SEARCH · PubMed Health

Results for “Generations”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

PubMed2001

Cerebrospinal fluid from subarachnoid haemorrhage patients causes excessive oxidative metabolism compared to vascular smooth muscle force generation.

Cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients can stimulate vascular smooth muscle to generate force in vitro. CSF from SAH patients suffering from delayed ischaemic neurological deficits due to cerebral vasospasm can generate near maximal force in vitro and previous experiments have ascribed this generation of force to be a calcium mediated event. The intracellular calcium concentration has been demonstrated to rise during the vasospastic process. Calcium also stimulates oxidative metabolism as does adenosine diphosphate (ADP), the product of adenosine triphosphate (ATP) hydrolysis. Significant alteration in high energy metabolites such as ATP, ADP and phosphocreatine have also been demonstrated in various models of SAH mediated vasospasm. Vascular smooth muscle predominantly uses oxidative metabolism for force generation and reserves glycolytic metabolism for ion homeostasis. A decrease in oxidative metabolism during force generation would imply failing mitochondria and increased glycolytic high-energy phosphate supply. Increased oxidative metabolism would imply a decreased efficiency of the contractile apparatus or mitochondria. The aim of this study was to see if SAH CSF stimulation of porcine carotid artery oxidative metabolism was altered during force generation when compared with incremental calcium stimulation with potassium chloride depolarisation. CSF from patients (n = 10) who had subarachnoid haemorrhage stimulated force generation but with a significant 'right shift' in oxygen consumption. This 'right shift' is indicative of an increased energy cost for contractile work. These results suggest that vascular smooth muscle contractile apparatus, when stimulated by subarachnoid cerebrospinal fluid, is consuming excess adenosine triphosphate during force generation.

Adult↗

PubMed1987

Evaluation of pacemaker pulse generator and patient longevity in patients aged 1 day to 20 years.

The longevity of pediatric patients requiring pacemakers and the survival rates of the implanted generators were evaluated. From January 1970 to December 1985, 96 patients aged 1 day to 20 years underwent 162 pulse generator implantation procedures. Indication for initial implantation was surgically induced heart block in 52 patients, sick sinus syndrome in 20, congenital complete heart block with symptoms of low cardiac output in 19 and tachydysrhythmia control in 5. Modal age at initial implantation was less than 1 year; median age was 5 years. During this period 90 generators were removed from service: 49 (54%) because of generator failure, 22 (24%) because the patient died, 12 (13%) because of elective upgrade at the time of lead failure or cardiac surgery, 5 (6%) because of generator pocket infection and 2 (2%) because of manufacturer's recall. Pulse generators were separated into 4 groups based upon generator technology. Group I (n = 16) were asynchronous units with mercury-zinc batteries; group II (n = 18) were single-chamber demand units with mercury-zinc batteries; group III (n = 14) were single-chamber demand units with rechargeable batteries; and group IV (n = 114) were single- or dual-chamber demand units with lithium batteries. Patient survival rate was 84% at 6 months and 70% by 109 months. There was no further decrease to the end of the study period. Six-month generator survival rate was 82% for all groups, mostly a reflection of patient deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMed1986

The indirectly obtained fetal heart rate: comparison of first- and second-generation electronic fetal monitors.

Fetal heart rate variability has become an essential component in evaluation of the fetus during continuous electronic fetal monitoring. Because of technical deficiencies of monitoring equipment, fetal heart rate variability may not always be available, such as during indirect monitoring of the fetus. In lieu of integration, a mathematical procedure called autocorrelation has, with the use of microprocessors, been incorporated into the fetal monitor, creating the "second generation" of electronic fetal monitoring. This study examined the accuracy of the first- and second-generation monitors by comparing simultaneously obtained indirect and direct real-time fetal heart rate data. The second-generation monitor produced an indirectly obtained fetal heart rate that was more accurate when compared with the directly obtained data than that with the first-generation fetal monitor. In addition, the variation in data from the first-generation monitor was substantially higher than that with the second-generation monitor. It is concluded that the fetal heart rate tracing from the second-generation monitor is more accurate when compared with the fetal electrocardiogram and may facilitate a truer interpretation of fetal heart rate variability than that obtained with the first-generation monitor.

Electrocardiography↗

PubMed1990

Diacylglycerol generated in the phospholipid vesicles by phospholipase C is effectively utilized by diacylglycerol lipase in rat liver cytosol.

