Regulation of CO2 by the sea in areas around Latin America in a context of climate change.

Anthropogenic activities are increasing the atmospheric carbon dioxide (CO2); around a third of the CO2 emitted by these activities has been taken up by the ocean. Nevertheless, this marine ecosystem service of regulation remains largely invisible to society, and not enough is known about regional differences and trends in sea-air CO2 fluxes (FCO2), especially in the Southern Hemisphere. The objectives of this work were as follows: first to put values of FCO2 integrated over the exclusive economic zones (EEZ) of five Latin-American countries (Argentina, Brazil, Mexico, Peru, and Venezuela) into perspective regarding total country-level greenhouse gases (GHG) emissions. Second, to assess the variability of two main biological factors affecting FCO2 at marine ecological time series (METS) in these areas. FCO2 over the EEZs were estimated using the NEMO model, and GHG emissions were taken from reports to the UN Framework Convention on Climate Change. For each METS, the variability in phytoplankton biomass (indexed by chlorophyll-a concentration, Chla) and abundance of different cell sizes (phy-size) were analyzed at two time periods (2000-2015 and 2007-2015). Estimates of FCO2 at the analyzed EEZs showed high variability among each other and non-negligible values in the context of greenhouse gas emissions. The trends observed at the METS indicated, in some cases, an increase in Chla (e.g., EPEA-Argentina) and a decrease in others (e.g., IMARPE-Peru). Evidence of increasing populations of small size-phytoplankton was observed (e.g., EPEA-Argentina, Ensenada-Mexico), which would affect the carbon export to the deep ocean. These results highlight the relevance of ocean health and its ecosystem service of regulation when discussing carbon net emissions and budgets.

MicroRNA-4463 facilitates the development of colon cancer by suppression of the expression of PPP1R12B.

PURPOSE: In the present work, we investigated the expression pattern of miR-4463 in the non-metastasis and metastasis colorectal cancer (CRC) patients and its regulation axis. METHODS: RT-qPCR assay was performed to assess miR-4463 expression in the serum and tissues of patients with non-metastasis and metastasis, and in the CRC cell lines. MTT assay, colony formation assay, transwell assay, and flow cytometry assay were used to examine the role of miR-4463 in CRC cell viability, proliferation, and migration. Bioinformatic analysis was used to identify the potential target gene of miR-4463, and the targeting relationship between miR-4463 and PPP1R12B was verified in vitro using dual luciferase assay. Western blotting assay was used to determine the protein level of the target gene PPP1R12B in CRC cells under the transfections of miR-4463 mimic, inhibitor and vectors overexpressing PPP1R12B. RESULTS: miR-4463 was markedly increased in the non-metastasis CRC tissues, and increased even higher in the metastasis CRC tissues, while miR-4463 expression had no significant difference in serum from non-metastasis and metastasis CRC samples. Besides, miR-4463 was upregulated in CRC cell lines. Functionally, miR-4463 promoted CRC cell proliferation, migration, and inhibiting cell apoptosis. Further analysis revealed that the miR-4463/PPP1R12B axis was responsible for the role of this miRNA. CONCLUSION: We reported the roles of miR-4463 in CRC proliferation and migration, supporting that miR-4463 could be a potential predictive diagnostic marker for colon cancer.

Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer.

Iodine is an essential constituent of thyroid hormone. Active iodide accumulation in the thyroid is mediated by the sodium iodide symporter (NIS), comprising the first step in thyroid hormone biosynthesis, which relies on the functional expression of NIS on the cell membrane. The retention of NIS expressed in differentiated thyroid cancer (DTC) cells allows further treatment with post-operative radioactive iodine (RAI) therapy. However, compared with normal thyroid tissue, differentiated thyroid tumors usually show a decrease in the active iodide conveyance and NIS is generally retained within the cells, indicating that posttranslational protein transfer to the plasma membrane is abnormal. In recent years, through in vitro studies and studies of patients with DTC, various methods have been tested to increase the transport rate of NIS to the cell membrane and increase the absorption of iodine. An in-depth understanding of the mechanism of NIS transport to the plasma membrane could lead to improvements in RAI therapy. Therefore, in this review, we discuss the current knowledge concerning the post-translational mechanisms that regulate NIS transport to the cell membrane and the current status of redifferentiation therapy for patients with RAI-refractory (RAIR)-DTC.

