Acute effects of 17β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats

Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition.     

Effect of 17 β-estradiol on adherence of escherichia coli to human endometrial stromal cells

Summary The effect of 17 -estradiol onin vitro adherence of six strains of uropathicEscherichia coli to human endometrial stromal cells was examined. In contrast to the findings of earlier investigations using murine urogenital cells and malignant human urogenital cell lines, our studies showed no significant effect of 17 -estradiol on adherence.

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Einflu von 17 -Östradiol auf die Adhärenz von Escherichia coli an menschliche Endometrium-Stromazellen

Zusammenfassung Der Einfluß von 17 -Ostradiol auf dieIn-vitro-Adhärenz von sechs uropathogenenEscherichia-coli-Stämmen an menschliche Endometrium-Stromazellen wurde untersucht. Im Gegensatz zu früheren Untersuchungen, bei denen urogenitale Zellen von Mäusen und maligne urogenitale Zellinien verwendet wurden, zeigten unsere Versuche keinen signifikanten Einfluß des 17 -Östradiol auf die Adhärenz.

     

Distinctive serum globulin responses to parenteral treatment with 17-β-estradiol in female NZB/NZW mice

After 6 weeks of treatment with 17-β-estradiol, two distinct groups of female NZB/NZW mice were identified. Group I females developed significant increases in serum α₂, β- and γ-globulins and had few serologic abnormalities. Serum globulins did not increase in Group II females. This blunted response correlated with a pretreatment increase in the frequency of positive tests for ANA, LE phenomena and cryoproteins in 4-week-old Group II mice.     

The levels of β-thromboglobulin in female rheumatoid arthritis patients as activation criteria

The activation of the platelets plays a key role in the formation of thrombosis. The variables such as mean platelet volume, platelet factor 4 and β-thromboglobulin have been used in the demonstration of the platelet activation. However, when the literature was reviewed, there was not found any study investigating the level of β-thromboglobulin in patients with rheumatoid arthritis. Our goal is to evaluate the β-thromboglobulin levels together with mean platelet volume in patients with arthritis. This study is a clinical study which has a control group that has been designed prospectively, and in this study, Rheumatology Outpatient Clinic follow-up patients with rheumatoid arthritis and healthy control group were studied. All patients and healthy volunteers were examined β-thromboglobulin and mean platelet volume. Twenty-two patients with rheumatoid arthritis and 21 healthy volunteers participated in the study. β-Thromboglobulin mean was found as 98.00 ± 60.49 ng/mL in rheumatoid arthritis group and it was 62.38 ± 30.41 ng/mL in healthy control group. The differences between these groups were significant in terms of the levels of β-thromboglobulin (p = 0.02). We found significant differences between the groups in terms of mean platelet volume (p = 0.049). In this study, the level of β-thromboglobulin was found significantly higher in patients with rheumatoid arthritis, which is a chronic inflammatory disease. This result could be an indicator, such as platelet activation in patients with rheumatoid arthritis, or it may be a helper marker in the follow-up and treatment of developing cardiovascular risk.     

The ratio of α-galactosidase to β-glucuronidase activities in dried blood for the identification of female Fabry disease patients

Summary Female heterozygous patients with Fabry disease are difficult to identify because of the relatively high residual activity of α-galactosidase. We systematically evaluated the activities of various lysosomal enzymes in dried blood samples from Fabry patients and found that the β-glucuronidase activity was frequently elevated. The ratio of α-galactosidase to β-glucuronidase proved to be a helpful tool for the diagnosis of female Fabry disease patients.     