Diacylglycerol was generated in phosphatidylcholine vesicles by incubation with Clostridium welchii phospholipase C. Newly formed diacylglycerol was rapidly converted to monoacylglycerol and glycerol when rat liver cytosol fraction was present in the incubation mixture, suggesting the presence of di- and monoacylglycerol lipase activities in this subcellular fraction. On the other hand, 3H-labeled diacylglycerol co-emulsified with non-radioactive phosphatidylcholine was found to be a poor substrate for the diacylglycerol lipase. These results indicate that enzymatic generation of diacylglycerol provide a substrate having a suitable physical state for the expression of diacylglycerol lipase activity. It was also found that the rate of diacylglycerol hydrolysis was dependent upon the rate of diacylglycerol generation, but not upon the absolute concentration in the incubation mixture. When the rate of diacylglycerol hydrolysis was plotted against the rate of diacylglycerol generation, a saturation curve was obtained and the double-reciprocal plot gave a straight line. It is not known why a relationship similar to Michaelis-Menten type kinetics was obtained between the rate of diacylglycerol hydrolysis and diacylglycerol generation instead of diacylglycerol concentration, but it may be best explained by the following assumptions: (1) diacylglycerol molecules are generated at the surface of the lipid vesicles where they are readily accessible to diacylglycerol lipase; (2) soon after the generation, diacylglycerol molecules migrate into inside the vesicles where they are inaccessible to the enzyme; (3) the effective concentration of diacylglycerol, i.e., the concentration of diacylglycerol located in the surface layer of the vesicles is proportional to the rate of diacylglycerol generation.

Animals↗

PubMed1986

The role of IL-2 and T4+ cells in the generation of human influenza virus-specific CTL activity.

Stimulation of human peripheral blood lymphocytes (PBL) with influenza A virus leads to the generation of virus-specific cytotoxic T lymphocyte (CTL) activity as well as natural killer (NK)-like activity. In this study, we show that exogenous IL-2 augments the in vitro generation of virus-specific CTL activity, only when added some days after the initiation of the culture. Apparently, the endogenously produced IL-2 can be a limiting factor in the in vitro generation of CTL activity. The increase of influenza virus-specific CTL activity after addition of exogenous IL-2 does not affect the restriction pattern of the CTL response. So, the preferential use of certain HLA antigens as restriction elements is not due to a limiting amount of endogenously produced IL-2. Depletion of T4+ cells completely abrogates the generation of virus-specific CTL activity. Addition of exogenous IL-2 to T4+-cell-depleted cultures fully restores the generation of HLA-restricted virus-specific CTL activity. We conclude that in the in vitro generation of virus-specific CTL activity in bulk cultures of human PBL the sole function of T4+ cells in human virus-specific CTL generation is the production of IL-2, no cognitive cell interaction of T8+ CTL precursors with T4+ cells is required, and in bulk cultures T8+ cells themselves are not able to produce sufficient amounts of IL-2 to ascertain the maturation of virus-specific CTL precursors into cytolytic T cells. Finally, we show that exogenous IL-2 also has a stimulatory effect on the NK-like or lymphokine-activated killer activity, which is always concomitantly induced in virus-specific CTL generation cultures, but has no influence on the levels of IFN produced in such cultures.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

Augmentation of the generation of cytotoxic T lymphocytes against syngeneic tumor cells by recombinant human tumor necrosis factor.

In order to clarify the effect of recombinant human tumor necrosis factor (rHu-TNF) on the antitumor T cell immune response, we examined the effect of rHu-TNF on the generation of cytotoxic T cells (CTL) against syngeneic tumor cells. Spleen cells from X5563 plasmacytoma-transplanted mice were stimulated in vitro with mitomycin C-treated X5563 cells in the presence or absence of rHu-TNF. The generation of CTL was augmented in a dose-dependent manner by the addition of rHu-TNF. The augmenting effect of rHu-TNF was more marked when indomethacin was added to the culture. The augmenting effect was observed only when rHu-TNF was added at the early stage of the generation of CTL. The cell surface phenotype of CTL generated was L3T4- and Lyt2+. The augmentation was shown not only by the chromium-51 release assay but also by the Winn assay. As to the specificity, the augmentation of CTL generation was observed by the addition of rHu-TNF when responder-primed spleen cells were stimulated with the tumor cells in vitro. On the other hand, augmentation was not observed when responder spleen cells were not stimulated with the tumor cells in vitro, or when responder spleen cells were obtained from normal mice. The CTL generated was not cytotoxic against other tumor cells of the same haplotype. Thus, rHu-TNF augmented the generation of CTL against syngeneic tumor cells in an antigen-specific manner. The in vivo effect of rHu-TNF was examined by administering rHu-TNF into X5563-bearing mice. The spleen cells of rHu-TNF-injected mice generated a much higher CTL activity against X5563 cells in vitro than did the spleen cells of uninjected mice. From these results, a possibility can be considered that in some cases, rHu-TNF may exert its antitumor activity by stimulating the immune system.

