Volumen 51 (2017): Edición 2 (April 2017)

Objective. Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1) activate Fos expression in the brain areas selected; 2) activate tyrosine hydroxylase (TH)-synthesizing cells displaying Fos presence; and 3) be modulated by CMS preconditioning.

Methods. Control (CON), ASE, CMS, and CMS+ASE groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. Th e ASE and CMS+ASE groups received a single dose of ASE (0.3 mg/kg, s.c.) and CON and CMS saline (300 μl/rat, s.c.). The animals were sacrificed 90 min aft er the treatments. Fos protein and TH-labeled immunoreactive perikarya were analyzed on double labeled histological sections and enumerated on captured pictures using combined light and fluorescence microscope illumination.

Results. Saline or CMS alone did not promote Fos expression in any of the structures investigated. ASE alone or in combination with CMS elicited Fos expression in two parts of the SN (SNC, SNR) and the VTA. Aside from some cells in the central gray tegmental nuclei adjacent to LC, where a small number of Fos profiles occurred, none or negligible Fos occurrence was detected in the other structures investigated including the LC and sLC, PON-A5, NTS-A2, AP, and VLM-A1. CMS preconditioning did not infl uence the level of Fos induction in the SN and VTA elicited by ASE administration. Similarly, the ratio between the amount of free Fos and Fos colocalized with TH was not aff ected by stress preconditioning in the SNC, SNR, and the VTA.

Conclusions. Th e present study provides an anatomical/functional knowledge about the nature of the acute ASE treatment on the catecholamine-synthesizing neurons activity in certain brain structures and their missing interplay with the CMS preconditioning.

Objective. The aim of the present study was to examine the effect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic effects of these nanoparticles.

Methods. Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titanium nitride nanoparticles (20 nm) with food every working day for 2 months. The expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction.

Results. Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3 and CD36 genes was increased in mouse liver upon treatment with chromium disilicide nanoparticles. We have also shown that treatment with titanium nitride nanoparticles resulted in down-regulation of the expression of IGFBP2 and SNARK genes in the liver with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3, IGFBP4, and CD36 genes was increased in the liver of mice treated with titanium nitride nanoparticles. Furthermore, the effect of chromium disilicide nanoparticles on IGFBP2 and CD36 genes expression was significantly stronger as compared to titanium nitride nanoparticles.

Conclusions. The results of this study demonstrate that chromium disilicide and titanium nitride nanoparticles have variable effects on the expression of IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver, which may reflect the genotoxic activities of the studied nanoparticles.

Objectives. Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse effects of different type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro effects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility.

Methods. The GCs isolated from porcine ovarian follicles were incubated with the different concentrations of PEG-b-PLA NPs (PEG average Mn=350 g/mol and PLA average Mn=1000 g/mol; 0.2-100 μg/ml) or poly(ethylene glycol) with an average molecular weight of 300 (PEG-300; 0.2- 40 mg/ml) in the presence or absence of stimulators, follicle-stimulating hormone (FSH; 1 μg/ml), androstenedione (100 nM), forskolin (10 μM) or 8Br-cAMP (100 μM), for different time periods (24, 48, 72 h). At the end of the incubation, progesterone and estradiol levels produced by GCs were measured in the culture media by radioimmunoassay. Th e viability of GCs was determined by the method using a colorimetric assay with MTT.

Results. Treatment of GCs with PEG-b-PLA NPs induced a significant decrease in basal as well as FSH-stimulated progesterone secretion above the concentration of 20 and 4 μg/ml, respectively. Moreover, PEG-b-PLA NPs reduced forskolin-stimulated, but not cAMP-stimulated progesterone production by GCs. A dose-dependent inhibition of androstenedione-stimulated estradiol release by GCs was found by the action of PEG-b-PLA NPs. Incubation of GCs with PEG-300 significantly inhibited basal as well as FSH-stimulated progesterone secretion above the concentration of 40 mg/ml. PEG-b-PLA NPs and PEG-300 significantly reduced the viability of GCs at the highest tested concentrations (100 μg/ml and 40 mg/ml, respectively).

Conclusions. The obtained results indicate that polymeric NPs PEG-b-PLA might induce alterations in steroid hormone production by ovarian GCs and thereby could modify reproductive functions.

Objective. We investigated the effects of hydroalcoholic extract of Nigella sativa (NS) on renal tissue oxidative damage associated with propylthiouracil (PTU)-induced hypothyroidism during neonatal and juvenile growth in rats.

Methods. Pregnant rats were divided into five groups designated as: 1) control; 2) propylthiouracil (PTU); 3) PTU-NS100; 4) PTU-NS200, and 5) PTU-NS400. All mothers except the control group received 0.005% PTU in their drinking water during lactation. Besides PTU, mothers in groups 3-5 received 100, 200, and 400 mg/kg of NS extract. After lactation period, the off spring continued to receive the same experimental treatment for the first 8 weeks of their life. Ten male off springs of each group were randomly selected, blood samples collected, and the kidney tissues removed.

Results. The serum thyroxin concentration in PTU group was lower than control group and improved by extract. PTU increased the renal malondialdehyde (MDA), while reduced the total thiols concentrations and catalase (CAT) and superoxide dismutase (SOD) activity compared to control group. Administration of 200 and 400 mg/kg of NS extract decreased MDA level, while it increased the total thiols and 400 mg/kg increased CAT and SOD activity in renal tissues compared to PTU group. Serum creatinine and blood urea nitrogen (BUN) in PTU group was higher than in comparison with the control group. 400 mg/kg decreased creatinine, but both 200 and 400 mg/kg improved BUN concentration compared to PTU group.

Conclusion. The results of this study demonstrate that the hydroalcoholic extract of NS has a protective effect on the renal tissue oxidative damage associated with PTU-induced hypothyroidism during neonatal and juvenile growth in rats.

A 31-year-old lady, diagnosed to have premature ovarian failure in the gynecology clinic, was referred for endocrine assessment because of an abnormal thyroid function test. Clinical examination revealed hypotension, and fungal skin infection under her atrophic breasts. Thyroid stimulating hormone (TSH) level was very high. Assessment of the suprarenal function revealed evidence of Addison’s disease. Polyglandular autoimmune dysfunction was diagnosed. She was treated with prednisone, fludrocortisone, and levothyroxine with significant improvement of her general condition and blood pressure.

Thyrostimulin is a glycoprotein heterodimer of GPA2 and GPB5, first described in 2002. It is involved in the physiological function of several tissues. Moreover, evidence points towards the ability of thyrostimulin’s individual monomers to induce a biological effect, which could denote the circulatory/systemic effects of the molecule when found in higher concentrations. From the evolutionary point of view, thyrostimulin shares a binding epitope with the thyroid-stimulating hormone for the thyroid stimulating hormone receptor, whilst possessing affinity for another unique binding site on the same receptor. Although thyrostimulin can be involved in the hypothalamicpituitary- thyroid axis, its presence in various tissues in an eclectic array of different species renders it multifunctional. From weight loss via increasing metabolic rate to progression of cancer in human ovaries, it is certainly not a signaling molecule to overlook. Furthermore, thyrostimulin has been implicated in bone metabolism, acute illness, and reproductive function. In summary, to our knowledge, this is the first review dealing with the physiological role of thyrostimulin and its potential applications in the clinical practice.