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Showing papers on "Intraperitoneal injection published in 1986"


Journal ArticleDOI
12 Sep 1986-Science
TL;DR: Isolated hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, can be attached to collagen-coated dextran microcarriers and transplanted by intraperitoneal injection into rats and survival and function of the transplanted hepatocytes have been demonstrated.
Abstract: Isolated hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, can be attached to collagen-coated dextran microcarriers and transplanted by intraperitoneal injection into rats. Survival and function of the transplanted hepatocytes have been demonstrated in mutant rats lacking bilirubin-uridine diphosphate glucuronosyltransferase activity (Gunn strain) and rats with inherited lack of plasma albumin (Nagase analbuminemia rat strain). This simple technique promises to be useful in the treatment of acute liver failure in humans.

295 citations


Journal ArticleDOI
01 Sep 1986-Vaccine
TL;DR: DAC-70 showed no effect on the production of tumour necrosis factor in vivo and did not stimulate the production by spleen cells of interleukin 2, interferon, colony-stimulating or macrophage-activating factor or of interferons by macrophages in vitro.

162 citations


Journal ArticleDOI
TL;DR: A single intraperitoneal injection of 250 micrograms dextran sulphate 500 (DS500) reduced the susceptibility of mice to scrapie given by the same route, consistent with either of these strains of scrapie in 11 different inbred strains of mice.
Abstract: A single intraperitoneal injection of 250 micrograms dextran sulphate 500 (DS500) reduced the susceptibility of mice to scrapie given by the same route. A lower dose (25 micrograms) was less effective but still produced significant incubation period lengthening, while a high dose (2.5 mg) further increased the degree of prolongation. This reduced susceptibility occurred with DS500 administered up to at least 4 weeks prior to intraperitoneal scrapie inoculation and up to at least 2 weeks after scrapie inoculation. A reduced average effect, but more variable between mice, was obtained with DS500 given 1 month or 2 months after scrapie. The effective scrapie titre was reduced by 90% when DS500 was injected either 72 h before or 7 h after ME7 scrapie. Using a relatively lower but normally still fatal dose of the 22A strain of scrapie approximately 50% of the treated mice survived. The effective 90% loss of titre was consistent with either of these strains of scrapie in 11 different inbred strains of mice (BALB/c, BSC, BRVR, C3H, C57BL, IM, LM, MM, RIII, VL and VM). No significant increase in the prolongation effect was obtained using multiple DS500 doses in two different time combinations. DS500 causes long-term interference in both the early processing and the replication of scrapie agent, unlike those immunomodulators which increase susceptibility.

138 citations


Journal ArticleDOI
TL;DR: Antitumor activities of MY-1 were also abolished if the animals were pretreated with anti-asialo GM1 antiserum or carrageenan, suggesting that the activities can be ascribed mainly to activated NK cells.
Abstract: A fraction extracted from BCG and designated MY-1, which was composed of 70.0% DNA and 28.0% RNA, was previously reported to possess strong antitumor activities against various syngeneic mouse and guinea pig tumors. An intraperitoneal injection of MY-1 (100 micrograms) 1 day before rendered mouse peritoneal cells cytotoxic to YAC-1 cells. The effector cells were nonadherent to plastic dishes, and the activity was destroyed by treatment with anti-asialo GM1 antiserum plus complement or carrageenan in vitro, but not with carbonyl-iron or anti-Thy 1.2, suggesting that the cells are natural killer (NK) cells. In vivo augmentation of NK activity was dependent on MY-1 dose, and reached the peak 1 day after MY-1 injection. Since NK activity in lipopolysaccharide (LPS)-nonresponder mice could be augmented by MY-1, the possibility that LPS contaminated the MY-1-augmented NK was excluded. MY-1 digested preliminarily with DNase lost its NK-inducing activity, suggesting that the DNA entity of MY-1 was essential for the activity. When mice were pretreated with anti-asialo GM1 or carrageenan, MY-1 could not render the peritoneal cells cytotoxic. Antitumor activities of MY-1 were also abolished if the animals were pretreated with anti-asialo GM1 antiserum or carrageenan, suggesting that the activities can be ascribed mainly to activated NK cells.

97 citations


Journal ArticleDOI
TL;DR: This procedure involves the intraperitoneal injection of packed red cells to give transfusions to severely affected isoimmunized fetuses and the success of this procedure depends on the patient’s immune status.
Abstract: TRADITIONALLY, attempts to give transfusions to severely affected isoimmunized fetuses have involved the intraperitoneal injection of packed red cells.1 2 3 The success of this procedure depends on...

