Bioactive Vitamins and Epigenetic Modifications in Diabetes: A Perspective.

Diabetes is a complex metabolic disease that has been associated with epigenetic changes. External factors such as dietary patterns can induce an imbalance in the pools of micronutrients and macronutrients in the body. Consequently, bioactive vitamins may influence epigenetic mechanisms via several pathways: involvement in the control of gene expression, and in protein synthesis, by acting as coenzymes and co-factors in the metabolism of methyl groups or methylation of DNA and histones. Herein, we present a perspective on the relevance of bioactive vitamins in the epigenetic modifications that occur in diabetes.

Acute myocardial infarction in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage. Affected individuals are at increased risk for cardiovascular and thrombotic events. Myocardial infarction (MI) may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease. In the present review, we examine the epidemiology, pathogenesis, clinical presentation, and management of MI in MPNs based on the available literature. Moreover, we review potential biomarkers that could mediate the MI-MPNs crosstalk, from classical biochemical tests, e.g., lactate dehydrogenase, creatine kinase and troponins, to pro-inflammatory cytokines, oxidative stress markers, and clonal hematopoiesis.

Oxidative Stress and Inflammation Levels in a Population of Eastern European Naïve Versus Treated Psoriasis Patients.

Psoriasis is a chronic inflammatory disease, with a major impact on the patients' quality of life. Oxidative stress (OS) is represented by the imbalance between oxidant and antioxidant mechanisms of the organism, with increased levels being described in the majority of chronic diseases. We present the first prospective study in Romania to evaluate the redox balance changes (using a CR3000 analyzer) in patients with moderate-severe psoriasis based on treatment regimens: treatment-naïve (A), treatment with novel targeted agents (B) and methotrexate (C). The study group included 53 Caucasian patients divided into three groups (A- 27 patients, B - 15 patients, and C - 11 patients) for which OS, antioxidant status, standard blood count, and inflammatory status were evaluated. Our findings demonstrate that patients with psoriasis display high levels of OS, with elevated Free Oxygen Radical Test (FORT) (p-value for group A (pA)<0.0001, p-value for group B (pB)=0.0019 and p-value for group C (pC)=0.0063) and reduced Free Oxygen Radical Defense (FORD) (pB=0.018) values noted in our subjects. Higher erythrocyte sedimentation rate (ESR) values were detected in groups B (pB=0.00012) and C (pC<0.00001). Psoriasis treatments alleviate FORT and FORD levels, but their impact is not sufficient to restore the oxidative balance to normal ranges. Moreover, despite adequate treatment, patients with psoriasis display elevated inflammation levels. Future research should explore in more detail the interplay between OS and inflammation in psoriasis, namely the long-term impact on the redox balance of biotherapies.

Molecular Aspects of Hematological Malignancies and Benign Hematological Disorders.

Hematology represents a dynamic specialty in clinical medicine that requires solid knowledge of normal and pathological hematopoiesis, cytomorphology, pathology, immunology, genetics and molecular biology [...].

Budd-Chiari syndrome in myeloproliferative neoplasms: A review of literature.

Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e., polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g., portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations (e.g., the V617F point mutation in the JAK2 gene), microparticles, circulating endothelial cells, and other factors, to name a few. Herein, we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs, with a particular focus on its epidemiology, pathogenesis, histopathology, risk factors, classification, clinical presentation, diagnosis, and management.

Primary Arterial Hypertension and Drug-Induced Hypertension in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review.

The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on cardiovascular risk factors as a singular entity or on organ-specific HTN. Furthermore, available studies reporting findings on drug-induced HTN in MPNs report varying and contradictory findings. In consideration of the above, this study set out to systematically review the available literature and shed light on the occurrence of HTN in MPNs, its association with thrombosis, as well as the drugs used in MPN management that could increase blood pressure. The literature search yielded 598 potentially relevant records of which 315 remained after the duplicates (n = 283) were removed. After we screened the titles and the abstracts of these publications, we removed irrelevant papers (n = 228) and evaluated the full texts of 87 papers. Furthermore, 13 records did not meet the inclusion criteria and were excluded from the systematic review. Finally, a total of 74 manuscripts were entered into the qualitative synthesis and included in the present systematic review. Our systematic review highlights that HTN is the most common comorbidity encountered in MPNs, with an impact on both the occurrence of thrombosis and survival. Moreover, drug-induced HTN remains a challenge in the management of MPNs. Further research should investigate the characteristics of patients with MPNs and HTN, as well as clarify the contribution of HTN to the development of thrombotic complications, survival and management in MPNs. In addition, the relationship between clonal hematopoiesis of indeterminate potential, HTN, cardiovascular disease and MPNs requires examination in upcoming assessments.

