resistance indexes being noted. Insulin resistance indexes were stronger associated with adiponectin in the group with isolated IFG and with leptin and leptin-to-adiponectin ratio in the IFG+IGT group. Conclusions: Our data suggest a similar anthropometric and metabolic profile in subjects with isolated IFG and with IFG+IGT. In isolated IFG, insulin resistance seems to correlate better with adiponectin, while in IFG+IGT it seems to associate mostly with leptin and derived parameters