Sex differences in angiotensin II- induced hypertension

Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG II-induced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen a receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

Animal model for age- and sex-related genotoxicity of diethylstilbestrol

Environmental xenoestrogens pose a significant health risk for all living organisms. There is growing evidence concerning the different susceptibility to xenoestrogens of developing and adult organisms, but little is known about their genotoxicity in pre-pubertal mammals. In the present study, we developed an animal model to test the sex- and age-specific genotoxicity of the synthetic estrogen diethylstilbestrol (DES) on the reticulocytes of 3-week-old pre-pubertal and 12-week-old adult BALB/CJ mice using the in vivo micronucleus (MN) assay. DES was administered intraperitoneally at doses of 0.05, 0.5, and 5 µg/kg for 3 days and animals were sampled 48, 72 and 96 h, and 2 weeks after exposure. Five animals were analyzed for each dose, sex, and age group. After the DES dose of 0.05 µg/kg, pre-pubertal mice showed a significant increase in MN frequency (P < 0.001), while adults continued to show reference values (5.3 vs 1.0 MN/1000 reticulocytes). At doses of 0.5 and 5 µg/kg, MN frequency significantly increased in both age groups. In pre-pubertal male animals, MN frequency remained above reference values for 2 weeks after exposure. Our animal model for pre-pubertal genotoxicity assessment using the in vivo MN assay proved to be sensitive enough to distinguish age and sex differences in genome damage caused by DES. This synthetic estrogen was found to be more genotoxic in pre-pubertal mice, males in particular. Our results are relevant for future investigations and the preparation of legislation for drugs and environmentally emitted agents, which should incorporate specific age and gender susceptibility.

The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1) overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4) and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old) were treated for three weeks with T4 (50 µg/day, Hyper) or with saline (control). Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM) or T3 (100 nM). PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA). Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

The novel p.E89K mutation in the SRY gene inhibits DNA binding and causes the 46,XY disorder of sex development

Male sex determination in humans is controlled by the SRY gene, which encodes a transcriptional regulator containing a conserved high mobility group box domain (HMG-box) required for DNA binding. Mutations in the SRY HMG-box affect protein function, causing sex reversal phenotypes. In the present study, we describe a 19-year-old female presenting 46,XY karyotype with hypogonadism and primary amenorrhea that led to the diagnosis of 46,XY complete gonadal dysgenesis. The novel p.E89K missense mutation in the SRY HMG-box was identified as a de novo mutation. Electrophoretic mobility shift assays showed that p.E89K almost completely abolished SRY DNA-binding activity, suggesting that it is the cause of SRY function impairment. In addition, we report the occurrence of the p.G95R mutation in a 46,XY female with complete gonadal dysgenesis. According to the three-dimensional structure of the human SRY HMG-box, the substitution of the conserved glutamic acid residue by the basic lysine at position 89 introduces an extra positive charge adjacent to and between the positively charged residues R86 and K92, important for stabilizing the HMG-box helix 2 with DNA. Thus, we propose that an electrostatic repulsion caused by the proximity of these positive charges could destabilize the tip of helix 2, abrogating DNA interaction.

From Escherichia coli heat-stable enterotoxin to mammalian endogenous guanylin hormones

The isolation of heat-stable enterotoxin (STa) from Escherichia coli and cholera toxin from Vibrio cholerae has increased our knowledge of specific mechanisms of action that could be used as pharmacological tools to understand the guanylyl cyclase-C and the adenylyl cyclase enzymatic systems. These discoveries have also been instrumental in increasing our understanding of the basic mechanisms that control the electrolyte and water balance in the gut, kidney, and urinary tracts under normal conditions and in disease. Herein, we review the evolution of genes of the guanylin family and STa genes from bacteria to fish and mammals. We also describe new developments and perspectives regarding these novel bacterial compounds and peptide hormones that act in electrolyte and water balance. The available data point toward new therapeutic perspectives for pathological features such as functional gastrointestinal disorders associated with constipation, colorectal cancer, cystic fibrosis, asthma, hypertension, gastrointestinal barrier function damage associated with enteropathy, enteric infection, malnutrition, satiety, food preferences, obesity, metabolic syndrome, and effects on behavior and brain disorders such as attention deficit, hyperactivity disorder, and schizophrenia.

Effect of genotype, finishing system, and sex on physiochemical characteristics of goat meat

Seventy-eight kids of both sexes and five genotypes were used: Alpine, ½ Boer + ½ Alpine (½ BA), ¾ Boer + ¼ Alpine, ½ Anglo-nubian + ½ Alpine and "tricross" (½ Anglo-nubian + ¼ Boer + ¼ Alpine) with initial average weight of 14.1 ± 2.5. The objective was to evaluate the effect of genotype, finishing system, and sex on the physiochemical characteristics of goat meat. Finishing systems were: ST1 - kid + dam in pasture and ST2 - weaned kid and feedlot. Kids in ST1 were kept in an area with Panicum maximum cv. Tanzania, and after grazing, water and mineral salt/mix were fed ad libitum to the animals. The animals in ST2 were confined in collective pens distributed according to genotypes and received diet with 16% CP and 73% TDN. The values of pH, a* (red content), Cooking Loss (CL), and Ether Extract (EE) percentage were influenced by genotype. Values for red content (a*) and L* (brightness), CL and percentages of moisture, protein, EE, and ash were influenced by the finishing system. Longissimus dorsi muscle from animals ½ BA exhibited better physiochemical characteristics. For greater tenderness and higher percentages of fat, consumers should choose female kid goat meat.