Animals↗

PubMed1984

Control in previous and present generations of preparation for entry into S phase and the relationship to resting state in 3Y1 rat fibroblastic cells.

In both the presence and absence of serum, 3Y1 rat fibroblastic cells synchronized at early S phase by aphidicolin entered M phase 6 h after removal of aphidicolin. However, in the second generation their entry into S phase in the presence of serum was delayed due to the deprivation of serum in the first generation. A similar delaying effect in the second generation was observed when the resting cells were stimulated by serum and then deprived of serum during a period of 8 h preceding mitosis. In both cases, the interval between mitosis and entry into S phase in the second generation was almost equal to that required for the resting cells to enter S phase when stimulated by serum. A similar delaying effect was also observed when the cells, synchronized at early S phase, were kept in suspension culture in the presence of serum for a period in the first generation. Results of a similar type of experiments using various combinations of growth factors showed that, when the G1 period in the second generation was shortened by exposure to growth factors in the first generation, and when the resting cells were stimulated to enter S phase, the same combination of growth factors was required. These and previous results suggest that the preparation for entry into S phase is controlled in both previous and present generations of 3Y1 cells.

Animals↗

PubMed1986

Serum-dependent control of entry into S phase of next generation in rat 3Y1 fibroblasts. Effect of large T antigen of simian virus 40.

When rat 3Y1 fibroblasts are deprived of serum in S phase and/or G2 phase in the first generation, the cells delay entry into S phase in the second generation for the duration of the serum deprivation. We can now show that when resting 3Y1 cells are infected with Simian virus 40 (SV40), the removal of serum through S and G2 phases in the first generation does not markedly delay entry into S phase in the second generation. These observations suggest that the serum-dependent control of entry into S phase of the second generation continues from the first generation, and that the abolition of this control by infection with SV40 in the first generation involves the mechanism operative when the resting cells are stimulated to enter S phase (of the first generation) by infection with SV40.

Alpha-Globulins↗

PubMed1983

Effect of transmethylation-reaction and increased levels of cAMP on superoxide generation of guinea-pig macrophages induced with wheat germ agglutinin and phorbor myristate.

Superoxide (O2-) generation of guinea-pig macrophages induced by wheat germ agglutinin (WGA) was suppressed to a great extent by the inhibition of transmethylation with 3'-deazaadenosine. When macrophages were stimulated with phorbor myristate (PMA) instead of WGA, the suppression of O2- generation of macrophages was observed to be slight despite the presence of 3'-deazaadenosine. These results were confirmed under various conditions. Thus the WGA-stimulated O2- generation of macrophages is probably associated with transmethylation, but the PMA-stimulated O2- generation is not. WGA-stimulated O2- generation of macrophages was also inhibited in the presence of dibutyryl cAMP or prostaglandin E2 (PGE2), substances that increase intracellular cAMP, but PMA-stimulated O2- generation was only slightly affected by these compounds. These results suggest that the mechanism for O2- generation of macrophages caused by WGA is different from that for O2- generation caused by PMA.

Animals↗

PubMed1983

Effects of dietary protein level on hepatic microsomal mixed-function oxidase systems during aging in two generations of Syrian hamsters.

Syrian hamsters were fed one of three levels of lactalbumin (10, 20, or 40%) from 4 weeks of age. Parents (F0 generation) and their offspring (F1 generation) remained for life on the parental diet. Randomly selected hamsters from both generations were killed at 0, 6, 18, 30, and 60 weeks to evaluate hepatic microsomal drug metabolism systems. Microsomal protein content rose with increased dietary protein in both generations of females at 30 and 60 weeks and in both generations of males at 18 weeks. Microsomal protein rose during life, but the timing and magnitude of the increase varied with sex, diet, and generation. Cytochrome P-450 content increased with elevation in dietary protein at most measurement times in females and at all measurement times in F1 generation males. Hepatic aryl hydrocarbon hydroxylase (AHH) and aniline hydroxylase (ANH) activities were influenced by dietary protein, primarily at 6, 18, and 30 weeks, and these values tended to decline between maturity and senescence. AHH generally increased as dietary protein rose, except at 30 weeks, at which time the group fed the medium protein level usually had the highest activity. ANH activity was either elevated in groups fed the 20 or 40% lactalbumin levels or depressed in these groups at 6 and 18 weeks when these values were influenced by dietary protein. The effects depended upon sex and generation. Age effects on hepatic microsomal metabolism in hamsters varied by sex and dietary protein and were somewhat different than those reported for other rodents.

