The role of gamma-aminobutyric acid mechanisms of the zona incerta-lateral hypothalamus in the catalepsy and muscle rigidity evoked by morphine

Picrotoxin or bicuculline were injected bilaterally into the zona incerta-lateral hypothalamus (ZI-LH) of the rat. Each drug (50 ng) inhibited or abolished the catalepsy induced by 20 mg/kg s.c. of morphine. Each drug also strongly inhibited the tonic electromyographic activity (EMG) induced by 10 mg/kg s.c. of morphine in the gastrocnemius soleus muscle (GS). The obtained results demonstrate participation of the ZI-LH in both catalepsy and rigidity induced by a systemic administration of morphine.     

Multivariable non-linear controller for a synchronous generator

The problem of multivariable controller synthesis for a turbogenerator is considered. Using the feedback linearization approach for multi-input non-linear systems, the existence of a linearizing state feedback for the improved reduced-order model of a turbogenerator is proved and the simplest form of this feedback is derived. Application of the obtained non-linear controller to the multivariable control of a turbogenerator provides very good results not only for the reduced-order model but also for the ‘exact’ (Park's) model of a turbogenerator. Simulations of fault and post-fault conditions in the obtained nonlinear control system confirm its superiority over a system with a voltage regulator and power system stabilizer.     

The striopallidal pathway is involved in antiparkinsonian-like effects of the blockade of group I metabotropic glutamate receptors in rats

The aim of the study was to examine the influence of the blockade of group I metabotropic glutamate receptors (mGluRs) on the haloperidol-induced catalepsy and proenkephalin mRNA expression in the rat striatum. Bilateral, intrastriatal injection of AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid, 3-15 microg/0.5 microl), a selective antagonist of group I mGluRs, inhibited catalepsy induced by haloperidol (0.5 mg/kg i.p.). Repeated intrastriatal AIDA administrations (3 x 15 microg/0.5 microl, 3 h apart) counteracted the haloperidol-induced (3 x 1.5 mg/kg s.c., 3 h apart) increase in the proenkephalin mRNA expression in that structure. The present study indicates that the blockade of the striatal group I mGluRs may inhibit parkinsonian akinesia by normalizing the function of the striopallidal pathway.     

The results of the interference of nitrates and vitamin E in the metabolism in the connective tissue of rat''s liver

We examined 72 female Wistar rats which were divided into 6 groups. The animals were administered sodium nitrate (V), vitamin E or both compounds at the same time. In order to estimate the interference of nitrates in the presence of vitamin E with the metabolism of rat's liver, we determined the composition and the amount of glycosoaminoglycans (GAGs). It was stated that the total amount of GAGs increased in livers of all rats. Basing on all fractions of the examined GAGs it was determined that the most significant differences between individual groups appeared in the amount of heparane sulphate (HS). The results obtained confirmed the fact of the changes taking place in the picture of liver GAGs in the process of ageing of the examined animals. The results obtained, however, allowed to state the normalising influence of vitamin E on the quantitative composition of GAGs of rats which drank nitrates.     

Risk of macrovascular and microvascular complications in Type 2 diabetes: results of longitudinal study design

Type 2 diabetes is associated with the increased risk of microvascular and macrovascular complications. The aim of this study was to determine risk factors for the development of long-term complications of Type 2 diabetes. We analyzed medical records of all patients, who came with newly diagnosed Type 2 diabetes to one regional outpatient diabetes clinic from 1980 to 1994 (n=2175). The data, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure and body mass index (BMI), were assessed. Also, the time from the diagnosis of Type 2 diabetes to the occurrence of complications was obtained. Using the regression model in the survival analysis, we examined which of the risk factors determined the rate of the development of nephropathy, proliferative retinopathy, cardiovascular disease and stroke. Patients with higher fasting plasma glucose and higher mean blood pressure had higher risk of developing nephropathy and proliferative retinopathy. Higher mean arterial blood pressure was associated with higher rate of stroke and cardiovascular disease. High total cholesterol increased the hazard of coronary artery disease and proliferative retinopathy. In conclusion, blood pressure and fasting plasma glucose are major risk factors for microvascular complications in Type 2 diabetes. An increased blood pressure determined the macrovascular complications in Type 2 diabetes, but the effect of increased fasting plasma glucose could not be proved.     

