Association of haptoglobin phenotypes with ceruloplasmin ferroxidase activity in β-thalassemia major

BackgroundHaptoglobin (Hp) and ceruloplasmin (CP) are 2 plasma antioxidants playing a role in preventing iron-induced oxidative damage. This study presents data related to Hp phenotypes and ceruloplasmin ferroxidase activity in relation to iron store markers in patients with β-thalassemia major.MethodsBlood specimens were collected from 196 subjects (124 β-thalassemia major patients and 72 healthy controls). Serum levels of iron, total iron binding capacity (TIBC), ferritin, high sensitivity C-reactive protein (hs-CRP), ceruloplasmin, and ferroxidase activity were determined using conventional methods. Haptoglobin phenotypes were determined by polyacrylamide gel electrophoresis.ResultsAs expected, the mean levels of iron store markers, except TIBC, were significantly higher in patients than in controls. Ceruloplasmin concentrations (mg/dl) and its ferroxidase activity (U/l) were significantly higher in patients than in controls (57.9 ± 18.8 vs 46.9 ± 14.2 and 159.9 ± 47.8 vs 95.3 ± 20.9; p < 0.001, for CP and Hp, respectively). As for Hp phenotypes, no significant differences were observed between iron store markers and ferroxidase activity among the control group. In the patients group however, significantly higher concentrations of ceruloplasmin and its ferroxidase activity were observed among patients with Hp2-2 phenotype as compared to patients with the other phenotypes. Additionally, correlations according to Hp phenotypes revealed strong association between ceruloplasmin ferroxidase activity and serum ferritin in patients with Hp 2-2 phenotype and not in the others (r = 0.331, p < 0.05).ConclusionThalassemia patients with Hp 2-2 phenotype are under greater iron-driven oxidative stress than patients with other phenotypes.     

The effect of quercetin on iron overload and inflammation in β-thalassemia major patients: A double-blind randomized clinical trial

ObjectivesThe aim of this study was to determine whether quercetin can reduce iron overload and inflammation in thalassemic patients.MethodsEighty four patients were recruited to this study and randomly assigned to two groups: 42 patients received a 500 mg/day quercetin tablet and 42 others took a 500 mg/day starch placebo for 12 weeks. Demographic, anthropometric and biochemical evaluation were performed.ResultsANCOVA analysis revealed that compared to the control group, quercetin could reduce high sensitivity C-reactive protein (hs-CRP) (P = 0.046), iron (p = 0.036), ferritin (p = 0.043), and transferrin saturation (TS) (p = 0.008) and increase transferrin (p = 0.045) significantly, but it had no significant effect on total iron binding capacity (TIBC) (p = 0.734) and tumor necrosis factor α (TNF-α) (p = 0.310).ConclusionsQuercetin could ameliorate the iron status in thalassemia major, but its effect on inflammation is indistinctive.     

Improvement in oxidative stress and antioxidant parameters in β-thalassemia/Hb E patients treated with curcuminoids

ObjectivesTo evaluate the hematological profile, oxidative stress, and antioxidant parameters in β-thalassemia/Hb E patients treated with curcuminoids for 12 months.Design and methodsTwenty-one β-thalassemia/Hb E patients were given 2 capsules of 250 mg each of curcuminoids (a total of 500 mg) daily for 12 months. Blood was collected every 2 months during treatment and 3 months after withdrawal and was determined for complete blood count, malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) in red blood cells (RBC), and non-transferrin bound iron (NTBI) in serum.ResultsThe increased oxidative stress in β-thalassemia/Hb E patients was shown by higher levels of MDA, SOD, GSH-Px in RBC, serum NTBI, and lower level of RBC GSH. Curcuminoids administration resulted in improvement of all the measured parameters as long as they were administered. After 3 months withdrawal of treatment, all parameters returned close to baseline levels.ConclusionCurcuminoids may be used to ameliorate oxidative damage in patients with β-thalassemia/Hb E disease.     

Fanconi syndrome in a patient with β-thalassemia major after using deferasirox for 27 months