93 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of intraperitoneal administration of cadmium and exposure to the metal in the water on rainbow trout, Salmo gairdneri, were studied.

92 citations


Journal ArticleDOI
TL;DR: Focal injection into the prepiriform cortex of an N-methyl-D-aspartate receptor antagonist, 2-amino-7-phosphonoheptanoic acid (APH), 1-10 pmol, potently protects against motor limbic seizures and their pathological consequences.

66 citations


Journal ArticleDOI
TL;DR: It is suggested that intraperitoneal injection of immunotoxins may have a role in the treatment of ovarian cancer.
Abstract: An immunotoxin composed of Pseudomonas toxin coupled to an antibody to the human transferrin receptor was evaluated for its effect on ovarian cancer. In the tumor model employed, 60 million human ovarian cancer cells were injected into the peritoneal cavity of an immunodeficient nude mouse. By day 5, cancer cells were implanted and growing in small clusters throughout the peritoneal cavity. On days 5-8, 0.3-2 micrograms of immunotoxin was injected into the peritoneal cavity. Control mice died with malignant ascites at 34-58 days after the implantation of tumor cells, whereas immunotoxin-treated mice lived to 100 days or longer. Irrelevant immunotoxins or antibody alone had no antitumor activity. These findings suggest that intraperitoneal injection of immunotoxins may have a role in the treatment of ovarian cancer.

64 citations


Journal ArticleDOI
TL;DR: Both in vitro and in vivo clonogenic assays demonstrated that the photodynamic inactivation of the tumors was significantly greater after direct injection than after intraperitoneal injection.
Abstract: The distribution, retention, and phototoxicity of the sensitizer hematoporphyrin derivative (HPD) were studied following intraperitoneal and direct intraneoplastic injections of the agent into subcutaneous or intracerebral gliosarcomas in rats. Forty-eight hours after intraperitoneal injection, the ratio of tritiated (3H) HPD in subcutaneous tumor: adjacent normal skin was about 1.4:1 and the ratio in tumor: normal brain was 3:1. In contrast, direct injection of 3H-HPD into subcutaneous tumors resulted in tumor: adjacent normal skin concentration ratios of approximately 44:1 and tumor: normal brain ratios of about 61:1. For rats bearing intracerebral gliosarcomas, intraperitoneal administration of 3H-HPD resulted in approximately 1.3-fold sensitization in tumor tissue relative to adjacent edematous brain. In contrast, after direct injection into intracerebral tumors, the tumor: adjacent edematous brain and tumor: skin 3H-HPD ratios were 3:1 and 32:1, respectively. In all cases, 3H-HPD was found in every portion of the tumor, even at a distance from the injection site. For the 3H-HPD doses used in this study, after direct injection both subcutaneous and intracerebral tumor tissue contained about three to four times more 3H-HPD than tumors in rats receiving intraperitoneal 3H-HPD. Both in vitro and in vivo clonogenic assays demonstrated that the photodynamic inactivation of the tumors was significantly greater after direct injection than after intraperitoneal injection.

63 citations


Journal Article
TL;DR: Repeated intraperitoneal injections of ferric nitrilotriacetate (Fe-NTA) induce nephrotoxic features such as proximal tubular necrosis and renal failure, an unexpected phenomenon for a ferric compound.
Abstract: Repeated intraperitoneal injections of ferric nitrilotriacetate (Fe-NTA) induce nephrotoxic features such as proximal tubular necrosis and renal failure, an unexpected phenomenon for a ferric compound. The mechanism of Fe-NTA toxicity was investigated by electron microscopy and respiration studies of renal cortical mitochondria in rats. Four hours after a single intraperitoneal injection of Fe-NTA, 5 mg iron/kg body wt, loss of microvilli, increased number of cytoplasmic vacuoles, electron-dense cytoplasmic deposits, mitochondrial swelling, karyorrhexis, and rupture of cytoplasmic membrane were observed in proximal tubular epithelia. At 24 hours, an increased number of cells had become necrotic. Polarographic studies of mitochondria from renal cortex 4 hours after Fe-NTA treatment showed a significant decrease in State 3 respiration and DNP-uncoupled respiration, whereas little change was observed in State 4 respiration and ADP/O.

63 citations


Journal ArticleDOI
TL;DR: There was a difference between the measured osmolality and the calculated osmolarity of the plasma of the diabetic animals which was not seen in the controls and this difference was probably due to the presence of unidentified solutes.
Abstract: 1 Intakes and urine outputs of fluid and electrolytes were measured daily in rats before, and for 3 weeks after, induction of diabetes by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg); control animals received saline 2 Water intakes and urine outputs were increased on and after the first day after injection with STZ; after a transient period of negative water balance, fluid intakes and urine outputs increased in parallel 3 Food intake was reduced for the first 3 days after injection of STZ but thereafter there was a steady increase On the final experimental day, the food intake of the diabetic group was 60% greater than that of the control group 4 Urinary electrolyte excretion was increased after injection of STZ; at the end of the experiment, the increase in urinary sodium excretion was similar to the increase in intake but the increase in urinary potassium excretion was less 5 On day 21 after injection of STZ plasma sodium concentration and packed cell volume were significantly reduced in the diabetic group but plasma potassium concentration was not 6 There was a difference between the measured osmolality and the calculated osmolarity of the plasma of the diabetic animals which was not seen in the controls This difference was not due to pseudohyponatraemia, but was probably due to the presence of unidentified solutes, since there was a significant gap between the urinary osmolal and osmolar excretion in the diabetic animals that was not present in the control animals

Journal ArticleDOI
TL;DR: These studies have focussed on three neoplastic entities in the kidney, renal mesenchymal neoplasia, renal cell carcinoma, and nephroblastoma, finding each one of these animal models suitable for the sequential tracing of tumor pathogenesis, and in depth analysis of the biochemical and molecular mechanisms involved in the initiation and formation of different types of renal cancer.
Abstract: In order to discriminate non-specific toxicity from the early precursor lesions of neoplasia, emphasis in these studies has been on the use of models requiring only a single administration of chemical. Our interests have focussed on three neoplastic entities in the kidney, renal mesenchymal neoplasia, renal cell carcinoma, and nephroblastoma. Dimethylnitrosamine administered as a single intraperitoneal injection to immature female Wistar rats, pre-conditioned for several days with a no-protein/sugar-only diet, has been used for investigating the complex morphological nature of renal mesenchymal tumors, their pathogenesis and the development of cell culture correlates. The near 100% tumor incidence and its facility for cell culture manipulation makes this a particularly potent model for studying chemical carcinogenesis and the evolution of cell transformation. Discovery that the rat kidney response to DMN was biphasic with respect to the time of treatment led to the subsequent development of a high incidence system for inducing renal adenocarcinoma, using older rats. Renal cell carcinomas could also be induced in mice by a single intravenous injection of streptozotocin. The tumor frequency in female CBA/H/T6J mice was almost 100%, providing a new model for the investigation of renal carcinogenesis in this species. Nephroblastoma has been a poorly comprehended neoplasm in both lower animals and man because of the lack of a high incidence model in conventional laboratory mammals. Recently, we have exploited an increased spontaneous predisposition of the Nb rat to nephroblastoma using a single intraperitoneal dose of N-ethylnitrosourea in pregnant females on day 18 of gestation, producing a frequency of 50% for this tumor type. More potent however, was a system which utilized the partially inbred IIIVO/J strain of rabbit using the same carcinogen and transplacental route of administration. The resultant incidence of nephroblastomas in the progeny was in excess of 90%, and like their counterparts in man, the neoplasms developed rapidly and had a potential for distant metastasis. Each one of these animal models is suitable for the sequential tracing of tumor pathogenesis, and in depth analysis of the biochemical and molecular mechanisms involved in the initiation and formation of different types of renal cancer.

Journal ArticleDOI
TL;DR: It is concluded that vitamin D exerts its major regulation of active calcium transport in the rat duodenum via CaBP on transport steps beyond brush-border entry.
Abstract: Vitamin D-replete (+D) and vitamin D-deficient (-D) rats received by intraperitoneal injection varying amounts of 1,25-dihydroxyvitamin D3, and 4 h (+D) or 9 h (-D) later everted duodenal sacs were...

Journal ArticleDOI
TL;DR: In this paper, the occurrence and activity of hepatic regenerative stimulator substance was investigated in the partially hepatectomized rabbit and related to biochemical and morphological parameters of liver regeneration.

Journal ArticleDOI
TL;DR: Results suggest that lipid peroxidation may be an important mechanism responsible for LPS toxicity and increased concentrations of malondialdehyde were found in crude homogenates of livers obtained from mice 16 h after administration of 20 mg of LPS per kg.
Abstract: Ethane has been identified and quantitated in air exhaled by mice following intraperitoneal injection of 20, 40, or 200 mg of Escherichia coli O111:B4 lipopolysaccharide (LPS) per kg. Significant increases in ethane concentration occurred within 1 to 5 h after LPS administration. In addition, increased concentrations of malondialdehyde were found in crude homogenates of livers obtained from mice 16 h after administration of 20 mg of LPS per kg. These results suggest that lipid peroxidation may be an important mechanism responsible for LPS toxicity.