Low-dose sirolimus-eluting hydroxyapatite coating on stents does not increase platelet activation and adhesion ex vivo

We previously found paclitaxel-eluting polymer-coated stents causing more human platelet-monocyte complex formation than bare metal stents in vitro. Presently, we examined patterns of platelet activation and adhesion after exposure to 6 nanofilm HAp-coated (HAp-nano) stents, 6 HAp-microporous-coated (HAp-micro) stents, 5 HAp sirolimus-eluting microporous-coated (HAp-SES) stents and 5 cobalt-chromium stents (BMS) deployed in an in vitro flow system. Blood obtained from healthy volunteers was circulated and sampled at 0, 10, 30 and 60 min. By flow cytometry, there were no significant differences in P-Selectin expression between the 4 stent types (HAp-nano = 32.5%; HAp-micro = 42.5%, HAp-SES = 10.23%, BMS = 7% change from baseline at 60 min, p = NS); PAC-1 antibody binding (HAp-nano = 11.8%; HAp-micro = 2.9%, HAp-SES = 18%, BMS = 6.4% change from baseline at 60 min, p = NS) or PMC formation (HAp-nano = 21.6%; HAp-micro = 4%, HAp-SES = 6.6%, BMS = 17.4% change from baseline at 60 min, p = NS). The 4 stent types did not differ in the average number of platelet clusters >10 μm in diameter by SEM (HAp-nano = 2.39 ± 5.75; HAp-micro = 2.26 ± 3.43; HAp-SES = 1.93 ± 3.24; BMS = 1.94 ± 2.41, p = NS). The majority of the struts in each stent group were only mildly covered by platelets, (HAp-nano = 80%, HAp-micro = 61%, HAp-SES = 78% and BMS = 52.1%, p = NS). The HAp-microporous-coated stents (ECD) attracted slightly more proteinaceous material than bare metal stents (HAp-micro = 35% struts with complete protein coverage, P < 0.0001 vs. other 3 stent types). In conclusion, biomimetic stent coating with nanofilm or microporous hydroxyapatite, even when eluting low-dose sirolimus, does not increase the platelet activation in circulating human blood, or platelet adhesion to stent surface when compared to bare metal stents in vitro.     

Effects of Adenosine Receptor Antagonists on the In Vivo LPS-Induced Inflammation Model of Parkinson’s Disease

The study shows effects of the nonselective adenosine A₁/A_2A receptor antagonist caffeine and the selective A_2A receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A_2A receptor density in the rat striatum. Intrastriatal LPS (10 μg) injection decreased extracellular level of DA and increased the level of adenosine, glutamate, and hydroxyl radical on the ipsilateral side 24 h after LPS administration. Caffeine (10 and 20 mg/kg i.p.) and KW6002 (1.5 and 3 mg/kg i.p.) given once daily for 6 days and on the 7th day 2 h before and 4 h after LPS injection reversed the LPS-induced changes in extracellular levels of DA, adenosine, glutamate, and hydroxyl radical production. Moreover, LPS-induced decrease in the striatal A_2A receptor density was increased by caffeine and KW6002. In order to show the late LPS effect on oxidative damage of DA neurons, the contents of DA, DOPAC, HVA, and hydroxyl radical were determined 72 h after LPS (10 μg) administration into both striata. LPS decreased striatal and substantia nigra content of DA, DOPAC, and HVA while increased striatal but not nigral content of hydroxyl radical. Caffeine (20 mg/kg) and KW60002 (3 mg/kg) given once daily for 6 days and on the 7th day 2 h before and 4 h after intrastriatal injection of LPS normalized the content of DA and its metabolites in both brain regions as well as decreased LPS-induced increase in the striatal level of hydroxyl radical. In conclusion, our data demonstrated antioxidant effects of caffeine and KW6002 in the inflammatory model of PD.     

MPTP‐induced dopamine neuron degeneration and glia activation is potentiated in MDMA‐pretreated mice

Clinical observations report a greater propensity to develop Parkinson's disease (PD) in amphetamine users. 3,4‐Methylenedioxymethamphetamine (MDMA; “ecstasy”) is an amphetamine‐related drug that is largely consumed by adolescents and young adults, which may have neuroinflammatory and neurotoxic effects. Here, the objective was to evaluate in mice whether consumption of MDMA during adolescence might influence the neuroinflammatory and neurotoxic effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a toxin known to induce PD in humans. The activation of astroglia and microglia by glial fibrillary acidic protein (GFAP) and complement receptor type 3 (CD11b) immunohistochemistry and the degeneration of dopaminergic neurons by tyrosine hydroxylase (TH) immunohistochemistry were evaluated. MPTP (20 mg/kg × 4) was administered to mice treated from ages 8 weeks to 17 weeks with MDMA (10 mg/kg twice daily, two times a week). In mice that were chronically treated with MDMA, administration of MPTP induced a higher microglial and astroglial response in both the striatum and the substantia nigra pars compacta (SNc) compared with vehicle‐treated or vehicle + MPTP‐treated mice. Inflammatory changes were associated with a decrease in TH immunoreactivity in the SNc of MDMA‐treated mice and with a further decrease in the striatum and the SNc of MDMA + MPTP‐treated mice compared with vehicle‐treated, MDMA‐treated, and MPTP‐treated mice. The results demonstrate that chronic administration of MDMA during late adolescence in mice exacerbates the neurodegeneration and neuroinflammation caused by MPTP, suggesting that MDMA may constitute a risk factor for dopaminergic neuron degeneration. © 2013 International Parkinson and Movement Disorder Society