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Patients with diabetes mellitus (DM) type 1 and 2 are at a higher risk of cognitive decline and dementia; however, the underlying pathology is poorly understood. Kynurenic acid (KYNA), endogenous kynurenine metabolite, displays pleiotropic effects, including a blockade of glutamatergic and cholinergic receptors. Apart from well-known glial origin, kynurenic acid is robustly synthesized in the endothelium and its serum levels correlate with homocysteine, a risk factor for cognitive decline. Studies in an experimental DM model suggest that a selective, hippocampal increase of the kynurenic acid level may be an important factor contributing to diabetes-related cognitive impairment. The aim of this study was to assess the effects of chronic, four-week administration of losartan, angiotensin receptor blocker (ARB), on the brain KYNA in diabetic rats. Chromatographic and rt-PCR techniques were used to measure the level of KYNA and the expression of genes encoding kynurenine aminotransferases, KYNA biosynthetic enzymes, in the hippocampi of rats with streptozotocin-induced DM, treated with losartan. The effect of losartan on KYNA synthesis de novo was also evaluated in vitro , in brain cortical slices. The hippocampal increase of KYNA content occurred in diabetic rats treated and nontreated with insulin. Losartan did not affect KYNA levels when administered per se to naïve or diabetic animals but normalized KYNA content in diabetic rats receiving concomitantly insulin. The expression of CCBL1 ( kat 1 ), AADAT ( kat 2 ), and KAT3 ( kat 3 ) genes did not differ between analyzed groups. Low concentrations of losartan did not affect KYNA production in vitro . The neuroprotective effect of ARBs in diabetic individuals may be, at least partially, linked to modulation of KYNA metabolism. The ability of ARB to modulate synthesis of KYNA in diabetic brain does not seem to result from changed expression of genes encoding KATs. We propose possible involvement of angiotensin AT 4 receptors in the observed action of losartan., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Iwona Chmiel-Perzyńska et al.)

Objectives: The aim of the study is to determine the impact of the experimental diabetes and the chronic hypoxia on pregnancy development and rat fetal body weight., Material and Methods: The experiment was performed on female Wistar rats. Animals were divided into the experimen-tal groups. I - Controls, II - Untreated diabetes, III - Insulin-treated diabetes, IV - No diabetes with chronic hypoxia, V - Untreated diabetes and chronic hypoxia, VI - Insulin- treated diabetes and chronic hypoxia. Diabetes was induced in groups II, III, V and VI with intraperitoneal injection of streptozocin (STZ) at a dose of 40 mg/kg. Chronic hypoxia was induced by placing dams (groups IV, V and VI) in conditions of 10.5% oxygen and 89.5%. Insulin was administered subcutaneously at the dose of 9 IU/kg. Starting from the 6th day after STZ injection and chronic hypoxia conditions animals were caged together for 12 hours for 3 consecutive days to ensure fertilization. On day 21 of gestation the animals were decapitated, the fetuses were removed and weighted., Results: Mean fetal body weight in separate groups were: I - 5.38 g, II - 6.04g, III - 5.32g, IV- 5.56 g, V - 3.45 g, VI - 6.23 g., Conclusions: Pre-existing type 1 diabetes does not affect fetal body weight compared to healthy newborn control rats. Pro-longed hypoxia does not impact on fetal body weight. Chronic hypoxia during pregnancy complicated with untreated type 1 diabetes mellitus leads to significant reduction of fetal body weight. Insulin treatment reversed the detrimental effect of chronic hypoxia on fetal development.

Background: Diabetes mellitus (DM) is frequently associated with peripheral and central complications and has recently emerged as a risk factor for cognitive impairment and dementia. Kynurenic acid (KYNA), a unique tryptophan derivative, displays pleiotropic effects including blockade of ionotropic glutamate and α7 nicotinic receptors. Here, the influence of experimental diabetes on KYNA synthesis was studied in rat brain., Methods: DM was induced by i.p. administration of streptozotocin (STZ). Five weeks later, KYNA content and the activity of semi-purified kynurenine aminotransferases (KATs) were measured in frontal cortex, hippocampus and striatum of diabetic and insulin-treated rats, using HPLC-based methods., Results: Hippocampal but not cortical or striatal KYNA concentration was considerably increased during DM, either untreated or treated with insulin (220% and 170% of CTR, respectively). The activity of kynurenine aminotransferase I (KAT I) was not affected by DM in all of the studied structures. KAT II activity was moderately increased in cortex (145% of CTR) and hippocampus (126% of CTR), but not in striatum of diabetic animals. Insulin treatment normalized cortical but not hippocampal KAT II activity., Conclusions: A novel factor potentially implicated in diabetic hippocampal dysfunction has been identified. Observed increase of KYNA level may stem from the activation of endogenous neuroprotection, however, it may also have negative impact on cognition., (Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Ketone bodies formed during ketogenic diet or non-treated diabetes mellitus may exert neuroprotective and antiepileptic effects. Here, we assessed the influence of ketone body, β-hydroxybutyrate (BHB) on the brain synthesis of kynurenic acid (KYNA), an endogenous antagonist of glutamatergic and α7-nicotinic receptors. In brain cortical slices and in primary glial cultures, BHB enhanced KYNA production. KT 5270, an inhibitor of protein kinase A, has prevented this action. At hypoglycemia, under pH 7.0 and 7.4, profound (15 mM BHB), but not mild (3 mM) ketosis increased synthesis of KYNA. In paradigm resembling diabetic ketoacidosis in vitro (30 mM glucose, pH 7.0), neither mild nor profound ketosis influenced the production of KYNA. At pH 7.4 and in 30 mM glucose though, both mild and severe ketonemia evoked an increase of KYNA production. The activity of KYNA biosynthetic enzymes, KAT I and KAT II, in cortical homogenate was not altered by BHB (0.05-10.0 mM). However, in cultured glial cells exposed to BHB (10 mM), the activity of KATs increased. This effect was reversed by the co-incubation of cells with KT 5270. Presented data reveal a novel mechanism of action of BHB. Increased synthesis of KYNA in the presence of BHB is most probably mediated by protein kinase A-dependent stimulation of KATs expression/activity leading to an increase of KYNA formation. Ensuing attenuation of the excessive excitatory glutamate-mediated neurotransmission may, at least in part, explain the neuroprotective actions of BHB.

One of the solutions aimed at improving the functioning of the healthcare system in Poland is to introduce patients' co-payment for public healthcare services. In all countries where the healthcare system is at a high level there already exists a co-payment system and it is regarded by many specialists as a necessary and indispensable condition for the proper functioning of healthcare. The aim of this study was to show respondents' attitudes and opinions regarding the proposal of introduction co-payments as and additional form of financing medical care. The questionnaire survey covered a group of 2,409 persons (50.7% men and 49.3% women). Most respondents, despite the overall rising dissatisfaction with the quality and availability of medical services do not see the need for co-payments. The opinion about the implementation of co-payments. The opinion about the implementation of co-payments depends on many factors, to the most important belong age, education, place of residence and income. More often, the co-payments is in favour of young people in good health condition, who live in big cities, having a university degree and determining their financial situation as good. Before the introduction of co-payment - certain social groups, which would be exempt from additional fees, should be specified. To the highest costs that patients are able to carry belong: paying for a home visit of family doctor or specialist, for surgical procedures, and for complex tests performed during the hospital stay (including computed tomography, magnetic resonance imaging).

Gynecomastia is a benign, abnormal, growth of the male breast gland which can occur unilaterally or bilaterally, resulting from a proliferation of glandular, fibrous and adipose tissue. Gynecomastia is characterised by the presence of soft, 2-4 cm in diameter, usually discusshaped enlargement of tissues under the nipple. It is estimated that this pathology occurs in 32-65% of men over the age of 17. Gynecomastia is a psychosocial problem and may lead to a perceived lowering of quality of life. The main cause of gynecomastia is a loss of equilibrium between oestrogens and androgens. Increased sensitivity for oestrogens of the breast gland, or local factors (e.g. an excessive synthesis of oestrogens in breast tissues or changes in oestrogen and androgen receptors) may cause gynecomastia. Also, prolactin, thyroxine, cortisol, human chorionic gonadotropin, leptin and receptors for human chorionic gonadotropin, prolactin and luteinizing hormone localised in tissues of the male breast may participate in the etiopathogenesis of gynecomastia. Usually three types of gynecomastia are distinguished: physiological, idiopathic and pathological gynecomastia. The latter is the consequence of relative or absolute excess of oestrogens. In this paper, frequent as well as casuistic causes of gynecomastia will be described. A diagnosis of gynecomastia is usually possible after a palpation examination. Ultrasonographic, mammographic or histopathological examinations are useful in aiding diagnosis. The five degree scale devised by Tanner and Marshall is useful in estimating disease progression.

We have evaluated the effect of diabetes-mimicking conditions on the inhibition of kynurenic acid (KYNA) production exerted by mitochondrial toxins: 3-nitropropionic acid (3-NPA) and aminooxyacetic acid (AOAA), by endogenous agonists of glutamate receptors: L-glutamate and L-cysteine sulfinate, and by a risk factor of atherosclerosis, D,L-homocysteine. Hyperglycemia (30 mM; 2 h) itself did not influence KYNA synthesis in brain cortical slices. However, it significantly enhanced the inhibitory effects of 3-NPA, AOAA and D,L-homocysteine, but not of L-glutamate and L-cysteine sulfinate, on KYNA production. Their IC(50) values were lowered from 5.8 (4.5-7.4) to 3.7 (3.1-4.5) mM (p < 0.01), from 11.6 (8.6-15.5) to 7.1 (4.9-10.3) microM (p < 0.05), and from 4.5 (3.5-5.8) to 2.4 (1.8-3.2) mM (p < 0.01), respectively. The obtained data suggest that during hyperglycemia, the mitochondrial impairment and high levels of D,L-homocysteine evoke stronger inhibition of KYNAsynthesis what may further exacerbate brain dysfunction and play a role in central complications of diabetes.