Oxidative Stress Induced by Chemotherapy: Evaluation of Glutathione and Its Related Antioxidant Enzyme Dynamics in Patients with Colorectal Cancer.

One of the mechanisms of chemotherapy is to increase the oxidative stress of cancer cells, leading to their apoptosis. Glutathione (GSH) and its related antioxidant enzymes might be stimulated to cope with increased oxidative stress during chemotherapy. Here, we studied the fluctuation in oxidative stress and GSH-related antioxidant capacities before tumor resection, after tumor resection, and after resection either with or without chemotherapy in patients with colorectal cancer (CRC). This was a cross-sectional and follow-up design. We followed patients before having tumor resection (pre-resection), one month after tumor resection (post-resection), and after the first scheduled chemotherapy (post-chemo). If patients were required to receive chemotherapy after tumor resection, they were assigned to the chemotherapy group. Eligible patients were scheduled to undergo six to twelve cycles of chemotherapy at 2-week intervals and received single, double, or triple chemotherapeutic drugs as required. Those patients who did not require chemotherapy were assigned to the non-chemotherapy group. Indicators of oxidative stress and GSH-related antioxidant capacities were determined at the above three time points. We found in 48 patients of the chemotherapy group and in 43 patients of the non-chemotherapy group different fluctuations in levels of oxidative stress indicators and GSH-related antioxidant capacities starting from pre-resection, post-resection through the post-chemo period. Both groups showed significantly or slightly increased levels of advanced oxidation protein products (AOPP), GSH, and its related enzymes in tumor tissues compared to adjacent normal tissues. Patients in the chemotherapy group had significantly lower plasma levels of GSH and glutathione disulfide (GSSG), but had significantly higher plasma glutathione peroxidase and glutathione reductase activities than patients in the non-chemotherapy group post-chemo. Plasma levels of malondialdehyde and AOPP were positively or negatively associated with GSH and GSSG levels post-chemo after adjustment for age, sex, and histological grading in patients receiving chemotherapy. These significant associations were, however, not seen in patients without chemotherapy. Patients with CRC may require higher GSH demands to cope with a greater oxidative stress resulting from chemotherapy.

Trace Elements Status and Their Associations With Related Antioxidant Enzyme Activities in Patients Receiving Peritoneal Dialysis and Hemodialysis.

OBJECTIVE: It remains ambiguous as to whether the status of trace elements would affect their related enzyme activities toward defending a possible higher oxidative stress in patients receiving peritoneal dialysis (PD) or hemodialysis (HD) treatment. We investigated copper (Cu), zinc (Zn), and selenium (Se) status in patients receiving PD or HD treatments and further determined the association of these trace elements with their related antioxidant capacities in those patients. METHODS: Sixty PD and 80 HD patients before and after HD treatment had their blood drawn. Demographic, clinical, and 24-hour diet recall data were recorded and collected. Plasma trace elements, oxidative stress indicators, and antioxidant enzyme activities were measured. RESULTS: Patients receiving PD or HD treatments experienced similar Zn and Cu intakes. PD and HD patients displayed adequate mean plasma Cu, Zn, and Se levels. Patients receiving PD treatment showed significantly higher levels of Cu, Zn, advanced oxidation protein products (AOPPs), and superoxide dismutase (SOD) activity, but had significantly lower levels of Se and total antioxidant capacity when compared to levels in the HD patients at the pre-HD session. The levels of 3 trace elements and AOPP increased significantly, while the levels of glutathione (GSH), oxidized glutathione (GSSG), GPx, and SOD activities decreased significantly after receiving HD treatment than did the levels in the pre-HD session. Plasma Cu, Se, and Zn levels had a different correlation with plasma AOPP level, GPx, and SOD activities during PD, pre- or post-HD sessions. Plasma Cu, Zn, and Se levels did not have any association with their associated enzyme activities in patients with PD, while plasma Cu and Zn levels may have influenced SOD activity in HD patients. CONCLUSIONS: An adequate Cu, Zn, and Se status is required in order to help their associated enzyme activity cope with increased oxidative stress during PD or HD sessions.

Cysteine Regulates Oxidative Stress and Glutathione-Related Antioxidative Capacity before and after Colorectal Tumor Resection.

Cysteine might scavenge free radicals and is a limiting substrate for the cellular synthesis of glutathione (GSH). We investigated the association of cysteine with oxidative stress and GSH-related antioxidant capacity in colorectal cancer (CRC) patients. Plasma samples were drawn from 66 patients 1 day before (pre-resection) and 4 weeks after resection (post-resection). Tumor and adjacent normal tissues were collected. We measured levels of plasma and tissue cysteine, homocysteine, oxidative stress indicators (malondialdehyde, MDA; advanced oxidation protein products, AOPP), GSH, and antioxidant enzyme activities. After tumor resection, patients had significantly higher levels of plasma cysteine, homocysteine, MDA, AOPP, and GSH-related antioxidant enzyme activities when compared with pre-resection. Levels of cysteine, homocysteine, AOPP and all antioxidant capacity indicators in tumor tissue were significantly higher than those levels in the adjacent normal tissue. Plasma cysteine levels measured at pre-resection were positively associated with MDA levels in the tumor and in the adjacent normal tissues. Cysteine levels in tumor and adjacent normal tissues were significantly associated with tissue levels of homocysteine, almost as indicators of oxidative stress and antioxidant capacities. Cysteine in the circulation was likely utilized to mediate GSH-related antioxidant capacity and further cope with increased oxidative stress in tumor and adjacent normal tissues.

Indoxyl sulfate, homocysteine, and antioxidant capacities in patients at different stages of chronic kidney disease.

BACKGROUND/OBJECTIVES: Increased levels of uremic toxins and decreased antioxidant capacity have a significant impact on the progression of chronic kidney disease (CKD). However, it remains unclear whether they interact with each other to mediate the damage of kidney function. The purpose of this study was to investigate whether uremic toxins (i.e., homocysteine and indoxyl sulfate [IS]), as well as glutathione-dependent antioxidant enzyme activities are dependently or independently associated with kidney function during different stages of CKD patients. SUBJECTS/METHODS: One hundred thirty-two patients diagnosed with CKD at stages 1 to 5 participated in this cross-sectional study. RESULTS: Patients who had reached an advanced CKD stage experienced an increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activity. Plasma homocysteine, cysteine, and IS concentrations were all positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting for potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS, and GSH-Px levels were significantly associated with kidney function, only plasma IS levels still had a significant association with kidney function after these parameters were simultaneously adjusted. In addition, plasma IS could interact with GSH-Px activity to be associated with kidney function. CONCLUSIONS: IS plays a more dominant role than homocysteine and GSH-Px activity in relation to kidney function.

Reduction of invasion and cell stemness and induction of apoptotic cell death by Cinnamomum cassia extracts on human osteosarcoma cells.

Cinnamomum cassia possesses antioxidative activity and induces the apoptotic properties of various cancer types. However, its effect on osteosarcoma invasion and cancer stemness remains ambiguous. Here, we examined the molecular evidence of the anti-invasive effects of ethanoic C. cassia extracts (CCE). Invasion and migration were obviously suppressed after the expression of urokinase-type plasminogen activator and matrix metalloprotein 2 in human osteosarcoma 143B cells were downregulated. CCE reversed epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor ß1 and downregulated mesenchymal markers, such as snail-1 and RhoA. CCE suppressed self-renewal property and the expression of stemness genes (aldehyde dehydrogenase, Nanog, and CD44) in the 143B cells. CCE suppressed cell viability, reduced the colony formation of osteosarcoma cancer cells, and induced apoptotic cell death in the 143B cells, as indicated by caspase-9 activation. The xenograft tumor model of immunodeficient BALB/c nude mice showed that CCE administered in vivo through oral gavage inhibited the growth of implanted 143B cells. These findings indicated that CCE inhibited the invasion, migration, and cancer stemness of the 143B cells. CCE reduced proliferation of 143B cell possibly because of the activation of caspase-9 and the consequent apoptosis, suggesting that CCE is a potential anticancer supplement for osteosarcoma.

The Prognostic Role of Glutathione and Its Related Antioxidant Enzymes in the Recurrence of Hepatocellular Carcinoma.

The imbalance of high oxidative stress and low antioxidant capacities is thought to be a significant cause of the development and progression of hepatocellular carcinoma (HCC). However, the impact of oxidative stress, glutathione (GSH), and its related antioxidant enzymes on the recurrence of HCC has not been investigated. The purpose of this study was to compare the changes to oxidative stress and GSH-related antioxidant capacities before and after tumor resection in patients with HCC recurrence and non-recurrence. We also evaluated the prognostic significance of GSH and its related enzymes in HCC recurrence. This was a cross-sectional and follow-up study. Ninety-two HCC patients who were going to receive tumor resection were recruited. We followed patients' recurrence and survival status until the end of the study, and then assigned patients into the recurrent or the non-recurrent group. The tumor recurrence rate was 52.2% during the median follow-up period of 3.0 years. Patients had significantly lower plasma malondialdehyde level, but significantly or slightly higher levels of GSH, glutathione disulfide, trolox equivalent antioxidant capacity, glutathione peroxidase (GPx), and glutathione reductase (GR) activities after tumor resection compared to the respective levels before tumor resection in both recurrent and non-recurrent groups. GSH level in HCC tissue was significantly higher than that in adjacent normal tissue in both recurrent and non-recurrent patients. Decreased plasma GPx (HR = 0.995, p = 0.01) and GR (HR = 0.98, p = 0.04) activities before tumor resection, and the increased change of GPx (post-pre-resection) (HR = 1.004, p = 0.03) activity were significantly associated with the recurrence of HCC. These findings suggest there might be a possible application of GPx or GR as therapeutic targets for reducing HCC recurrence.

Rutin and Gallic Acid Regulates Mitochondrial Functions via the SIRT1 Pathway in C2C12 Myotubes.

Mitochondria are highly dynamic organelles, balancing synthesis and degradation in response to increases in mitochondrial turnover (i.e., biogenesis, fusion, fission, and mitophagy) and function. The aim of this study was to investigate the role of polyphenols in the regulation of mitochondrial functions and dynamics in C2C12 myotubes and their molecular mechanisms. Our results indicate that gallic acid and rutin are the most potential polyphenol compounds in response to 15 phenolic acids and 5 flavonoids. Gallic acid and rutin were associated with a significantly greater mitochondrial DNA (cytochrome b and COX-II), mitochondrial enzymatic activities (including citrate synthase and cytochrome c oxidase), and intracellular ATP levels in C2C12 myotubes. Moreover, gallic acid and rutin significantly increased the gene expressions of mitochondrial turnover in C2C12 myotubes. Our findings indicated that gallic acid and rutin may have a beneficial effect on mitochondrial dynamics via regulation of the SIRT1-associated pathway in C2C12 myotubes.

Gossypol Reduces Metastasis and Epithelial-Mesenchymal Transition by Targeting Protease in Human Cervical Cancer.

Metastasis is the most prevalent cause of cancer-associated deaths amongst patients with cervical cancer. Epithelial-mesenchymal transition (EMT) is essential for carcinogenesis, and it confers metastatic properties to cancer cells. Gossypol is a natural polyphenolic compound with anti-inflammation, anti-oxidant, and anticancer activities. In this study, we investigated the antimetastatic and antitumour effects of gossypol on human cervical cancer cells (HeLa and SiHa cells). Gossypol exerted a strong inhibition effect on the migration and invasion of human cervical cancer cells. It reduced the focal adhesion kinase (FAK) pathway-mediated expression of matrix metalloproteinase-2 and urokinase-type plasminogen activator, subsequently inhibiting the invasion of SiHa cells. In addition, gossypol reversed EMT induced by transforming growth factor beta 1 (TGF-[Formula: see text]1) and up-regulated epithelial markers, such as E-cadherin but significantly suppressed Ras homolog family member (Rho)A, RhoB, and p-Samd3. The tail vein injection model showed that gossypol treatment via oral gavage reduced lung metastasis. Gossypol also decreased tumour growth in vivo in the nude mouse xenograft model. All these findings suggest that gossypol suppressed the invasion and migration of human cervical cancer cells by targeting the FAK signaling pathway and reversing TGF-[Formula: see text]1-induced EMT. Hence, gossypol warrants further attention for basic mechanistic studies and drug development.

Higher glutathione demand may be necessary for assisting haemodialysis patients to cope with increased oxidative stress.

AIM: The removal of cysteine during a dialysis procedure may affect glutathione (GSH) concentration, allowing haemodialysis (HD) patients to become more susceptible to oxidative damage. This study was performed to determine whether the change of GSH/glutathione disulfide (GSSG) redox state and GSH redox potential were linked with the change of cysteine or oxidative stress in patients receiving HD treatment. METHODS: Sixty-seven HD patients who had received regular HD treatment were recruited. Plasma GSH, GSSG, cysteine and malondialdehyde (MDA) were measured at both pre- and post-HD. RESULTS: Plasma cysteine, GSH and GSSG levels significantly decreased after the completion of HD, compared to the levels at pre-HD. Plasma MDA concentration, GSH/GSSG ratio and GSH redox potential remained constant during the dialysis session. Plasma GSH and GSSG were positively associated with plasma MDA at post-HD, while GSH redox potential was negatively associated with plasma MDA at post-HD. However, plasma GSH, GSSG, GSH/GSSG ratio and GSH redox potential were not associated with plasma cysteine at either pre- or post-HD. CONCLUSION: The GSH and GSSG levels were significantly utilized during a HD session, and their levels were significantly associated with increased oxidative stress. HD patients may require higher GSH demands to cope with increased oxidative stress during an HD session.

Plasma Homocysteine and Glutathione Are Independently Associated With Estimated Glomerular Filtration Rates in Patients With Renal Transplants.

BACKGROUND: Elevated levels of plasma homocysteine could, through homocysteine oxidation, induce the overproduction of reactive oxygen species, leading to a reduction in glutathione-related antioxidants, and may impair graft functions in patients with renal transplants. The purpose of this study was to determine whether plasma homocysteine, glutathione, or its related antioxidants were related to graft functions in patients with renal transplants. PATIENTS AND METHODS: We recruited 66 patients (mean age 48.4 years) with renal transplants (mean transplant duration 8.3 years). Patients were divided into 2 groups, based on their estimated glomerular filtration rate (eGFR): the moderate graft function group (eGFR ≥ 60 mL/min/1.73 m2, n = 37) and low graft function group (eGFR < 60 mL/min/1.73 m2, n = 29). We then determined their fasting levels of the following: malondialdehyde (MDA), homocysteine, cysteine, pyridoxal 5'-phosphate (PLP), glutathione (GSH), oxidized glutathione (GSSG), GSH/GSH ratio, glutathione peroxidase (GSH-Px) activity. RESULTS: We found in the low graft function group significantly higher levels of plasma homocysteine, cysteine, GSH, and GSH/GSSG ratios. But an intergroup difference was not found regarding levels of MDA, PLP, GSSG, and GSH-Px activity. After adjusting for potential confounders, the increased plasma homocysteine and GSH levels were independently associated with lower eGFR. No interaction existed between homocysteine and GSH levels in association with eGFR. CONCLUSION: Increased plasma homocysteine and GSH levels appeared to be independent indicators of decreased graft functions in patients with renal transplants.

Possible Synergistic Effects of Glutathione and C-Reactive Protein in the Progression of Liver Cirrhosis.

Liver cirrhosis is often associated with increased inflammatory responses and changes of glutathione (GSH) status. The possible interactions between these two factors in mediating damages of liver function remain unclear. Here, we measured the inflammatory responses and GSH status in liver cirrhotic patients and compared them with healthy subjects. In addition, we assessed the relationship of the GSH status and levels of inflammatory markers with the severity of the disease. This was a cross-sectional study. In total, we recruited 63 liver cirrhotic patients with Child⁻Turcotte⁻Pugh class A scores, and 12 patients with class B⁻C scores, together with 110 healthy subjects. Patients with class B⁻C scores showed the highest level of high-sensitivity C-reactive protein (hs-CRP) when compared with class A patients or healthy subjects. Patients in class A group had significantly higher GSH levels when compared with class B⁻C group or healthy subjects. After adjusting for potential confounders and each other, serum hs-CRP levels showed positive association with the Child⁻Turcotte⁻Pugh scores, while GSH levels showed negative association with Child⁻Turcotte⁻Pugh scores. Interactions were found between levels of plasma GSH and serum hs-CRP (ß = 0.004, p = 0.016). CRP and GSH levels, which had showed interactions, were associated with the severity of liver cirrhosis.

Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection.

Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n = 16) group or the vitamin B-6 50 mg/d (n = 17) group for 12 weeks. Plasma pyridoxal 5'-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (ß = -2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (ß = -162.0, p = 0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov.

Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress.

BACKGROUND: Vitamin B6 may directly or indirectly play a role in oxidative stress and the antioxidant defense system. OBJECTIVE: The purpose of this study was to examine the associations of vitamin B6 status with cysteine, glutathione, and its related enzyme activities in mice with homocysteine-induced oxidative stress. DESIGN: Four-week-old male BALB/c mice were weighed and divided into one of four dietary treatment groups fed either a normal diet (as a control group and a homocysteine group), a vitamin B6-deficient diet (as a B6-deficient group), or a B6-supplemented diet (a pyridoxine-HCl-free diet supplemented with 14 mg/kg of pyridoxine-HCl, as a B6 supplement group) for 28 days. Homocysteine thiolactone was then added to drinking water in three groups for 21 days to induce oxidative stress. At the end of the study, mice were sacrificed by decapitation and blood and liver samples were obtained. RESULTS: Mice with vitamin B6-deficient diet had the highest homocysteine concentration in plasma and liver among groups. Significantly increased hepatic malondialdehyde levels were observed in the vitamin B6-deficient group. Among homocysteine-treated groups, mice with vitamin B6-deficient diet had the highest plasma glutathione concentration and relatively lower hepatic glutathione concentration. The glutathione peroxidase activities remained relatively stable in plasma and liver whether vitamin B6 was adequate, deficient, or supplemented. CONCLUSIONS: Mice with deficient vitamin B6 intakes had an aggravate effect under homocysteine-induced oxidative stress. The vitamin B6-deficient status seems to mediate the oxidative stress in connection with the redistribution of glutathione from liver to plasma, but not further affect glutathione-related enzyme activities in mice with homocysteine-induced oxidative stress.

High serum folate might have a potential dual effect on risk of colorectal cancer.

BACKGROUND & AIMS: The possible dual role of serum folate in the development and progression of colorectal cancer (CRC) has not been well established in human studies. This study investigated the association between serum folate and the risk of CRC in subjects with CRC or colorectal adenomatous polyps (AP, a precursor of CRC), and healthy subjects. METHODS: This study has a case-control design. Two hundred and thirty-seven men and 171 women were recruited with 156 subjects in the CRC group, 70 subjects in the AP group and 182 healthy subjects in the control group. RESULTS: The risk of CRC was significantly increased in the third (OR, 3.46; 95% CI, 1.16-10.34) and fourth (OR, 4.86; 95% CI, 1.42-16.58) quartiles of serum folate concentration after adjusting for potential confounders among subjects with AP or CRC. Furthermore, serum folate concentration had no significant effect on the risk of CRC among subjects in the control and CRC groups. CONCLUSIONS: Higher serum folate concentration was significantly correlated with increased CRC risk in subjects with AP, while serum folate had no effect on CRC risk in healthy controls. Serum folate might possess potential dual modulatory effects on the risk of CRC.

The metabolic syndrome is associated with an increased risk of colorectal polyps independent of plasma homocysteine.

BACKGROUND/AIMS: The links between the metabolic syndrome and homocysteine in relation to the risk of colorectal polyps are not understood. The purpose of this study was to investigate the association between the metabolic syndrome and homocysteine and further analyze the relationship between these two factors and the risk of colorectal polyps. METHODS: This was a case-control study. A total of 135 participants with colorectal polyps (cases) and 110 participants without polyps (controls) were recruited. RESULTS: There were 59 participants with the metabolic syndrome in the case group and 36 participants with the metabolic syndrome in the control group. The metabolic syndrome and its individual components, except for serum triglycerides, and homocysteine were associated with the risk of colorectal polyps. When the association of the metabolic syndrome and homocysteine with the risk of colorectal polyps was simultaneously considered, the association between homocysteine and the risk of colorectal polyps disappeared, but waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, and the metabolic syndrome itself were still significant risk factors for the development of colorectal polyps. CONCLUSION: Although the metabolic syndrome and plasma homocysteine were individually related to the risk of colorectal polyps, the metabolic syndrome was a major contributing factor in relation to the risk of colorectal polyps independent of plasma homocysteine.

High homocysteine is associated with increased risk of colorectal cancer independently of oxidative stress and antioxidant capacities.

