Alterations in Trace Elements and Oxidative Stress in Uremic Patients with Dementia

The present study was conducted to compare the trace elements and oxidative status between uremic patients with and without dementia. Chronic hemodialysis patients with dementia (n = 20) and without dementia (n = 25), and age-matched healthy volunteers (n = 20) were enrolled. The nutritional status, blood levels of trace elements aluminum (Al), zinc (Zn), copper (Cu), magnesium (Mg) and iron (Fe), malondialdehyde (MDA), and protein carbonyl production, antioxidant enzymes glutathione peroxidase (GPx), and glutathione reductase (GR) activities were measured. No significant difference in nutritional status or clinical characteristics was observed between nondementia and dementia patients. However, uremic patients with dementia have significantly higher Al, Cu, and Mg and lower Zn concentrations, as well as increased Cu/Zn ratio in comparison to nondementia patients. There were statistically significant increased MDA and carbonyl production and decreased GPx and GR activities in dementia patients. Furthermore, the significant associations of Al, Mg, and Cu/Zn ratio with oxidative status in patients with dementia were noted. The dementia may initially worsen with abnormal metabolism of trace elements and oxidative stress occurrence. Our results suggest that abnormalities in trace element levels are associated with oxidative stress and may be a major risk factor in the dementia development of uremic patients.     

Influence of smoking on serum and milk malondialdehyde, superoxide dismutase, glutathione peroxidase, and antioxidant potential levels in mothers at the postpartum seventh day

The aim of the study was to investigate simultaneously serum and milk malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, and antioxidant potential (AOP) in active-smoking, passive-smoking, and nonsmoking mothers and to search if there is any difference between serum and milk oxidant/ antioxidant status caused by smoking. According to their smoking status, 60 mothers (age range: 20–35 yr) were classified into one of three groups: the active-smoking mothers (n=15), the passive-smoking mothers (n=22), and the nonsmoking mothers (n=23). Serum and milk MDA, SOD, GPx, and AOP values were determined in mothers on the postpartum seventh day by the spectrophotometric method. Serum Zn and Cu concentrations were determined by atomic absorption spectrophotometry (AAS). There was no significant difference in serum samples with respect to MDA (p=0.17), SOD (p=0.51) and AOP (p=0.36) levels, but there was a significant difference in serum GPx (p=0.002) levels among the study groups. The significant differences were also found in milk samples in terms of MDA (p=0.002) and SOD (p=0.011), but not in GPx (p=0.11) and AOP (p=0.29) levels among the study groups. No significant difference was seen in serum zinc concentration (p=0.49), but copper concentration differed significantly among the groups (p=0.005). These observations suggest that human milk is more vulnerable to oxidative stress and lipid peroxidation than serum samples in smoking mothers, even if they are passive smokers.     

Evaluation of Oxidative Stress, Antioxidant Status and Serum Vitamin C Levels in Cancer Patients

Taking into account the importance role of lipid peroxidation and antioxidants in the prevention and incidence of cancer, the present study was carried out to determine oxidative stress, serum total antioxidant (TAS), and vitamin C levels in cancer patients. Malondialdehyde(MDA), total antioxidant status, and vitamin C levels of 57cancer patients aged 19–80 years and 22 healthy subjects (control group) aged 22–76 years were evaluated. Serum concentrations of MDA as thiobarbitaric acid complexes were measured by fluorometry method, the serum TAS by using commercial test kits from Randox Laboratories, and vitamin C by using spectrocolorimetric method. The mean serum MDA concentrations of all cancer groups except lung cancer were significantly higher than control group (P < 0.004). The mean total antioxidant status was insignificantly higher than control group. The mean serum vitamin C level was significantly lower in patients as compared to the healthy subjects (PV < 0.0001). In conclusion, an alteration in the lipid peroxidation with concomitant changes in antioxidant defense system in cancer patients may be due to excessive oxidative stress. Serum low levels of vitamin C in the different type of cancer patients in spite of adequate daily intake may be due to increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells.     

