Gold nanoparticles carrying or not anti-VEGF antibody do not change glioblastoma multiforme tumor progression in mice.

AIMS: Glioblastoma multiforme (GBM) is the most devastating malignant primary brain tumor known. Life expectance is around 15 months after diagnosis. Several events contribute to the GBM progression such as uncontrolled genetic cancer cells proliferation, angiogenesis (mostly vascular endothelial growth factor (VEGF)-mediated), tissue invasion, glioma stem cell activity, immune system failure, and a hypoxic and inflammatory tumor microenvironment. Tumor cells antiproliferative effect of 20 nm citrate-covered gold nanoparticles (cit-AuNP) has been reported, along with anti-inflammatory and anti-oxidative effects. We aimed to test whether either chronic treatment with 20 nm cit-AuNP or anti-VEGF antibody (Ig)-covered AuNP could reduce GBM progression in mice. MAIN METHODS: Effect of the gold nanoparticles on the GL261 glioblastoma cells proliferation in vitro, and on the GL261-induced glioblastoma cell growth in C57BL/6 mice in vivo were tested. Besides, fluorophore-conjugated gold nanoparticles penetration through the GL261 plasma cell membrane, gold labelling in brain parenchyma of glioblastoma-carrying mice, and VEGF expression into the tumor were evaluated. KEY FINDINGS: We observed cit-AuNP did no change the GL261 cells proliferation. Similarly, we demonstrated chronic treatment with either cit-AuNP or anti-VEGF Ig-covered AuNP did not modify the GL261 cells-induced GBM progression in mice. By the end, we showed AuNPs did not trespass in appreciable amount both the GL261 plasma cell membrane and the tumoral blood brain barrier (BBB), and did not change the VEGF expression into the tumor. SIGNIFICANCE: 20 nm cit-AuNP or anti-VEGF Ig covered-AuNP are not good tools to reduce GBM in mice, probably because they do not penetrate both tumor cells and BBB in enough amount to reduce tumor growing.

Systemic arterial hypertension leads to decreased semen quality and alterations in the testicular microcirculation in rats.

Arterial hypertension is a cardiovascular disease that leads to important systemic alterations and drastically impairs normal organ function over time. Hypertension affects around 700 million men of reproductive age and hypertensive men present increased risk for reproductive disorders, such as erectile dysfunction. However, the link between arterial hypertension and male reproductive disorders is associative at best. Moreover, many studies have reported associations between decreased male fertility and/or semen quality and alterations to general male health. In this study we aim to investigate the effect of systemic high blood pressure in sperm quality, sperm functional characteristics and testicular physiology in a rat model. Hypertensive rats presented altered testicular morphology - mainly vascular alterations and impaired testicular vasomotion. Hypertensive rats also presented decrease in sperm concentration, DNA integrity and increased percentages of sperm with dysfunctional mitochondria, intracellular superoxide anion activity and abnormal morphology. This study provides mechanistic insights by which arterial hypertension affects the testes, evidencing the testes as another target organ for hypertension as well as its impact on sperm quality.

Treatment with Standard and Low Dose of Conjugated Equine Estrogen Differentially Modulates Estrogen Receptor Expression and Response to Angiotensin II in Mesenteric Venular Bed of Surgically Postmenopausal Hypertensive Rats.

Standard hormone therapy for menopausal women [conjugated equine estrogen (CEE) 0.625 mg] has been associated with increased risk of venous thrombosis. Regimens containing a lower CEE dose (0.30 mg) have been used clinically to decrease side effects of supraphysiologic doses of estrogen. In this study, we determined the effects of standard (SD) and low dose (LD) of CEE on venular function in ovariectomized (OVX) spontaneously hypertensive rats (SHR). Contractions by angiotensin-II (Ang-II 10 µM) in perfused mesenteric venular bed were markedly increased in OVX (21.5 ± 1.3 mmHg) compared with Sham (14.7 ± 1.1 mm Hg, P < 0.05). CEE-SD did not modify Ang-II responses in OVX, whereas CEE-LD restored Ang-II contraction to Sham levels. Endothelial nitric oxide synthase (eNOS) inhibition by L-NAME increased Ang-II contractions in Sham and CEE-LD and was without effect in venules of OVX SHR and CEE-SD. In OVX there was decreased NO generation in association with diminished eNOS phosphorylation and increased O2- generation in the venular wall. CEE-LD reverted the deleterious effects of ovariectomy. Although CEE-SD augmented eNOS phosphorylation in OVX, it was unable to increase NO levels, probably owing to its inability to reduce O2- Distinct effects by CEE-SD and CEE-LD parallel the differential modulation of Ang-II and estrogen receptors. Compared with Sham, CEE-LD increases Ang II receptor type 2, whereas CEE-SD modified ERß expression in the venous bed. Interestingly, both CEE doses increased G protein-coupled estrogen receptor in OVX. Our data suggest that estrogen dose is an important factor for venous function. Although CEE-LD reversed deleterious effects of OVX, CEE-SD showed null effects despite its ability to increase eNOS activity.