OBJECTIVETo examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing systemic inflammatory response to acute cadmium intoxication in animals of the two sexes.

METHODSBasic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) and of major rat acute phase protein alpha 2-macroglobulin (alpha2-M), as soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation.

RESULTSDifferential increases of IL-6 and alpha2-M (higher in males than in females) in peripheral blood cell counts and types (leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females) and in levels of neutrophil priming (higher in males vs females) were noted.

CONCLUSIONThe data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.

Animals ; Cadmium ; administration & dosage ; toxicity ; Female ; Inflammation ; chemically induced ; Interleukin-6 ; blood ; Leukocyte Count ; Male ; Neutrophils ; drug effects ; Rats ; Rats, Inbred Strains ; Sex Factors ; Tumor Necrosis Factor-alpha ; blood ; alpha-Macroglobulins ; analysis

BACKGROUND: This study aims to detect any causative genetic alterations and to demonstrate any correlations of these genes in the pathogenesis of mostly late-occurring sporadic type of Alzheimer's disease (AD). METHODS: A total of 67 registered cases of autopsy-confirmed brain tissues were analyzed. Included here was sporadic AD (n=41), vascular dementia (n=17), and non-demented physiologically aging control brains (n=9). ApoE genotyping was done with the enzymatic digestion, and allele specific PCR was done to analyze the -491 A/T polymorphism of ApoE. Detection of polymorphism of alpha 2-macroglobulin (A2M) was done with enzymatic digestion and DNA sequencing. RT-PCR products were electrophoresed to detect mRNA expression of alpha 1-antichymotrypsin (ACT). RESULTS: A prevalence rate of ApoE E4 genotype (E3/E4, E4/E4) showed significantly higher in patients with AD than in patients with vascular dementia (43.8% vs. 11.7%, p=0.019). Only 1 out of 4 cases of sporadic AD was associated with the E4/E4 allele. -491A/ T polymorphism of the ApoE promoter was found only in AD (2/41 cases, 4.9%). The incidence of heterozygous allelic polymorphism with 5 bp deletions in exon 18 of A2M-2 was 4.9% (2 out of 41) in AD. Messenger RNA expression of ACT, which is closely associated with the ApoE E4 allele, was increased in AD in comparison with normal control (p=0.0002). CONCLUSIONS: ApoE4 genotype and ACT are closely related to the pathogenesis of late-onset sporadic AD. Neither -491 polymorphism of ApoE promoter nor A2M-2 showed close association with AD in these brain samples.
Aging ; Alleles ; alpha 1-Antichymotrypsin* ; alpha-Macroglobulins ; Alzheimer Disease* ; Apolipoprotein E4 ; Apolipoproteins E ; Apolipoproteins* ; Brain* ; Dementia, Vascular ; Digestion ; Exons ; Genotype ; Humans ; Incidence ; Polymerase Chain Reaction ; Prevalence ; RNA, Messenger ; Sequence Analysis, DNA

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.
Adult ; Biological Markers/blood ; Chronic Disease ; Fatty Liver/complications ; Female ; Fibrosis ; Haptoglobins/analysis ; Hepatitis B/complications ; Hepatitis C/complications ; Humans ; Hyaluronic Acid/blood ; Liver Cirrhosis/complications/*diagnosis ; Liver Diseases/complications/*diagnosis ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; alpha-Macroglobulins/analysis