Characterization and Distribution of the Selected Metals in the Scalp Hair of Cancer Patients in Comparison with Normal Donors

Eighteen metals were estimated in the scalp hair samples from cancer patients (n = 111) and normal donors (n = 113). Nitric acid–perchloric acid wet digestion procedure was used for the quantification of the selected metals by flame atomic absorption spectrophotometry. In the scalp hair of cancer patients, highest average levels were found for Ca (861 μg/g), followed by Na (672 μg/g), Zn (411 μg/g), Mg (348 μg/g), Fe (154 μg/g), Sr (129 μg/g), and K (116 μg/g), whereas in comparison, the dominant metals in the scalp hair of normal donors were Ca (568 μg/g), Zn (177 μg/g), Mg (154 μg/g), Fe (110 μg/g), and Na (103 μg/g). The concentrations of Ca, Cd, Co, Cr, Fe, K, Mg, Mn, Na, Ni, Pb, Sb, Sr, and Zn were notably higher in the hair of cancer patients as compared with normal donors, which may lead to a number of physiological disorders. Strong positive correlations were found in Mn–Pb (0.83), Cd–Cr (0.82), Cd–Li (0.57), Fe–Pb (0.56), and Fe–Mn (0.55) in the hair of cancer patients whereas Na–Cd, Li–Cr, Li–Co, Co–Cd, Li–Cd, Na–Co, Na–Li, Ca–Mg and Na–Cr exhibited strong relationships (r > 0.50) in the hair of normal donors. Principal Component Analysis (PCA) of the data revealed seven PCs, both for cancer patients and normal donors, but with significantly different loadings. Cluster Analysis (CA) was also used to support the PCA results. The study evidenced significantly different pattern of metal distribution in the hair of cancer patients in comparison with normal donors. The role of trace metals in carcinogenesis was also discussed.     

Alterations in plasma essential trace elements selenium, manganese, zinc, copper, and iron concentrations and the possible role of these elements on oxidative status in patients with childhood asthma

The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r=0.485, p<0.021), and a negative correlation between TAC and MDA values (r= −0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.     

Protective agent, erdosteine, against cisplatin-induced hepatic oxidant injury in rats

Cisplatin, one of the most active cytotoxic agents against cancer, has several toxicities. Hepatotoxicity is one of them occurred during high doses treatment. The aim of this study was to determine the effects of erdosteine against cisplatin-induced liver injury through tissue oxidant/antioxidant parameters and light microscopic evaluation. The rats were randomly divided into three groups: control (n=5), cisplatin (10 mg/kg, n=6) and cisplatin+erdosteine (50 mg/kg/day oral erdosteine, n=8) groups. The rats were sacrificed at the 5th day of cisplatin treatment. The liver tissues were examined with light microscopy and oxidant/antioxidant biochemical parameters. The malondialdehyde (MDA) and nitric oxide (NO) levels were increased in the cisplatin group in comparison with the control and cisplatin+erdosteine groups (p<0.05). There was no significant difference in MDA and NO levels between control and cisplatin+erdosteine groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were higher in cisplatin+erdosteine group than cisplatin group (p<0.05). However, the CAT and GSH-Px activities were significantly lower in cisplatin group than in control group (p<0.05). The light microscopic examination revealed that cytoplasmic changes especially around cells of central vein were observed in cisplatin group. Hepatocellular vacuolization was seen in these cells. In the cisplatin plus erdosteine group, a decrease in cytoplasmic changes with the hepatocytes and sinusoidal dilatations around cells of central vein were noticed in as compared to cisplatin group. In the light of microscopic and biochemical results, it was concluded that cisplatin-induced liver damage in high dose and erdosteine prevented this toxic side effect by the way of its antioxidant and radical scavenging effects. (Mol Cell Biochem 278: 79–84, 2005)     

