Sympathetic hyperactivity and relative NO deficiency are characteristic alterations in both genetic and salt hypertension. The contribution of these abnormalities to blood pressure (BP) maintenance can be determined in conscious rats using a consecutive blockade of particular vasoactive systems. Thus, the contribution of pressor effects of angiotensin II to the maintenance of high BP is usually small, but the role of renin-angiotensin system in the development of hypertension mediated by central and peripheral effects of angiotensin II on sympathetic activity is highly important. This is even true in angiotensin-dependent hypertension of heterozygous Ren-2 transgenic rats in which sympathetic hyperactivity is increasing with age. Central sympathoexcitation in this hypertensive model can be inhibited by lower losartan doses than peripheral angiotensin II-dependent vasoconstriction. This experimental model also yielded important knowledge on nephroprotective effects of new therapeutic drugs - endothelin receptor type A blockers. A considerable part of sympathetic vasoconstriction is dependent on the interaction of Ca2+ sensitization (RhoA/Rho kinase pathway) and Ca2+ influx (through L-VDCC). The blockade of these pathways prevents a major part of sympathetic vasoconstriction. Ca2+ sensitization seems to be attenuated in genetic hypertension in order to compensate increased Ca2+ influx. In contrast, enhanced Ca2+ sensitization is a hallmark of salt sensitivity in Dahl rats in which salt hypertension is dependent on increased Ca2+ influx. The attention should also be paid to the impairment of arterial baroreflex sensitivity which permits enhanced BP responses to pressor or depressor stimuli. Some abnormalities can be studied in blood vessels isolated from hypertensive rats but neither conduit arteries nor mesenteric resistance arteries represent the vascular beds decisive for the increased peripheral resistance and high BP. Keywords: Sympathetic vasoconstriction, NO-dependent vasodilatation, Calcium sensitization, Calcium influx, Arterial baroreflex, Spontaneously hypertensive rats, Salt hypertensive Dahl rats, Ren-2 transgenic rats, RAS blockade, SNS blockade, NOS inhibition, Endothelin, Vascular contraction and relaxation, Isolated conduit and resistance arteries, EDCF, PGI2, BKCa channels.

• MeSH
• hypertenze * patofyziologie   metabolismus   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• renin-angiotensin systém účinky léků   fyziologie   MeSH
• sympatický nervový systém patofyziologie   účinky léků   MeSH
• vazodilatace účinky léků   fyziologie   MeSH
• vazokonstrikce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Neuropsychiatrické příznaky demence jsou závažnou skupinou poruch u demencí. Z nich nejnápadnější a nejvíce rušivé jsou příznaky neklidu - agitovanost, hrubý neklid, agresivita. Tyto příznaky často vedou k tomu, že je pacient hospitalizován nebo umístěn ve specializovaném zařízení sociálních služeb. K mírnění neklidu se používají především nefarmakologické přístupy, které však často nestačí. Proto je nutno použít farmakoterapie. V článku jsou rozebrány možnosti takovéhoto typu léčby, jeho výhody i nevýhody.

Neuropsychiatrical symptoms of dementia are a serious group of disorders in dementia. Among them, the most noticeable and most disturbing are the symptoms of restlessness - agitation, gross restlessness, aggressiveness. These symptoms often lead to the patient being hospitalized or placed in a specialized social service facility. Mainly non-pharmacological approaches are used to alleviate restlessness, but they are often not enough. Therefore, it is necessary to use pharmacotherapy. The article discusses the possibilities of this type of treatment, its advantages and disadvantages.