Journal ArticleDOI
TL;DR: The experiments demonstrate the effect of small structural differences on the cytotoxicity of this group of environmental pollutants and also illustrate the sensitivity of the Clara cell as a target for xenobiotics.
Abstract: Male Swiss-Webster mice were exposed to naphthalene, 1-methyl-, 2-methyl-, 1-nitro- and 2-nitronaphthalene by intraperitoneal injection of peanut oil solutions over a dose range of 0.5-3.0 mmol kg-1 body weight. Treated mice were killed at times from 6 hours to 14 days post-treatment. Tissues were analyzed for cytotoxic effects by optical and electron microscopy, and for cell proliferation by autoradiography following in vitro labeling of lung slices with 3H-thymidine. The naphthalene derivatives varied widely in their cytotoxic effects. The most toxic was 1-nitronaphthalene with no mice surviving doses greater than 1 mmol kg-1. Naphthalene and 2-methylnaphthalene were about equally toxic, followed by 2-nitro- and 1-methylnaphthalene, in decreasing order of toxicity. In all cases the first evidence of cytotoxic effects was seen in the Clara cells of the bronchiolar epithelium, and, at the highest doses, toxic effects were found in the adjacent ciliated cells. Changes could be detected at the ultrastructural level at all doses, and within 6 hours after treatment. Only slight effects were seen in other cell types. Increased cell proliferation following chemical treatment was seen only in the bronchiolar epithelium, among cells tentatively identified as Clara cells or their precursors. Cytotoxic effects of naphthalene and its 1- and 2-methyl derivatives were confined to the lung, with minimal evidence of toxicity in the liver and kidney. The mononitronaphthalenes both produce small areas of centrizonal necrosis in the liver, but no discernible effects in the kidney. The experiments demonstrate the effect of small structural differences on the cytotoxicity of this group of environmental pollutants and also illustrate the sensitivity of the Clara cell as a target for xenobiotics.

Journal ArticleDOI
TL;DR: The results of the present study show that brain energy metabolism seems to be subject to only partial tolerance to central stimulation by caffeine.

Journal ArticleDOI
TL;DR: It is concluded that an elevated conversion of serine into glycine via serine hydroxymethyltransferase (SHMT) may be responsible for the enhanced NH biosynthesis.
Abstract: Porphyria was induced in adult male Wistar rats starved for 24 hr by SC injection of 400 mg/kg allylisopropylacetamide (AIA). The presence of porphyria was shown by measuring excretion of δ-aminolevulinic acid (σ-ALA) and porphobilinogen (PBG) into the urine during 24 hr after AIA administration. Plasma levels of glycine, serine and of a number of other amino acids were decreased in porphyric rats as compared to controls. Intraperitoneal injection of 2 mmol/kg serine 24 hr after AIA administration was used as an animal model for an acute psychosis, by measuring catelepsy scores 30 min after serine injection. The concentration of 5 different β-carbolines in platelet rich plasma (PRP) was measured using an HPLC-fluorometric method. An increase in the concentration of norharman (NH) in PRP, ranging from 0.57 nmoles/l in control rats to 1.88 nmoles/l in serine treated porphyric rats was found. The catalepsy duration was exponentially correlated with the NH concentrations in PRP. It is concluded that an elevated conversion of serine into glycine via serine hydroxymethyltransferase (SHMT) may be responsible for the enhanced NH biosynthesis.

Journal ArticleDOI
TL;DR: In RIF-1, WR-3689 is taken up most avidly, but the three drugs tend to be equally protective, and for the three protectors, the dose modifying factors for the Rif-1 tumor irradiated in vivo and assayed in vitro do not vary as predicted by differential uptake of drug into this neoplasm.
Abstract: The organ level biodistribution and tumor radioprotective properties of three drugs have been compared: WR-2721 (NSC 296961), WR-3689 (NSC 327729), and WR-77913 (NSC 318809). The three drugs have similar distribution patterns in normal mouse tissues. At 30 minutes after intraperitoneal injection, highest levels of 35S from radiolabeled protector are found in kidney and submandibular salivary gland, with lowest levels in brain and moderately low values in tumor and skin. Three of four tumors examined take up less WR-3689 than the other two protectors. For the three protectors, the dose modifying factors for the RIF-1 tumor irradiated in vivo and assayed in vitro are 1.5-1.7, but do not vary as predicted by differential uptake of drug into this neoplasm. In RIF-1, WR-3689 is taken up most avidly, but the three drugs tend to be equally protective.

