EVALUATION OF ANTIANXIETY, ANTIDEPRESSANT AND SEDATIVE EFFECTS OF NIMODIPINE IN SWISS ALBINO MICE

Objective: Study of Nimodipine, a calcium channel blocker was done on experiments involving tail suspension test (TST), elevated plus maze (EPM) test and Phenobarbitone induced sleeping time in Swiss albino mice.Methods: Nimodipine was given by intraperitoneal (i. p.) route in the dose of 2.5 & 5 mg/kg body wt respectively in albino mice of either sex (n=6) and effects were evaluated on (i) TST for antidepressant activity (ii) EPM for anti-anxiety and (iii) Loss of righting reflex for hypnotic activity and results were compared with the standard drugs like sertraline, diazepam and phenobarbitone respectively. Statistical analysis was done by ANOVA followed by Post hoc Tukey's test using SPSS v.20.0 software.Results: Nimodipine at a dose of 2.5 mg/kg has shown moderate anti-anxiety and antidepressant activities compared to control with no changes in the activity of acute sertraline; however, the antidepressant activity of subacute sertraline (14 d treatment) was summed up by 2.5 mg/kg dose without any hypnosis. While at higher doses of 5 mg/kg depression, behavior (prolonged time of immobilization on TST) and sedation (prolonged phenobarbitone induced sleep time) were seen.Conclusion: Nimodipine has shown moderate antidepressant and anti-anxiety activities at low doses and can be used as add-on therapy to routine drugs with least of peripheral side effects.Keywords: Nimodipine, Diazepam, Sertraline, Elevated plus maze (EPM), Tail suspension test (TST) and righting refle

Clinical phenotypes of infantile onset CACNA1A-related disorder

BACKGROUND: CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events: epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients. OBJECTIVE: To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations. MATERIAL AND METHODS: This study was a multicenter international collaboration. A retrospective chart review of CACNA1A patients was performed. Clinical, radiological, and genetic data were collected and analyzed in 47 patients with infantile-onset disorder. RESULTS: Paroxysmal non-epileptic events (PNEE) were observed in 68% of infants, with paroxysmal tonic upward gaze (PTU) noticed in 47% of infants. Congenital cerebellar ataxia (CCA) was diagnosed in 51% of patients including four patients with developmental delay and only one neurological sign. PNEEs were found in 63% of patients at follow-up, with episodic ataxia (EA) in 40% of the sample. Cerebellar ataxia was found in 58% of the patients at follow-up. Four patients had epilepsy in infancy and nine in childhood. Seven infants had febrile convulsions, three of which developed epilepsy later; all three patients had CCA. Cognitive difficulties were demonstrated in 70% of the children. Cerebellar atrophy was found in only one infant but was depicted in 64% of MRIs after age two. CONCLUSIONS: Nearly all of the infants had CCA, PNEE or both. Cognitive difficulties were frequent and appeared to be associated with CCA. Epilepsy was more frequent after age two. Febrile convulsions in association with CCA may indicate risk of epilepsy in later childhood. Brain MRI was normal in infancy. There were no genotype-phenotype correlations found

Modes of Neuronal Calcium Entry and Homeostasis following Cerebral Ischemia

One of the major instigators leading to neuronal cell death and brain damage following cerebral ischemia is calcium dysregulation. The neuron's inability to maintain calcium homeostasis is believed to be a result of increased calcium influx and impaired calcium extrusion across the plasma membrane. The need to better understand the cellular and biochemical mechanisms of calcium dysregulation contributing to neuronal loss following stroke/cerebral ischemia is essential for the development of new treatments in order to reduce ischemic brain injury. The aim of this paper is to provide a concise overview of the various calcium influx pathways in response to ischemia and how neuronal cells attempts to overcome this calcium overload