• MeSH
• aberantní motorické chování u demence farmakoterapie   terapie   MeSH
• antipsychotika aplikace a dávkování   klasifikace   MeSH
• demence * farmakoterapie   patologie   terapie   MeSH
• látky ovlivňující centrální nervový systém aplikace a dávkování   klasifikace   MeSH
• lidé MeSH
• psychomotorický neklid * etiologie   farmakoterapie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Toxoplasmosis is caused by Toxoplasma gondii (Nicolle et Manceaux, 1908), a coccidian protist (Apicomplexa). It has a strong predilection for infecting the central nervous system. Researchers have therefore investigated its association with several neurological and psychiatric disorders, including Alzheimer's disease, attention-deficit hyperactivity disorder, autism, bipolar disorder, cerebral palsy, depression, Guillain-Barre syndrome, multiple sclerosis, obsessive compulsive disorder, Parkinson's disease, personality disorders, and schizophrenia. Among these disorders the strongest evidence for a role of T. gondii exists for psychosis in general and schizophrenia in particular. This paper reviews the origins of this association, briefly summarises the current evidence in support, and discusses future research strategies.

• MeSH
• lidé MeSH
• schizofrenie * MeSH
• Toxoplasma fyziologie   MeSH
• toxoplazmóza * komplikace   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

ADHD tvoří součást spektra neurovývojových poruch, stejně jako např. Aspergerův syndrom, a jako každá z nich je definována poruchou růstu a zrání neuronů vedoucí ke strukturálním i funkčním odchylkám centrálního nervového systému. Pokusy o systematičtější definici biomarkerů těchto odchylek souvisí se snahou najít souvislost s funkčními charakteristikami této skupiny diagnóz. Postupující možnosti vyšetření vycházejí především z magnetické rezonance a od volumometrie se přesouvají k pokusu stanovit strukturální odchylky v bílé hmotě mozkové. Tak jako u neurovývojových poruch existují překrývající se oblasti v aspektech struktury bílé hmoty a genomových odchylek, tak u nich existuje i paralela v překrývání se klinických projevů. Všechny neurovývojové poruchy sdílí obecně kognitivní narušení, jehož profil je do jisté míry charakteristický pro konkrétní diagnózu, ale současně bývá jeho podoba u každého jednotlivého pacienta velmi individuální, většinou složená z více typů deficitu různě do sebe zapadajících. Odlišení jednotlivých aspektů kognice je možné při podrobném psychodiagnostickém vyšetření. Kazuistika 33leté pacientky tak nabízí pohled na neurovývojové poruchy jako na kontinuum, nikoliv jako na přísně oddělené nozologické jednotky. V terapii každého individuálního pacienta je výhodné namísto fixace na diagnostickou entitu raději vybrat jednotlivé příznaky, u kterých předpokládáme možnost farmakologického ovlivnění. V případě složeného deficitu s komorbiditami se nevyhneme polyfarmakoterapii, pokud možno co nejšetrnější.

ADHD, as well as Asperger syndrome belong to the spectrum of neurodevelopmental disorders. Like each of them, it is defined among others by impaired growth and maturation of neurons leading to structural and functional abnormalities of the central nervous system. Attempts to a more systematic definition of their biomarkers are related to the effort to find a connection with the functional characteristics of this group of disorders. The progress of brain imaging methods offered by magnetic resonance has evolved from mere volumetry to determination of the structural abnormalities, herein focused at the white matter. As in all neurodevelopmental disorders overlapping areas exist in findings of white matter structure and in genomic findings, as well as an existing parallel in overlap of clinical manifestations. All neurodevelopmental disorders in general share a cognitive impairment the profile of which being characteristic for a particular diagnostic unit to some extent. However, its form in each individual patient is at the same time unique, being mostly composed of several types of deficits. The differentiation of individual aspects of cognition can be found in a detailed neurocognitive examination. The case report describing a 33-year-old patient thus offers a view of a neurodevelopmental continuum, not being strictly separated in diagnostic units. In each patient, instead of being fixed to diagnostic units it is advisable to focus on individual symptoms where we expect the possible benefit of pharmacotherapy. In case of a multiple deficit with comorbidities, we cannot avoid polypharmacotherapy, though as considerate as possible.

