Empoisonnement accidentel par le chlore gazeux dans une usine cellulose sulfatee et de papier

Opisan je slučaj smrtnog, zadesnog trovanja mladog radnika gasovitim hlorom u tvornici sulfatne celuloze i papira. Otrovani radnik je odmah bio smješten na Internom odjeljenju, gdje je preduzeta intenzivna terapija, ali i pored ovoga smrt je nastupila krajem trećeg dana, zbog jakog edema pluća. Sve analize i klinički simptomi, kao i okolnosti slučaja govore da je smrt nastupila kao posljedica zagušenja otrovnim gasom. Slučaj smo prikazali kao rijetko trovanje u nas, ali mogućnosti ovakvih akcidenata u savremenoj industriji gdje se hlor upotrebljava nisu male.Dans ce travail est décrit le cas de la mort accidentelle d\u27un jeune ouvrier empoisonné par le chlore gazeux dans une usine de cellulose sulfatée et de papier à Ivangrad. L\u27empoisonnement a eu lieu à la suite de la rupture d\u27une conduite usée qui transportait le gaz suffocant dans la citerne. Des 7 ouvriers étaient présents, 6 ont été légèrement empoisonnés mais le septième a succombé par suite de son ignorance. Il a immédiatement été transporté à l\u27hôpital (Section de médecine interne) où les mesures nécessaires ont été prises, mais malgré les grands efforts des médecins, le jeune homme est mort au bout de 3 jours. La mort a été provoquée par le liquide envahissant les poumons. Après le décès on a pratiqué l\u27autopsie clinique du cadavre en se servant de l\u27analyse histopathologique des fragments prélevés ainsi que de l\u27attestation toxicologique de l\u27empoisonnement à l\u27aide de l\u27analyse du matériel provenant du cadavre, envoyé à l\u27Institut de Médecine légale à Belgrade. Toutes les analyses et les symptômes cliniques ainsi que les circonstances, indiquent que la mort a eu lieu par asphyxie dûe au gaz toxique. Elle s\u27est produite sous une forme aiguë par suite de la présence du liquide de l\u27oedème dans les organes respiratoires. En effectuant l\u27autopsie, on a trouvé toutes les formes de l\u27effet toxique du gaz suffocant sur les organes et les tissus. Le chlore et ses acides appartiennent chimiquement au groupe des gaz suffocants. Ils ont un effet direct sur les organes et un effet indirect sur le système respiratoire. C\u27est une forme d\u27accident très rare en Yougoslavie mais le risque d\u27un tel accident dans l\u27industrie moderne où l\u27on utilise le chlore devient de plus en plus grand

Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata

An efficient synthesis of methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate (7) has been developed starting from 1-benzylpiperidin-4-one (1). The compound is a key intermediate in the synthesis of new generation, highly active narcotic analgesics, such as remifintanil, as well as the novel classes of fentanyl analogues. An optimized Strecker-type condensation of piperidone 1 with aniline and HCN yielded the anilino-nitrile 2(≈90%) which, upon selective hydrolysis with conc. H2SO4, gave the anilino-amide 3.After vigorous basic hydrolysis of 3, followed by acidification and successive treatment with SOCl2 and MeOH, the anilino-ester 5 was obtained (40–45%, in 3 steps). N-Acylation of 5 with propionyl chloride yielded the anilido-ester 6(70–80%) In the final step, the catalytic N-debenzylation of 6 was examined under various conditions and optimized to yield 7 in near quantitative yields.U ovom radu razvijena je efikasna sinteza metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata (7), prolazeći od 1-benzil piperidin-4-on-1 (1). Jedinjenje 7 je ključni intermedijer u sintezi nove generacije visoko aktivnih narkotičkih analgetika, kao što je remifentanil a takođe i novih klasa analoga fentanyla. U optimizovanoj Strecker-ovoj kondenzaciji priperidona 1 sa anilinom i HCN, dobijen je anilino-nitril 2 (≈90%) prinos čijom je selektivnom hidrolizom pomoću konc. H2SO4 postao anilino-amid 3. Intenzivnom baznom hidrolizom ovog intermedijera, zakišeljavanjem a zatim sukcesivno reakcijom sa SOCl2 i MeOH sintetisan je anilino-estar 5 (≈40–45% prinos u 3 faze). N-acelovanjem anilino-estra 5 sa propionil hloridom postao je anilido-estar 6 (≈70–80% prinos). U poslednjom fazi sinteze izvršena je optimizacija katalitičkog N-debenzilovanja anilido-estra 6 do finalnog proizvoda 7, u približno kvantitativnom prinosu

Vascularisation of the geniculate ganglion

Background: Lack of the relevant data in the literature and possible clinical significance of the geniculate ganglion vasculature inspired us to examine the vessels of this ganglion. Materials and methods: Twelve temporal bones were taken during autopsy and microdissected. Four geniculate ganglions were taken as well, serially sectioned and used for haematoxylin-eosin and trichrome staining, and for CD34 immunostaining. Results: The geniculate ganglion was supplied by the petrosal artery, which averaged 1.1 in number, 0.44 mm in the outer diameter, 0.24 mm in the luminal diameter, and 17.1 mm in length. The artery approached the greater petrosal nerve, giving off 1–3 twigs to it with a mean diameter of 24 μm, and entered the nerve hiatus or a small bone opening close to the ganglion. Before the artery continued to the tympanic segment of the facial nerve, it gave rise to 1 (8.33%), 2 (75.00%) or 3 (16.67%) branches to the geniculate ganglion, which ranged in diameter between 18 μm and 56 μm (mean 29 μm). From the formed superficial network, several twigs penetrated the ganglion and built an intraganglionic plexus. The counting, performed in microscopic fields, each measuring 341.7 μm × 250.0 μm in size, contained between 20 and 38 (mean 28.1) ganglion cells, as well as from 87 to 143 microvessels (mean 99.8), so that the neuron/vessel ratio was 1:3.6. Conclusions: This is the first detailed examination of the geniculate ganglion vasculature. The obtained data could be of clinical importance, especially in relation to the Bell’s palsy, ganglionitis, geniculate neuralgia, petrous bone imaging, and operations in the same region.

Ispitivanje neurotoksičnosti analoga fentanila kod pacova

This study aimed at evaluating the neurotoxicity of fentanyl analogs: (+/-)-cis-3-carbomethoxy fentanyl (C) and (+/-)-trans-3-carbomethoxy fentanyl (T) in rats. C and Tare less potent (2.4-3.1 and 8.4-12.3 times, respectively) than fentanyl (F) in producing both antinociception and morphine-like neurotoxic effects: loss of pinna reflex, Straub tail, impairment of motor coordination, catalepsy, loss of corneal reflex and loss of righting reflex. All of the effects tested were dose-dependent and they were abolished by pretreatment with naloxone, nonselective antagonist of opioid receptors, indicating that they are mediated via opioid receptors. Further, F, C and T exhibited similar relative potencies in producing all tested effects, indicating that similar receptors are involved in producing antinociceptive and neurotoxic effects, most probably of mu type. By using equiantinociceptive doses, C and T produced significantly shorter duration of both antinociception and neurotoxicity than F No significant differences between therapeutic indices for F, C and T were found, indicating that these compounds are equally safe and tolerable in respect to the neurotoxic effects tested. Neurotoxicity testing presented in this paper may be useful in studying the structure-activity relationship of opioid congeners.Cilj studije bio je da se ispita neurotoksičnost analoga fentanila: (±)-cis-3-karbometoksi fentanila (C) i (±)-trans-3-karbometoksi fentanil (T) kod pacova. C je oko 2,4-3,1, a T oko 8,4-12,3 puta manje potentan od fentanila u izazivanju antinocicepcije i morfinu-sličnih neurotoksičnih efekata u koje spadaju: refleks ušne školjke, Straub-ov rep, poremećaj motorne koordinacije, katalepsija, gubitak kornealnog refleksa i gubitak refleksa uspravljanja. Svi ispitivani efekti su dozno-zavisni i bivaju poništeni ako se u pretretmanu primeni nalokson, neselektivni antagonist opioidnih receptora, što ukazuje da se efekti odigravaju posredstvom opioidnih receptora. Dalje, F, C i T ispoljavaju sličnu relativnu jačinu u izazivanju ispitivanih efekata, što ukazuje da su slični receptori uključeni u mehanizam antinocicepcije i neurotoksičnih efekata, i to su najverovatnije μ receptori. Kad se primenjuju ekviantinociceptivne doze, C i T izazivaju značajno kraće i antinociceptivno i neurotoksično dejstvo od F. Nisu dokazane značajne razlike u terapijskim indeksima između F, C i T, što ukazuje da su ovi lekovi jednako bezbedni i podnošljivi kad su u pitanju ispitivani neurotoksični efekti. Ispitivanje neurotoksičnosti prikazano u ovom radu može biti korisno u proučavanju odnosa između strukture i aktivnosti hemijski srodnih opioida

Dynamic adsorption characteristics of thin layered activated charcoal materials used in chemical protective overgarments

The efficiency of a thin layered activated charcoal material used in chemical protective overgarments has been evaluated. The study has been conducted with the aim to obtain protective materials with best characteristics considering resistance to benzene effect under dynamic conditions and to create a new filtration protection device. In order to evaluate dynamic adsorption characteristics of thin layered sorption materials, sophisticated dynamic gas chromatography method is used. The curves of benzene penetration are determined for sandwich materials, and sorption layers used in filtrating protective clothing shows that thin layered carbon sorption materials (type MOO) have good protective properties as compared to other similar materials. The findings will help to create conditions for developing a functional model for producing a new protective overgarment in the near future

Veterinarski informacioni menadžment sistem (VIMS) u procesu prijavljivanja i menadžmenta zaraznih bolesti

A prerequisite to the development of an efficient animal health, food safety and traceability management system in the animal food production chain is the implementation of an integrated veterinary informational management system (VIMS) capable for the capture, storage, analysis and retrieval of data and providing the opportunity for the cumulative gathering of the knowledge and capability for its competent interpretation. Such a system will enable collecting appropriate data, including quality management and inspection controls, from all establishments and commodities in the 'from farm to fork' food production chain (farms, holdings, slaughterhouses, laboratories, traders etc.) in a structured, predefined format, and facilitate competent analyses and reporting of such data, as well as the improvement of the existing programs and strategies. The role of information system in animal disease diagnosis, surveillance and notification, control of national and international trade of commodities, food safety management, investigation of diseases, predictive microbiology and quantitative risk assessment is of great importance for the quality of veterinary service. Integral part of the VIMS is animal disease notification system designed according to and in compliance with international requirements, standards and recommendation and able to exchange relevant information with similar information systems. The aim of this contribution is to describe national animal disease notification system which is in place in Serbia as a part of VIMS.Preduslov za uspostavljanje efikasnog sistema menadžmenta zdravstvene zaštite životinja, bezbednosti hrane i sledljivosti u lancu proizvodnje hrane je uvođenje integrisanog veterinarskog informacionog menadžment sistema (VIMS) razvijenog na takav način da omogući prikupljanje, čuvanje, analizu i povlačenje podataka i obezbedi kumulativno skupljanje saznanja i njihovu stručnu interpretaciju. Takav sistem će omogućiti prikupljanje podataka, uključujući one iz upravljanja kvalitetom i u okviru inspekcijskih kontrola, od svih objekata u sistemu proizvodnje hrane 'od farme do viljuške' (farme, gazdinstva, klanice, laboratorije, lica koja se bave prometom i dr.) u strukturirano, unapred definisanom obliku, i obezbediti kompetentnu analizu takvih podataka kao i unapređenje postojećih programa i strategija. Uloga informacionih sistema u dijagnostici, nadzoru i prijavljivanju zaraznih bolesti, kontroli unutrašnjeg i međunarodnog prometa, upravljanju bezbednošću hrane, istraživanju žarišta zaraznih bolesti, prediktivnoj mikrobiologiji i kvantitativnoj analizi rizika je od izuzetnog značaja za kvalitet veterinarske službe. Sastavni deo VIMS-a je sistem za prijavljivanje zaraznih bolesti dizajniran prema i u saglasnosti sa međunarodnim zahtevima, standardima i preporukama i osposobljen da vrši razmenu određenih podatka sa sličnim informacionim sistemima. Cilj ovog rada je da se opiše nacionalni sistem za prijavljivanje zaraznih bolesti koji je u Srbiji u primeni kao deo VIMS-a

Chloride and Bromide Complexes of Lead(II) in Aqueous Melts of Calcium Dinitrate - Ammonium Nitrate

The formation constants of PbCl+, PbCh, PbBr• and PbBr2 in melts of Ca(N03)2 • a NH4N03 · x H20 (a = 1.5, 2.33; x = 3-9) at 323 and 338 K have been determined from E 1lF measurements in suitable concentration cells. The results are discussed in terms of Braunstein\u27s ionic association model based on quasi-lattice statistical mechanics

Sinteza i farmakološko ispitivanje (±)-2,3-seco-analoga fentanila

An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1-5.5 (all new compounds) were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting beta-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methyl phenethylamine, (93% yield), was successively reacted with NaH and BuLi, to form the highly reactive alpha,gamma-dienolate anion 1.1a. Regio and chemoselective gamma-alkylation of the dienolate with various primary and secondary alkyl halides furnished the beta-keto-amides 1.2-1.5 (76-91%). Reductive amination of the keto-amides 1.1-1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1-2.5. afforded the beta-anilino amides 3.1-3.5 (74-85%). After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1-4.5 were obtained (87-97%). The synthesis of (+/-)-2,3-seco-fentanyls 5.1-5.5 was completed by N-acylation of the diamines 4.1-4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86-95%). The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5-6 times more active than morphine in rats. while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance. the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers.Razvijen je efikasan postupak za dobijanje različitih acikličnih 1,3-diamina u pet faza, i primenjen u sintezi nove klase analoga fentanila otvorenog niza. Derivati 5.1–5.5 (svi su nova jedinjenja) sintetisani su sa ciljem da se proceni uticaj piperidinskog prstena na opioidnoanalgetičku aktivnost anilido-piperidina. Polazni β-keto-amid 1.1, dobijen aminolizom metilacetoacetata metilfenetilaminom (prinos 93 %), bio je sukcesivno tretiran sa NaH i BuLi, pri čemu je postao veoma reaktivni α,γ-dienolatni anjon 1.1a. Regio- i hemoselektivnim γ-alkilovanjem ovog dienolata različitim primarnim i sekundarnim alkil-halogenidima, dobijeni su β-keto-amidi 1.2–1.5 (prinos 76–91 %). Reduktivnim aminovanjem keto-amida 1.1–1.5 pomoću Zn praha i sirćetne kiseline, preko enaminskih intermedijera 2.1–2.5, postali su -anilino-amidi 3.1–3.5 (prinos 74–85 %). Posle reduktivne deoksigenacije tercijene amidne funkcije, koristeći in situ generisani diboran, odgovarajući 1,3-diamini 4.1–4.5 izolovani su u prinosima 87–97 %. Sinteza (±)-2,3-seco-fentanila 5.1–5.5 završena je N-acilovanjem diamina 4.1–4.5 propionil-hloridom, a zatim taloženjem u obliku monooksalatnih soli (prinos 86–95 %). Nađeno je da je osnovno jedinjenje, 2,3-seco fentanil 5.1, 40 puta slabiji narkotički analgetik od fentanila, ali još uvek 5–6 puta aktivniji od morfina u pacova, dok je i-Pr derivat 5.3 bio neaktivan. Osim farmakološkog značaja, opštim postupkom prikazanim u ovom radu, mogu se sintetisati različiti 1,3-diamini, uključujući i one sa funkcionalnim grupama. Ova jedinjenja mogu biti potencijalno značajna kao kompleksirajući agensi i kao intermedijeri u sintezi aza-kraun-etara

Pharmacological evaluation of 3-carbomethoxy fentanyl in mice

In many animal species, as well as in humans, high doses of fentanyl (F) produce marked neurotoxic effects, such as muscular rigidity and respiratory depression. The antinociception (hot-plate test), impairment of motor coordination (rotarod test) and acute toxicity of intraperitoneal newly synthesized analogs, (±)cis-3-carbomethoxy- fentanyl (C) and (±)trans-3-carbomethoxyfentanyl (T) were evaluated in mice. The compounds tested induced antinociception, impairment of performance on the rotarod, and lethality in a dosedependent manner. The relative order of antinociceptive potency was similar to motor impairment potency, as well as lethality: F gt C gt T. Naloxone hydrochloride (1 mg/kg; sc) abolished all the effects observed, suggesting that they are mediated via opioid receptors, most probably of μ type. There were no significant differences between the therapeutic indices of F, C and T. It is concluded, the introduction of 3-carbomethoxy group in the piperidine ring of the fentanyl skeleton reduced the potency, but did not affect tolerability and safety of the compound. © 2011 by the authors

Dynamic adsorption characteristics of thin layered activated charcoal materials used in chemical protective overgarments

The efficiency of a thin layered activated charcoal material used in chemical protective overgarments has been evaluated. The study has been conducted with the aim to obtain protective materials with best characteristics considering resistance to benzene effect under dynamic conditions and to create a new filtration protection device. In order to evaluate dynamic adsorption characteristics of thin layered sorption materials, sophisticated dynamic gas chromatography method is used. The curves of benzene penetration are determined for sandwich materials, and sorption layers used in filtrating protective clothing shows that thin layered carbon sorption materials (type MOO) have good protective properties as compared to other similar materials. The findings will help to create conditions for developing a functional model for producing a new protective overgarment in the near future