Journal ArticleDOI
TL;DR: Intraperitoneal injection of D-Penicillamine at a dose range of 20-500 mg/kg increased rat hepatic but not renal and pancreatic metallothionein and lead to synchronous redistribution of Zn from endogenous sources to newly synthesized MT.

Journal ArticleDOI
TL;DR: Analysis of distribution of tritiated (3H)-HPD in a transplantable canine glioma model following intraperitoneal or direct intraneoplastic injection indicated that outside the central nervous system the distribution of 3H-HPD is dose-related, regardless of route of injection.
Abstract: ✓ Hematoporphyrin derivative (HPD) is a photosensitizing agent that has been used to locate and kill tumors. The distribution of tritiated (3H)-HPD was studied in a transplantable canine glioma model following intraperitoneal or direct intraneoplastic injection. Compared to intraperitoneal adminstration of 3H-HPD, direct injection resulted in levels that were more than 2.5 times higher in tumor tissue and approximately 10 times lower in skin. Dose-corrected analysis of the data indicated that outside the central nervous system (CNS) the distribution of 3H-HPD is dose-related, regardless of route of injection. Within the CNS, direct injection leads to more efficient uptake of 3H-HPD, especially at the tumor periphery. Fluorescence microscopy confirmed the selective biodistribution of HPD fluorescence within the cytoplasm of tumor cells.

Journal ArticleDOI
TL;DR: TIDA neurons were very sensitive to changes in circulating concentrations of PRL; their activity was increased if serum PRL concentrations were merely doubled by infusing a low concentration of rPRL for 4 h; this effect exhibited a very steep dose-response relationship.
Abstract: The present study was designed to characterize the time and dose relationships of the response of tuberoinfundibular dopaminergic (TIDA) neurons in the rat to systemically administered prolactin (PRL). The activity of TIDA neurons was estimated by measuring the rate of dopamine (DA) synthesis in the median eminence (DOPA accumulation following the administration of a decarboxylase inhibitor). Rats were pretreated with bromocriptine, a dopaminergic agonist, so as to inhibit the release of endogenous PRL from the anterior pituitary, and thereby reduce the activity of TIDA neurons to a 'basal' level from which it could be increased subsequently by exogenously administered PRL. In control animals an intraperitoneal injection of ovine PRL (oPRL) increased DOPA accumulation at 16 h, but not before, whereas in bromocriptine-pretreated animals an intraperitoneal injection of oPRL increased DOPA accumulation after 4 h ('tonic' component) and caused a further increase after 16 h ('induction' component). Continuous intravenous infusions of oPRL into bromocriptine-pretreated rats increased DOPA accumulation in the median eminence by 4 h, and when infused into control rats oPRL reduced serum concentrations of endogenous rat PRL (rPRL) by 2 and 4 h. Continuous intravenous infusions of rPRL increased DOPA accumulation in the median eminence after 2 h; this effect exhibited a very steep dose-response relationship (possibly an 'all-or-none' response). TIDA neurons were very sensitive to changes in circulating concentrations of PRL; their activity was increased if serum PRL concentrations were merely doubled by infusing a low concentration of rPRL for 4 h. Three daily injections of haloperidol elevated circulating rPRL concentrations and increased the rate of DOPA accumulation in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: The enhancing effect of PH on the induction of the preneoplastic liver foci was affected by the type of chemical and the timing of the operation.

Journal ArticleDOI
TL;DR: This alternate injection method for RBC allows for extravascular targeting of RBC to peritoneal macrophages and indicates a 20-day half-life for C-RBC in mice.