• MeSH
• Aspergerův syndrom diagnóza   farmakoterapie   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• hyperkinetická porucha * diagnóza   farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• neurovývojové poruchy * diagnóza   MeSH
• obsedantně kompulzivní porucha diagnóza   farmakoterapie   MeSH
• psychotropní léky aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Spontaneously hypertensive rats (SHR) are characterized by sympathetic hyperactivity and insufficient parasympathetic activity, and their high blood pressure (BP) can be lowered by long-term inhibition of the renin-angiotensin system. The aim of our study was to determine the influence of chronic inhibition of angiotensin converting enzyme (ACE) by captopril on cardiovascular regulation by the sympathetic and parasympathetic nervous system. Implanted radiotelemetric probes or arterial cannulas were used to measure mean arterial pressure (MAP), heart rate (HR), and arterial baroreflex in adult SHR and Wistar-Kyoto (WKY) rats under basal or stress conditions. MAP and the low-frequency component of systolic blood pressure variability (LF-SBPV, marker of sympathetic activity) were greater in SHR than in WKY rats. Under basal conditions chronic captopril treatment reduced both parameters more effectively in SHR, and the same was true during acute restraint stress. HR was similar in control rats of both strains, but WKY rats showed greater heart rate variability (HRV), indicating higher parasympathetic activity. Captopril administration increased HR in both strains, whereas HRV was decreased only in WKY. Chronic captopril treatment improved the impaired baroreflex-HR control in SHR by increasing the sensitivity but not the capacity of vagal arm of arterial baroreflex. Captopril treatment attenuated BP changes elicited by dimethylphenylpiperazinium (DMPP, agonist of nicotinic acetylcholine receptors), especially in SHR, indicating that sympathetic nerve transmission is facilitated by angiotensin II more in hypertensive than in normotensive animals. Thus, chronic ACE inhibition improves baroreflex sensitivity and lowers BP through both central and peripheral attenuation of sympathetic tone.

• MeSH
• baroreflex * účinky léků   MeSH
• hypertenze farmakoterapie   patofyziologie   enzymologie   MeSH
• inhibitory ACE * farmakologie   MeSH
• kaptopril * farmakologie   MeSH
• krevní tlak * účinky léků   MeSH
• krysa rodu rattus MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• srdeční frekvence * účinky léků   MeSH
• sympatický nervový systém * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• pediatrie MeSH

• Konspekt
• Pediatrie
• NLK Obory
• pediatrie
• NLK Publikační typ
• učebnice vysokých škol

Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1-3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.

• MeSH
• hyperkinetická porucha * farmakoterapie   MeSH
• krysa rodu rattus MeSH
• methylfenidát * farmakologie   terapeutické užití   MeSH
• motivace MeSH
• odměna MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému * farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Primary treatment of central neurocytomas is surgical resection. Gamma Knife surgery is considered a valuable therapeutic option in case of residual (after subtotal resection) or recurrent central neurocytomas. Here, we focused on the role of F-18 fluroethyltyrosine as a marker to document tumor progression after initial resection, in the context of an atypical central neurocytoma. We also describe MIB-1's role in evaluating therapeutic decision-making. CASE PRESENTATION: Two patients with central neurocytomas were treated by Gamma Knife surgery in our center. The first case (31-year-old Caucasian male) had atypical central neurocytoma. Four and a half years after surgical resection, magnetic resonance imaging and F-18 fluroethyltyrosine documented clear progression of residual central neurocytoma, further treated by Gamma Knife surgery (18 Gy at 50%, target volume 1.4 cc, and prescription isodose volume 1.8 cc). The initial post-Gamma Knife surgery clinical course was uneventful, with progressive volumetric reduction of residual tumor up to 4.5 years, when out-of-field recurrence was suspected and confirmed by local F-18 fluroethyltyrosine hyperactivity. Second single-fraction Gamma Knife surgery was performed (18 Gy at 50%, target volume 0.49 cc, prescription isodose volume 0.72 cc). The second (32-year-old Caucasian female) had previous subtotal resection and typical central neurocytoma. Seven years later, she had residual tumor progression. Single-fraction Gamma Knife surgery was performed (16 Gy at 50% isodose line, target volume 1.7 cc, and prescription isodose volume 2.5 cc). Last follow-up showed tumor volume reduction. Follow-up magnetic resonance imaging showed important volumetric reduction of both treated lesions. CONCLUSIONS: In atypical central neurocytomas, F-18 fluroethyltyrosine could be used as postoperative examination to detect small tumor remnants, follow-up evaluation following the Gamma Knife surgery or, in select cases, following surgical resection. The role of MIB-1 is important in therapeutic decision-making, as tumors with MIB-1 exceeding 2% are characterized by more aggressive clinical course. Single-fraction Gamma Knife surgery remains a valuable therapeutic option for postoperative residual atypical central neurocytomas and central neurocytoma recurrences.

