Inducing sterile pyramidal neuronal death in mice to model distinct aspects of gray matter encephalitis

Up to one person in a population of 10,000 is diagnosed once in lifetime with an encephalitis, in 50–70% of unknown origin. Recognized causes amount to 20–50% viral infections. Approximately one third of affected subjects develops moderate and severe subsequent damage. Several neurotropic viruses can directly infect pyramidal neurons and induce neuronal death in cortex and hippocampus. The resulting encephalitic syndromes are frequently associated with cognitive deterioration and dementia, but involve numerous parallel and downstream cellular and molecular events that make the interpretation of direct consequences of sudden pyramidal neuronal loss difficult. This, however, would be pivotal for understanding how neuroinflammatory processes initiate the development of neurodegeneration, and thus for targeted prophylactic and therapeutic interventions. Here we utilized adult male NexCre‑ ERT2xRosa26-eGFP-DTA (= ‘DTA’) mice for the induction of a sterile encephalitis by diphtheria toxin-mediated ablation of cortical and hippocampal pyramidal neurons which also recruits immune cells into gray matter. We report multifaceted aftereffects of this defined process, including the expected pathology of classical hippocampal behaviors, evaluated in Morris water maze, but also of (pre)frontal circuit function, assessed by prepulse inhibition. Importantly, we modelled in encephalitis mice novel translationally relevant sequelae, namely altered social interaction/cognition, accompanied by compromised thermoreaction to social stimuli as convenient readout of parallel autonomic nervous system (dys)function. High resolution magnetic resonance imaging disclosed distinct abnormalities in brain dimensions, including cortical and hippocampal layering, as well as of cerebral blood flow and volume. Fluorescent tracer injection, immunohistochemistry and brain flow cytometry revealed persistent blood–brain-barrier perturbance and chronic brain inflammation. Surprisingly, blood flow cytometry showed no abnormalities in circulating major immune cell subsets and plasma high-mobility group box 1 (HMGB1) as proinflammatory marker remained unchanged. The present experimental work, analyzing multidimensional outcomes of direct pyramidal neuronal loss, will open new avenues for urgently needed encephalitis research

Associative diazotrophs of pearl millet <i>(Pennisetum glaucum) </i>from semi arid region - Isolation and characterization

341-345Diversity of the native diazotrophs associated with the rhizosphere of pearl millet (P. glaucum), grown in nutritionally poor soils of semi-arid regions was studied with a view to isolate effective nitrogen fixing<span style="font-size:16.0pt; font-family:HiddenHorzOCR;mso-hansi-font-family:" times="" new="" roman";mso-bidi-font-family:="" hiddenhorzocr"=""> and plant growth stimulating bacteria with root associative characteristics. The native population varied from 103-104 g-1 of rhizosphere soil after 40 d growth and belonged to genera Azospirillum, Azotobacter and Klebsiella. Another non-diazotrophic root associative group was Pseudomonas sp., which also produced IAA and enhanced plant growth. Some of these rhizobacteria showed high in vitro acetylene reduction activity along with production of indole acetic acid. Out of 11 selected diazotrophs used as seed inoculants, M10B (Azospirillum sp.), M11E  (Azotobacter sp.) and M12D4 (Klebsiella sp.) resulted in significant increase in total root and shoot nitrogen at 45 and 60 days of plant growth under pot culture conditions. </span

<span style="font-size: 21.0pt;mso-bidi-font-size:14.0pt;font-family:"Times New Roman","serif"">Symbiotic effectiveness of bacteriocin producing and non-producing strains of <i><span style="font-size:21.5pt;mso-bidi-font-size:14.5pt;font-family:"Times New Roman","serif"">Rhizobium </span></i><span style="font-size:21.0pt;mso-bidi-font-size:14.0pt;font-family: "Times New Roman","serif"">in green gram <i><span style="font-size:21.5pt; mso-bidi-font-size:14.5pt;font-family:"Times New Roman","serif"">(Vigna radiata)</span></i> </span></span>

821-823Rhizobium <span style="font-size:15.0pt;mso-bidi-font-size:8.0pt;font-family: " times="" new="" roman","serif""="">strains nodulating green gram [Vigna radiata <span style="font-size:14.5pt;mso-bidi-font-size:7.5pt; font-family:" arial","sans-serif""="">(L.) <span style="font-size:15.0pt; mso-bidi-font-size:8.0pt;font-family:" times="" new="" roman","serif""="">Wilczek] were found to produce bacteriocin on modified Bergersen' s medium and inhibited the growth of homologous <span style="font-size:15.5pt;mso-bidi-font-size: 8.5pt;font-family:" times="" new="" roman","serif""="">Rhizobium strains. Four bacteriocin producing and four bacteriocin non-producing strains were compared for their effect on nodulation, <span style="font-size:15.5pt; mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman","serif""="">in planta nitrogenase activity and plant dry weight of green gram. The bacteriocin producers formed more nodules in comparison to non-bacteriocin producers.  However, the symbiotic effectiveness of bacteriocin producers was less in terms of plant dry weight in comparison to nonbacteriocin producers.<span style="font-size:15.5pt;mso-bidi-font-size: 8.5pt;font-family:" times="" new="" roman","serif""=""> </span

Priprava i vrednovanje tableta metoprolol tartarata s odgođenim i produljenim oslobađanjem koristeći hidrofilne polimere koji bubre

In view of the circadian rhythm of cardiovascular diseases, a delayed-onset extended-release (DOER) formulation of metoprolol tartrate (MT) was prepared. This was achieved through dissolution-guided optimization of the proportion of Methocel K4M and Methocel K15M. Core erosion ratio was greater than 50 %, thereby showing steady release of the drug after the lag time until complete dissolution. Optimized formulation produced a lag phase of 6 h followed by complete release of 98.7 ± 2.1 % in 24 h. Water uptake study revealed that Methocel K15M has lower water uptake (30 ± 1 %) than methocel K4M (40 ± 2 %) after 24 h. Axial swelling of polymers was higher than swelling in the radial direction. Drug-polymer interaction study precludes any interaction between drug and polymer. Such a drug delivery system may provide a viable alternative for effective management of hypertension and other related disorders. This work also proposes an approach to attain DOER for a hydrophilic drug by using a hydrophilic swellable polymer in press coat.Vodeći računa o cirkadijanom ritmu kardiovaskularnih bolesti, pripravljene su formulacije metoprolol tartarata (MT) s odgođenim i produljenim oslobađanjem (DOER). Optimizacija je provedena praćenjem oslobađanja pri čemu je mijenjan omjer hidroksipropilmetil celuloza Methocela K4M i Methocela K15M. Erozija obložnog sloja bila je veća od 50 %, što pokazuje ujednačeno oslobađanje ljekovite tvari nakon početne odgođene faze do potpunog oslobađanja. U optimiziranoj formulaciji oslobađanje je započelo nakon 6 h, nakon čega slijedi potpuno oslobađanje (98.7 ± 2.1 %) tijekom 24 h. Nakon 24 h ulazak vode u Methocel K15M bio je manji (30 ± 1 %) nego u Methocel K4M (40 ± 2 %). Aksijalno bubrenje polimera bilo je značajnije nego radijalno bubrenje. Nije zapažena interakcija lijeka i polimera. Opisani sustav za isporuku lijekova može biti korisna alternativa za učinkovitu terapiju hipertenzije i srodnih poremećaja. DOER s ovojnicom od hidrofilnih polimera koji bubre upotrebljiv je i za druge hidrofilne lijekove