Development of a SPE-LC-MS Method for the Quantitation of Palbociclib and Abemaciclib in Human Plasma.

Palbociclib and abemaciclib are two cyclin-dependent kinases 4 and 6 used for breast cancer treatment. Levels of these medicines present a significant interindividual variability, so monitoring those concentrations might be necessary in therapy. Most of the methods presented so far in the literature use simple protein precipitation of plasma proteins as sample preparation method followed by direct injection of the supernatant into the LC instrument, preceded or not by a simple filtration step. Within that approach, the probability of injecting proteins in the chromatographic system is increased. With the purpose of obtaining a cleaner extract of the drugs, we developed and validated a simple and accurate LC-MS method for determining palbociclib and abemaciclib in human plasma. Solid phase extraction (SPE) using Oasis PRiME HLB® cartridges was used for plasma sample preparation. The method provided clean extracts with a recovery extraction higher than 85% for both compounds. Separation was achieved by high-performance liquid chromatography (HPLC), using a C18 (4.6 × 50 mm) column, with a gradient elution of ammonium acetate/acetic acid-acetonitrile as the mobile phase. Detection was performed by mass spectrometry (MS) in single ion recording (SIR) mode. Intra-day and inter-day precision data for both analytes were 3.8-7.2% and 3.6-7.4%, respectively. Calibration curves were both linear between 2 and 400 ng/mL with a correlation coefficient higher than 0.998. The LC-MS method can be used to quantify the drugs in human plasma in routine analysis. The method proved to be useful in determining real plasma levels in patients involved in cancer therapy. Drug concentrations were determined in a 10 min run-time, including re-equilibration of the column.

The Involvement of Oxidative Stress in Psoriasis: A Systematic Review.

Psoriasis is a chronic, immune-mediated inflammatory dermatosis characterized by the appearance of erythematous plaques, covered by white scales, occasionally pruritogenic, and distributed mainly on the extensor areas. Oxidative stress is defined as an imbalance or a transient or chronic increase in the levels of free oxygen/nitrogen radicals, either as a result of the exaggerated elevation in their production or the decrease in their ability to be eliminated by antioxidant systems. Although the pathogenesis of psoriasis remains far from elucidated, there are studies that delineate an involvement of oxidative stress in this skin disorder. Thus, a systematic search was computed in PubMed/Medline, Web of Science and SCOPUS and, in total, 1293 potentially eligible articles exploring this research question were detected. Following the removal of duplicates and the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 995), 298 original articles were selected for full-text review. Finally, after we applied the exclusion and inclusion criteria, 79 original articles were included in this systematic review. Overall, the data analyzed in this systematic review point out that oxidative stress markers are elevated in psoriasis and share an association with the duration and severity of the disease. The concentrations of these biomarkers are impacted on by anti-psoriasis therapy. In addition, the crosstalk between psoriasis and oxidative stress is influenced by several polymorphisms that arise in genes encoding markers or enzymes related to the redox balance. Although the involvement of oxidative stress in psoriasis remains undisputable, future research is needed to explore the utility of assessing circulating serum, plasma, urinary and/or skin biomarkers of oxidative stress and of studying polymorphisms in genes regulating the redox balance, as well as how can these findings be translated into the management of psoriasis, as well in understanding its pathogenesis and evolution.

Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review.

Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates (n = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.

Crosstalk of Magnesium and Serum Lipids in Dyslipidemia and Associated Disorders: A Systematic Review.

Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of lipid abnormalities and related disorders, such as the metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease. In this review, we explored the associations of Mg (dietary intake, Mg concentrations in the body) and the lipid profile, as well as the impact of Mg supplementation on serum lipids. A systematic search was computed in PubMed/MEDLINE and the Cochrane Library and 3649 potentially relevant papers were detected and screened (n = 3364 following the removal of duplicates). After the removal of irrelevant manuscripts based on the screening of their titles and abstracts (n = 3037), we examined the full-texts of 327 original papers. Finally, after we applied the exclusion and inclusion criteria, a number of 124 original articles were included in this review. Overall, the data analyzed in this review point out an association of Mg concentrations in the body with serum lipids in dyslipidemia and related disorders. However, further research is warranted to clarify whether a higher intake of Mg from the diet or via supplements can influence the lipid profile and exert lipid-lowering actions.