• MeSH
• dospělí MeSH
• lidé MeSH
• neurocytom * diagnostické zobrazování   radioterapie   chirurgie   MeSH
• progrese nemoci MeSH
• radiochirurgie * MeSH
• reziduální nádor MeSH
• zákroky plastické chirurgie * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The cerebellum hosts more than half of all neurons of the human brain, with their organized activity playing a key role in coordinating motor functions. Cerebellar activity has also been implicated in the control of speech, communication, and social behavior, which are compromised in autism spectrum disorders (ASD). Despite major research advances, there is a shortage of mechanistic data relating cellular and molecular changes in the cerebellum to autistic behavior. We studied the impact of tuberous sclerosis complex 2 haploinsufficiency (Tsc2+/-) with downstream mTORC1 hyperactivity on cerebellar morphology and cellular organization in 1, 9, and 18 m.o. Eker rats, to determine possible structural correlates of an autism-like behavioural phenotype in this model. We report a greater developmental expansion of the cerebellar vermis, owing to enlarged white matter and thickened molecular layer. Histochemical and immunofluorescence data suggest age-related demyelination of central tract of the vermis, as evident from reduced level of myelin-basic protein in the arbora vitae. We also observed a higher number of astrocytes in Tsc2+/- rats of older age while the number of Purkinje cells (PCs) in these animals was lower than in wild-type controls. Unlike astrocytes and PCs, Bergmann glia remained unaltered at all ages in both genotypes, while the number of microglia was higher in Tsc2+/- rats of older age. The convergent evidence for a variety of age-dependent cellular changes in the cerebellum of rats associated with mTORC1 hyperactivity, thus, predicts an array of functional impairments, which may contribute to the developmental onset of an autism-like behavioral phenotype in this model. LAY SUMMARY: This study elucidates the impact of constitutive mTORC1 hyperactivity on cerebellar morphology and cellular organization in a rat model of autism and epilepsy. It describes age-dependent degeneration of Purkinje neurons, with demyelination of central tract as well as activation of microglia, and discusses the implications of these changes for neuro-behavioral phenotypes. The described changes provide new indications for the putative mechanisms underlying cerebellar impairments with their age-related onset, which may contribute to the pathobiology of autism, epilepsy, and related disorders.

• MeSH
• autistická porucha * MeSH
• demyelinizační nemoci * komplikace   metabolismus   MeSH
• epilepsie * komplikace   MeSH
• fenotyp MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mozeček metabolismus   MeSH
• mTORC1 genetika   metabolismus   MeSH
• poruchy autistického spektra * MeSH
• tuberózní skleróza MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• dítě MeSH
• hyperkinetická porucha diagnóza   etiologie   terapie   MeSH
• lidé MeSH
• mentální retardace diagnóza   etiologie   terapie   MeSH
• poruchy autistického spektra diagnóza   psychologie   terapie   MeSH
• poruchy chování u dětí MeSH
• poruchy motorických dovedností diagnóza   etiologie   terapie   MeSH
• vývojové poruchy řeči diagnóza   etiologie   terapie   MeSH
• vývojové poruchy u dětí * diagnóza   etiologie   terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH