Uloga receptora 5HT1a i 5HT2a unutar preBotzingerova kompleksa i ventalne respiracijske grupe u postizanju respiracijskog odgovora na sistemsku primjenu selektivnih agonista serotonina [The role of 5HT1a and 5HT2a receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) in eliciting respiratory response to systemic administration of selective serotonin agonists]

Selective serotonin agonists can prevent opioid-induced depression of breathing without diminishing analgesia. When given systemically (IV), it is unclear where this effect is produced within the respiratory control network. The preBötzinger (pBC) complex has been suggested as the primary site where that happens. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine if 5- HT1A and 5-HT2A receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) contributed to the breathing rate response produced by IV administration of (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8OH-DPAT) and (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) in vagotomized, decerebrate, paralyzed and mechanically ventilated dogs. Inhalational anesthesia was induced by mask and maintained with isoflurane at 1.5-2.5% (1-2 MAC) end-tidal concentration. The animals were monitored for signs of inadequate anesthesia such as salivation, lacrimation, and increases in blood pressure and heart rate. The animal was then decerebrated by midcollicular transection and isoflurane was discontinued. After decerebration the animal was ventilated with an air-O2 mixture and maintained in hyperoxic normocapnia (FiO2 >0.6) to exclude possible effect of anesthesia. Multibarrel micropipettes were used to record extracellular neuronal activity and to pressure eject drugs onto single neurons or into localized groups of respiratory neurons. The phrenic neurogram (PNG), cyclic TI and TE, airway CO2 concentration and systemic blood pressure were continuously displayed/recorded. We used three criteria to locate the pBC complex: 1) predetermined stereotaxic coordinates, 2) presence of a mixture of respiratory neuron subtypes within the VRC, and 3) tachypneic response of the phrenic nerve (PNG) to DLH microinjections (30-40 nl; 10 mM). Three protocolos were made. In protocol one we measured responses of pBC complex neurons to picoejection of 8OH-DPAT and DOI. Picoejection of 1, 10, and 100 μM 8OH-DPAT on single inspiratory (I) and expiratory (E) pBC neurons produced dosedependent decreases in discharge frequency (Fn) with a ceiling of ~40%. DOI had no effect on single pBC neurons. In second protocol we were looking into effects of microinjections of 8OH-DPAT, DOI and 5-HT into the VRC including the pBC on phase-timing and peak phrenic nerve activity. Microinjections of 8OH-DPAT (200 μM), DOI (200 μM) and 5-HT (5 mM) within the VRC from the obex to 9 mm rostral had no effect on I-duration (TI), E-duration (TE) and peak phrenic activity (PPA). Our last (third) protocol showed effects of IV administration of 8OH-DPAT and DOI on phase-timing and peak phrenic nerve activity.IV 8OHDPAT (19±2μg/kg) reduced TI and TE by ~40%, but had no effect on PPA. IV DOI (235±48μg/kg) increased TI by 17.4±5.1%, but had no effect on TE or PPA. The findings of this study indicate respiratory neurons in the pBC complex are inhibited maximally 40% by the 5-HT1A receptor agonist 8OH-DPAT and pBC I-neurons are depressed at lower agonist concentrations (1 μM) than E-neurons. Our findings also suggest that 5-HT2A receptors are not present or not functional on canine pBC neurons, since their discharge was unaltered by picoejection of the selective agonist DOI at relatively high concentrations (100 μM). Furthermore, our results suggest that changes in phasetiming produced by systemic administration (IV) of 8OH-DPAT and DOI are not secondary to activation of 5-HT receptors in the pBC complex. Other possible locations have been suggested. Parabrachial and Kölliker-Fuse regions of the pons are one of those

Epidemiološke karakteristike i čimbenici povezani sa smrtnošću teško opečenih bolesnika - iskustvo hrvatskog opeklinskog centra

The authors conducted a single-center retrospective study during the last 6.5 years. The study aimed to describe demographic data of burn patients in the Croatian Burn Center and investigate factors affecting mortality for the first time after the Center was established. The study included 109 severely burned patients with a total body surface area (TBSA) burned ≥20%, admitted to the burn intensive care unit. The relationship between the fatal outcome and age, sex, comorbidity, mechanism of injury, TBSA burned, and inhalation injury was investigated. The mean patient age was 54.50±20.21 years and the mean TBSA burned was 42.48±18.64%, with the mortality rate of 50%. The results demonstrated that patients with 2 or more comorbidities compared with those with no comorbidities had a higher chance of lethal outcome (p<0.0001). With an increase of TBSA by 1%, the odds of lethal outcome are expected to increase by 7% (p<0.0001). Other variables included in the analysis did not show statistical significance. TBSA percentage is a well-known predictor of mortality and numerous studies indicate an association between comorbidities and mortality but there are conflicting results about other demographic factors and injury characteristics.Provedena je prva retrospektivna studija u tercijarnom centru u Hrvatskoj u posljednjih 6,5 godina s ciljem opisivanja demografskih podataka te čimbenika koji utječu na smrtnost teško opečenih bolesnika. U istraživanje je uključeno 109 teško opečenih bolesnika s ukupnom opečenom površinom ≥20%, hospitaliziranih u Jedinici intenzivnog liječenja. Analizirana je povezanost smrtnog ishoda i dobi, spola, supostojećih bolesti, mehanizma ozljede, postotka opečene površine i prisutnosti inhalacijske ozljede. Srednja dob bolesnika uključenih u istraživanje bila je 54,50±20,21 godina, srednja vrijednost postotka opečene površine bila je 42,48±18,64%, a smrtnost je iznosila 50%. Rezultati pokazuju veće izglede za smrtni ishod kod bolesnika s 2 ili više supostojećih bolesti u odnosu na one bez takvih bolesti (p<0,0001). Porastom postotka opečene površine kože za 1% izgledi za smrtni ishod rastu za 7% (p<0,0001). Analizom nije nađena statistički značajna razlika za ostale varijable. Postotak opečene površine je dobro poznati prediktor smrtnosti i brojne studije ukazuju na povezanost supostojećih bolesti i smrtnosti, dok su za ostale demografske čimbenike i značajke ozljede rezultati studija oprečni

Remimazolam: Patient satisfaction and safety for procedural sedation

Remimazolam je novi intravenski anestetik iz skupine benzodiazepina. Molekularna struktura remimazolama omogućuje mu poseban farmakokinetički profil te ga izdvaja od drugih lijekova u istoj skupini. Zbog bočnoga esterskog lanca u strukturi remimazolam metaboliziraju nespecifične esteraze na inaktivne metabolite, što rezultira njegovim ultrakratkim djelovanjem i brzim oporavkom koji nije ovisan o funkciji niti jednog organskog sustava. S mehanizmom djelovanja nalik klasičnim benzodiazepinima, prvenstveno midazolamu, i jedinstvenom farmakokinetikom u ovoj skupini lijekova, remimazolam se čini kao idealan sedativ za proceduralnu sedaciju za vrijeme kratkih zahvata. Učinkovitost remimazolama za proceduralne sedacije ispitivana je u tri multicentrična klinička istraživanja. Sva tri ispitivanja pokazala su učinkovitost remimazolama u proceduralnoj sedaciji, s visokim stopama uspjeha, brzim početkom i kratkim vremenom oporavka uočenim u skupinama s remimazolamom. U našoj ustanovi ispitivali smo djelovanje remimazolama za proceduralnu sedaciju za dijagnostičke gastroskopije i kolonoskopije. Cilj istraživanja bio je ustanoviti djelotvornost i sigurnost remimazolama kao sedativa za proceduralnu sedaciju. Iako na manjem uzorku, naši rezultati su u skladu s rezultatima velikih kliničkih studija.Remimazolam is a new intravenous anesthetic from the benzodiazepine group. The molecular structure of remimazolam enables it to have a special pharmacokinetic profile and sets it apart from other drugs in the same group. Due to the ester side chain in the structure, remimazolam is metabolized by non-specific esterase into inactive metabolites resulting in its ultra-short action and rapid recovery, which is not dependent on the function of any organ system. With a mechanism of action similar to classic benzodiazepines, primarily midazolam, and unique pharmacokinetics in this group of drugs, remimazolam appears to be an ideal sedative for procedural sedation during short procedures. The efficacy of remimazolam for procedural sedation was investigated in three multicenter clinical trials. All three trials demonstrated the efficacy of remimazolam in procedural sedation with a high success rates and rapid onset and short recovery times observed in the remimazolam groups. In our institution, we examined the effect of remimazolam for procedural sedation for diagnostic gastroscopies and colonoscopies. The goal of our study was to establish the effectiveness and safety of remimazolam as a sedative for procedural sedation. Although based on a smaller sample, our results are consistent with the results of large clinical studies

The role of 5HT1a and 5HT2a receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) in eliciting respiratory response to systemic administration of selective serotonin agonists

Nedavna istraživanja pokazala su kako selektivni agonisti 5HT receptora mogu spriječiti opioidima induciranu depresiju disanja bez djelovanja na njihov analgetski učinak. Primijenjeni sistemski (intravenski tj. IV) imaju modulirajući učinak na disanje, ali je mjesto djelovanja nepoznato. PreBötzinger kompleks (pBC) smatra se mogućim mjestom. Ova studija napravljena je u svrhu određivanja uloge 5HT1A i 5HT2A receptora unutar pBC kompleksa i ventalne respiratorne grupe (VRC) pri promjeni ritma disanja, a koja nastaje nakon sistemske primjene agonista istih receptora. Korišteni su agonist 5HT1A receptora 8OH-DPAT ((±)-8-Hydroxy-2- dipropylaminotetralin hydrobromide) i agonist 5HT2A receptora DOI ((±)-1-(2,5- Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride). Pokusi su provođeni na vagotomiziranim, decerebriranim, paraliziranim i mehanički ventiliranim psima. Primijenjena je inhalacijska anestezija maskom i održavana isofluranom (ISO) (1.5- 2,5% end-tidal koncentracija (1-2 MAC)). Istodobno su praćeni znakovi nedovoljne anestezije kao što su salivacija, lakrimacija, porast krvnog tlaka i pulsa, te je po potrebi anestezija produbljivana. Zatim je napravljena decerebracija midkolikularnom transekcijom. Nakon decerebracije prekinut je isofluran (kako bi se otklonio moguć utjecaj anestezije na rezultate), a ventilacija nastavljena mješavinom ~60% zrak i O2 te je održavana hiperoksična normokapnija (Fi > 0,6). Staklena elektroda korištena je za pronalazak i snimanje neuralne aktivnosti respiratornih neurona unutar pBC kompleksa i VRC te za aplikaciju testiranih supstanci. Testirane supstance administrirane su i sistemski (IV). Tijekom pokusa kontinuirano je praćen neurogram freničnog živca (PNG), frekvencija izbijanja respiratornih neurona, vrijeme inspirija (TI) i ekspirija (TE), etCO2 te sistemski krvni tlak. Za lokalizaciju pBC kompleksa unutar ventralne respiratorne grupe (VRC) u produženoj moždini korištena su tri kriterija. Prvi kriterij bile su već utvrđene stereotaksične koordinate. Drugi korišteni kriterij bio je prisutnost različitih tipova respiratornih neurona unutar VRC (inspiratornih i ekspiratornih neurona). Treći kriterij bio je karakteristični tahipnoični odgovor PNG-a na injektiranje (30-40 nl, 10 mM) glutamat agonista DLH-a (Dhomocisteična kiselina) u pBC kompleks. Hipoteza je da ako 5HT1A i 5HT2A receptori unutar pBC kompleksa i VRC pridonose promjeni ritma disanja, tada će lokalna primjena njihovih agonista postići isti učinak kao i nakon sistemske primjene. 47 Pikoinjektiranje 1, 10 i 100 μM 8OH-DPAT na pojedinačne inspiratorne (I) i ekspiratorne (E) neurone unutar pBC kompleksa smanjilo je frekvenciju izbijanja istih (Fn) za ~40%. DOI nije imao nikakav učinak na frekvenciju istih pojedinačnih respiratornih neurona unutar pBC kompleksa. Mikroinjektiranje 8OH-DPAT (200 μM), DOI (200 μM) i 5-HT (5 mM) na grupu respiratornih neurona unutar VRC od obeksa do 9 mm rostralno nije utjecalo na vrijeme inspirija (TI), vrijeme ekspirija (TE) i vršnu aktivnost freničnog živca (PPA). Sistemski (IV) administriran 8OHDPAT (19±2μg/kg) doveo je do smanjenja TI i TE za ~40%, ali nije imao učinak na PPA. Sistemski primijenjen DOI (235±48μg/kg) uzrokovao je porast TI za 17.4±5.1%, ali bez učinka na TE i PPA. Rezultati ove studije upućuju na to kako agonisti 5HT receptora sistemski administrirani mijenjaju ritam disanja. Spomenuti učinak ne postižu djelovanjem na respiratorne neurone unutar VRC(uključujući i pBC kompleks) već negdje izvan tih mjesta. Parabrahijalna i Kölliker-Fuse regija unutar mosta moguća su mjesta djelovanja agonista.Selective serotonin agonists can prevent opioid-induced depression of breathing without diminishing analgesia. When given systemically (IV), it is unclear where this effect is produced within the respiratory control network. The preBötzinger (pBC) complex has been suggested as the primary site where that happens. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine if 5- HT1A and 5-HT2A receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) contributed to the breathing rate response produced by IV administration of (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8OH-DPAT) and (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) in vagotomized, decerebrate, paralyzed and mechanically ventilated dogs. Inhalational anesthesia was induced by mask and maintained with isoflurane at 1.5-2.5% (1-2 MAC) end-tidal concentration. The animals were monitored for signs of inadequate anesthesia such as salivation, lacrimation, and increases in blood pressure and heart rate. The animal was then decerebrated by midcollicular transection and isoflurane was discontinued. After decerebration the animal was ventilated with an air-O2 mixture and maintained in hyperoxic normocapnia (FiO2 >0.6) to exclude possible effect of anesthesia. Multibarrel micropipettes were used to record extracellular neuronal activity and to pressure eject drugs onto single neurons or into localized groups of respiratory neurons. The phrenic neurogram (PNG), cyclic TI and TE, airway CO2 concentration and systemic blood pressure were continuously displayed/recorded. We used three criteria to locate the pBC complex: 1) predetermined stereotaxic coordinates, 2) presence of a mixture of respiratory neuron subtypes within the VRC, and 3) tachypneic response of the phrenic nerve (PNG) to DLH microinjections (30-40 nl; 10 mM). Three protocolos were made. In protocol one we measured responses of pBC complex neurons to picoejection of 8OH-DPAT and DOI. Picoejection of 1, 10, and 100 μM 8OH-DPAT on single inspiratory (I) and expiratory (E) pBC neurons produced dosedependent decreases in discharge frequency (Fn) with a ceiling of ~40%. DOI had no effect on single pBC neurons. In second protocol we were looking into effects of microinjections of 8OH-DPAT, DOI and 5-HT into the VRC including the pBC on phase-timing and peak phrenic nerve activity. Microinjections of 8OH-DPAT (200 μM), DOI (200 μM) and 5-HT (5 mM) within the VRC from the obex to 9 mm rostral had no effect on I-duration (TI), E-duration (TE) and peak phrenic activity (PPA). Our last (third) protocol showed effects of IV administration of 8OH-DPAT and DOI on phase-timing and peak phrenic nerve activity.IV 8OHDPAT (19±2μg/kg) reduced TI and TE by ~40%, but had no effect on PPA. IV DOI (235±48μg/kg) increased TI by 17.4±5.1%, but had no effect on TE or PPA. The findings of this study indicate respiratory neurons in the pBC complex are inhibited maximally 40% by the 5-HT1A receptor agonist 8OH-DPAT and pBC I-neurons are depressed at lower agonist concentrations (1 μM) than E-neurons. Our findings also suggest that 5-HT2A receptors are not present or not functional on canine pBC neurons, since their discharge was unaltered by picoejection of the selective agonist DOI at relatively high concentrations (100 μM). Furthermore, our results suggest that changes in phasetiming produced by systemic administration (IV) of 8OH-DPAT and DOI are not secondary to activation of 5-HT receptors in the pBC complex. Other possible locations have been suggested. Parabrachial and Kölliker-Fuse regions of the pons are one of those

The role of 5HT1a and 5HT2a receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) in eliciting respiratory response to systemic administration of selective serotonin agonists

Nedavna istraživanja pokazala su kako selektivni agonisti 5HT receptora mogu spriječiti opioidima induciranu depresiju disanja bez djelovanja na njihov analgetski učinak. Primijenjeni sistemski (intravenski tj. IV) imaju modulirajući učinak na disanje, ali je mjesto djelovanja nepoznato. PreBötzinger kompleks (pBC) smatra se mogućim mjestom. Ova studija napravljena je u svrhu određivanja uloge 5HT1A i 5HT2A receptora unutar pBC kompleksa i ventalne respiratorne grupe (VRC) pri promjeni ritma disanja, a koja nastaje nakon sistemske primjene agonista istih receptora. Korišteni su agonist 5HT1A receptora 8OH-DPAT ((±)-8-Hydroxy-2- dipropylaminotetralin hydrobromide) i agonist 5HT2A receptora DOI ((±)-1-(2,5- Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride). Pokusi su provođeni na vagotomiziranim, decerebriranim, paraliziranim i mehanički ventiliranim psima. Primijenjena je inhalacijska anestezija maskom i održavana isofluranom (ISO) (1.5- 2,5% end-tidal koncentracija (1-2 MAC)). Istodobno su praćeni znakovi nedovoljne anestezije kao što su salivacija, lakrimacija, porast krvnog tlaka i pulsa, te je po potrebi anestezija produbljivana. Zatim je napravljena decerebracija midkolikularnom transekcijom. Nakon decerebracije prekinut je isofluran (kako bi se otklonio moguć utjecaj anestezije na rezultate), a ventilacija nastavljena mješavinom ~60% zrak i O2 te je održavana hiperoksična normokapnija (Fi > 0,6). Staklena elektroda korištena je za pronalazak i snimanje neuralne aktivnosti respiratornih neurona unutar pBC kompleksa i VRC te za aplikaciju testiranih supstanci. Testirane supstance administrirane su i sistemski (IV). Tijekom pokusa kontinuirano je praćen neurogram freničnog živca (PNG), frekvencija izbijanja respiratornih neurona, vrijeme inspirija (TI) i ekspirija (TE), etCO2 te sistemski krvni tlak. Za lokalizaciju pBC kompleksa unutar ventralne respiratorne grupe (VRC) u produženoj moždini korištena su tri kriterija. Prvi kriterij bile su već utvrđene stereotaksične koordinate. Drugi korišteni kriterij bio je prisutnost različitih tipova respiratornih neurona unutar VRC (inspiratornih i ekspiratornih neurona). Treći kriterij bio je karakteristični tahipnoični odgovor PNG-a na injektiranje (30-40 nl, 10 mM) glutamat agonista DLH-a (Dhomocisteična kiselina) u pBC kompleks. Hipoteza je da ako 5HT1A i 5HT2A receptori unutar pBC kompleksa i VRC pridonose promjeni ritma disanja, tada će lokalna primjena njihovih agonista postići isti učinak kao i nakon sistemske primjene. 47 Pikoinjektiranje 1, 10 i 100 μM 8OH-DPAT na pojedinačne inspiratorne (I) i ekspiratorne (E) neurone unutar pBC kompleksa smanjilo je frekvenciju izbijanja istih (Fn) za ~40%. DOI nije imao nikakav učinak na frekvenciju istih pojedinačnih respiratornih neurona unutar pBC kompleksa. Mikroinjektiranje 8OH-DPAT (200 μM), DOI (200 μM) i 5-HT (5 mM) na grupu respiratornih neurona unutar VRC od obeksa do 9 mm rostralno nije utjecalo na vrijeme inspirija (TI), vrijeme ekspirija (TE) i vršnu aktivnost freničnog živca (PPA). Sistemski (IV) administriran 8OHDPAT (19±2μg/kg) doveo je do smanjenja TI i TE za ~40%, ali nije imao učinak na PPA. Sistemski primijenjen DOI (235±48μg/kg) uzrokovao je porast TI za 17.4±5.1%, ali bez učinka na TE i PPA. Rezultati ove studije upućuju na to kako agonisti 5HT receptora sistemski administrirani mijenjaju ritam disanja. Spomenuti učinak ne postižu djelovanjem na respiratorne neurone unutar VRC(uključujući i pBC kompleks) već negdje izvan tih mjesta. Parabrahijalna i Kölliker-Fuse regija unutar mosta moguća su mjesta djelovanja agonista.Selective serotonin agonists can prevent opioid-induced depression of breathing without diminishing analgesia. When given systemically (IV), it is unclear where this effect is produced within the respiratory control network. The preBötzinger (pBC) complex has been suggested as the primary site where that happens. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine if 5- HT1A and 5-HT2A receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) contributed to the breathing rate response produced by IV administration of (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8OH-DPAT) and (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) in vagotomized, decerebrate, paralyzed and mechanically ventilated dogs. Inhalational anesthesia was induced by mask and maintained with isoflurane at 1.5-2.5% (1-2 MAC) end-tidal concentration. The animals were monitored for signs of inadequate anesthesia such as salivation, lacrimation, and increases in blood pressure and heart rate. The animal was then decerebrated by midcollicular transection and isoflurane was discontinued. After decerebration the animal was ventilated with an air-O2 mixture and maintained in hyperoxic normocapnia (FiO2 >0.6) to exclude possible effect of anesthesia. Multibarrel micropipettes were used to record extracellular neuronal activity and to pressure eject drugs onto single neurons or into localized groups of respiratory neurons. The phrenic neurogram (PNG), cyclic TI and TE, airway CO2 concentration and systemic blood pressure were continuously displayed/recorded. We used three criteria to locate the pBC complex: 1) predetermined stereotaxic coordinates, 2) presence of a mixture of respiratory neuron subtypes within the VRC, and 3) tachypneic response of the phrenic nerve (PNG) to DLH microinjections (30-40 nl; 10 mM). Three protocolos were made. In protocol one we measured responses of pBC complex neurons to picoejection of 8OH-DPAT and DOI. Picoejection of 1, 10, and 100 μM 8OH-DPAT on single inspiratory (I) and expiratory (E) pBC neurons produced dosedependent decreases in discharge frequency (Fn) with a ceiling of ~40%. DOI had no effect on single pBC neurons. In second protocol we were looking into effects of microinjections of 8OH-DPAT, DOI and 5-HT into the VRC including the pBC on phase-timing and peak phrenic nerve activity. Microinjections of 8OH-DPAT (200 μM), DOI (200 μM) and 5-HT (5 mM) within the VRC from the obex to 9 mm rostral had no effect on I-duration (TI), E-duration (TE) and peak phrenic activity (PPA). Our last (third) protocol showed effects of IV administration of 8OH-DPAT and DOI on phase-timing and peak phrenic nerve activity.IV 8OHDPAT (19±2μg/kg) reduced TI and TE by ~40%, but had no effect on PPA. IV DOI (235±48μg/kg) increased TI by 17.4±5.1%, but had no effect on TE or PPA. The findings of this study indicate respiratory neurons in the pBC complex are inhibited maximally 40% by the 5-HT1A receptor agonist 8OH-DPAT and pBC I-neurons are depressed at lower agonist concentrations (1 μM) than E-neurons. Our findings also suggest that 5-HT2A receptors are not present or not functional on canine pBC neurons, since their discharge was unaltered by picoejection of the selective agonist DOI at relatively high concentrations (100 μM). Furthermore, our results suggest that changes in phasetiming produced by systemic administration (IV) of 8OH-DPAT and DOI are not secondary to activation of 5-HT receptors in the pBC complex. Other possible locations have been suggested. Parabrachial and Kölliker-Fuse regions of the pons are one of those

The role od innovation in gaining a competitive advantage

Stvaranje konkurentskih prednosti odražava se na nivou cijelog poduzeća. Tehnološke sposobnosti poduzeća strateški su resurs kojim mu se omogućava ostvarivanje konkurentske prednosti unutar industrije i njene osnovne djelatnosti pa su tako poduzeća s boljim tehnološkim kompetencijama nedvojbeno inovativnija, a zbog toga i uspješnija na tržištima na kojima je inovacija osnova konkurentskog nadmetanja. U međunarodnim uvjetima, one su vrlo intenzivne i kompleksne. Posebno su izražene u pojedinim granama industrije koje su uvelike globalizirane ili su na putu globalizacije. Stoga su strateški okviri konkurentske prednosti izuzetno značajni, kako za efektivno, tako i efikasno, odnosno rentabilno poslovanje. Na svjetskom tržištu se pod konkurentskom prednošću podrazumijeva relativno velika moć, odnosno snaga jednog poduzeća ili jednog proizvoda u odnosu na druge.The creation of competitive advantages is reflected at the level of the entire company. A company's technological capabilities are a strategic resource that enables it to achieve a competitive advantage within the industry of it's core business, so companies with better technological competencies are undoubtedly more innovative, and therefore more successful in markets where innovation is the basis of competitive bidding. In international conditions, they are very intensive and complex. They are especially pronounced in certain branches that are largely globalized or are on the way to globalization. Therefore, strategic frameworks of competitive advantage are extremely important, both for effective and efficient, i.e. profitable business. In the world market, competitive advantage means relatively great power, that is, the strength of one company or one product in relation to others

The role of 5HT1a and 5HT2a receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) in eliciting respiratory response to systemic administration of selective serotonin agonists

Nedavna istraživanja pokazala su kako selektivni agonisti 5HT receptora mogu spriječiti opioidima induciranu depresiju disanja bez djelovanja na njihov analgetski učinak. Primijenjeni sistemski (intravenski tj. IV) imaju modulirajući učinak na disanje, ali je mjesto djelovanja nepoznato. PreBötzinger kompleks (pBC) smatra se mogućim mjestom. Ova studija napravljena je u svrhu određivanja uloge 5HT1A i 5HT2A receptora unutar pBC kompleksa i ventalne respiratorne grupe (VRC) pri promjeni ritma disanja, a koja nastaje nakon sistemske primjene agonista istih receptora. Korišteni su agonist 5HT1A receptora 8OH-DPAT ((±)-8-Hydroxy-2- dipropylaminotetralin hydrobromide) i agonist 5HT2A receptora DOI ((±)-1-(2,5- Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride). Pokusi su provođeni na vagotomiziranim, decerebriranim, paraliziranim i mehanički ventiliranim psima. Primijenjena je inhalacijska anestezija maskom i održavana isofluranom (ISO) (1.5- 2,5% end-tidal koncentracija (1-2 MAC)). Istodobno su praćeni znakovi nedovoljne anestezije kao što su salivacija, lakrimacija, porast krvnog tlaka i pulsa, te je po potrebi anestezija produbljivana. Zatim je napravljena decerebracija midkolikularnom transekcijom. Nakon decerebracije prekinut je isofluran (kako bi se otklonio moguć utjecaj anestezije na rezultate), a ventilacija nastavljena mješavinom ~60% zrak i O2 te je održavana hiperoksična normokapnija (Fi > 0,6). Staklena elektroda korištena je za pronalazak i snimanje neuralne aktivnosti respiratornih neurona unutar pBC kompleksa i VRC te za aplikaciju testiranih supstanci. Testirane supstance administrirane su i sistemski (IV). Tijekom pokusa kontinuirano je praćen neurogram freničnog živca (PNG), frekvencija izbijanja respiratornih neurona, vrijeme inspirija (TI) i ekspirija (TE), etCO2 te sistemski krvni tlak. Za lokalizaciju pBC kompleksa unutar ventralne respiratorne grupe (VRC) u produženoj moždini korištena su tri kriterija. Prvi kriterij bile su već utvrđene stereotaksične koordinate. Drugi korišteni kriterij bio je prisutnost različitih tipova respiratornih neurona unutar VRC (inspiratornih i ekspiratornih neurona). Treći kriterij bio je karakteristični tahipnoični odgovor PNG-a na injektiranje (30-40 nl, 10 mM) glutamat agonista DLH-a (Dhomocisteična kiselina) u pBC kompleks. Hipoteza je da ako 5HT1A i 5HT2A receptori unutar pBC kompleksa i VRC pridonose promjeni ritma disanja, tada će lokalna primjena njihovih agonista postići isti učinak kao i nakon sistemske primjene. 47 Pikoinjektiranje 1, 10 i 100 μM 8OH-DPAT na pojedinačne inspiratorne (I) i ekspiratorne (E) neurone unutar pBC kompleksa smanjilo je frekvenciju izbijanja istih (Fn) za ~40%. DOI nije imao nikakav učinak na frekvenciju istih pojedinačnih respiratornih neurona unutar pBC kompleksa. Mikroinjektiranje 8OH-DPAT (200 μM), DOI (200 μM) i 5-HT (5 mM) na grupu respiratornih neurona unutar VRC od obeksa do 9 mm rostralno nije utjecalo na vrijeme inspirija (TI), vrijeme ekspirija (TE) i vršnu aktivnost freničnog živca (PPA). Sistemski (IV) administriran 8OHDPAT (19±2μg/kg) doveo je do smanjenja TI i TE za ~40%, ali nije imao učinak na PPA. Sistemski primijenjen DOI (235±48μg/kg) uzrokovao je porast TI za 17.4±5.1%, ali bez učinka na TE i PPA. Rezultati ove studije upućuju na to kako agonisti 5HT receptora sistemski administrirani mijenjaju ritam disanja. Spomenuti učinak ne postižu djelovanjem na respiratorne neurone unutar VRC(uključujući i pBC kompleks) već negdje izvan tih mjesta. Parabrahijalna i Kölliker-Fuse regija unutar mosta moguća su mjesta djelovanja agonista.Selective serotonin agonists can prevent opioid-induced depression of breathing without diminishing analgesia. When given systemically (IV), it is unclear where this effect is produced within the respiratory control network. The preBötzinger (pBC) complex has been suggested as the primary site where that happens. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine if 5- HT1A and 5-HT2A receptors within the preBötzinger complex (pBC) and ventral respiratory column (VRC) contributed to the breathing rate response produced by IV administration of (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8OH-DPAT) and (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) in vagotomized, decerebrate, paralyzed and mechanically ventilated dogs. Inhalational anesthesia was induced by mask and maintained with isoflurane at 1.5-2.5% (1-2 MAC) end-tidal concentration. The animals were monitored for signs of inadequate anesthesia such as salivation, lacrimation, and increases in blood pressure and heart rate. The animal was then decerebrated by midcollicular transection and isoflurane was discontinued. After decerebration the animal was ventilated with an air-O2 mixture and maintained in hyperoxic normocapnia (FiO2 >0.6) to exclude possible effect of anesthesia. Multibarrel micropipettes were used to record extracellular neuronal activity and to pressure eject drugs onto single neurons or into localized groups of respiratory neurons. The phrenic neurogram (PNG), cyclic TI and TE, airway CO2 concentration and systemic blood pressure were continuously displayed/recorded. We used three criteria to locate the pBC complex: 1) predetermined stereotaxic coordinates, 2) presence of a mixture of respiratory neuron subtypes within the VRC, and 3) tachypneic response of the phrenic nerve (PNG) to DLH microinjections (30-40 nl; 10 mM). Three protocolos were made. In protocol one we measured responses of pBC complex neurons to picoejection of 8OH-DPAT and DOI. Picoejection of 1, 10, and 100 μM 8OH-DPAT on single inspiratory (I) and expiratory (E) pBC neurons produced dosedependent decreases in discharge frequency (Fn) with a ceiling of ~40%. DOI had no effect on single pBC neurons. In second protocol we were looking into effects of microinjections of 8OH-DPAT, DOI and 5-HT into the VRC including the pBC on phase-timing and peak phrenic nerve activity. Microinjections of 8OH-DPAT (200 μM), DOI (200 μM) and 5-HT (5 mM) within the VRC from the obex to 9 mm rostral had no effect on I-duration (TI), E-duration (TE) and peak phrenic activity (PPA). Our last (third) protocol showed effects of IV administration of 8OH-DPAT and DOI on phase-timing and peak phrenic nerve activity.IV 8OHDPAT (19±2μg/kg) reduced TI and TE by ~40%, but had no effect on PPA. IV DOI (235±48μg/kg) increased TI by 17.4±5.1%, but had no effect on TE or PPA. The findings of this study indicate respiratory neurons in the pBC complex are inhibited maximally 40% by the 5-HT1A receptor agonist 8OH-DPAT and pBC I-neurons are depressed at lower agonist concentrations (1 μM) than E-neurons. Our findings also suggest that 5-HT2A receptors are not present or not functional on canine pBC neurons, since their discharge was unaltered by picoejection of the selective agonist DOI at relatively high concentrations (100 μM). Furthermore, our results suggest that changes in phasetiming produced by systemic administration (IV) of 8OH-DPAT and DOI are not secondary to activation of 5-HT receptors in the pBC complex. Other possible locations have been suggested. Parabrachial and Kölliker-Fuse regions of the pons are one of those

Programiranje industrijskih robota za potrebe robotiziranog zavarivanja

U ovom radu opisano je programiranje industrijskih robota. Opisan je pojam, povijest i struktura industrijskih robota. Nabrojane su i opisane metode programiranja industrijskih robota te njihove karakteristike. Detaljno su opisani postupci on-line i off-line programiranja na realnim primjerima. On-line programiranje izvršeno je u Laboratoriju za zavarivanje, Fakulteta strojarstva i brodogradnje, Sveučilišta u Zagrebu. Primjer on-line programiranja je robotsko zavarivanje testnog CAD modela radnog komada. Off-line programiranje izvršeno je u programskom alatu RobotStudio, tvrtke ABB, na istom modelu radnog komada. Navedene su i smjernice prema kojima će se dalje razvijati ovaj rad

Odnos okolišnih čimbenika i razine pogodnosti poljoprivrednoga zemljišta za uzgoj soje određene strojnim učenjem

The relationship between cropland suitability and the surrounding environmental factors has an important role in understanding and adjusting agricultural land management systems to natural cropland suitability. In this study, the relationship between soybean cropland suitability, determined by a novel machine learningbased approach, and three major environmental factors in continental Croatia was evaluated. These constituted of two major land cover classes (forests and urban areas), utilized soybean growth seasons per agricultural parcels during a 2017–2020 study period and soil types. The sensitivity analysis in geographic information system (GIS) using a raster overlay method, along with auxiliary spatial processing, was performed. The proximity of soybean agricultural parcels to forests showed a high correlation with suitability values, indicating a potential benefit of implementing agroforestry in land management plans. A notable amount of suitable agricultural parcels for soybean cultivation, which were previously not utilized for soybean cultivation was observed. A disregard of crop rotations was also noted, with the same soybean parcels within the study period in three and four years. This analysis showed considerable potential in understanding the effects of environmental factors on cropland suitability values, leading to more efficient land management policies and future suitability studies.Odnos između pogodnosti poljoprivrednoga zemljišta i okolnih čimbenika okoliša ima važnu ulogu u razumijevanju i prilagodbi sustava upravljanja poljoprivrednim zemljištem prirodnoj razini pogodnosti. U ovoj studiji procijenjen je odnos između pogodnosti poljoprivrednoga zemljišta za uzgoj soje, utvrđene suvremenim pristupom temeljenom na strojnome učenju, i triju čimbenika okoliša u kontinentalnoj Hrvatskoj. Njih su činile dvije najzastupljenije klase zemljišnoga pokrova (šume i urbana područja), broj sezone uzgoja soje po poljoprivrednim česticama tijekom razdoblja istraživanja od 2017. do 2020. te vrste tla. Provedena je analiza osjetljivosti u geografskome informacijskom sustavu (GIS) metodom rasterskoga preklapanja, uz dopunske prostorne analize. Blizina poljoprivrednih čestica soje šumama pokazala je visoku korelaciju s vrijednostima pogodnosti, što ukazuje na potencijalnu korist od implementacije agrošumarstva u planove upravljanja zemljištem. Detektirana je značajna količina visoko pogodnih poljoprivrednih čestica za uzgoj soje, koje se tijekom razdoblja istraživanja nisu koristile za njezin uzgoj. Uočeno je i zanemarivanje plodoreda, na kojima je soja uzgajana uzastopno tijekom triju ili četiriju godina. Ova analiza pokazala je značajan potencijal u razumijevanju učinaka čimbenika okoliša na pogodnost poljoprivrednoga zemljišta, što dovodi do učinkovitijih politika upravljanja zemljištem i budućih studija prikladnosti

Epidemiological Characteristics and Factors Associated with Mortality in Severely Burned Patients – Croatian National Burn Center Report

The authors conducted a single-center retrospective study during the last 6.5 years. The study aimed to describe demographic data of burn patients in the Croatian Burn Center and investigate factors affecting mortality for the first time after the Center was established. The study included 109 severely burned patients with a total body surface area (TBSA) burned ≥20%, admitted to the burn intensive care unit. The relationship between the fatal outcome and age, sex, comorbidity, mechanism of injury, TBSA burned, and inhalation injury was investigated. The mean patient age was 54.50±20.21 years and the mean TBSA burned was 42.48±18.64%, with the mortality rate of 50%. The results demonstrated that patients with 2 or more comorbidities compared with those with no comorbidities had a higher chance of lethal outcome (p<0.0001). With an increase of TBSA by 1%, the odds of lethal outcome are expected to increase by 7% (p<0.0001). Other variables included in the analysis did not show statistical significance. TBSA percentage is a well-known predictor of mortality and numerous studies indicate an association between comorbidities and mortality but there are conflicting results about other demographic factors and injury characteristics