BACKGROUND & AIMS: Increased homocysteine concentration and oxidative stress and decreased antioxidant capacities are thought to affect carcinogenesis. However, the associations of homocysteine, cysteine, pyridoxal 5'-phosphate (PLP) and folate with oxidative stress and antioxidant capacities in patients with colorectal cancer are unclear. The purpose of this study was to determine the associations of homocysteine, cysteine, PLP and folate with oxidative stress indicators and antioxidant capacities, and to further analyze their relationships with respect to risk for colorectal cancer. METHODS: One hundred and sixty-eight subjects with colorectal cancer (cases) and 188 healthy subjects (controls) were recruited. RESULTS: There were no significant associations of homocysteine, cysteine and folate with oxidative stress indicators and antioxidant capacities in cases; however, PLP positively correlated with glutathione S-transferase activities after adjusting for potential confounders in cases. Subjects with higher plasma homocysteine concentration exhibited significantly increased risk of colorectal cancer with or without adjustment for potential confounders. The associations of cysteine, PLP and folate with the risk of colorectal cancer were not observed when potential confounders were adjusted. CONCLUSIONS: Increased homocysteine was strongly associated with the risk of colorectal cancer independently of oxidative stress indicators and antioxidant capacities. However, cysteine, PLP and folate were not found to be related to oxidative stress, antioxidant capacities and the risk of colorectal cancer.

Reexamining transcriptional regulation of the Bacillus subtilis htpX gene and the ykrK gene, encoding a novel type of transcriptional regulator, and redefining the YkrK operator.

HtpX is an integral cytoplasmic membrane metalloprotease well conserved in numerous bacteria. A recent study showed that expression of the Bacillus subtilis htpX gene is under dual negative control by Rok and a novel type of transcriptional regulator, YkrK. Here we report that expression of the B. subtilis htpX gene is strongly heat inducible. Contrary to the previous prediction, ykrK expression has been found to be not subject to autoregulation. We have identified the htpX promoter and the authentic ykrK promoter, which is also distinct from the previously predicted one. We have redefined a conserved inverted repeat sequence to be the YkrK operator, which is somewhat different from the previously proposed one. We provide evidence that YkrK is not a substrate of HtpX and that heat induction of htpX is not YkrK mediated. We have also found that the absence of FtsH or HtpX alone did not impair B. subtilis cell viability on LB agar plates at high temperature, whereas the absence of both FtsH and HtpX caused a severe growth defect under heat stress. This finding supports the notion that FtsH and HtpX may have partially overlapping functions in heat resistance. Finally, we show that htpX expression is subject to transient negative control by sigB under heat stress in a Rok- and YkrK-independent manner. Triple negative control of htpX expression at high temperature by rok, sigB, and ykrK may help cells to prevent uncontrolled and detrimental oversynthesis of the HtpX protease.

Plasma pyridoxal 5'-phosphate is not associated with inflammatory and immune responses after adjusting for serum albumin in patients with rheumatoid arthritis: a preliminary study.

BACKGROUND/AIMS: Plasma pyridoxal 5'-phosphate (PLP) has been shown to be associated with inflammatory and immune responses.Rheumatoid arthritis (RA) is an autoimmune and chronic systemic inflammatory disease and patients with RA have lower plasma PLP levels. We studied the relationship between plasma PLP and inflammatory or immune responses in patients with RA. METHODS: This study was designed as an observational cross-sectional study. Forty-three patients with RA were allocated to the adequate (PLP ≥20 nmol/l) (n = 30) or deficient vitamin B(6) (PLP <20 nmol/l) (n = 13) group according to their fasting plasma PLP concentration on the day blood was taken. Plasma PLP, inflammatory parameters [i.e. high-sensitivity CRP (hs-CRP), erythrocyte sedimentation rate, interleukin-6, tumor necrosis factor-α] and immune parameters (i.e. white blood cells, total lymphocytes, neutrophils, T lymphocytes, B lymphocytes, T helper cells and T suppressor cells) were measured. RESULTS: Patients with deficient plasma PLP concentration were mostly considered to have a systemic inflammatory status (hs-CRP >3 mg/l) and apparently had significantly higher mean hs-CRP levels and immune parameters than patients with adequate plasma PLP concentration. There was no significant association between plasma PLP levels and inflammatory parameters. The significantly inverse correlation of plasma PLP with the numbers of white blood cells, neutrophils, total lymphocytes, T lymphocytes and T helper cells remained after adjusting for serum hemoglobin concentration, but the significant correlation disappeared after serum albumin concentration was also considered. CONCLUSIONS: RA patients with deficient plasma PLP concentration had more severe inflammatory and immune responses than patients with adequate plasma PLP concentration. However, there was a lack of association of low plasma PLP concentration with inflammatory and immune parameters after serum albumin concentration was considered in patients with RA.