Journal Article
TL;DR: Although the cytotoxic effect of T-2 toxin on lymphoid tissue was marked, enhanced resistance to Listeria infection was revealed by significant decreases in mortality caused by listeriosis in the toxin-treated mice.
Abstract: The effect of T-2 toxin on cell-mediated resistance to bacterial infection was evaluated in mice challenge exposed with Listeria monocytogenes. Mice were treated orally on days -5, -4, -3, -2, -1, +1, and +3 with 2.0, 1.0, 0.5, or 0 mg of T-2 toxin/kg of body weight and were exposed to 10(6) (LD100) or 10(5) (LD50) L monocytogenes by intraperitoneal injection on day 0. Necrosis and depletion of lymphocytes in the thymus and spleen, decrease in thymus weight, reductions in the number of circulating total leukocytes and lymphocytes, and necrotizing gastroenteritis occurred in the toxin-treated mice. Although the cytotoxic effect of T-2 toxin on lymphoid tissue was marked, enhanced resistance to Listeria infection was revealed by significant (P less than 0.01) decreases in mortality caused by listeriosis in the toxin-treated mice. Mortality decreased from 100% to 64% in the mice exposed to 10(6) Listeria and from 50% to 20% in the mice exposed to 10(5) Listeria. Percentage of mortality after Listeria challenge exposure was dependent on the T-2 toxin dose and was progressively decreased in the mice given 0.5, 1.0, or 2.0 mg of toxin/kg.

Journal ArticleDOI
TL;DR: The results suggest that formation of the tetrafunctional reducible crosslink histidinohydroxymerodesmosine proceeds relatively rapidly in vivo, and conclude that such labelled crosslinks are apparently quite stable after biosynthesis, suggesting the possibility of studies of the metabolic fate of collagen crosslinks over appreciable fractions of the lifetime of a rat.
Abstract: Collagen crosslinks in neonatal rats were labelled in vivo by a single intraperitoneal injection of 200 uCi of [14C]lysine. Rats were killed at times ranging from 30 minutes to 10 weeks after injection. Whole skin, tendon, and bone were analyzed, after reduction and hydrolysis, for collagen crosslink content by HPLC. Crosslinks and amino acids were visualized by their incorporation of radioactivity from [14C]lysine and also fluorometrically by post-column derivatization with o-phthalaldehyde. The incorporation of 14C from labelled lysine into the principal difunctional reducible crosslinks, N6.6'-dehydro-5,5'-dihydroxylysinonorleucine and N6.6'-dehydro-5-hydroxylysinonorleucine, increased most rapidly between 4 and 12 hours after injection, results similar to those observed by others studying crosslink biosynthesis in vitro. Incorporation of 14C into the tetrafunctional crosslink histidinohydroxymerodesmosine proceeded more slowly than it did for the difunctional crosslinks. Values for the amount of radio...

Journal ArticleDOI
TL;DR: Results support the suggestion that alterations in calcium homeostasis may underlie age-related changes in neurotransmitter metabolism, and decline in brain calcium concentrations in brain stem and midbrain but did not significantly vary with age in the other regions.

Journal ArticleDOI
TL;DR: A combination of the basal clearance test and the renal concentrating test appears to provide the most efficient means for detecting the presence of prenatally induced functional alterations of the kidneys.
Abstract: Pregnant Sprague-Dawley rats were exposed to adriamycin and offspring were evaluated for renal functional competence. Exposure consisted of 0, 1.0 or 1.5 mg/kg/day by intraperitoneal injection on either gestational days 7–10 or 10–12. The exposed offspring were evaluated for 1) growth and viability; 2) serum concentrations and renal clearances of creatinine, urea, glucose, sodium, potassium, chloride, and total osmotic particles; 3) the ability to excrete an osmotically concentrated urine following fluid deprivation; 4) the ability to excrete an osmotically dilute urine following isotonic volume expansion; and 5) the ability to secrete hydrogen ions following administration of a fixed acid. Exposure during days 7–10 of gestation produced greater evidence of overt developmental toxicity than did exposure during days 10–12 of gestation. The reverse was true, however, for the effects of adriamycin on renal function, as the majority of effects on these measures were found in the high dose pups exposed during days 10–12 of gestation. The application of the renal function tests did not lower the observed effect level for adriamycin-induced developmental toxicity, but it did provide confirmatory information on the nature of the effect, on the magnitude of the effect in the exposed population, and on the possible morphological site of observed functional lesion. For reasons discussed in the text, a combination of the basal clearance test and the renal concentrating test appears to provide the most efficient means for detecting the presence of prenatally induced functional alterations of the kidneys.

Journal ArticleDOI
TL;DR: The results suggested that accelerated brain BCAA catabolism in acute hepatic failure rats reduce the neurotoxicity of ammonia by promoting the synthesis of glutamic acid and glutamine from BCAA.

Journal ArticleDOI
TL;DR: Selenium deficiency in rats impairs the ability of neutrophils and peritoneal macrophages to kill Candida albicans organisms in vitro, and a 5-fold increase in the dose led to a significantly greater mortality in the Se deficient rats.