Sex Quartetter för 2 Violiner, Alt och Violoncello. Op. 1.

Erik Tulindberg (1761–1814) on maamme ensimmäisiä nimeltä tunnettuja taidesäveltäjiä. Hänen sävellyskäsikirjoituksensa hautautuivat sukuarkistojen kätköihin yli sadaksi vuodeksi, eikä tänä aikana tiedetty säveltäjästä mitään. Vuonna 1925 kirjastonhoitaja Arne Jörgensen löysi Kansalliskirjaston yksityisestä vanhojen nuottien kokoelmasta kolme käsin kirjoitettua nuottivihkoa, joiden todettiin sisältävän Tulindbergin ensiviulun, alttoviulun ja sellon äänet kuuteen jousikvartettoon. Toisen viulun stemmat puuttuvat. Tarkkaa sävellysvuotta kvartetoissa ei ole merkittynä, mutta on arveltu että ne sijoittuisivat 1780-luvulle.

Sueciae magnae, totius orbis regni antiquissimi, hodierna in sex principales suas partes, Gothiam nempe, Sueciam propriam sive stricté sumptam, Nordlandiam, Finniam, Ingriam, Livoniam, earundemque subdivisionum, ac adiacentium insularum geographica distinctio

Nimeke ylämarginaalissa.

historiae ecclesiasticae gentis Anglorum libri quinque : authore Beda, Presbytero ; praemittitur epitaphium discipulorum sex sancti Gregorii, Papae.

Colbertinus

historiae Longobardorum libri sex : initio et ad calcem occurrunt folia aliquot loco suo mota ; authoris nomen non comparet, is autem est Paulus Diaconus.

Faurianus

1.° Petri Pauli Vergerii, Justinopolitani, liber de politia Venetorum, eorumque legibus ac moribus, urbis situ, naturaque regionis. — 2.° Ejusdem liber de situ veteris Romae. — 3.° Anonymi chronica Italica. — 4.° Historiae ecclesiasticae omnium temporum libri sex : authore anonymo. — 5.° Sexti Rufi, viri Consularis, historiae Romanae breviarium. — 6.° Benevenuti de Rambaldis, Imolensis, liber augustalis de vitis Caesarum.

Faurianus

sancti Gregorii Turonensis historiae Francorum libri novem : primus liber integer, secundi sex priora capitula et alia passim desiderantur : ad calcem libri noni subjicitur Fredegarii chronicon ab anno quo desierat Gregorius, deductum ad annum 656. quod quidem à variis authoribus productum fuit ad annum 741. porrò chronicon Fredegarii cum additamentis, decimus Gregorii Turonensis liber in hoc codice inscribitur.

Colbertinus

rerum Sicanicarum libri sex : authore Francisco Maurolyco, Abbate Messanensi ; exemplar autographum.

Colbertinus

1.° L. Annaei Senecae libri duo de clementia, ad Neronem. — 2.° Ejusdem epistolarum libri viginti duo. — 3.° Ejusdem liber de remediis fortuitorum, ad Gallionem. — 4.° Ejusdem liber de septem liberalibus artibus. — 5.° Ejusdem, sive potiùs, Martini Dumiensis liber de quatuor virtutibus. — 6.° Declamationum libri decem. — 7.° L. Annaei Senecae libri sex de quaestionibus naturalibus. — 8.° Proverbia, sive Senecae, Publii Syri et aliorum sententiae. — 9.° Liber de moribus. — 10.° Senecae de beneficiis libri septem. — 11.° Ejusdem libri duo de providentia. — 12.° Ejusdem liber de beata vita, ad Gallionem. — 13.° Ejusdem liber de tranquillitate animi, ad Serenum. — 14.° Ejusdem liber de brevitate vitae, ad Paulinum. — 15.° Ejusdem de ira libri tres, ad Novatum. — 16.° Ejusdem liber de consolatione ad Martiam. — 17.° Ejusdem liber de consolatione ad Helviam matrem. — 18.° Pauli et Senecae epistolae mutuae supposititiae.

Colbertinus, antea Jacobi Augusti Thuani

1.° L. Annaei Senecae de quaestionibus naturalibus libri septem. — 2.° Fragmentum Adelardi, Bathensis, de quibusdam quaestionibus naturalibus. — 3.° Collatio Alexandri Magni et Dyndimi, Regis Brachmannorum, de philosophia, facta per litteras. — 4.° Senecae libri septem de beneficiis. — 5.° Ejusdem, sive potiùs, Martini Dumiensis liber de quatuor virtutibus. — 6.° Senecae liber de remediis fortuitorum. — 7.° Liber de verborum copia, qui Senecae tribuitur. — 8.° Ejusdem de clementia libri duo. — 9.° Pauli et Senecae epistolae mutuae supposititiae. — 10.° Senecae, Publii Syri et aliorum sententiae. — 11.° Senecae epistolae ad Lucilium centum viginti et sex.

Colbertinus, antea Jacobi Augusti Thuani