Sacrifice Date Research Articles

Comparative investigations of the biodurability of mineral fibers in the rat lung.

The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates.

Biodistribution and excretion of a mixed fluorocarbon-hydrocarbon "dowel" emulsion as determined by 19F NMR.

To investigate the biodistribution, possible metabolism and excretion of mixed fluorocarbon-hydrocarbon "dowel" molecules used as stabilizers of fluorocarbon emulsions, we have prepared a 25% w/v emulsion of such a molecule, and quantitatively evaluated, by means of 19F NMR, its behavior in the blood and reticuloendothelial system (RES) of rats. C6F13CH = CHC10H21 (F6H10E) was emulsified using egg yolk phospholipids (EYP). The emulsion (F6H10E/EYP: 25/6% w/v) was injected intravenously into 33 Sprague Dawley female rats at a 3.6 g/kg body weight dose of F6H10E. The animals were sacrificed at regular intervals of time. 24 hours after the injection, 70% of the injected dose was located in the liver, 17% in the spleen, 4% in the lungs, 2% in the kidneys and 2% in the blood. The half-time retention of the dowel molecule in the liver was estimated to be 25 +/- 5 days. None of the 33 treated animals died prior to the planned sacrifice date. The dowel molecule F6H10E proved to be well tolerated, and excreted reasonably fast, without metabolism. This appears to warrant the use of such molecules as stabilizers in injectable fluorocarbon emulsions destined to serve as oxygen carriers, contrast agents or drug delivery systems.

Peripheral Nerve Lesions of Experimental Leprosy in Monkeys

Histopathological findings of intrafascicular-edema found in n. ulnaris running at forearm, palmside of hand and fingers of rhesus monkey 8664 and african green monkey 8175 were studied by semithin section method. These two monkeys were inoculated with leprosy bacilli from lepromata of mangabey monkey A022. The mangabey monkey A022 had been experimental leprosy after inoculum of the leprosy bacilli from lepromata of the mangabey monkey A015-natural infection. Period between date of inoculum and sacrifice of the rhesus monkey 8664 was about 2 years, and the african green monkey 8175 was about 5 years. Results found were: 1. Intrafascicular-edema found in n. ulnaris running at forearm, palmside of hand and fingers was remarkable at some of peculiar anatomical areas where were put on mechanical pressure. 2. The intrafascicular-edema inside many fascicles was remarkable around the small blood vessels. 3. Obsruction of the small blood vessels and congestion of blood stream at surrounded of the intrafascicular-edema with fibrous elements and cellular elements were observed inside some of fascicles. 4. Bundles of peripheral nerve fibers inside some of fascicles were pressed by the intrafascicular-edema, and the fibrous elements, especially collagen fibers, were increased around the pressed bundles of nerve fibers and each nerve fiber inside the fascicles. 5. Vacuolar degeneration and swelling of axon were observed at some of myelinated nerve fibers. 6. Not only the intrafascicular-edema but also a large amount of intracytoplasmic foamy structures with solid leprosy bacilli were observed inside many fascicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain.

The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.

The rabbit as an experimental animal for tracheal surgery.

The circumferential resection of the trachea with end-to-end anastomosis is a well-established clinical procedure. Still, some problems remain to be solved, such as the choice of optimal suture material. Dogs are primarily used for experimental work in this field, but are difficult to obtain. This operation was performed on nine rabbits, eight of whom survived to the preplanned date of sacrifice. Two of the survivors were found to have severe stricture at the anastomosis. This study indicates that the rabbit is a suitable experimental animal for circumferential resection and anastomosis of the trachea.

The Differential Protection by WR2721 of Skin versus Growing Cartilage Following Irradiation in Weanling Rats

The potential for radioprotection of growing cartilage by the thiophosphate WR2721 was evaluated in weanling rats using single fractions of irradiation. Protection of acute skin toxicity was monitored simultaneously. Single doses of 600, 1200, 1800, or 2400 cGy were administered to the left tibia of CrL:CD(SD)BR female rats in groups of 12. Identically treated groups were injected with 310 mg/kg WR2721 (2/3 the determined LD50/30) in a concentration of 26 mg/ml intraperitoneally 15 min prior to irradiation. Rats untreated or given WR2721 without radiation served as control groups. Radiographs of the irradiated and unirradiated tibiae for each animal were obtained weekly to the date of sacrifice at 80 days following the initial treatment. Skin toxicity was assessed weekly starting on the second week using Moulder's scale (J.E. Moulder, J.J. Fischer, and A. Casey, Radiology 115, 465-470 (1975]. No significant difference in bone growth as measured by tibial lengths for the WR2721-treated or untreated animals was observed. Skin toxicity including moist desquamation occurred in irradiated limbs and was substantially less in rats treated with WR2721. As opposed to previous work with cysteamine, WR2721 as administered had no significant radioprotective effect on tibial growth in weanling rats but substantially reduced the accompanying skin toxicity.