Assessment of Oxidative Stress in Patients with Chronic Myeloid Leukemia Depending on Associated Comorbidities.

Oxidative stress (OS) implies an imbalance between the amount of tissue level of prooxidant and antioxidant compounds. It is involved in the pathophysiology of multiple pathological entities (neoplasms, disorders of carbohydrate and lipid metabolism, cardiovascular and renal pathology etc.), as well as in the pharmacokinetics of specific treatments for these pathologies. Chronic myeloid leukemia (CML) is a chronic myeloproliferative disease for which current standard treatment is BCR-ABL tyrosine kinase inhibitors (TKIs). It is known that OS is involved in CML pathogenesis and response to TKIs therapy, but in reality, there are a number of additional factors (associated comorbidities, specific therapies) that modulate oxidative status, possibly affecting the evolution and prognosis of CML. In the present paper we proposed the evaluation of OS in a group of patients with CML following treatment with TKIs, depending on the presence of comorbidities and associated treatments. There were considered associated comorbidities: diabetes mellitus, dyslipidemia, arterial hypertension, heart failure, chronic kidney disease. The variability of the oxidative status was found depending on the type of associated comorbidity, but also according to the associated treatment, with the possibility of producing drug interactions between the standard treatment of CML and the associated specific therapies. Their impact on the prognosis of CML patients in treatment with TKIs is not negligible and may represent a future research topic.

Evaluation of oxidative stress levels in obesity and diabetes by the free oxygen radical test and free oxygen radical defence assays and correlations with anthropometric and laboratory parameters.

BACKGROUND: Obesity and diabetes are associated with high levels of oxidative stress. In Romanian patients with obesity and (or) diabetes, this association has not been sufficiently explored. AIM: To evaluate oxidative stress in obese and (or) diabetic subjects and to investigate the possible correlations between oxidative stress and anthropometric/biochemical parameters. METHODS: Oxidative stress was evaluated from a single drop of capillary blood. Reactive oxygen species (ROS) were evaluated using the free oxygen radical test (FORT). The free oxygen radical defence (FORD) assay was used to measure antioxidant levels. RESULTS: FORT levels were higher in obese subjects (3.04 ± 0.36 mmol/L H2O2) vs controls (2.03 ± 0.14 mmol/L H2O2) (P < 0.0001). FORD levels were lower in obese subjects (1.27 ± 0.13 mmol/L Trolox) vs controls (1.87 ± 1.20 mmol/L Trolox) (P = 0.0072). Obese diabetic subjects had higher FORT values (3.16 ± 0.39 mmol/L H2O2) vs non-diabetic counterparts (2.99 ± 0.33 mmol/L H2O2) (P = 0.0233). In obese subjects, FORT values correlated positively with body mass index (BMI) (r = 0.48, P = 0.0000), waist circumference (WC) (r = 0.31, P = 0.0018), fasting plasma glucose (FPG) (r = 0.31, P = 0.0017), total cholesterol (TC) (r = 0.27, P = 0.0068) and uric acid (r = 0.36, P = 0.0001). FORD values correlated negatively with BMI (r = -0.43, P = 0.00001), WC (r = -0.28, P = 0.0049), FPG (r = -0.25, P = 0.0130), TC (r = -0.23, P = 0.0198) and uric acid (r = -0.35, P = 0.0002). In obese diabetic subjects, FORT values correlated positively with BMI (r = 0.49, P = 0.0034) and TC (r = 0.54, P = 0.0217). FORD values were negatively associated with BMI (r = -0.54, P = 0.0217) and TC (r = -0.58, P = 0.0121). CONCLUSION: Oxidative stress levels, as measured by the FORT and FORD assays, were higher in obese subjects vs controls. ROS levels were elevated in diabetic obese patients vs obese non-diabetic patients and controls.

Involvement of Oxidative Stress in Resistance to Tyrosine-Kinase Inhibitors Therapy in Chronic Myeloid Leukemia.

