Prednost parenteralne primjene Mi-ADMS pred DMSA u snižavanju tjelesnog opterećenja živom (203Hg) u štakora

The efficiency of meso-2,3-dirnercaptosuccinic acid (DMSA) and the mono-isoamyl ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) in decreasing 203Hg retention was evaluated in rats in relation to age and time of treatment. The experiments were performed on six-week- and seven- day-old Wistar rats, which received 203Hg by intraperitoneal administration. The chelators DMSA or Mi-ADMS were also administered intraperitoneally, twice, on two consecutive days, in doses of 0.25 mmol/kg body weight as early (0.5 and 24 h) or delayed treatment (24 and 48 h, or 48 and 72 h) after 203Hg administration. The retention of 203Hg was determined in the carcass, liver, kidneys and brain six days after administration using gamma scintillation counters (double crystal, well type). In all experimental conditions, regardless of the animals\u27 age and time of chelation therapy, Mi-ADMS was found to be superior to DMSA in reducing the body burden of 203Hg in whole body and organs. Mi-ADMS therefore seems to be a very promising chelator in the treatment of mercury poisoning.Procjenjivana je učinkovitost mezo-2,3-dimerkaptojantarne kiseline (DMSA) i monoizoamilnog estera mezo-2,3-dimerkaplojantarne kiseline (Mi-ADMS) u snižavanju opterećenja živom (203Hg) u štakora u odnosu na dob i vrijeme primjene. Pokusi su provedeni na šestotjednim ženkama i sedmodnevnim sisajućim bijelim štakorima Wistar iz uzgoja Instituta u Zagrebu, kojima je intraperi-tonejski davana 203Hg. Kelati DMSA i Mi-ADMS davani su, također intraperitonejski, dva dana zaredom u dozi od 0,25 mmol/kg tjelesne težine kao neposredna/rana primjena (El - 0,5 i 24 h) ili kao odgođena/kasna primjena (E2 - 24 i 48 h, E3 - 48 i 72 h) nakon davanja 203Hg. Retencija 203Hg mjerena je u karkasu (tijelo nakon odstranjenja probavila), u jetri, u bubrezima i u mozgu sest dana nakon primjene Hg u odgovarajućim gamascintilacijskim brojačima. U šestotjednih životinja i DMSA i Mi-ADMS primijenjeni kao rana terapija (El) snizili su retenciju 203Hg u karkasu i u organima u odnosu na vrijednosti u kontrolnih (netretiranih) životinja. Odgođena primjena (E2 i E3) jednog i drugog kelata snizila je retenciju 203Hg u karkasu i bubrezima, nije imala učinka na retenciju u jetri, a retenciju u mozgu snizio je samo Mi-ADMS. U sedmodnevne sisančadi oba kelata značajno su snizila tjelesnu retenciju 203Hg i nakon rane (El) i nakon kasne primjene (E2), a jedino DMSA u kasnijoj primjeni (E2) nije imao učinka na retenciju Hg u mozgu. U svim eksperimentalnim uvjetima neovisno o dobi životinja i vremenu kad je primijenjen kelat, terapija s Mi-ADMS bila je učinkovitija od DMSA u snižavanju tjelesnog opterećenja 203Hg u tijelu i u organima. To je glavni nalaz ovog istraživanja. Čini se da je Mi-ADMS kelat koji puno obećava u budućnosti kao lijek izbora u terapiji otrovanja živom

The effect of exposure to lead on histopathological changes in the rat liver and kidney in relation to age

Promatrane su patohistološke promjene jetre i bubrega u odraslih ženki štakora i u njihove mladunčadi iz dvaju rasploda nakon oralne izloženosti olovu (acetat) u koncentraciji od 7500 ppm u vodi za piće. Izloženost je trajala do ukupno 20 tjedana. Reverzibilnost ovih promjena procjenjivana je u skupini tzv. oporavljenih ženki kojima je prekinuto izlaganje olovu 5 tjedana prije drugog parenja s neizloženim mužjacima. U skupini izloženih odraslih ženki, kao i u skupinama njihove mladunčadi iz prvog (kraća izloženost) i drugog potomstva (duža izloženost), nađene su istovjetne patohistološke promjene u parenhimnim organima. Tako su u obih opažene masna i/ili hidropska degeneracija u jetri i bubrezima, te hemosideroza jetre. U preparatima jetre izložene mladunčadi opažena su također brojna i krupna ekstramedularna krvotvorna žarišta. U bubrezima izloženih ženki viđene su i izraženije nespecifične kronične upalne promjene. U skupinama oporavljenih ženki, nakon prekida oralne izloženosti olovu, patohistološki nalazi upućivali su na reverzibilnost morfoloških promjena. U njihove „oporavljene“ mladunčadi viđeni su gotovo uredni nalazi. Može se zaključiti da je mladunčad štakora osjetljivija od svojih majki na štetno djelovanje olova budući da su u njih opažene patohistološke promjene jetre i bubrega bile istovjetne onima u odraslih ženki, premda su bili izloženi tijekom mnogo kraćeg perioda i samo maloj frakciji ukupnog unosa olova u organizam majke.Histopathological alterations in the liver and kidneys were examined in adult female rats and in their offspring form two matings after oral exposure to 7500 ppm lead (acetate) in drinking water. The length of exposure was up to 20 weeks. To estimate the reversibility of the effects in a number of exposed females lead administration was discontinued five weeks before their second breeding with unexposed males (the recovered group). In the group of exposed adult females histopathological changes in parenchymal organs were analogous to those seen in their pups from the first (shorter exposure), and second offspring (longer exposure to lead). Fatty and/or hydropic degenerative changes in the liver and kidneys and haemosiderosis of the liver were observed in both adult females and their young. In the liver of exposed pups the presence of numerous large foci of extramedullary erythropoiesis was also detected. In the kidneys of exposed adult females non-specific chronic inflammatory changes were seen. In the group of recovered females, after discontinuation of oral exposure to lead, histopathological findings indicated the reversibility of morphological changes. In their “recovered” pups the findings were also almost normal. It may be concluded that young rats are more susceptible to adverse action of lead than their mothers. The histopathological changes observed in their livers and kidneys were analogous to those seen in adult females, although they had been exposed to lead for a much shorter period and to only a small fraction of the total mother\u27s lead intake

Utjecaj kombinirane terapije kod interne kontaminacije s više radionuklida na neke zdravstvene parametre u štakora

The health effects of a composite treatment for the early and late therapy of internal contamination with several radionuclides were evaluated in rats. The rats were given a mixture of calcium alginate, ferrihexacyanoferrate(II) and potassium iodide orally for 10 days together with the intraperitoneal administration of Ca-DTPA in the first three days and foe oral administration of Zn-DTPA daring the remaining seven days. The health effects of this treatment were evaluated by body weight measurements, haematological and histopathological examinations and trace element analysis. The treated animals had a slightly lower number of erythrocytes, slightly Iower haemoglobin and haematocrit values and very mild histopathological changes in the kidneys in the form of hydropic degeneration of proximal convoluted tubules. The observed changes were consistent with the known effects of individual therapeutic agents (alginate, Ca-DTPA) and therefore the simultaneous administration of several agents did not alter toxicity or produce new adverse effects.U .radu su određeni zdravstveni učinci kombinirane terapije za ranu i kasnu primjenu kod interne kontaminacije s više radionuklida u štakora. Terapija se sastojala u istodobnoj oralnoj primjeni mješavine kalcijeva alginata, ferifenocijanida i kalijeva jodida tijekom 10 dana, intraperitonealnoj primjeni Ca-DTPA tijekom prva tri dana pokusa te oralnoj primjeni Zn-DTPA tijekom preostalih 7 dana pokusa. Zdravstveni učinci takvog tretmana određeni su mjerenjem tjelesne težine, hematoloških parametara, analizom elemenata u tragovima i histopatološkom pretragom. Tretirane životinje su imale nešto niži broj eritrocita, nešto niže vrijednosti hemoglobina i hematokrita i vrlo diskretne promjene u tkivu bubrega karakterizirane kao granularno-hidropska degeneracija zavinutih kanalića. Takve promjene mogu se pripisati učinku pojedinih terapijskih sredstava (alginata, kelatogene terapije) koji su poznati i opisani u literaturi, dok nova djelovanja odnosno štetni učinci na zdravlje koji bi nastali zbog istodobne primjene više terapijskih sredstava nisu opaženi

Quantum Hall effect in a high-mobility two-dimensional electron gas on the surface of a cylinder

The quantum Hall effect is investigated in a high-mobility two-dimensional electron gas on the surface of a cylinder. The novel topology leads to a spatially varying filling factor along the current path. The resulting inhomogeneous current-density distribution gives rise to additional features in the magneto-transport, such as resistance asymmetry and modified longitudinal resistances. We experimentally demonstrate that the asymmetry relations satisfied in the integer filling factor regime are valid also in the transition regime to non-integer filling factors, thereby suggesting a more general form of these asymmetry relations. A model is developed based on the screening theory of the integer quantum Hall effect that allows the self-consistent calculation of the local electron density and thereby the local current density including the current along incompressible stripes. The model, which also includes the so-called `static skin effect' to account for the current density distribution in the compressible regions, is capable of explaining the main experimental observations. Due to the existence of an incompressible-compressible transition in the bulk, the system behaves always metal-like in contrast to the conventional Landauer-Buettiker description, in which the bulk remains completely insulating throughout the quantized Hall plateau regime