Down-regulation of LINC00667 hinders renal tubular epithelial cell apoptosis and fibrosis through miR-34c.

PURPOSE: This study aimed to down-regulate LINC00667 and inhibit apoptosis and fibrosis of renal tubular epithelial cells through miR-34c. METHODS: Altogether, 98 patients with chronic kidney disease treated in our hospital were selected as the study group, and 67 normal people were selected as the control group. Epithelial cells of proximal convoluted tubules in human renal cortex were purchased. TGF-ß1 was used to induce fibrosis of HK-2 renal tubular epithelial cells. The expression of LINC00667, miR-34c, type I collagen (Col 1) and type III collagen (Col 3) were detected by qRT-PCR and WB. RESULTS: LINC00667 was highly expressed in cancer tissues and HK-2, while miR-34c was poorly expressed. Inhibition of LINC00667 and over-expression of miR-34c could inhibit the proliferation and invasion of chronic kidney disease cells, but increase the apoptosis rate. Down-regulation of LINC00667 could significantly reduce of Col 1 and Col 3 in renal interstitial fibroblasts induced by TGF-ß1, while up-regulation of miR-34c could also achieve this effect. Double luciferase report confirmed that there was a targeted regulatory relationship between LINC00667 and miR-34c. CONCLUSION: LINC00667 could reduce the proliferation and invasion of chronic kidney disease cells, increase the apoptosis rate by regulating miR-34c, and improve renal fibrosis.

Pancreatic ß-cell function is inhibited by miR-3666 in type 2 diabetes mellitus by targeting adiponectin.

Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder, and poses threats to human health worldwide. Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of T2D. In this study, we explored the role of miR-3666 in T2D. miR-3666 was significantly down-regulated in the serum of T2D patients when compared to that of healthy volunteers, and miR-3666 expression level was negatively correlated with blood glucose levels of T2D patients. Overexpression of miR-3666 inhibited cell proliferation, reduced insulin secretion, and promoted cell apoptosis of pancreatic ß-cell line (INS-1 cells). On the other hand, knockdown of miR-3666 had the opposite effects in INS-1 cells. The bio-informatics analysis using TargetScan revealed that adiponectin (ADIPOQ) was a downstream target of miR-3666, and the interaction between miR-3666 and ADIPOQ was validated by luciferase reporter assay. In addition, miR-3666 negatively regulated the mRNA and protein expression of ADIPOQ. Overexpression of ADIPOQ promoted insulin secretion after glucose stimulation, promoted cell proliferation, inhibited cell apoptosis, and partially abolished the effects of miR-3666 overexpression on insulin secretion, cell proliferation, and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-3666 inhibited pancreatic cell proliferation, reduced insulin sensitivity, and promoted apoptosis by targeting ADIPOQ.

Pancreatic ß-cell function is inhibited by miR-3666 in type 2 diabetes mellitus by targeting adiponectin

Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder, and poses threats to human health worldwide. Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of T2D. In this study, we explored the role of miR-3666 in T2D. miR-3666 was significantly down-regulated in the serum of T2D patients when compared to that of healthy volunteers, and miR-3666 expression level was negatively correlated with blood glucose levels of T2D patients. Overexpression of miR-3666 inhibited cell proliferation, reduced insulin secretion, and promoted cell apoptosis of pancreatic β-cell line (INS-1 cells). On the other hand, knockdown of miR-3666 had the opposite effects in INS-1 cells. The bio-informatics analysis using TargetScan revealed that adiponectin (ADIPOQ) was a downstream target of miR-3666, and the interaction between miR-3666 and ADIPOQ was validated by luciferase reporter assay. In addition, miR-3666 negatively regulated the mRNA and protein expression of ADIPOQ. Overexpression of ADIPOQ promoted insulin secretion after glucose stimulation, promoted cell proliferation, inhibited cell apoptosis, and partially abolished the effects of miR-3666 overexpression on insulin secretion, cell proliferation, and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-3666 inhibited pancreatic cell proliferation, reduced insulin sensitivity, and promoted apoptosis by targeting ADIPOQ.

Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia.

Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.

Cloning of three genes involved in the flavonoid metabolic pathway and their expression during insect resistance in Pinus massoniana Lamb.

Pinus massoniana Lamb. is an important timber and turpentine-producing tree species in China. Dendrolimus punctatus and Dasychira axutha are leaf-eating pests that have harmful effects on P. massoniana production. Few studies have focused on the molecular mechanisms underlying pest resistance in P. massoniana. Based on sequencing analysis of the transcriptomes of insect-resistant P. massoniana, three key genes involved in the flavonoid metabolic pathway were identified in the present study (PmF3H, PmF3'5'H, and PmC4H). Structural domain analysis showed that the PmF3H gene contains typical binding sites for the 2OG-Fe (II) oxygenase superfamily, while PmF3'5'H and PmC4H both contain the cytochrome P450 structural domain, which is specific for P450 enzymes. Phylogenetic analysis showed that each of the three P. massoniana genes, and the homologous genes in gymnosperms, clustered into a group. Expression of these three genes was highest in the stems, and was higher in the insect-resistant P. massoniana varieties than in the controls. The extent of the increased expression in the insect-resistant P. massoniana varieties indicated that these three genes are involved in defense mechanisms against pests in this species. In the insect-resistant varieties, rapid induction of PmF3H increased the levels of PmF3'5'H and PmC4H expression. The enhanced anti-pest capability of the insect-resistant varieties could be related to temperature and humidity. In addition, these results suggest that these three genes maycontribute to the change in flower color during female cone development.

729G/C polymorphism in Toll-like receptor 4 results in increased susceptibility to bladder cancer.

In this study, the association between the 729G/C polymorphism in Toll-like receptor 4 (TLR4) and the risk of bladder cancer was investigated. A total of 376 patients with bladder cancer and 380 healthy volunteers from the Third Xiangya Hospital of Central South University (China) were enrolled in this study between January 2008 and February 2014. The TLR4-729G/C polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism assay. There was a significant difference in the distribution of the TLR4-729G/C genotype between bladder cancer patients and healthy controls (P < 0.001). Our analysis showed that the GC genotype (OR = 2.99; 95%CI = 1.01-4.81, P = 0.046) and CC genotype (OR = 3.67; 95%CI = 2.11-7.27, P = 0.017) were significantly associated with increased bladder cancer risk when the GG genotype served as a reference. Furthermore, carriers of the C allele had a significantly increased risk of developing bladder cancer (OR = 3.89; 95%CI = 2.88-8.53; P = 0.009). Our results suggest a correlation between the TLR4-729G/C polymorphism and the risk of developing bladder cancer in this Chinese population.

Lack of clinical significance of the ImmuKnow(TM)-Cylex assay for the detection of cellular immune function in patients with renal cell carcinoma.

This study aimed to explore the clinical value of the CD4(+) T cell ATP levels in patients with renal cell carcinoma through the application of the ImmuKnow(TM)-Cylex(®) assay. We recruited 104 patients with renal cancer who had undergone surgery at Fuzhou General Hospital from March 2009 to June 2012, and were subsequently treated by dendritic cell and cytokine-induced killer cell bio-therapy or interferon-α therapy. The changes in CD4(+) T cell ATP levels were detected at the perioperative period and at 10 days, 1 month, 3 months, and 1 year after the surgery using the ImmuKnow assay. In addition, the differences in ATP levels in different therapy groups were compared and the prognosis conditions were analyzed. Our results demonstrated that no significant difference in the ATP levels occurred at different time points; furthermore, there were no obviously different ATP levels between the different therapy groups, and the ATP levels were found to have no clinical significance for the assessment of renal cancer prognosis. Overall, this study suggested that CD4(+) T cell ATP levels as detected by the ImmuKnow assay have no obvious clinical value in patients with renal cancer.