Genomic data in prognostic models—what is lost in translation? The case of deletion 17p and mutant TP53 in chronic lymphocytic leukaemia

Genomic technologies are revolutionizing the practice of haematology-oncology, leading to improved disease detection, more accurate prognostication and targeted treatment decisions. These advances, however, have also introduced new clinical challenges, which include problems of prognostic underdetermination and its attendant risks of over- and undertreatment. Genomic data is generated from different technologies, from cytogenetics to next-generation sequencing, which are often interpreted interchangeably and in a binary fashion—as the presence or absence of a given chromosomal deletion or mutation—an oversimplification which may lead to mistaken prognosis. We discuss the clinical use of one such prognostic marker, represented by sequence and copy number alterations in TP53, located on chromosome 17p. Mutations in TP53 are strongly linked to poor prognosis in a variety of haematological malignancies, including chronic lymphocytic leukaemia (CLL). We review studies in CLL which utilize the 17p deletion or TP53 mutations for prognostic stratification with specific focus on the technologies used for detection, the thresholds established for clinical significance, and the clinical contexts in which these alterations are identified. The case of CLL illustrates issues arising from simplistic, binary interpretation of genetic testing and highlights the need to apply a critical lens when incorporating genomics into prognostic models.     

Diminished expression of β2-GPI is associated with a reduced ability to mitigate complement activation in anti-GPIIb/IIIa-mediated immune thrombocytopenia

Anti-GPIIb/IIIa-mediated complement activation has been reported to be important in the pathogenesis of immune thrombocytopenia (ITP). However, the role of the complement system and the involved regulatory mechanism remain equivocal. Beta2-glycoprotein I (β2-GPI), known as the main target for antiphospholipid autoantibodies, has been demonstrated as a complement regulator. Here, we investigated the complement-regulatory role of β2-GPI in anti-GPIIb/IIIa-mediated ITP. Plasma complement activation and enhanced complement activation capacity (CAC) were found in ITP patients with anti-GPIIb/IIIa antibodies in vivo and in vitro. Diminished plasma levels of β2-GPI were shown in patients of this group, which was inversely correlated with C5b-9 deposition. C5b-9 generation was inhibited by approximate physiological concentrations of β2-GPI, in a dose-dependent manner. Inhibition of C3a generation by β2-GPI and the existence of β2-GPI/C3 complexes in plasma indicated a regulation on the level of the C3 convertase. Furthermore, β2-GPI down-regulated the phosphorylation levels of c-Jun N-terminal kinase (JNK) and cleavage of BH3 interacting domain death agonist (Bid) and ultimately harbored platelet lysis. Our findings may provide a novel link between diminished plasma levels of β2-GPI and enhanced complement activation, indicating β2-GPI as a potential diagnostic biomarker and therapeutic target in the treatment of anti-GPIIb/IIIa-mediated ITP.     

The role of β-catenin in pulmonary artery endothelial-mesenchymal transformation in rats with chronic thromboembolic pulmonary hypertension

Journal of Thrombosis and Thrombolysis - Compared with Caucasian patients, East Asian patients with coronary artery disease (CAD) have demonstrated better clinical outcomes. We sought to compare...     

Effects of 17β-estradiol on the expressions of CTGF and PAIP-1 in MG-63 cells

Objective To observe the expressions of connective tissue growth factor (CTGF) and polyadenylate-binding protein interacting protein-1 (PAIP-1) mRNA during MG-63 cell proliferation and differentiation, and to investigate the effect of 17β-estradiol (E2) on the expressions of CTGF and PAIP-1 mRNA. Methods The expressions of typeⅠcollagen, alkaline phosphatase (ALP) and osteocalcin mRNA were determined by semiquantitative RT-PCR. Cultured cells were stained with     

Cardioprotection of 17β-estradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2

Estrogens have been suggested to exert cardioprotection through maintaining endogenous cardioprotective mechanisms. In the present study, we investigated whether estrogens protect cardiomyocytes against hypoxia/reoxygenation (H/R) via modulating urocortins (UCNs) and their receptor corticotrophin-releasing hormone receptor type 2 (CRHR2). We found that 17β-estradiol (E2) enhanced UCN cardioprotection against H/R and increased CRHR2 expression in neonatal rat cardiomyocytes. E2 protected cardiomyocytes against H/R, which was impaired by CRHR2 antagonist or knockdown of CRHR2. Estrogen receptor α (ERα) antagonist treatment or ERα knockdown could abolish E2-induced CRHR2 up-regulation. Moreover, knockdown of Sp1 also attenuated E2-induced CRHR2 up-regulation. Ovariectomy resulted in down-regulation of CRHR2 and Sp-1 in myocardium of mice, which was restored by E2 or ERα agonist treatment. These results suggest that estrogens act on ERα to up-regulate CRHR2 expression in cardiomyocytes, thereby enhancing cardioprotection of UCNs against H/R.     

Expression of vitellogenin in the testis and kidney of the spotted ray Torpedo marmorata exposed to 17β-estradiol

In vertebrates, the liver was long thought to be the only site of vitellogenin (Vtg) production, but recent studies demonstrated that Vtg is also expressed in extrahepatic districts. The aim of this paper is to assess, by in situ hybridization and immunohistochemistry, the expression of Vtg in the testis and kidney of Torpedo marmorata exposed to 17β-estradiol (E₂). In treated samples vtg mRNA and Vtg were detected contemporaneously only in the testis; differently the kidney cells were positive to Vtg antibody, but negative to vtg mRNA. This is the first study to assess that male germ cells, after an exposure to E₂, synthesize Vtg in a stage-dependent manner. The presence of Vtg and the modifications observed in the kidney after E₂ treatment are discussed.     

The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients

Background and aims: The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C?>?G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented. Since not all NAFLD with fibrosis evolve to cirrhosis, we investigated the specific risk of cirrhosis conferred in NAFLD patients by carrying this SNP. Methods: Three groups were studied: patients with NASH-cirrhosis; patients with biopsy-proven non-cirrhotic NAFLD; healthy subjects undergoing medicine check-ups. Epidemiological, anthropometric, and clinical data were collected, and the SNP was analyzed by pyrosequencing. Results: Sixty-one patients with NASH-cirrhosis, 60 with non-cirrhotic NAFLD, and 125 healthy controls were included. Frequency of the PNPLA3 minor (G) allele was increased in patients with NASH-cirrhosis compared with non-cirrhotic NAFLD and controls (allele frequency: 0.598 versus 0.367 versus 0.2, respectively, p?p?Conclusions: In NAFLD patients, carriage of the PNPLA3G allele, and particularly of the GG genotype, is significantly associated with the risk of cirrhotic evolution. If confirmed in larger series, these results would suggest that most of NASH cases require the contribution of an altered PNPLA3 function to progress until cirrhosis.     

The antidiabetic effect of Geigeria alata is mediated by enhanced insulin secretion, modulation of β-cell function, and improvement of antioxidant activity in streptozotocin-induced diabetic rats

In Sudanese folk medicine, Geigeria alata roots have been used for the management of diabetes for a long time. However, its antidiabetic activity is unreported. In this study, G. alata methanolic extract was tested for its antidiabetic, antioxidant, and β-cell modulatory effects in a streptozotocin-induced diabetic rat model. In this model of diabetic rats, the oral glucose tolerance test with G. alata extract at 125, 250, and 500?mg/kg doses revealed the efficacy of the 250?mg/kg dose in improving glucose tolerance comparable to the standard drug glibenclamide. Diabetic rats were treated with a 250?mg/kg dose of G. alata extract orally for 2?h (acute) or 14 days (chronic). In the case of acute treatment, the extract lowered blood glucose levels significantly at 120?min both in nondiabetic and diabetic rats. Chronic treatment of diabetic rats with 250?mg/kg of G. alata extract resulted in a significant decrease in blood glucose level closer to that of nondiabetic rats. Interestingly, increased serum insulin, improved β-cell function, and antioxidant status were observed in G. alata-treated diabetic rats. G. alata also showed strong antioxidant and α-glucosidase inhibitory activities in in vitro assays. These data show direct evidence that G. alata has antidiabetic activity and suggest that the antidiabetic activity is due to enhanced insulin secretion, modulation of β-cell function, and improvement of antioxidant status.     

Patterns of neurotrophin protein levels in male and female Fischer 344 rats from adulthood to senescence: how young is "young" and how old is "old"?

