Trend of fatal poisoning at national and provincial levels in Iran from 1990 to 2015.

OBJECTIVES: Comprehensive and up-to-date data on fatal injury trends are critical to identify challenges and plan priority setting. This study provides a comprehensive assessment of poisoning mortality trends across Iran. STUDY DESIGN: The data were gathered from various resources, including death registration systems, cemetery databases of Tehran and Esfahan, the Demographic and Health Survey of 2000, and three rounds of national population and housing censuses. METHODS: After addressing incompleteness for child and adult death data separately and using a spatio-temporal model and Gaussian process regression, the level and trend of child and adult mortality were estimated. For estimating cause-specific mortality, the cause fraction was calculated and applied to the level and trend of death. RESULTS: From 1990 to 2015, 40,586 deaths due to poisoning were estimated across the country. The poisoning-related age-standardized death rate per 100,000 was estimated to have changed from 3.08 (95% uncertainty interval [UI]: 2.32-4.11) in 1990 to 0.96 (95% UI: 0.73-1.25) in 2015, and the male/female ratio was 1.35 during 25 years of study with an annual percentage change of -5.4% and -4.0% for women and men, respectively. The annual mortality rate was higher among children younger than 5 years and the elderly population (≥70 years) in the study period. CONCLUSIONS: This study showed that mortality from poisoning declined in Iran over the period from 1990 to 2015 and varied by province. Understanding the reasons for the differences of poisoning mortality by province will help in developing and implementing measures to reduce this burden in Iran.

Modifying effect of intravenous laser therapy on the protein expression of arginase and epidermal growth factor receptor in type 2 diabetic patients.

The epidermal growth factor receptor (EGFR) signaling pathway may be involved in cell activation and may influence the neuronal microenvironment, microglia activation, and production of proinflammatory cytokines. Arginase and nitric oxide synthase (NOS) both use L-arginine as a common substrate. Decreasing the arginase expression may increase L-arginine consumption by NOS and increase nitric oxide (NO) synthesis. Intravenous laser blood irradiation (ILBI) is an effective systemic treatment for different pathologies including diabetes mellitus. Previous studies have shown that low-level laser therapy can have an effect on the release of certain cytokines and growth factors. The aim of this study was to evaluate the effects of ILBI on the expression of arginase and epidermal growth factor receptor in type 2 diabetic patients. We used 630 nm red laser light, 1.5 mW, continuous mode, intravenously for 30 min in 13 type 2 diabetic patients and compared their blood samples using the flow cytometry technique, before and after ILBI. The difference between the percentage of cells before and after therapy was analyzed using repeated-measures ANOVA, and the relationship between EGFR and arginase expression in blood and tissue was evaluated by calculating the Pearson correlation coefficient. We found a significant decrease in the expression of both arginase- and EGFR-positive cells after laser therapy (P < 0.01). In conclusion, laser therapy may have a beneficial effect for diabetic patients via decreasing arginase expression and activation of the NOS/NO pathway which increases NO production and vasodilation, and decreasing EGFR expression which may reduce neuroinflammation and its secondary damages.

Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory.

Ataxia telangiectasia mutated (ATM) is a key gene in DNA double-strand break (DSB), and therefore, most of its disabling genetic alterations play an important initiative role in many types of cancer. However, the exact role of ATM gene and its epigenetic alterations, especially promoter methylation in different grades of brain tumors, remains elusive. The current study was conducted to query possible correlations among methylation statue of ATM gene, ATM/ retinoblastoma (RB) protein expression, D1853N ATM polymorphism, telomere length (TL), and clinicopathological characteristics of various types of brain tumors. Isolated DNA from 30 fresh tissues was extracted from different types of brain tumors and two brain tissues from deceased normal healthy individuals. DNAs were treated with bisulfate sodium using DNA modification kit (Qiagen). Methylation-specific polymerase chain reaction (MSP-PCR) was implicated to determine the methylation status of treated DNA templates confirmed by promoter sequencing. Besides, the ATM and RB protein levels were determined by immunofluorescence (IF) assay using monoclonal mouse antihuman against ATM, P53, and RB proteins. To achieve an interactive correlation, the methylation data were statistically analyzed by considering TL and D1853N ATM polymorphism. More than 73% of the brain tumors were methylated in ATM gene promoter. There was strong correlation between ATM promoter methylation and its protein expression (p < 0.001). As a triangle, meaningful correlation was also found between methylated ATM promoter and ATM protein expression with D1853N ATM polymorphism (p = 0.01). ATM protein expression was not in line with RB protein expression while it was found to be significantly correlated with ATM promoter methylation (p = 0.01). There was significant correlation between TL neither with ATM promoter methylation nor with ATM protein expression nor with D1853N polymorphism. However, TL has shown strong correlation with patient's age and tumor grade (p = 0.01). Given the important role of cell cycle checkpoint proteins as well as RB and ATM in TL and cancer evolution, further assessment is warranted to shed more light on the pathway linking the telomere instability to tumor progression. High ATM methylation rate in brain tumor patients could open a new avenue toward early screening and cancer therapy.

The biomarker-based validity of a food frequency questionnaire to assess the intake status of folate, pyridoxine and cobalamin among Iranian primary breast cancer patients.

BACKGROUND/OBJECTIVES: Folate, pyridoxine and cobalamin are coenzymatically essential in one-carbon methyl metabolism, and their deficiencies could explain some alterations during breast carcinogenesis. We aimed to evaluate the validity of folate, pyridoxine and cobalamin estimates from a food frequency questionnaire (FFQ) on the basis of their corresponding fasting plasma biomarkers, in breast cancer (BC) patients. SUBJECTS/METHODS: In a prospective, consecutive case series, 149 women with primary BC aged between 30 and 69 years as a representative sample of Iranian women with BC were recruited. The 136-item FFQ was used for the validity assay. Fasting plasma folate and cobalamin were tested by automated electrochemiluminescence. The high-pressure liquid chromatography with fluorescence detection was used to determine the plasma levels of pyridoxal-5'-phosphate (PLP) and total homocysteine (tHcy). RESULTS: Area under the curve (AUC) for assessing the diagnostic accuracy of folate-related data through an FFQ was 0.74 (P<0.01) in the reference model (folate plasma level<5.9 ng/ml), with sensitivity and specificity of 68% and 63%, respectively. The positive and negative predictive values (PPV and NPV) were 96.9% and 96.8%, respectively. The AUC for cobalamin intake in the reference model (plasma cobalamin<260 pmol/l) was 0.64 (P<0.01), with 60% sensitivity and 61% specificity. Although tHcy ≥10.0 µmol/l was used as reference indicator, the folate intake (AUC=0.71, P<0.01) and cobalamin intake status (AUC=0.67, P<0.05) were also determined appropriately by FFQ. CONCLUSIONS: Dietary folate and cobalamin estimates from FFQ were significantly correlated with their fasting plasma concentrations. Our data supported the validity of new FFQ to rank individuals by dietary intake status of folate and cobalamin.

Novel evolutionary models and periodic charts in p- and q-individual chromosomes of auxiliary lymph node and buccal cells.

Signal copy number (SCN) and signal intensity (SI) of subtelomeres (ST) are investigated in auxiliary lymph node (ALN) and buccal (BUC) cells by fluorescence in situ hybridization. The extracted total cell of 38256 and 2309 was, respectively, analyzed from the benign ALN- and BUC-cells of an affected breast cancer patient. The Periodic model was based on ST behavior including normal-, down-, and upregulated clones with diverse SCN. The arm-p/q ratio based signature, as a subtelomeric array, reflects discordance and concordance of ST-behavior within individual chromosomes as a concept of "Individualization of Cells" rather than "Global Insight of Cells". The Periodic charts could be considered as a reliable and refreshable platform through which the cellular evolution could be patterned and characterized. Signature of ST-profile in the BUC and ALN cells and the nature of diverse SCN and SI as quantitative and qualitative value led to modeling the real personalized perspective of cellular evolution. Protein expression of Ki67, Cyclin D1, and Cyclin E was assayed, as a complementary panel. These targets could be applied as the predictive and preventive markers for an early detection at BUC and ALN levels to plan the required managements in the breast cancer patients.

Comparison of Ki-67 antigen expression and K-ras mutation in lung tumours induced by urethane in mice.

INTRODUCTION: This study aims to compare Ki-67 antigen expression and K-ras mutation in lung tumours induced by the interfering effects of urethane followed by sodium nitrite, sodium chloride and vitamin D3. METHODS: The samples were classified into six groups: control (C) group; urethane only (U) group; urethane and vitamin D (U+D) group which received 3.5 mg/kg vitamin D3 for four weeks; urethane and sodium nitrite (U+NS) group which was given sodium nitrite (50 mg/L); urethane and physiological serum (U+NaCl) group; and sodium nitrite and physiological serum (NS+NaCl) group which was given 50 mg/L sodium nitrite and physiological serum, instead of water. The four carcinogen groups receiving urethane were injected intraperitoneally with 600 mg/kg of urethane three times. After 20 weeks of intervention, the mice were killed; the tissues were removed and examined for histopathological changes and comparison of Ki-67 antigen expression and mutations in the exon 1 of the K-ras gene in lung tumours. RESULTS: There were significant differences in the Ki-67 index between the C group and the U (p-value is less than 0.006, 95 percent confidence interval [CI] -432.9 to -55.6), U+D (p-value is less than 0.05, 95 percent CI -408.3 to -4.6), U+NS (p-value less than 0.02, 95 percent CI -415.7 to -27.2), U+NaCl (p-value less than 0.002, 95 percent CI -478.8 to -90.3) groups. There was no difference between the C and NS+NaC1 groups. There was no mutation in the exon 1 of K-ras gene of the lung tumours. CONCLUSION: The expression of Ki-67 antigen was found to be increased by urethane in the present study. However, a study on a larger sample size may show anti-tumourogenic effect of vitamin D3. However, the K-ras exon 1 mutations do not play any role in the interfering effects of urethane followed by sodium nitrite and sodium chloride.

Laddering through pedigrees: family history of malignancies in primary breast cancer patients.

A family history (FH) of breast cancer (BC) is a long recognized risk factor for developing the disease. Also, there have been some reports of links between an FH and some other malignancies (mostly uterus, ovary, and prostate cancers), and an increased risk of developing BC. In this paper we present descriptive report of the occurrence pattern of malignancies in families of BC afflicted patients through 4 generations. Patients included 542 Iranian primary BC cases, presenting at an outpatient clinic for treatment and follow-up. Detailed pedigrees were drawn for each patient, and data for a total of 6220 relatives were gathered. Among the probands, 29.9% and 53.9% had a positive FH of BC and other malignancies (OM) respectively. Mean number of breast cancers was nearly double in maternal-lines versus paternal-line relatives. Also, occurrence of brain, uterus, and colorectal cancers was significantly higher in maternal-line relatives, but conversely, liver cancer showed a tendency toward paternal-line relatives (1st degree relatives excluded). The highest frequency of BC involvement was noted in 2nd degree/2nd generation, and 3rd degree/3rd generation relatives. For OMs, although gastric cancer was by far the most frequent OM across pedigrees, uterus cancer, and hematopoeitic system lesions (leukemia) predominated over gastric cancer through the 3rd and 4th generations respectively. We did not find any relation between having a positive FH of BC, and developing early-onset BC. The findings discussed in this paper were partially presented at the 18th UICC International Cancer Congress, Oslo-Norway, 30 June-5 July 2002.

Linking Histopathology and Family History in Breast Cancer.

In order to assess the prognostic value of family history (FH) of malignancies in patients afflicted with breast cancer (BC), we examined FH and histopathologic characteristics of 542 Iranian primary BC patients. Cases with distant metastasis at the time of diagnosis were excluded. Mean age of the studied population was 49 and the most common presenting stage was stage IIA followed by stage IIB. Data on a total of 6089 relatives (1st to 4th generations with the assumption of probands as the 3rd generation) were gathered. FH of BC and other malignancies (OM) was positive in 29 and 54% of cases, respectively. The most common OM's were gastric (67), lung (52) and uterus (47) cancers. We found that a FH of BC does not have any significant correlation with proven prognostic factors but a history of BC among relatives at or before the age of 36 is associated with more aggressive tumours. On the other hand, although FH of OM was associated with an older age of the probands (which is generally associated with a favourable prognosis), tumours of the cases with FH of OM had higher grades, lymphatic invasion being detected more frequently. Also we noted that the younger the age of the relatives diagnosed with cancer, the higher the stage of the probands themselves. All together our study indicates the possibility of a relation between FH of BC and OM, and histopathologic characteristics of the probands' tumours which would put forward FH as a prognostic factor rather than a simple risk factor in BC.