Genetic variation in microRNA genes and prostate cancer risk in North Indian population

Recent evidence indicates the involvement of microRNAs (miRNAs), in cell growth control, differentiation, and apoptosis, thus playing a role in tumorigenesis. Single-nucleotide polymorphisms (SNPs) located at miRNA-binding sites (miRNA-binding SNPs) are likely to affect the expression of the miRNA target and may contribute to the susceptibility of humans to common diseases. We genotyped SNPs hsa-mir196a2 (rs11614913), hsa-mir146a (rs2910164), and hsa-mir499 (rs3746444) in a case–control study including 159 prostate cancer patients and 230 matched controls. Patients with heterozygous genotype in hsa-mir196a2 and hsa-mir499, showed significant risk for developing prostate cancer (P = 0.01; OR = 1.70 and P ≤ 0.001; OR = 2.27, respectively). Similarly, the variant allele carrier was also associated with prostate cancer, (P = 0.01; OR = 1.66 and P ≤ 0.001; OR = 1.97, respectively) whereas, hsa-mir146a revealed no association in prostate cancer. None of the miRNA polymorphisms were associated with Gleason grade and bone metastasis. This is the first study on Indian population substantially presenting that individual as well as combined genotypes of miRNA-related variants may be used to predict the risk of prostate cancer and may be useful for identifying patients at high risk.     

Erratum: Interactions Between Cadmium and Zinc in the Biological Samples of Pakistani Smokers and Nonsmokers Cardiovascular Disease Patients

The pathogenesis of some cardiovascular diseases (CVDs) has been altered with changes in the balance of certain trace and toxic elements. The aim of the present study was to assess the role of zinc (Zn) and cadmium (Cd) in smoker and nonsmoker male CVD patients (n = 457) of two age groups (31–45) and (46–60). The both elements were determined in biological samples (scalp hair, blood, and urine) of CVD patients and healthy referents for comparison purpose. The concentrations of Zn and Cd were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. It was observed that the mean values of Cd were significantly higher in the biological samples of smokers CVD as compared to nonsmoker CVD patients, while the level of Zn was lower in both smoker and nonsmoker patients. The concentrations of Zn in whole blood and scalp hair samples were lower in CVD patients as compared to referents (p > 0.001). Results showed significant changes of levels of Cd and Zn in blood and scalp hair samples of CVD patients when compared with healthy referents, while reverse in the case of urine samples. It was observed that low Zn levels were associated with both smoker and nonsmoker CVD patients, while increased cadmium accumulation was observed in smoker patients as compared to nonsmoker patients (p > 0.025).     

Serum and tissue levels of six trace elements and copper/zinc ratio in patients with cervical cancer and uterine myoma

The aim of this study is to investigate the relationship between trace elements and the incidence of cervical cancer. Tissue and serum levels of six elements (Cu, Zn, Fe, Mn, Ca, and Se) and the Cu/Zn ratio in 40 cases of patients with cervical cancer, 30 cases of uterine myoma, and 50 healthy subjects were measured by atomic absorption spectrophotometry; the selenium content was determined by atomic fluorescence spectrometry. The results showed that the tissue contents of Zn, Se, and Ca were significantly lower and the Cu and Fe concentrations and Cu/Zn ratio were significantly higher in cervical cancer tissue than that for paired nonlesion tissue (p<0.02 and p<0.001, respectively). The serum levels of Zn, Se, Ca, and Fe were lower and Cu and Mn levels and Cu/Zn ratio were higher in patients with cervical cancer than in healthy subjects (p<0.01 and p<0.001, respectively) and in the uterine myoma group compared with healthy subjects (p< 0.05–0.001). There are no significant differences in the contents of six elements and the Cu/Zn ratio between uterine myoma tissue and paired nonlesion tissue. The results showed also that the Fe level and Cu/Zn ratio were significantly higher and the Zn and Se levels were significantly lower in cervical cancer tissue than in uterine myoma tissue (p<0.01 and p<0.001, respectively). The serum Cu level and Cu/Zn ratio were significantly higher in the cervical cancer group than the uterine myoma group (p<0.01). Data were also analyzed using multivarate logistic regression. After adjustment for age, occupation, life habit, and other covariates for the development of cervical cancer, the odds ratios were 22.64 (95% confidence interval [CI]: 5.64–90.88, p=0.001) for Cu, 0.11 (95% CI: 0.034–0.373; p=0.005) for Zn, and 0.60 (95% CI: 0.36–0.99, p=0.01) for Se. Thus, the serum and tissue levels of Cu increase and the deficiency of Zn and Se may be risk factors for the development of cervical cancer.     