Peripheral nerve lesions of experimental leprosy in monkeys. III. Intracytoplasmic foamy structure and fibrosis

Histopathological findings of ramus superficialis, n. peroneus of rhesus monkey A125 and ramus superficialis, n. plantaris lateralis of African green monkey 8178 were studied. These monkeys were inoculated with leprosy bacilli isolated from lepromata of mangabey monkey A015. Period between date of inoculum and date of sacrifice of the rhesus monkey was about 3 years, and in African green monkey 8178 it was about 5 years.

Histopatologia da esquistossomose mansoni em fígado de Mus musculus infectado por amostras humanas de fase aguda e crônica da periferia de Belo Horizonte, Minas Gerais

Exemplares de Biomphalaria glabrataforam infectados com miracídios obtidos de ovos de Schistosoma mansoni, encontrados em fezes de indivíduos de 7 a 18 anos, da região de Lagoa da Pampulha, Belo Horizonte, MG. Os pacientes de fase aguda se infectaram em uma primeira visita ao foco. Os da fase crônica eram moradores próximos aos focos. Para cada caso clínico, isolou-se a respectiva amostra do parasita. Foram infectados pela cauda 55 camundongos fêmeas com 70 ± 10 cercárias. Cortes histológicos de fígados, corados por HE, tricrômico de Gomori, impregnação metálica pela prata, e PAS foram observados à microscopia óptica. Não houve diferenças estatísticas em relação às médias das mensurações dos diâmetros dos granulomas referentes às amostras e datas de sacrifícios. Os granulomas apresentaram fase exsudativa do tipo Ha (reação de inflamação mista) e IIIa (granuloma com células epitelióides). Com amostras de pacientes em fase aguda o padrão predominante foi a Ha na 7ª semana. Na 10.ª semana predominaram granulomas do tipo IIIa. Nas amostras de pacientes em fase crônica, verificou-se uma mescla de granulomas do tipo Ha e IIIa na 7ª semana. Na 10ª semana predominou o tipo IIIa. Alguns aspectos histopatológicos de fígados foram descritos e comparados com aqueles existentes na literatura.

High-yield preparation of porcine hepatocytes for long survival after transplantation in the spleen.

The creation of an auxiliary liver by autotransplantation of liver parenchymal cells into the spleen has mainly been studied in rats for the treatment of acute liver failure. In order to apply this procedure to humans with chronic liver insufficiency the aim of this work was: To demonstrate that hepatocytes can survive for long periods after autotransplantation into the spleen; to increase the yield of the isolation of hepatocytes obtained from pig livers since this animal has a more fibrous liver than rats or normal humans and consequently one which is more difficult to dissociate. In 21 pigs isolated hepatocytes were obtained with in collagenase dissociation technique, the yield being 1-3 X 10(7) cells per gram of liver and the viability 70-95%. The hepatocytes survived and maintained normal morphological and histochemical characteristics up to 7 months after transplantation, the date of sacrifice of the last animal.

Determination of 90Sr and stable strontium in bones from sheep ewes and their fetuses

The concentrations of 90Sr and stable strontium were measured in the bone ash from pregnant sheep ewes and their fetuses. The fetuses weighed from 125 g ( 90Sr) and 110 g (stable strontium) to 2650 g. In the ewes the average concentration of 90Sr was 40.4 (s.d. 6.4) pc/g calcium in the metatarsal diaphyses and 38.4 (s.d. 3.9) pc/g calcium in the vertebrae. The average concentration of stable strontium was 321 (s.d. 37) p.p.m. in the metatarsal diaphyses and 324 (s.d. 26) p.p.m. in the vertebrae. No significant difference between the two bones in the concentrations of either 90Sr or stable strontium was found. In the fetuses the average concentrations of 90Sr and stable strontium in the ash from the ossified parts of the long bone diaphyses was 16.2 (s.d. 2.5) pc/g calcium and 152 (s.d. 27) p.p.m. respectively. The average ratio between the strontium concentrations in the long bones of each fetus and the metatarsal bones of its mother was 0.41 (s.d. 0.06) for 90Sr and 0.48 (s.d. 0.08) for stable strontium. The strontium concentrations in the fetal and maternal bone ash, and the ratio between these concentrations, were essentially independent of fetal weight and sacrifice date.

Autoradiographic Study with Tritiated Thymidine of Mouse Testis after 320 r and after 1000 r of Acute Localized X-Irradiation

Two groups of C57 black male mice approximately 100 days old were subjected to 320-r and 1000-r doses of acute localized x irradiation, respectively. The 320-r series was injected with tritiated thymidine 10 to 15 minutes before exposure; the 1000-r series, 24 hours previously. The distribution of stages showing labeled cells was compared in 320-r and control material and found to be synchronous in both series. After 320 r the respective range of stages at each sacrifice date is narrower than in the control, owing to selective killing of type B spermatogonia. Thus a narrower stream of labeled cells is fed into early meiosis. With 1000 r, synchrony also exists as long as cells are present to maintain it. Cell death is not limited to spermatogonia. After 320 r there is also some loss of spermatocytes and a severe loss of spermatids over and beyond the loss resulting from diminished recruitment. The thymidine label made it possible to trace labeled restitution cells from their original position in the tubule to the basement membrane, but the present study allows no statement concerning their life span and uitimate fate.