We reviewed the pleiotropic beneficial effects of the stable gastric pentadecapeptide BPC 157, three very recent demonstrations that may be essential in the gut-brain and brain-gut axis operation, ...and therapy application in the central nervous system disorders, in particular. Firstly, given in the reperfusion, BPC 157 counteracted bilateral clamping of the common carotid arteries-induced stroke, sustained brain neuronal damages were resolved in rats as well as disturbed memory, locomotion, and coordination. This therapy effect supports particular gene expression in hippocampal tissues that appeared in BPC 157-treated rats. Secondly, there are L-NG-nitro arginine methyl ester (L-NAME)- and haloperidol-induced catalepsy as well as the rat acute and chronic models of 'positive-like' schizophrenia symptoms, that BPC 157 counteracted, and resolved the complex relationship of the nitric oxide-system with amphetamine and apomorphine (dopamine agents application), MK-801 (non-competitive antagonist of the N-methyl-D-aspartate receptor) and chronic methamphetamine administration (to induce sensitivity). Thirdly, after rat spinal cord compression, there were advanced healing and functional recovery (counteracted tail paralysis). Likewise, in BPC 157 therapy, there is specific support for each of these topics: counteracted encephalopathies; alleviated vascular occlusion disturbances (stroke); counteracted dopamine disturbances (dopamine receptors blockade, receptors super sensitivity development, or receptor activation, over-release, nigrostriatal damage, vesicles depletion), and nitric oxide-system disturbances ("L-NAME non-responsive, L-arginine responsive," and "L-NAME responsive, L-arginine responsive") (schizophrenia therapy); inflammation reduction, nerve recovery in addition to alleviated hemostasis and vessels function after compression (spinal cord injury therapy). Thus, these disturbances may be all resolved within the same agent's beneficial activity, i.e., the stable gastric pentadecapeptide BPC 157.
Summary
CERN operates one of the most complex particle accelerator facilities in the world. Several different hazards, including fires, are present and need to be investigated and reduced to a ...tolerable level. Toward this goal, CERN aims at developing a catalog containing detailed fire dynamics descriptions of combustible items present in its facilities. This paper contributes to this catalog in two ways. First, through the development of a design fire calculator for electrical cabinets that allows the determination of potential design fire curves for any number of electrical cabinets/racks. The second contribution was to experimentally characterize the smoke production rates and smoke particle properties of the most common cables and insulating oils used at CERN by coupling a fast particle mobility analyzer to a cone calorimeter. The two particle size modes (accumulation and nucleation mode) could be linked to the fire properties and heat release rate. Accumulation mode particles (~200 nm) were associated with high heat release rates and high soot emissions from the flame. This study identifies a necessity to consider ultrafine particle emissions with low mass emissions but high number emissions in relation to risk assessments pertaining to nuclear facilities and dispersion of radioactive aerosols to the surrounding environment.
Sažetak. Prevalencija stenoze spinalnog kanala slabinske regije u stalnom je porastu zbog starenja pučanstva. Naime, unatoč etiološkoj raznovrsnosti, ona najčešće nastaje kao posljedica ...degenerativnih promjena na kralježnici. Nema općeprihvaćene klasifikacije stenoze spinalnog kanala slabinske regije. Za postavljanje dijagnoze potrebno je povezati nalaze iz anamneze, kliničkog statusa i slikovnih metoda zajedno s elektrofiziološkim nalazima. Liječenje bolesnika sa stenozom spinalnog kanala slabinske regije može biti konzervativno (farmakološko i nefarmakološko) i kirurško, s tim da se u potonjem u posljednje vrijeme preferiraju minimalno invazivne tehnike. U ovom radu dajemo sveobuhvatni suvremeni pogled na stenozu spinalnog kanala slabinske regije.
We focused on the therapeutic effects of the stable gastric pentadecapeptide BPC 157 in spinal cord injury using a rat model. BPC 157, of which the LD1 has not been achieved, has been implemented as ...an anti-ulcer peptide in inflammatory bowel disease trials and recently in a multiple sclerosis trial. In animals, BPC 157 has an anti-inflammatory effect and therapeutic effects in functional recovery and the rescue of somatosensory neurons in the sciatic nerve after transection, upon brain injury after concussive trauma, and in severe encephalopathies. Additionally, BPC 157 affects various molecular pathways.
Therefore, BPC 157 therapy was administered by a one-time intraperitoneal injection (BPC 157 (200 or 2 μg/kg) or 0.9% NaCl (5 ml/kg)) 10 min after injury. The injury procedure involved laminectomy (level L2-L3) and a 60-s compression (neurosurgical piston (60-66 g) of the exposed dural sac of the sacrocaudal spinal cord). Assessments were performed at 1, 4, 7, 15, 30, 90, 180, and 360 days after injury.
All of the injured rats that received BPC 157 exhibited consistent clinical improvement, increasingly better motor function of the tail, no autotomy, and resolved spasticity by day 15. BPC 157 application largely counteracted changes at the microscopic level, including the formation of vacuoles and the loss of axons in the white matter, the formation of edema and the loss of motoneurons in the gray matter, and a decreased number of large myelinated axons in the rat caudal nerve from day 7. EMG recordings showed a markedly lower motor unit potential in the tail muscle.
Axonal and neuronal necrosis, demyelination, and cyst formation were counteracted. The functional rescue provided by BPC 157 after spinal cord injury implies that BPC 157 therapy can impact all stages of the secondary injury phase.