A primer for ZooMS applications in archaeology

Collagen peptide mass fingerprinting by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, also known as zooarchaeology by mass spectrometry (ZooMS), is a rapidly growing analytical technique in the fields of archaeology, ecology, and cultural heritage. Minimally destructive and cost effective, ZooMS enables rapid taxonomic identification of large bone assemblages, cultural heritage objects, and other organic materials of animal origin. As its importance grows as both a research and a conservation tool, it is critical to ensure that its expanding body of users understands its fundamental principles, strengths, and limitations. Here, we outline the basic functionality of ZooMS and provide guidance on interpreting collagen spectra from archaeological bones. We further examine the growing potential of applying ZooMS to nonmammalian assemblages, discuss available options for minimally and nondestructive analyses, and explore the potential for peptide mass finger-printing to be expanded to noncollagenous proteins. We describe the current limitations of the method regarding accessibility, and we propose solutions for the future. Finally, we review the explosive growth of ZooMS over the past decade and highlight the remarkably diverse applications for which the technique is suited

Hodnocení vlivu sanace chlorovaných etylenů na původní mikrobiální společenstva pomocí nástrojů molekulární biologie

Tato práce se soustředí na hodnocení vlivu sanačního zásahu na složení mikrobiálního společenstva a jeho změny v čase a sleduje přítomnost degradačních enzymů důležitých pro dekontaminaci polutantů. Soustředí se na rozklad chlorovaných etylenů, které představují jedny z nejrozšířenějších kontaminantů podzemních vod. Sleduje skupiny bakterií, které jsou schopny degradovat chlorované etyleny (tzv. organohalid-respirující bakterie; OHRB), a také geny kódující enzymy metabolických drah degradace těchto látek. Izolace deoxyribonukleové kyseliny (DNA) z podzemní vody byla komplikovaná pro vysoký obsah chlorovaných etylenů ve vzorcích, proto musel být extrakční protokol optimalizován a ověřen pro každou studovanou lokalitu. Pomocí metody polymerázové řetězové reakce v reálném čase (qPCR) byly následně detetekovány OHRB a specifické bakteriální geny v jednotlivých vzorcích. qPCR primery pro jejich detekci musely být otestovány pro co největší selektivitu a reakční podmínky optimalizovány pro každý vzorek zvlášť kvůli přítomnosti inhibitorů ve vzorcích. Změny ve složení a zastoupení přítomných bakteriálních populací byly dále sledovány metodou 16S rRNA amplikonové sekvenace, pomocí které lze detailně popsat složení celého autochtonního bakteriálního společenstva.Bylo zjištěno, že aplikace činidel pro cílenou oxidaci (peroxid vodíku pro spuštění Fentonovy reakce) a redukci (nulmocné nanoželezo v kombinaci s aplikací elektrického napětí a nulmocné železo uchycené v aktivním uhlí) chlorovaných etylenů mohou způsobit pokles v hladinách sledovaných degradačních bakterií. Tento pokles je však pouze dočasný a po krátké době dochází k obnovení populací OHRB díky vhodně nastaveným sanačním podmínkám a v některých případech i k podpoře jejich růstu.Aplikace biostimulačních substrátů laktátu sodného a glycerolu podpořila růst OHRB na kontaminovaných lokalitách. Pomocí sekvenační analýzy bylo také zjištěno, že po aplikaci glycerolu došlo primárně k proliferaci glycerol-fermentujících bakterií, které produkují zdroj uhlíku (acetát) a elektronů (molekulární vodík; H2) pro růst OHRB, současně se také zvýšily hladiny degradačních enzymů. Došlo i ke snížení oxidačně-redukčního potenciálu podzemní vody na hodnoty vhodné pro růst sulfát a železo-redukujících bakterií, které sice kompetují s OHRB o zdroj elektronů, ale současně produkují kofaktory enzymů důležité pro jejich růst. Tato dizertační práce ukázala, že pro úspěšnou dekontaminaci chlorovaných etylenů je nezbytné před sanačním zásahem co nejlépe charakterizovat vybranou lokalitu, a to jak z hydrochemického hlediska, tak za pomoci metod molekulární biologie, protože OHRB i další bakterie, které fungují jako primární či sekundární čističi lokality, potřebují k úspěšnému růstu a práci nejen určité environmentální podmínky, jako je vhodný oxidačně-redukční potenciál, pH, koncentrace rozpuštěného kyslíku, sulfátů či nitrátů, ale také dostatek živin, zdroj elektronů, a v neposlední řadě se ukázalo, že i celé bakteriální společenstvo poskytující dostatek syntropních interakcí. V monitoringu přítomných degradačních bakterií a jejich enzymů je třeba pokračovat v průběhu celého sanačního zásahu, aby bylo možné ve správný čas znovu podpořit optimální biodegradaci.This study assessed the effect of different remediation techniques on microbial community composition in the treated area and its changes over time. The research focused on sites polluted by chlorinated ethenes (CEs), one of the most common groundwater contaminants. The presence of organohalide-respiring bacteria (OHRB) capable of CE degradation was monitored along with the genes encoding enzymes of their degradation pathways. Isolation of deoxyribonucleic acid (DNA) from groundwater samples was challenging due to high concentration of CEs. As such, DNA extraction protocol had to be optimized and verified for each site studied. Furthermore, all primers for the detection of OHRB and specific genes had to be tested for their accuracy before standard use in real-time polymerase chain reaction (qPCR) and all qPCR reactions optimized due to the presence of inhibitors in the samples. Changes in the composition of the bacterial community and the shifts in selected populations were further analysed by the 16S rRNA amplicon sequencing, which was used to describe the composition of the whole autochthonous bacterial community in detail.The application of reagents for oxidation (hydrogen peroxide to trigger the Fenton-like reaction) and reduction (nanoscale zero-valent iron in combination with electrokinetic treatment and zero-valent iron attached to activated carbon) of chlorinated ethenes caused a decrease in the levels of degrading bacteria. However, this effect was only temporary and, after a short time, OHRB populations recovered due to the inflow of untreated water and well-adjusted and favorable soil conditions during remediation.The application of biostimulation substrates sodium lactate and glycerol supported the growth of OHRB at the contaminated site. 16S rRNA sequencing also showed that glycerol-fermenting bacteria, which produce an essential source of carbon (acetate) and electrons (molecular hydrogen; H2) for OHRB growth, were the first to proliferate after glycerol application, followed by OHRB. Levels of degradation enzymes also increased. Oxidation-reduction potential of the groundwater was reduced after the application to levels suitable for the growth of sulfate and iron-reducing bacteria, which compete with OHRB for electron source but also produce enzyme cofactors essential for their growth.This thesis demonstrates the importance of autochthonous microbial community characterization of the polluted site before and during remediation for successful CE decontamination. OHRB and other bacteria that act as primary or secondary cleaners of a remediated site need not only certain soil conditions for successful growth, such as suitable oxidation-reduction potential, pH, dissolved oxygen, sulfate, or nitrate concentration, but also sufficient supply of nutrients and electron sources. Last but not least, it was revealed that besides OHRB, a whole bacterial community providing sufficient syntrophic interactions is very important for CE degradation. Monitoring of degrading bacteria and their enzymes should be continued throughout the whole remediation action to support optimal biodegradation rates at the right time

Escala de Claridad en el Autoconcepto: adaptación y validación para su uso con adolescentes de Argentina

The present study aims to present the argentine adaptation and validation process of the Self-concept Clarity Scale for adolescents. For this purpose, three studies were conducted. In total 551 adolescents (13 to 19 years old and of both genders) from schools in the Buenos Aires Metropolitan Area (AMBA). Study 1: It presents the linguistic adaptation and psychometric properties analysis of the scale (exploratory factor analysis and content validity). Study 2: It confirms the internal structure of the scale (confirmatory factor analysis). Study 3: It strengthens the construct validity by relating self-concept clarity with the possible selves of the adolescents. The results show that linguistic and conceptual adaptation of the scale has been achieved. At the same time, it has an adequate content, factorial and construct validity, and a good internal consistencyEl presente estudio tiene como objetivo presentar el proceso de adaptación y validación argentina de la Escala de Claridad en el Autoconcepto (SCCS) para adolescentes. Para ello se realizaron tres estudios. En total participaron 551 adolescentes (13 a 19 años y de ambos sexos) de escuelas del Área Metropolitana Bonaerense (AMBA). Estudio 1: Presenta la adaptación lingüística de la escala y el análisis de sus propiedades psicométricas (análisis factorial exploratorio y validez de contenido). Estudio 2: Confirma la estructura interna de la escala (análisis factorial confirmatorio) e indaga sobre las diferencias en función del género y la edad. Estudio 3: Profundiza la validez de constructo relacionando la claridad en el autoconcepto con los posibles si mismos de los adolescentes. Los resultados muestran que se ha logrado la adaptación lingüística y conceptual de la escala. A su vez, posee una adecuada validez de contenido, factorial y de constructo, y una buena consistencia interna

Paraoxonase 1 in patients with diabetes mellitus

Humana serumska paraoksonaza 1 (PON1) je protein molekularne mase 43 kDa čija je katalitička aktivnost hidroliza organofosfatnih estera, aromatskih estera karboksilnih kiselina i karbamata. PON1 se sintetizira u jetri, a uglavnom je povezana sa lipoproteinom visoke gustoće (HDL). Enzim smanjuje nakupljanje lipidnih peroksida na lipoproteinu niske gustoće (LDL) s obzirom na svoju sposobnost metaboliziranja hidroperoksida. Aktivnost PON1 smanjena je u šećernoj bolesti. PON1 ima zaštitnu ulogu protiv razvoja šećerne bolesti zbog svoje antioksidative uloge. Visoke koncentracije glukoze u dijabetičkom serumu mogu objasniti odvojenost PON1 od HDL-a. Nadalje, oksidativni stres kao posljedica šećerne bolesti može povećati stvaranje lipidnih peroksida i umanjiti aktivnost serumske PON1. Polimorfizmi u promotorskoj i kodirajućoj regiji gena za PON1 određuju njegovu ekspresiju i enzimsku aktivnost samog enzima, međutim aktivnost serumske PON1 može biti regulirana i s nekoliko okolišnih faktora. Patološka stanja kao što su bubrežne bolesti, šećerna bolest, kardiovaskularne bolesti i ciroza jetre mogu biti povezane sa smanjenom paraoksonaznom aktivnošću, dok prehrambene navike i stil života također mogu utjecati na aktivnost samog enzima. Razlika u paraoksonaznoj aktivnosti među pojedincima dijelom je objašnjena varijacijama u kodirajućoj regiji gena za paraoksonazu. Najpoznatije varijacije su supstitucija arginina glutaminom na položaju 192 (Q192R) te supstitucija metionina leucinom na položaju 55 (M55L). Polimorfizam M55L bitna je odrednica serumske koncentracije PON1.Human serum paraoxonase 1 (PON1) is a 43-kDa protein which catalyses the hydrolysis of organophosphate esters, aromatic carboxylic acid esters, and carbamates. PON1 is synthesized in the liver and is mainly associated with high-density lipoprotein (HDL). The enzyme decreases accumulation of the lipid peroxides in low-density lipoprotein (LDL) due to its ability to reduce hydroperoxides. PON1 activity was found to be decreased in diabetes mellitus. PON1 has a protective role against diabetes development, secondary to its unique antioxidant properties. The high concentrations of glucose in diabetic serum could account for PON1 dissociation from HDL. Furthermore, oxidative stress as a consequence of diabetes can increase the formation of lipid peroxides and reduce the activity of serum PON1. Polymorphisms in the promoter and coding regions of the paraoxonase gene are the main determinants of its expression and the enzymatic activity, but serum paraoxonase activity can be modulated by several environmental factors. Pathologic states such as renal disease, diabetes mellitus, cardiovascular disease, and liver cirrhosis are asociated with decreased paraoxonase activity, and various dietary and lifestyle factors have been reported to influence serum paraoxonase activity. The differences in paraoxonase activity among individuals are explained partly by genetic variation in th coding region of paraoxonase gene. The most famous variations are supstitution pf arginine for glutamine at position 192 (Q192R) and methionine for leucine at position 55 (M55L). The M55L polymorphisam is also a significant determinant of the serum concetration of paraoxonase