Expression of TNF-α, VEGF, and MMP-3 mRNAs in synovial tissues and their roles in fibroblast-mediated osteogenesis in ankylosing spondylitis.

The aim of this study was to explore the mRNA levels of tumor necrosis factor-α (TNF-α), vessel endothelial growth factor (VEGF), and matrix metalloproteinase-3 (MMP-3) in synovial tissues in ankylosing spondylitis (AS), and to analyze the functions of these proteins in the differentiation of AS synovial tissue fibroblasts into osteoblasts (OB) and osteoclasts. Synovial tissue samples from 22 AS patients and 22 normal individuals were collected. In situ hybridization was utilized to detect TNF-α, VEGF, and MMP-3 transcripts. After counting numbers of positive cells, Spearman analysis was used to determine the correlation between transcriptional levels of the three mRNAs and the AS disease activity index (BASDAI) and the C-response protein (CRP) levels. With the addition of TNF-α, VEGF, or both factors into cultured normal synovial fibroblasts, osteocalcin (bone gla protein, BGP) secretion levels were compared. We found that expression of TNF-α, VEGF, and MMP-3 was identified exclusively in the disease group. mRNA levels were significantly positively correlated with BASDAI (r = 0.42, 0.38, and 0.47, respectively; P < 0.05) and CRP (r = 0.44, 0.34, and 0.47 respectively; P < 0.05) scores. The secretion level of BGP in normal synovial fibroblasts increased progressively with increasing concentrations of VEGF or TNF-α (P < 0.01 compared to levels before treatment). Furthermore, co-incubation using both VEGF and TNF-α significantly elevated BGP levels compared to the single addition of VEGF or TNF-α (P < 0.01). These results suggest TNF-α, VEGF, and MMP-3 might directly participate in the differentiation of fibroblasts into OBs.

Characteristics of immune cell changes before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion.

To investigate the characteristics of immune cells before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion (URSA), an analysis of 67 URSA patients, 67 sporadic spontaneous abortion (SA) patients, and 22 normal nonpregnant women (as controls) was conducted. URSA patients underwent immunotherapy using paternal lymphocytes. Peripheral blood from patients and controls was examined for lymphocytes and other markers of immune status. Before the immunotherapy, lymphocyte counts, CD4:CD8 cell ratios, and the relative proportion of natural killer (NK) cells were significantly higher in the URSA patient group than in the SA patient and control groups (P < 0.05). After the therapy, all of these three measures were decreased, whereas the percentage of T cells was increased, and statistically significant differences before and after the immunotherapy were detected (P < 0.05). Therefore, the immune system appears to be activated in the URSA patients, and the abnormal immunologic state in the URSA patients is more severe than in the SA patients. The alterations in T and NK cells may be involved in the etiopathogenesis of URSA. Lymphocyte immunotherapy appears to be an effective treatment for URSA patients.

Fetal fibronectin detection for preterm birth prediction.

To study preterm birth prediction based on fetal fibronectin (fFN) in pregnant women, we randomly selected 124 patients. Vaginal posterior fornix secretions were analyzed using fFN quick test strips. Leucorrhea routine samples were collected to detect bacterial vaginosis, mycoplasma, and chlamydia. Delivery data at 7 days, 14 days, 34 weeks, and 37 weeks were documented and the sensitivity, specificity, positive predictive value, and negative predictive value were analyzed. Of the 124 cases, we found 2, 4, 10, and 18 cases of maternity within 7 days, 14 days, 34 weeks, and 37 weeks, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were as follows: 100, 77.8, 6.9, and 100% for 7 days; 75, 78.3, 10.3, and 98.9% for 14 days; 50.0, 78.9, 17.2, and 94.7% for 34 weeks; 33.3, 78.3, 20.7, and 87.4% for 37 weeks, respectively. Except for 18 preterm births, 23 cases were fFN-positive, 17 cases had lower genital tract infection. Eighty-three cases were fFN-negative, of which 18 cases had the lower genital tract infections. This difference was statistically significant (P < 0.05). Eighteen cases (14.5% of the pregnant women) had preterm birth. Ten cases delivered within 34 weeks. The negative predictive value and recent predictive value of fFN testing were higher; the positive predictive value was limited due to the impact of lower genital tract infection. The fFN-positive patients need timely clinical processing. During the pregnancy, monitoring of fFN changes and early detection of abnormalities help to reduce perinatal morbidity and mortality.

Specific and straightforward molecular investigation of ß-thalassemia mutations in the Malaysian Malays and Chinese using direct TaqMan genotyping assays.

Beta-thalassemia is a life-threatening inherited blood disorder. Rapid characterization of ß-globin gene mutations is necessary because of the high frequency of Malaysian ß-thalassemia carriers. A combination real-time polymerase chain reaction genotyping assay using TaqMan probes was developed to confirm ß-globin gene mutations. In this study, primers and probes were designed to specifically identify 8 common ß-thalassemia mutations in the Malaysian Malay and Chinese ethnic groups using the Primer Express software. "Blind tests" using DNA samples from healthy individuals and ß-thalassemia patients with different genotypes were performed to determine the specificity and sensitivity of this newly designed assay. Our results showed 100% sensitivity and specificity for this novel assay. In conclusion, the TaqMan genotyping assay is a straightforward assay that allows detection of ß-globin gene mutations in less than 40 min. The simplicity and reproducibility of the TaqMan genotyping assay permit its use in laboratories as a rapid and cost-effective diagnostic tool for confirmation of common ß-thalassemia mutations in Malaysia.

Genetic variants on 17q21 are associated with asthma in a Han Chinese population.

A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.

Paraoxonase 1 status in keratoconus: a preliminary study of activity and polymorphism.

OBJECTIVE: To determine the activity of paraoxonase 1 (PON1) in keratoconus in a Malaysian population in comparison with non-keratoconic subjects. METHODS: Clinical eye examinations were performed on patients with keratoconus and non-keratoconic subjects after questionnaires were completed. Blood samples were collected and subjected to spectrophotometric analysis of paraoxonase and diazoxonase activities for the determination of the status of PON1 of every individual. RESULTS: Of the 11 keratoconic patients and 55 non-keratoconic control samples collected, eight patients of Indian ethnicity were keratoconic (73%), whereas 33 non-Indians were non-keratoconic (60%; p = 0.047). Paraoxonase activity was lower in Indians compared to the non-Indians ie Malays and Chinese (p = 0.008). Keratoconic subjects had a lower paraoxonase activity compared to non-keratoconics (p = 0.038). CONCLUSIONS: The reduced paraoxonase activity in keratoconic patients suggests that the keratoconic corneas were more susceptible to oxidative stress. Reduced paraoxonase activity and keratoconus status appears to be associated with ethnicity.

Inhibition of STAT3 by RNA interference suppresses angiogenesis in colorectal carcinoma

In order to investigate signal transduction and activation of transcription 3 (STAT3) signaling on angiogenesis in colorectal carcinoma (CRC) after inhibiting STAT3 expression, we constructed the HT-29-shSTAT3 cell line by lentivirus-mediated RNAi. Cell growth was assessed with MTT and the cell cycle distribution by flow cytometry. CRC nude mouse models were established and tumor growth was monitored periodically. On day 30, all mice were killed and tumor tissues were removed. Microvessel density (MVD) was determined according to CD34-positive staining. The expression of vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2 (MMP2) and basic fibroblast growth factor (FGF2) was monitored by quantitative real-time PCR and Western blot analysis. Knockdown of STAT3 expression significantly inhibited cell growth in HT-29 cells, with a significantly higher proportion of cells at G0/G1 (P < 0.01). Consistently, in vivo data also demonstrated that tumor growth was significantly inhibited in mice injected with HT-29-shSTAT3 cells. MVD was 9.80 ± 3.02 in the HT-29-shSTAT3 group, significantly less than that of the control group (P < 0.01). mRNA and protein levels of VEGFA and MMP2 in the HT-29-shSTAT3 group were significantly lower than in the control group (P < 0.05), but no significant difference was observed in the mRNA or protein level of FGF2 (P > 0.05). Taken together, these results demonstrate that STAT3 signaling is important to the growth of CRC and promotes angiogenesis by regulating VEGFA and MMP2 expression.