Angiotensin (1–7) and its receptor Mas are expressed in the human testis: implications for male infertility

The presence of classical components of the renin-angiotensin system has been demonstrated in the male reproductive tract, mainly in the testes and epididymis. The objective of this study was to verify the localization of angiotensin (Ang)-(1–7) and its receptor Mas in human testis. The study included 12 men with previously proven fertility submitted to orchiectomy for prostate cancer and 20 infertile men submitted to testicular biopsy for infertility work-up, comprising a subgroup with obstructive azoospermia/normal spermatogenesis (n = 8) and another with non-obstructive azoospermia and severely impaired spermatogenesis (n = 12). Testicular tissue samples were processed by immunohistochemistry and real time polymerase chain reaction. Ang-(1–7) was strongly expressed in the interstitial compartment, mainly in Leydig cells, with similar intensity in all groups evaluated. The peptide was also detected in the seminiferous tubules, but with much less intensity compared to interstitial cells. The receptor Mas was equally distributed between interstitial and tubular compartments and was found in all layers of the normal seminiferous epithelium. However, neither Ang-(1–7) nor Mas were detected in the seminiferous tubules of samples with impaired spermatogenesis. The testicular samples of infertile men with impaired spermatogenesis (non-obstructive azoospermia) expressed Mas and ACE2 mRNA at lower concentrations (fold change = 0.06 and 0.04, respectively, P < 0.05) than samples with full spermatogenesis (obstructive azoospermia). This shows, for the first time, the immunolocalization of Ang-(1–7) and its receptor Mas in testes of fertile and infertile men, and suggests that this system may be altered when spermatogenesis is severely impaired.     

The CAG repeat polymorphism of androgen receptor gene and prostate cancer: a meta-analysis

The association between the polymorphic CAG repeat in androgen receptor gene (AR) and prostate cancer susceptibility has been studied extensively. However, the results are contradictory. The purpose of our meta-analysis was to investigate whether CAG repeat related to prostate cancer risk and had genetic heterogeneity across different geographic regions and study designs. Random-effects model was performed irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. Publication bias was assessed by the fail-safe number and Egger’s test. There were 16 (patients/controls: 2972/3792), 19 (3835/4908) and 12 (3372/2631) study groups for comparisons of ≥20, 22 and 23 repeats of CAG sequence, respectively. Compared with CAG repeat <20, 22 or 23, carriers of ≥20, 22 or 23 repeats had 21% (95% CI: 0.61–1.02; P = 0.076), 5% (95% CI: 0.81–1.11; P = 0.508) and 5% (95% CI: 0.76–1.20; P = 0.681) decreased risk of prostate cancer. After classifying studies by geographic areas, carriers of ≥20 repeats had 11% decreased risk in populations from USA, 53% from Europe, and 20% from Asia (P > 0.05), whereas comparison of ≥23 repeats with others generated a significant prediction in European populations (OR = 1.17; P = 0.039). Stratification by study designs revealed no material changes in risk estimation. Meta-regression analysis found no significant sources of between-study heterogeneity for age, study design and geographic region for all comparisons. There was no identified publication bias. Taken together, our results demonstrated that AR CAG repeat polymorphism with ≥20 repeats might confer a protective effect among the prostate cancer patients with 45 years older but not all the prostate cancer patients.     