Untersuchung von Ghrelin in Speichel, Sulkusflüssigkeit und Blut bei Parodontitis und unterschiedlichem Körpergewicht

Es wurde das Hormon Ghrelin im Speichel, der Sulkusflüssigkeit und im Blut bei Parodontitis und unterschiedlichem Körpergewicht untersucht. Geklärt werden sollte, ob Ghrelin ein Parodontitismarker sein kann.:I Abkürzungsverzeichnis IV II Tabellenverzeichnis VII III Abbildungsverzeichnis VIII 1. Einleitung 1 1.1 Ghrelin 1 1.1.1 Aufbau und Produktion 1 1.1.2 Funktion 4 1.2 Speichel 8 1.2.1 Aufbau und Produktion 8 1.2.2 Funktion 10 1.2.3 Speichel und Ghrelin 11 1.3 Sulkusflüssigkeit 13 1.3.1 Produktion und Funktion 13 1.3.2 Sulkusflüssigkeit und Ghrelin 14 1.4 Blutserum 15 1.4.1 Aufbau und Funktion 15 1.4.2 Serum und Ghrelin 15 1.5 Parodontitis und Abwehr 16 1.6 Körpergewicht und Entzündung 18 2. Ziele der Studie 20 3. Methoden/ Experiment 21 3.1 Patientenkollektiv 21 3.1.1 Einschlusskriterien 21 3.1.2 Ausschlusskriterien 22 3.1.3 Ethikantrag und Menschenrechtskonvention 22 3.2 Klinische Variablen 23 3.2.1 Bestimmung des Body-Mass-Index 23 3.2.2 Bestimmung des Approximalraum-Plaqueindex 23 3.2.3 Bestimmung des Sulkusblutungsindex 24 3.2.4 Bestimmung des Bluten auf Sondieren 24 3.2.5 Erhebung der Sondierungstiefen und Attachmentlevel 25 3.3 Gewinnung der Proben 26 3.3.1 Gewinnung von Speichel 26 3.3.2 Gewinnung von Sulkusflüssigkeit 26 3.3.3 Gewinnung von Blut 26 3.4 Untersuchung der Proben 27 3.4.1 Quantitative Ghrelinbestimmung durch enzymgekoppelten Immunadsorptionstest (ELISA) 27 3.4.2 Statistische Methoden 28 4. Ergebnisse 30 4.1 Gruppeneinteilung 30 4.2 Demografische und klinische Daten 32 4.3 Gruppenvergleiche 34 4.3.1 Parodontitis vs. parodontal gesund / Gingivitis 34 4.3.2 Parodontitis übergewichtig vs. normalgewichtig 36 4.3.3 Gesund / Gingivitis übergewichtig vs. normalgewichtig 38 4.3.4 Parodontitis übergewichtig vs. gesund / Gingivitis übergewichtig 40 4.3.5 Parodontitis normalgewichtig vs. gesund / Gingivitis normalgewichtig 42   5. Diskussion 44 5.1 Methoden und klinische Durchführung 44 5.2 Bewertung und Beurteilung der Ergebnisse 45 6. Zusammenfassung 56 7. Literaturverzeichnis 60 8. Anhang 75 8.1 Anamnesebogen 76 8.2 Einwilligungserklärung 77 8.3 Formblatt Parodontalstatus 79 8.4 Tabelle Patientendaten und Ergebnisse 80 9. Selbständigkeitserklärung 82 10. Lebenslauf 83 11. Publikationen 84 12. Danksagung 85