Induction of cytotoxicity, aldehydic DNA lesions, and poly(ADP-ribose) polymerase-1 activation by catechol derivatives of pentachlorophenol in calf thymus DNA and in human breast cancer cells.

The purpose of this study was to investigate the degree of chlorination of catechol (CAT) derivatives of pentachlorophenol (PCP) on the induction of cytotoxicity and DNA damaging effects in calf thymus DNA (ct-DNA) and in two human breast carcinoma cell lines. Results indicated that with the addition of the transition metal copper(II), increases in the amount of aldehydic DNA lesions (ADL) were detected in ct-DNA exposed to PCP-derived CATs over the corresponding control. The DNA lesions induced by various degrees of chlorination of PCP-derived CATs decrease in the rank order CAT congruent with 4-chlorocatechol (4-ClCAT) > 4,5-dichlorocatechol (4,5-Cl2CAT) > 3,4,5-trichlorocatechol (3,4,5-Cl3CAT) > tetrachlorocatechol (Cl4CAT). In contrast, Cl4CAT was the only congeneric form of PCP-derived catechols that induced a significant increase in the number of ADL in human MCF-7 cells, and this only occurred when glutathione was depleted. Pretreatment with copper(I) and iron(II) chelators significantly reduced the formation of ADL in cells exposed to Cl4CAT. The data also indicated that the ADL induced by Cl4CAT in MCF-7 cells contain approximately 70% putrescine excisable ADL. This evidence confirmed that the ADL induced by Cl4CAT in MCF-7 cells were derived from oxidative events. In addition, we demonstrated that the depletion of NAD(P)H in human T47D cells exposed to chlorinated CATs decreased in the rank order Cl4CAT >> 4-ClCAT congruent with CAT. The depletion of NAD(P)H induced by Cl4CAT in T47D cells was partially blocked by catalase, superoxide dismutase, dimethyl sulfoxide, and copper(I) and iron(II) specific chelators. Additionally, the depletion of NAD(P)H in T47D cells exposed to Cl4CAT (1-10 microM) was completely blocked by three types of poly(ADP-ribose) polymerase-1 inhibitors. This evidence suggests that Cl4CAT induces an imbalance in DNA repair and the subsequent accumulation of DNA strand breaks in human cultured cells. Overall, these findings indicate that dechlorination may decrease the potentials of chlorinated catechols to induce oxidative DNA lesions and cytotoxic effects in living cells.

Correlation between the Gleason scores of needle biopsies and radical prostatectomy specimens.

BACKGROUND: The Gleason score has been shown to offer important information with regard to prognosis and therapy for patients with adenocarcinoma of the prostate gland. In this study, Gleason scores, as determined by 18-gauge core needle biopsies, were compared with both Gleason scores and the pathological staging of corresponding radical prostatectomy specimens. METHODS: Records of 78 consecutive patients undergoing a radical retropubic prostatectomy between 1998 and 2002 were reviewed. In total, 78 patients were enrolled, all of whom had been diagnosed with adenocarcinoma by transrectal needle biopsies using an 18-gauge automated spring-loaded biopsy gun. RESULTS: Grading errors were greatest with well-differentiated tumors. The accuracy was 6 (23%) for Gleason scores of 2-4 on needle biopsy. Of the 36 evaluable patients with Gleason scores of 5-7 on needle biopsy, 28 (78%) were graded correctly. All of the Gleason scores of 8-10 on needle biopsy were graded correctly. Eighteen (33%) of 54 patients with a biopsy Gleason score of < 7 had their cancer upgraded to above 7. Tumors in 6 patients (60%) with both a Gleason score < 7 on the needle biopsy and a Gleason score of 7 for the prostatectomy specimen were confined to the prostate. CONCLUSION: The potential for grading errors is greatest with well-differentiated tumors and in patients with a Gleason score of < 7 on the needle biopsy. Predictions using Gleason scores are sufficiently accurate to warrant its use with all needle biopsies, recognizing that the potential for grading errors is greatest with well-differentiated tumors.