Effect of zinc and melatonin supplementation on cellular immunity in rats with toxoplasmosis

The effects of zinc (Zn) and/or melatonin supplementation on cellular immunity were investigated in rats infested with Toxoplasma gondii. Fifty Sprague-Dawley male rats were used for this study. All animals were fed a normal diet, ad libitum, containing 97 mg Zn/kg. They were divided into five experimental groups, as follows. Group I (n=10) received intraperitoneal injections of zinc sulfate at a dose of 3 mg/kg/d for 3 wk. Group II (n=10) received intraperitoneal injections of melatonin at a dose of 3 mg/kg/d for 3 wk. Group III (n=10) received intraperitoneal injections of zinc sulfate (3 mg/kg/d) and melatonin (3 mg/kg/d) for 3 wk. Group IV (n=10) was infested controls. Group V (n=10) was healthy controls. There were no differences in the percentage of CD3+ lymphocytes among all groups. For groups I–III, the CD4+ and CD8+ ratios were higher than those of the groups IV and V controls (p<0.01). Similarly, the total lymphocyte ratios in groups I–III were higher than those of infested and healthy controls (p<0.01). The total lymphocyte ratios in group III were significantly higher than those of groups I and II (p<0.01). The plasma Zn levels in the supplemented groups were significantly higher than those of control groups IV and V (p<0.01). These results suggest that melatonin and/or Zn supplementation may activate cellular immunity by stimulating CD4+ and CD8+ production in infected rats with T. gondii.     

Leptin increases prostate cancer aggressiveness

Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.     

<Emphasis Type="Italic">TGFBR1</Emphasis>*6A/9A polymorphism and cancer risk: a meta-analysis of 13,662 cases and 14,147 controls

Published data on the association between TGFBR1*6A/9A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 32 studies including 13,662 cases and 14,147 controls were involved in this meta-analysis. Overall, significantly elevated cancer risks were associated with TGFBR1*6A in all genetic models (for allelic effect: OR = 1.11; 95% CI = 1.03–1.21; for 6A/6A vs. 9A/9A: OR = 1.30; 95% CI = 1.01–1.69; for 9A/6A vs. 9A/9A: OR = 1.08; 95% CI = 1.01–1.15; for dominant model: OR = 1.08; 95% CI = 1.02–1.15; for recessive model: OR = 1.29; 95% CI = 1.00–1.68). In the subgroup analysis by cancer types, significant associations were found in breast cancer (for allelic effect: OR = 1.16; 95% CI = 1.01–1.34) and ovarian cancer (for allelic effect: OR = 1.24; 95% CI = 1.00–1.54; for 6A/6A vs. 9A/9A: OR = 2.34; 95% CI = 1.03–5.33). However, no significant associations were found in colorectal cancer, bladder cancer, prostate cancer and lung cancer for all genetic models. In summary, this meta-analysis suggests that the TGFBR1*6A/9A polymorphism is associated with cancer susceptibility, increasing the risk of breast and ovarian cancer.     