Oxidative stress involves disruption of the cellular redox status through excessive production of reactive oxygen species or through deficiency in the cellular antioxidant capacity. It is involved in the pathogeny of multiple entities (hematological diseases, metabolic disorders, cardiovascular and renal pathology etc.), as well as in the pharmacokinetics of specific treatments for these pathologies. Chronic myeloid leukemia is a chronic myeloproliferative disease for which current standard treatment is BCR-ABL tyrosine kinase inhibitors. The innovation of this therapy has significantly improved life expectancy for patients with chronic myeloid leukemia, but in some cases, this treatment becomes ineffective, installing the resistance to tyrosine kinase inhibitors therapy. There were described two types of tyrosin kinase inhibitors resistance: primary and secondary resistance. In the present paper we proposed to evaluate the involvement of oxidative in the resistance to tyrosine kinase inhibitors therapy, in the clonal instability in chronic myeloid leukemia and in the progression of the disease to an advanced stage. We concluded that oxidative stress can play a dual role in the evolution of chronic myeloid leukemia: on the one hand it can promote genomic instability and accelerate the progression of the disease to advanced stages associated with tyrosin kinase inhibitors resistance and, on the other hand, it can contribute to leukemic cell apoptosis. It seems to be outlined a fragile balance between the pro- and anti-apoptotic effects of the reactive oxygen species, closely related to their level in the leukemic cells.

Anticonvulsant effect of anacardic acid in murine models: Putative role of GABAergic and antioxidant mechanisms.

Epilepsy is a neurological disease affecting people of all ages worldwide. Side effects of antiepileptic drugs and their association with oxidative stress stimulate the search for new drugs, which would be more affordable with fewer adverse effects. Accordingly, the aim of the present work is to evaluate the anticonvulsant effect of anacardic acid (AA), a natural compound extracted from cashew liquid (Anacardium occidentalis), in murine models, as well as its antioxidant actions in Saccharomyces cerevisiae. AA (>90% purity) was tested, in vivo, in male Swiss mice (25-30 g) with four convulsive models, (1) pentylenetetrazole, (2) pilocarpine, (3) electroshock, and (4) kainic acid, at doses of 25, 50, and 100 mg/kg, body weight (B.W.) Additionally, the effective dose, toxic dose, and protective index studies were also performed. Results revealed that AA exhibits anticonvulsive effects in models 1, 3, and 4, with a mean effective dose (ED50) of 39.64 (model 1) >100 mg/kg, B.W. (model 2), and 38.36 (model 3); furthermore, AA displays a protection index of 1.49 (model 1), <0.6 (model 2, and 1.54 (model 3). In addition, AA showed antioxidant activities in S. cerevisiae mutated for superoxide dismutases (SOD). In conclusion, these results show that AA exhibits significant anticonvulsant and antioxidant activities and may be used as a promising natural product for the treatment of epilepsy.

Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer.

The diterpene lactone andrographolide, isolated from Andrographis paniculata, has been proven to possess several important protective biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiseptic, antimicrobial, cytotoxic, hypolipidemic, cardioprotective, hepatoprotective, and neuroprotective effects. In addition, it has been reported to play a therapeutic role in the treatment of major human diseases, such as Parkinson's disease, rheumatoid arthritis, and colitis. This systematic review aims to highlight andrographolide as a promising agent in cancer treatment. To this purpose, a number of databases were used to search for the cytotoxic/anticancer effects of andrographolide in pre-clinical and clinical studies. Among 1703 identified literature articles, 139 were included in this review; 109 were investigated as non-clinical, whereas 24, 3, and 3 were pre-clinical, clinical, and non-pre-clinical trials, respectively. Among the model systems, cultured cell lines appeared as the most frequently (79.14%) used, followed by in vivo models using rodents, among others. Furthermore, andrographolide was found to exert cytotoxic/anticancer effects on almost all types of cell lines with the underlying mechanisms involving oxidative stress, cell cycle arrest, anti-inflammatory and immune system mediated effects, apoptosis, necrosis, autophagy, inhibition of cell adhesion, proliferation, migration, invasion, anti-angiogenic activity, and other miscellaneous actions. After careful consideration of the relevant evidence, we suggest that andrographolide can be one of the potential agents in the treatment of cancer in the near future.

The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain".

Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis.

Risk of thrombosis in patients with primary immune thrombocytopenia and antiphospholipid antibodies: A systematic review and meta-analysis.

Antiphospholipid antibodies (aPL) are common in ITP, but their role for the occurrence of ITP-related thrombosis is controversial. We performed a systematic review and a meta-analysis to investigate the risk of thrombosis associated with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-ß2GP-I antibodies in primary ITP. The literature search was run on Medline, Cochrane and ISI Web of Science from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-ß2GP-I antibodies. Random-effect models were used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Searches in electronic databases retrieved 776 citations. Twelve additional studies from unpublished literature were added. Eventually, 10 cohort studies totalizing 1574 patients were included in the analysis. The pooled OR for the risk of all thromboses associated with LA was 6.11, 95% CI [3.40-10.99]; it was 2.14, 95% CI [1.11-4.12] with aCL. The ORs were similar when stratifying on the type of thrombosis (arterial vs. venous). Only two studies assessed the risk of thrombosis associated with anti-ß2GP-I antibody positivity; consequently, no pooled OR was computed for these antibodies. This meta-analysis highly suggests that LA positivity, and to a less extent aCL antibodies, are associated with an enhanced risk of thrombosis in primary ITP patients. Further prospective studies are needed to identify the factors associated with the risk of thrombosis among LA patients before assessing prevention strategies.

The occurrence of chronic lymphocytic leukemia after chronic phase of chronic myeloid leukemia: case report and literature review.

The occurrence of chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) in the same patient is a rare event. In published literature, CML diagnosis follows CLL diagnosis or both leukemias are diagnosed simultaneously or rarely, CLL diagnosis follows CML diagnosis. We report the case of one patient with renal adenocarcinoma who was diagnosed with CLL 60 months after CML diagnosis. At that time, the patient was in complete cytogenetic response (CCyR) and major molecular response (MMR) of CML clone according to European LeukemiaNet (ELN) recommendations and presented clinical and hematological signs of progressive CLL clone. After 24 months of regular monitoring, the patient presented signs of CLL clone expansion. The FISH (fluorescence in situ hybridization) analysis for CLL prognostic factors, performed before treatment, was positive for tumor protein p53 (TP53) and 13q14.3 mutations. The Li-Fraumeni syndrome (LFS) was considered but TP53 mutation was considered acquired and patient's reduced overall, progression free and disease free survival might sustained that hypothesis. Imatinib (IM) was stopped and patient received chemotherapy until obtained a stable partial response. Twelve months after last cycle of chemotherapy, the patient received second line treatment due CLL clone progression signs but died due to neutropenia related complications. This article is the first Romanian report of CLL occurrence after CML diagnosis and as far as we know the fourth case report of such association in published literature.

A case of hairy cell leukemia variant.

Hairy cell leukemia variant (HCLv) is a rare B-cell chronic lymphoproliferative disorder with features of the classic HCL but presenting some particularities, a poor response to conventional therapy of classic HCL and a more aggressive course of disease with shorter survival than classic HCL. We present a case of a 52-year-old man hospitalized in July 2012 in the Clinic of Hematology of Craiova, Romania, having splenomegaly, leukocytosis with lymphocytosis, anemia and thrombocytopenia, without monocytopenia, which exposed, in the peripheral blood and bone marrow cells, intermediate morphology between hairy cells and prolymphocytes and immunophenotype of mature B-cell phenotype CD19, CD20, CD22, CD11c, CD103, low positive for CD25 and negative for CD3, diagnosed with HCL variant, with no response to conventional chemotherapy and interferon-alpha, an aggressive course of disease and a survival of less than a year from diagnosis.

The role of oxidative stress and the effects of antioxidants on the incidence of infectious complications of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by a predominant humoral immune deficiency predisposing the patients to infections. Oxidative stress leads to an increased immunoglobulin k light chain production in B cells and contributes to the antibodies' deficiency and hypogammaglobulinemia. Aim of the Study. To evaluate the global oxidative status in patients with CLL and to determine whether the administration of antioxidants decreases complications due to infections. Patients and Method. We studied 84 patients with CLL stratified by Binet staging. Free oxygen radicals and antioxidant status were determined by the FORT and FORD test, respectively, at diagnosis and in the presence of infections. The patients were distributed in two groups: group A, treated only with antileukemic treatment, and group B, treated with antileukemic treatment and antioxidants. Results. By FORD and FORT assay, all patients had at diagnosis a low antioxidant capacity, and high levels of hydroperoxides. Infectious complications were more frequent in group A (B/C stages of disease) than in group B. Administrations of antioxidants stimulated the immune response and decreased infectious complications in CLL. Conclusions. Administrations of antioxidants and a healthy life style may improve the quality of life of patients with CLL and reduce the risk of infectious complications.