Aging↗

PubMed1994

Comparative studies on the inhibitory spectrum of recombinant hirudin, DuP 714 and heparin on thrombin and factor Xa generation in biochemically defined systems.

The effect of antithrombotic drugs on the generation of serine proteases was studied in a biochemically defined system in which the prothrombin complex concentrate Konyne provided the necessary coagulation factors in the absence of plasma. The amount of thrombin and factor Xa generation was measured with a chromogenic substrate on a microcentrifugal analyzer. Furthermore, the assay was modified by supplementation with either purified antithrombin III or factor V. The synthetic peptide Ac-(D)Phe-Pro-boroArg-OH (DuP 714) was shown to be the most effective inhibitor of thrombin and also had strong inhibitor actions against factor Xa generation. Recombinant hirudin (rH) was nearly as active as DuP 714 on thrombin generation, however, it was less effective on factor Xa generation. With rH no concentration-dependent inhibition of factor Xa generation was found, i.e. over a wide range of concentration it only produced a steady inhibition of about 40-50% without further increase. The addition of AT-III to the system did not influence the action of DuP 714 or rH, but it strongly increased the inhibitory effects of unfractionated heparin (PMH) as well as of a low molecular weight heparin (LMWH) on both thrombin and factor Xa generation. The addition of factor V to the assay system did not cause any changes in the activity of all agents on protease generation.

Amino Acid Sequence↗

PubMed1984

Adenosine deaminase is not required for the generation of superoxide anion.

Neutrophils and macrophages generate superoxide anion during the respiratory burst in response to various stimuli, including microorganisms. It has recently been proposed that an important source of superoxide anion during the respiratory burst that stimulates murine macrophages is the sequential metabolism of adenosine via adenosine deaminase and xanthine oxidase to uric acid. Thus, the immunodeficiency state associated with adenosine deaminase deficiency may be caused at least in part by a defect in superoxide anion generation. The ability to generate superoxide anion of stimulated neutrophils isolated from three children with adenosine deaminase deficiency and associated severe combined immunodeficiency was tested. Neutrophils from all three patients were able to generate superoxide anion. One of these generated 19.1 nmol cytochrome c reduced/10(6) cells (normals = 5.3-33.0, mean 18.4 +/- 7.1) while the other two generated low normal levels. Neutrophils from all three children also generated more superoxide anion after addition of exogenous adenosine deaminase. Thus, no evidence to support a role for cellular adenosine deaminase in the release of superoxide anion by stimulated neutrophils was found. Although neutrophils from patients deficient in adenosine deaminase appear to have no inherent defect in the generation of superoxide anion, the abnormally high concentrations of adenosine found in the plasma of these patients could, in vivo, secondarily, inhibit superoxide anion release.

Adenosine↗

PubMed1989

Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma.

Airway inflammation with neutrophil infiltration may play a role in airway hyperreactivity. Neutrophils may exert their effects through the generation of superoxide O2- anion and other oxygen-derived free radicals. O2- generation by neutrophils has been demonstrated to be modulated by adenosine at physiologic concentrations. Therefore, we have investigated the function of peripheral blood neutrophils with respect to O2- anion generation and its regulation by adenosine in both subjects with asthma and normal subjects and also the relationship between O2- anion generation and airway hyperresponsiveness in subjects with asthma. Purified neutrophils were obtained from eight subjects with stable asthma and seven normal control subjects not taking chronic medications. O2- anion generation in subjects with asthma was significantly higher compared with that of normal subjects after stimulation with either N-formyl-methionyl-leucyl-phenylalanine (mean, 14.8 nmol/10(6) cells for subjects with asthma versus mean, 9.6 nmol/10(6) cells for normal subjects; p less than 0.01) or phorbol myristate acetate (mean, 13.6 nmol/10(6) cells versus mean, 8.1 nmol/10(6) cells; p less than 0.05). Adenosine inhibited N-formyl-methionyl-leucyl-phenylalanine-stimulated O2- anion generation in a dose-related fashion in subjects with asthma and normal subjects to a similar degree. Adenosine had no effect on O2- anion generation after phorbol myristate acetate stimulation. These results indicate that neutrophils from subjects with asthma produce more O2- anion when they are stimulated than do neutrophils from normal subjects and that this difference is not due to adenosine modulation. In subjects with asthma, O2- anion generation correlated with the degree of airway hyperresponsiveness to inhaled methacholine.