Zinc in Postmortem Body Tissues and Fluids

Data on zinc concentration in the human body may be used to interpret the results obtained in cases of chronic and acute poisonings with zinc compounds, i.e., in clinical and forensic toxicology. In this paper, the concentrations of zinc in human tissues and body fluids obtained from autopsy cases concerning non-poisoned people (n = 203), aged from 14 to 80 years, between 1995 and 2008, are presented. The following values were found by the flame atomic absorption method (mean ± SD, median, range, in microgram per gram or microgram per milliliter): brain 10.3 ± 1.36, 10.2, 7.99–13.8 (n = 48); stomach 14.2 ± 3.63, 13.6, 8.00–22.5 (n = 71); intestines 15.7 ± 5.22, 15.8, 8.36–28.1 (n = 35); liver 39.6 ± 16.1, 36.6, 16.0–78.8 (n = 109); kidney 33.8 ± 10.1, 31.8, 16.4–60.9 (n = 93); lung 12.0 ± 3.88, 11.0, 6.13–18.7 (n = 26); spleen 14.7 ± 2.53, 14.6, 11.4–18.3 (n = 5); heart 26.5 ± 3.63, 26.7, 22.5–31.8 (n = 5); blood 6.81 ± 1.21, 7.00, 4.02–8.68 (n = 50); urine 0.69 ± 1.70, 0.60, 0.39–1.00 (n = 5), and bile 4.92 ± 1.64, 3.75, 3.20–7.09 (n = 9). The accuracy of the method was checked through the use of SRM Bovine Liver 1577b (certified: 127 ± 16 μg Zn/g, found: 117 ± 0.7 μg Zn/g (n = 6)).     

Zinc and Copper Levels in Severe Heart Failure and the Effects of Atrial Fibrillation on the Zinc and Copper Status

Oxidative stress is involved in the pathogenesis of congestive heart failure (CHF). Some trace elements serve as antioxidant defenses. The purpose of this study was to analyze the effect of atrial fibrillation (AF) on zinc (Zn) and copper (Cu) levels in patients with advanced CHF. In this prospective study, serum Zn and Cu levels in 78 patients with clinically advanced CHF, i.e., New York Heart Association (NYHA) functional class III or IV (40 patients with AF and 38 in sinus rhythm) were measured using atomic absorption spectrophotometry. All patients also had a left ventricular ejection fraction (EF) of <35%. We recruited 40 volunteers with nearly the same age and weight as control. They had normal EF. There was no significant difference between patients with AF and those with sinus rhythm regarding serum Zn and Cu levels. However, both groups showed significant hypozincemia (p < 0.000) and a decreased Zn/Cu ratio (p < 0.03) compared with control group. Serum Cu levels were similar in the two groups and did not differ significantly from the control group. In patients with advanced CHF, irrespective of the rhythm, profound hypozincemia, and a decreased Zn/Cu ratio were present, which could be secondary to the activation of the renin–angiotensin–aldosterone system and CHF medications. The results suggest the need for more studies focusing on possible benefits with Zn nutriceutical replacement in patients with advanced CHF.     

The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma

Purpose  We have previously demonstrated an association of the human leukocyte antigen (HLA), HLA-A2 allele with ovarian and prostate cancer mortality as well as a segregation of the ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] in patients with stage III–IV serous ovarian cancer. The objective of the present study was to determine the role of the HLA phenotype on the prognosis in stage III–IV malignant melanoma patients. Patients and methods  A cohort of metastatic malignant melanoma patients (n = 91), in stage III (n = 26) or IV (n = 65) were analysed for HLA-A, -B, -Cw and -DRB1 types by PCR/sequence-specific primer method. The frequencies of HLA alleles in the patients were compared to that of healthy Swedish bone marrow donors. The effect of HLA types on prognosis was defined by Kaplan–Meier and Cox analysis. Results  The presence of the AHH 62.1 in clinical stage IV patients was significantly and independently associated with the worst survival rate recorded from the appearance of metastasis (HR = 2.14; CI = 1.02–4.4; P = 0.04). In contrast, the period from the primary diagnosis to metastasis was the longest in patients with this haplotype (HR = 0.40; CI = 0.17–0.90; P = 0.02). Conclusions  Melanoma patients in our cohort with 62.1 AHH which is associated with autoimmune diseases have an initial strong anti-tumour control with longer metastasis-free period. These patients have rapid progression after the appearance of metastasis, responding poorly to chemo- or/and immunotherapy. This apparently paradoxical clinical process could be due to the interplay between tumour clones escape and immune surveillance ending up with a rapid disease progression. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Association of GSTM1T1 genes with COPD and prostate cancer in north Indian population