The current study assessed neurotrophin protein levels in male and female rat brain tissues at four different ages ranging from postpuberty to senescence. In both sexes nerve growth factor (NGF) increased, and brain-derived neurotrophic factor (BDNF) decreased, from 4 to 24 months of age. Using a slightly older age for the young group, or a slightly younger age for the aged group, had profound effects on whether age effects were realized. There were no sex differences in the pattern of change in neurotrophin levels across age, and neurotrophin levels did not correlate with estrogen levels in females or estrogen or testosterone levels in males. The current findings suggest that profound changes in neurotrophin protein levels can occur within only a few months time, and that these changes influence whether age-related neurotrophin alterations are realized.     

The Diminishing Trend of β-Thalassemia in Southern Iran From 1997 to 2011: The Impact of Preventive Strategies

The marginal zones of the Caspian Sea and the Persian Gulf have a higher prevalence of thalassemia compared to other regions of Iran. This disease has disabled many people and resulted in increasing health care costs. The aim of this study was to assess the incidence of β-thalassemia (β-thal) and to evaluate the outcome of applied preventive strategies over a 14-year period in Fars Province, Southern Iran. This cross-sectional study comprised all new cases of β-thal recorded during 1997–2011. The data were obtained from the Non-Communicable Diseases Surveillance Department of Shiraz University of Medical Sciences, Shiraz, Iran, and are presented as mean?±?standard deviation (SD).

?The Fars Health Network System screened 840 686 males and females applying for marriage certificates. Among the carriers, 50.5% cancelled their marriages, 42.5% married, and 7.0% did not show up at the clinics. The rate of cancelled marriages has reduced since 2000, when marriage candidates were given the option of prenatal diagnosis. From 2000 to 2011, a total of 3539 married couples were referred for prenatal diagnosis. Of these, 806 fetuses were found to carry thalassemia and 800 aborted. It is impressive to note that while 101 cases of thalassemia were recorded in 1997, this figure was reduced to two cases by 2011. This study has established that an integrated primary health care approach, with good infrastructure for implementing successful strategies, can significantly reduce the incidence of β-thal.     

Aberrant TGF-β1 signaling contributes to the development of primary biliary cirrhosis in murine model

AIM:To investigate whether transforming growth factor-β1(TGF-β1)signaling pathway is involved in the pathogenesis of primary biliary cirrhosis(PBC).METHODS:A murine model of PBC was developed by injection of polyinosinic polycytidylic acids(polyⅠ:C)in C57BL/6 mice,and the liver expressions of TGFβ1,TGF-βreceptorⅠ(TβRⅠ),TGF-βreceptorⅡ(TβRⅡ),p-Smad2/3,monoclonalα-smooth muscle actin antibody(α-SMA)andα1(Ⅰ)collagen in the mouse model and control mice were evaluated by immunohistochemistry,immunoblotting and real-time polymerase chain reaction(RT-PCR).Lymphocyte subsets in liver were analyzed using flow cytometry.RESULTS:The mouse model had several key phenotypic features of human PBC,including elevated levels of alkaline phosphatase,antimitochondrial antibodies,portal bile ducts inflammation,and progressive collagen deposition.Compared with control mice,protein and mRNA levels of TGFβ1,TβRⅠ,TβRⅡ,p-Smad2/3,α-SMA andα1(Ⅰ)collagen in liver(1.7±0.4 vs 8.9±1.8,0.8±0.2 vs 5.1±1.5,0.6±0.01 vs5.1±0.1,0.6±0.3 vs 2.0±0.3,0.9±0.4 vs 3.4±0.6,0.8±0.4 vs 1.7±0.3,1.1±1.2 vs 11.8±0.6,P<0.05),and the total number and percentage of CD4+CD25+FOXP3+and CD8+lymphocytes(0.01±0.001vs 0.004±0.00,0.12±0.04 vs 0.52±0.23,P<0.01)were higher in the mouse model.CONCLUSION:TGFβ1 might play a dual role in the development of PBC:it suppresses inflammatory response but operates to enhance fibrogenesis.The aberrant activity of TGF-β1 signaling contributes to the development of PBC.