Inhibition of STAT3 by RNA interference suppresses angiogenesis in colorectal carcinoma.

In order to investigate signal transduction and activation of transcription 3 (STAT3) signaling on angiogenesis in colorectal carcinoma (CRC) after inhibiting STAT3 expression, we constructed the HT-29-shSTAT3 cell line by lentivirus-mediated RNAi. Cell growth was assessed with MTT and the cell cycle distribution by flow cytometry. CRC nude mouse models were established and tumor growth was monitored periodically. On day 30, all mice were killed and tumor tissues were removed. Microvessel density (MVD) was determined according to CD34-positive staining. The expression of vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2 (MMP2) and basic fibroblast growth factor (FGF2) was monitored by quantitative real-time PCR and Western blot analysis. Knockdown of STAT3 expression significantly inhibited cell growth in HT-29 cells, with a significantly higher proportion of cells at G0/G1 (P < 0.01). Consistently, in vivo data also demonstrated that tumor growth was significantly inhibited in mice injected with HT-29-shSTAT3 cells. MVD was 9.80 ± 3.02 in the HT-29-shSTAT3 group, significantly less than that of the control group (P < 0.01). mRNA and protein levels of VEGFA and MMP2 in the HT-29-shSTAT3 group were significantly lower than in the control group (P < 0.05), but no significant difference was observed in the mRNA or protein level of FGF2 (P > 0.05). Taken together, these results demonstrate that STAT3 signaling is important to the growth of CRC and promotes angiogenesis by regulating VEGFA and MMP2 expression.

Chelation therapy with desferrioxamine does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese beta-thalassaemia major patients.

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in beta-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxamine-chelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese beta-thalassaemia major patients.

Comparison of baseline sister-chromatid exchanges (SCE), cyclophosphamide-, ethylnitrosourea (ENU)-induced SCE, ENU-induced cell-cycle delay and chromosome aberrations between Peru and laboratory mice.

The baseline sister-chromatid exchange (SCE) frequency and sensitivity to the effects of the mutagens cyclophosphamide (CPP) and ethylnitrosourea (ENU) in bone-marrow cells of descendants of wild mice trapped from Rimac valley in Peru (Peru mice) were studied and compared to the same effects in laboratory mice. Baseline SCE of the Peru mice were significantly higher than those of the C57BL/6J and DBA/2 mice. The average SCE/cell of 4 Peru mice was 5.4 (range 3.8-7.6), while the average of SCE/cell of either 4 C57BL or 5 DBA mice was 3.2 (range 3.0-3.4). The variation of SCE/cell among Peru mice studied was statistically significant whereas among C57BL or DBA mice it was not. SCE frequencies of primary cultures derived from the ear tissue of 10 Peru (mean SCE/cell = 8.5) were also significantly higher than those of 6 C57BL mice (mean SCE/cell = 7.4). CPP treatment resulted in a dose-dependent increase of SCE frequencies in bone-marrow cells of all the mice. However, some of Peru mice treated with CPP had significantly higher SCE than the other Peru mice and than all of the C57BL and DBA mice treated with equivalent dose. ENU induced increased SCE frequencies in Peru and C57BL mice. Again some of Peru mice either had significantly higher SCE, greater extent induced cell-cycle delay or chromosome aberrations (CA) than other Peru mice and than of all the C57BL mice treated with equivalent dose.(ABSTRACT TRUNCATED AT 250 WORDS)