The glutathione S-transferase (GST) family of enzymes is known to play a pivotal role in phase II of biotransformation of xenobiotics, environmental carcinogens and pharmacological drugs. The objective of the present study was to investigate the role of GSTM1 and GSTT1 null genotypes as risk factors for chronic obstructive pulmonary disease (COPD) and prostate cancer. The subjects appraised were 200 COPD cases, 150 prostate cancer cases, 150 benign prostatic hyperplasia (BPH) cases, 200 age matched controls for COPD and 172 age matched controls for prostate cancer. GSTM1 and GSTT1 null genotype was found to confer 2.5 (OR 2.45; 95% CI 1.56–3.82; P value = 0.00008) and 2.4-fold (OR 2.39; 95% CI 1.36–4.20; P value = 0.002) significant higher risk for prostate cancer. Smoking imparted a 2.2-fold significant risk of prostate cancer cases (OR 2.23; 95% CI 1.36–3.65 P value = 0.001) and twofold risk in BPH (OR 2.09; 95% CI 1.26–3.46; P value = 0.005). In case of COPD only null genotype of GSTT1 has shown 2.1-fold (OR 2.11; 95% CI 1.22–3.62; P value = 0.007) significant increased risk.     

Investigation of Serum Trace Element,Malondialdehyde and Immune Status in Drug Abuser Patients Undergoing Detoxification

Drug abuser patients (n = 104), age ranging from 19 to 42 years, were randomly recruited to investigate the serum levels of trace elements (Cu, Zn, Fe, and Mg), malondialdehyde (MDA), and immunoglobulin (IgG, IgA, and IgM) before and after clinical intervention. Control group also included 104 healthy individuals. Blood samples were analyzed for determining trace elements, MDA, and immunoglobulin using atomic absorption spectroscopy, Ultraviolet-Visible (UV-VIS) spectroscopy, and turbidimetry method, respectively. For serum level of Zn and Fe, the differences between the groups (before intervention, after intervention, and control) were not significant (p > 0.05). However, significant differences were found in serum copper levels between control group, drug abuser patients, and before and after intervention (p < 0.05). The concentration of Mg was found to be significantly higher (p = 0.007) in drug abuser patients than the controls, and after intervention, the level was restored to control value. A displacement of elemental homeostasis was observed in drug abuser patients compared to control, and it was improved after intervention. An increase in serum concentration of MDA was found in drug abuser patients compared to control subjects (p > 0.05) but was not statistically significant. After intervention, the concentration was restored to control value (p > 0.05). The serum concentrations of IgA and IgM were found to be significantly higher (p < 0.05) in drug abuser patients before intervention than the controls, and the level tended to be restored to control level after clinical intervention. Serum IgG level was found to be lower in drug abuser patients compared to controls and further declined significantly (p < 0.05) after intervention. These findings may suggest a possible imbalance in the levels of micronutrients, antioxidants, and immunoglobulin in drug abuser patients, which tend to be restored to control values after detoxification.     

Antioxidative metabolism in down syndrome

Down syndrome is the most common cause of mental retardation, affecting 1 in 700–800 liveborn infants. Although numerous biochemical abnormalities accompanying the syndrome have not yet been completely clarified, the antioxidant defense system enzymes have shown to be altered due to increased gene dosage on chromosome 21 and overproduction of superoxide dismutase (SOD-1 or Cu/Zn SOD). The purpose of this study was to investigate the activities of SOD-1 and glutathione peroxidase (GSH-Px) enzymes and the levels of their cofactors zinc (Zn), copper (Cu) and selenium (Se) in plasma of 20 Down syndrome patients. In comparison with age and sex-matched controls (n=15), plasma GSH-Px, SOD, and Cu levels were significantly decreased in the patient group, but Zn and Se concentrations remained unchanged. This study was presented as a poster in 29th Annual Meeting of European Society of Human Genetics held in Genoa in May, 1997.