Recently, marked therapeutic effects pertaining to the recovery of injured rat spinal cords (1 min compression injury of the sacrocaudal spinal cord (S2-Co1) resulting in tail paralysis) appeared ...after a single intraperitoneal administration of the stable gastric pentadecapeptide BPC 157 at 10 min post-injury. Besides the demonstrated rapid and sustained recovery (1 year), we showed the particular points of the immediate effect of the BPC 157 therapy that began rapidly after its administration, (i) soon after injury (10 min), or (ii) later (4 days), in the rats with a definitive spinal cord injury. Specifically, in counteracting spinal cord hematoma and swelling, (i) in rats that had undergone acute spinal cord injury, followed by intraperitoneal BPC 157 application at 10 min, we focused on the first 10-30 min post-injury period (assessment of gross, microscopic, and gene expression changes). Taking day 4 post-injury as the definitive injury, (ii) we focused on the immediate effects after the BPC 157 intragastric application over 20 min of the post-therapy period. Comparable long-time recovery was noted in treated rats which had definitive tail paralysis: (iii) the therapy was continuously given per orally in drinking water, beginning at day 4 after injury and lasting one month after injury. BPC 157 rats presented only discrete edema and minimal hemorrhage and increased
,
, and
values (30 min post-injury, (i)) or only mild hemorrhage, and only discrete vacuolation of tissue (day 4, (ii)). In the day 4-30 post-injury study (iii), BPC 157 rats rapidly presented tail function recovery, and no demyelination process (Luxol fast blue staining).
The structural fire safety of tunnels is a highly debated theme at international level. Car accidents in road tunnels, failures on the power lines in railway tunnels 1,2 and electrical related issues ...of technological installations in underground research infrastructures can lead to trigger a fire. Fire due to cars, trains and combustion of cable insulations can be considerably dangerous. Fire in such infrastructures causes the stress increases and the losses of bearing capacity in the exposed concrete linings. Thus, in presence of a relevant fire risk, both new and existing underground structures need to be assessed. This paper shows the analyses carried out on the cavern UX15 of the ATLAS experiment, located at the Point 1 of the Large Hadron Collider (LHC) of CERN – Meyrin, Switzerland. The structural fire assessment of tunnels requires to model the lining restrain conditions, the related structural resistance and the spalling phenomena. This modelling is done by Finite Element Method (FEM) code taking into account the spalling in advanced thermo‐mechanical analyses. The shell elements have been used due to their relatively conservative temperature distribution predictions, the acceptable accuracy of the displacement estimates, and a reasonable computational burden.
SAŽETAK
Adultne deformacije kralježnice značajno pridonose morbiditetu, napose starije popupacije. Iako je spektar uzroka raznolik najčešće se radi o novonastalim deformacijama na temelju ...degenerativnih promjena kralježnice. Osim bolova, osjećaja napetosti i drugih neugodnih simptoma, adultne deformacije rezultiraju biomehaničkim poremećajima, smanjenom pokretljivosti, a ponekad i neurološkim deficitima. Sveukupno, deformacije kralježnice u odraslih osoba uzrokuju značajnu onesposobljenost i lošiju kvalitetu života (fizičku i psihičku), dok su s druge strane u svakodnevnoj kliničkoj praksi relativno zanemarena patologija odrasle dobi. Stoga u ovom radu dajemo natativni pregled najnovijih spoznaja o etiopatogenezi, kliničkoj slici, slikovnoj dijagnostici, liječenju (konzervativnom i kirurškom) i postoperativnoj rehabilitaciji bolesnika s adultnim deformacijama najčešćih uzroka.
Adaptive cytoprotection in the stomach was originally defined by applying the exogenous irritants only. The contribution of endogenous irritants as inductors of initial lesions was not specially ...evaluated. No attempt was made to either focus antiulcer agent activity on adaptive cytoprotection, or split their `cytoprotection' into complex adaptive cytoprotective activity and simple cytoprotective effects. Agents had so far not been applied simultaneously with the second challenge with ethanol (or irritant), when differences between cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for 24 h in rats was introduced as new model for analyzing cytoprotection/adaptive cytoprotection. The contribution of the up-normal level of endogenous irritants and the endogenous small irritant-induced minor lesions during the adaptive cytoprotection were studied. The effect of late challenge with 96% ethanol in the presence of an up-normal level of endogenous irritants and endogenous small irritant-induced minor lesions was compared with results of classic studies of ethanol-induced gastric lesions in normal rats (1 ml/rat i.g.). Antiulcer agents or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic studies, were given at several points during injury induction: (i) surgery, (ii) mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable period following either mild ethanol or surgery). Their effects were compared in rats treated as follows: exogenous irritant studies (96% or 20% ethanol), exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol), endogenous irritant studies (gastrojejunal anastomosis for 24 h), and endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before 96% ethanol). Characteristic of the various irritants differed: the (preceding) small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous irritant studies) vs. endogenous (e.g., (increased) gastric acid secretion, duodenal reflux in gastric content in rats with termino-lateral gastrojejunal anastomosis) (endogenous irritant studies)). These factors caused modifications of agents' activities not, as initially thought, giving simple `cytoprotection', but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had only cytoprotective activity (exogenous irritant-studies), whereas pentadecapeptide BPC157 (10 μg or 10 ng), and omeprazole (10 mg) had mainly adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both cytoprotective and adaptive cytoprotective activities (exogenous/exogenous irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.), showed that only events preceding the late challenge with ethanol may be prostaglandin-dependent in both models. The second, adaptive cytoprotective part, seen after late ethanol challenge, may be either prostaglandin-dependent (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous irritant studies). Both spontaneous lesion reduction, as an essential mechanism of adaptive cytoprotection, and the further lesion reduction by agents, such as pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as an essential link between the various reactions in cytoprotection/adaptive cytoprotection.
PDF