BACKGROUND: Deferasirox (DFRA) is a new approved oral iron chelator. Its advantages are that it is convenient and better tolerated and adhered to due to “once‐daily” oral dosage. However, its use in the field is limited and it is yet to be subjected to postmarketing surveillance. CASE REPORT: A 18.75‐year‐old male with β‐thalassemia major received oral DFRA therapy due to transfusional iron overload for 27 months. He had received iron chelation therapy with deferoxamine injection together with oral deferiprone. However, his compliance was poor (very high routine serum ferritin level, ranging from 1059 to 6030 ng/mL). After 25 months of DFRA therapy, the serum ferritin level declined from 4097 to 1343 ng/mL. He experienced five hospital admissions including coma, Fanconi syndrome, hepatic dysfunction, and thrombocytopenia after using DFRA as oral iron chelator. After we discontinued DFRA, he recovered fully without hepatic dysfunction, thrombocytopenia, proteinuria, glucosuria, and hypophosphatemia. CONCLUSIONS: Our case illustrates the potential risks of DFRA‐induced renal toxicity, hepatic dysfunction, and thrombocytopenia. Meticulous monitoring of kidney, liver, and hematopoietic function is mandatory for patients undergoing treatment with DFRA. Further investigation of the potential risk and adverse effects of long‐term DFRA use is necessary.     

Lower β-endorphin content of peripheral blood mononuclear cells in patients with complex regional pain syndrome

Recent studies have demonstrated that immune cell-derived β-endorphin inhibits peripheral nociception. Changes in the β-endorphin content of peripheral blood mononuclear cells (PBMC) were also reported in various human disorders. These findings suggest the modulation of pain by immuno-neural interaction through opioid-dependent mechanisms. The aim of this study, therefore, was to determine whether the levels of β-endorphin in PBMC of patients with complex regional pain syndrome (CRPS) differ from those of healthy subjects. Heparinized venous blood was collected from ten CRPS patients (7 women and 3 men; mean age 39.4 ± 13.0 years) and 13 age-matched healthy volunteers (6 women and 7 men; mean age 38.4 ± 10.8 years). PBMC were separated by density gradient centrifugation. β- endorphin was extracted from the cells in a commercial cell lysis buffer and its concentration was measured by enzyme immunoassay technique. Immunoreactive β-endorphin levels in PBMC from the CRPS patients were significantly lower than those from the healthy volunteers (101.5 ± 57.5 versus 222.1 ± 77.6, P < 0.001), and were not correlated to the present pain intensity or pain duration. The results indicate an altered condition of the immune-linked opioid system underlying CRPS. Further immunological approaches may provide new insight into the pathophysiology of CRPS.     

Changes of PPARγ protein expression and activity in peripheral blood lymphocytes of patients with sepsis

Objective To investigate the changes of PPARγ protein expression and activity of peripheral blood lymphocytes in patients with sepsis and its association with severity and prognosis of sepsis. Method Ac-cording to the guidelines to sepsis set by ACCP/SCCM consensus conference in 2003, 48 patients with sepsis ad-mitted in Emergency and Surgical ICU from December 2007 to March 2008 were enrolled in this perspective study. Sixteen healthy individuals were selected as controls. Patients with metastatic tumors, autoimmune disease, AIDS or under immunosuppressive therapy were excluded. This study was approved by the ethical committee of Zhong-shan Hospital, Fudan University. All patients were divided into mild and severe sepsis groups. Patients were also divided into survivor and non-survivor groups as per 28-day mortality. Peripheral blood lymphocytes were isolated by using Ficoll density gradient centrifugation. PPART protein expression was determined by using Westem Blot-ting. The activity of PPARγ was analyzed by using EMSA. Differences among groups were analyzed by using one-way ANOVA. Results The protein expression and activity of PPARγ were significantly increased in mild sepsis patients (0.56±0.12 and 4.13±0.22, respectively) compared with both healthy controls (0.39±0.07 and 2.42±0.17, respectively) and severe sepsis patients (0.30±0.07 and 1.63±0.12, respectively) (P < 0.05). However, the protein expression and activity of PPARγ were obviously decreased in severe sepsis patients compared with healthy individuals and mild spsis patients (P < 0.05). Survivors from sepsis had significantly higher protein expression and activity (0.54±0.11 and 3.59±0.34, respectively) than non-survivors (0.21±0.08 and 1.94 ±0.25, respectively) (P < 0.05). Conclusions These data suggest that the protein expression and activity of PPARγ in peripheral blood lymphocytes might be valuable biomarkers in assessing the severity and outcome of pa-tients with sepsis.     

High excretion of β-aminoisobutyric acid in patients with ketoacidosis

High concentrations of β-aminoisobutyric acid (BAIBA) were found to be present in the urine from patients with ketoacidosis. The R-form was always the dominating isomer of BAIBA. The finding is discussed, and it is suggested that the mechanism might be a derangement in the degradation of valine.     

Observation of improvement of movement function by Chinese drugs through promoting circulation by removing blood stasis in patients with brain hemorrhage

Background：Disabilityratefollowingbrainhemorrhageishigh．Recoveryandimprovementofmovementfunctioniscloselyrelatedtomanagementofbrainhemorrhageduringacutephage，absorptionofhematoma．Accordingtotraditionalmedicineprinci－ple，Chinesedrugspromoteabsorptionandfunctionalrecoverythroughpromotingbloodcirculationbyremovingbloodstasis．TheChinesedrugsaresafeinclinic．Objective：ToobserveimprovementofmovementfunctionthroughpromotingbloodcirculationbyremovingbloodstasiswithChinesedrugs．Design：Rand…     

Plasma homocysteine levels in patients with β‐thalassaemia major

Objective. We investigated the level of homocysteine (HCY) and its relation with vitamin B12, folate and oxidative stress in patients with β‐thalassaemia major. Material and methods. Plasma HCY, methionine, advanced oxidation protein products (AOPP) and serum vitamin B12, folate, ferritin and total antioxidant capacity (TAC) were determined in 32 thalassaemic patients and 27 control subjects. Results. HCY (6.44±0.44 versus 8.71±0.57?µmol/L), methionine (12.57±1.8 versus 22.2±3.8?µmol/L), folate (9.14±0.48 versus 15.38±0.71?nmol/L) and TAC (0.34±0.03 versus 0.56±0.03?mmol/L) significantly decreased in thalassaemic patients, whereas AOPP (20.26±1.8 versus 11.30±0.2 μmol/L) and ferritin (3481.0±512 versus 46.9±4.6?ng/mL) significantly increased. Vitamin B12 levels were similar in both groups (259.1±16.6 versus 228.9±7.4 pmol/L). Conclusions. These findings suggest that increased and uncompensated oxidative stress may lead to an increment in HCY catabolism in thalassaemic patients.     

Correlated analysis of the leukocyte CD18 and CD54 of blood in patients with acute cerebral infarction

Background：Recentlytherelationshipbetweencelladhesionmolecule（CAM）andcerebralarterialthrombosisaremoreandmoreinterested．Withthedataoftheanimalexperimentbecomingmoreandmoreplentive，therehasbeensomesignificantfindings．Butthereisnotmuchresearchonpatients．NowinthisarticlewewilldetecttheexpressionofCD１８andCD５４inbloodleukocyteof８８patientswithACIbyusingflowcytometerandexploreitsclinicalsignificance．Objective：ToexploretherelationbetweentheexpressionofCD１８andCD５４inbloodleukocy…     

The analysis of blood vessels of brain and function of senile patients with cerebrovascular disease

BACKGROUND：Theischemiccerebrovasculardiseaseofsenilepatientshasthefeaturesofhighrecurrencerate，badprognosisandmanyinfluencefactors．ThecomingoutofCTmakesdiagnosisofcerebrovasculardiseasegettingreliablefoundation．ButthediagnosisofCTcannotdeterminethelocationofspecificbloodvesselsofresion，especiallytheischemicchangescausedbyspasmandnar－rownessofbloodvesselsinearlyperiod．Inaddition，examinationofcerebralangiographycancausetrauma，sopatientswithseverecerebrovasculardiseasecannotendurei…     

Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice

β-Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both disorders are characterized by low levels of hepcidin (HAMP), the hormone that regulates iron absorption. As a consequence, patients affected by these disorders exhibit iron overload, which is the main cause of morbidity and mortality. HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression. We identified second generation antisense oligonucleotides (ASOs) targeting mouse Tmprss6. ASO treatment in mice affected by hemochromatosis (Hfe^–/–) significantly decreased serum iron, transferrin saturation and liver iron accumulation. Furthermore, ASO treatment of mice affected by β-thalassemia (HBB^th3/+ mice, referred to hereafter as th3/+ mice) decreased the formation of insoluble membrane-bound globins, ROS, and apoptosis, and improved anemia. These animals also exhibited lower erythropoietin levels, a significant amelioration of ineffective erythropoiesis (IE) and splenomegaly, and an increase in total hemoglobin levels. These data suggest that ASOs targeting Tmprss6 could be beneficial in individuals with hemochromatosis, β-thalassemia, and related disorders.     

Analysis of anxiety and depression in patients with nontypical angina pectoris by coronary arteriography

INTRODUCTIONTherearedramaticdifferencesininductionfactors，nature，locus，duration，reliefmannerofpainbetweentypicalandnontypicalanginapectoris．Causesandpathogenesisofpainarecomplicated，andmaybecorrelatedwithanxietyanddepression．MATERIALSANDMETHODSMaterials３２PatientswithnontypicalanginapectorisandHADconfirmedanxietyanddepressionwereselectedintogroupA，including１４malesand１８females．Patienswithsuspiciousdepressionandanxietywereexcludedfromourstudy．３４patientssufferedfrom…