Adenosine↗

PubMed1992

Early detection of antibodies to HIV-1 by third-generation assays.

Third-generation immunoassays for detection of antibody to human immunodeficiency virus (HIV) have reduced the interval between infection and antibody detection. Might such earlier detection diminish the value of the western blot as a confirmatory assay? We compared the sensitivity of one second-generation and two third-generation anti-HIV enzyme immunoassays (EIAs) with the results from HIV-antigen testing and western blot. 1045 western-blot confirmed anti-HIV positive samples were tested with a detection rate of 100% for all three EIAs. The detection rate in 36 samples drawn from different persons in early stages of HIV infection was 89% for the second-generation EIA and 94% for both third-generation EIAs. With carefully selected seroconversion panels that included sampling intervals during seroconversion of one week or less, we found that both third-generation EIAs detected seroconversion on average 5 days earlier (range 0-13) than did the second-generation assay. Western blot is commonly used to confirm HIV infection. In 6 of 10 seroconversions, one or both third-generation EIAs were reactive before any band appeared in the western blot. Since HIV antigen was detectable in these cases, the HIV antigen test may serve as a confirmatory assay for anti-HIV EIA-positive, western-blot negative, samples.

AIDS Serodiagnosis↗

PubMed1983

Modification by biological products of the generation of suppressor cells in culture.

This report describes the effects of prostaglandin E2 (PGE2), indomethacin, and human prealbumin on the generation of culture-induced and allo-antigen-induced suppressor cells. The ability of the suppressor cells to affect cell-mediated immunity (CMI) generation cultures was assessed by 3H-thymidine uptake and cell-mediated lympholysis (CML). The generation of culture-induced suppressor cells is dependent on the fetal calf-serum (FCS) used in the medium and at least 4 days are necessary for their generation. Suppression is totally abolished by 2,000r X-irradiation of suppressor cells prior to their testing in CMI generation cultures. Spleen cells cultured in the presence of 0.03 to 3 microM PGE2 are not suppressive, while 3 nM PGE2 only partially abolishes their suppressive activity. Indomethacin has little effect on the development of this suppressor cell activity. Spleen cells cultured in the presence of human prealbumin have augmented cellular proliferation but do not develop suppressor cell activity. Alloantigen-activated cells added to CMI generation cultures suppress cellular proliferation (3H-thymidine uptake), but suppress CML development only after X-irradiation. PGE2 inhibits the proliferation of alloantigen-activated cells in a dose dependent manner. The ability of PGE2 to abolish their suppressive activity (after X-irradiation) in CMI generation cultures is directly proportional to its effects on cell proliferation. Indomethacin augments the proliferation of alloantigen-activated cells but does not further augment suppression. Human prealbumin augments the cellular proliferation of alloantigen-activated suppressor cell culture systems, but does not affect the generation of alloantigen-activated suppressor activity.

Animals↗

PubMed1990

Generation patterns of immunocytochemically identified cholinergic neurons in rat brainstem.

Combined [3H]thymidine autoradiographic and choline acetyltransferase (ChAT)-immunocytochemical techniques were used to answer questions concerning the generation of specific classes and subclasses of cholinergic neurons in rat brainstem. First, the generation of rostrally and caudally located neurons of the same class (i.e. somatic efferent oculomotor and hypoglossal nuclei, respectively) were compared. Results indicated that, although embryonic day 11 (E11) was the peak birthday for both nuclei, hypoglossal neurons were generated significantly earlier than oculomotor neurons, indicating a caudorostral generation gradient for brainstem somatic motor nuclei. Second, the generation patterns of 3 different subclasses of motor neurons at the same brainstem level were compared; namely those of the somatic efferent hypoglossal nucleus (XII), the general visceral efferent dorsal nucleus of the vagus (X), and the predominantly special visceral efferent nucleus ambiguus. All 3 subclasses of cholinergic cells had the same peak day (E11) and overall period of generation (E11-12). However, statistical analyses indicated a precocious generation of nucleus ambiguus, but no developmental differences between N, XII and N. X. It is suggested that nucleus ambiguus is formed earlier than N. XII and N. X, due to its more ventral location within a ventrodorsal neurogenetic gradient. Third, the generation patterns of different classes of large cholinergic neurons were examined. Specifically, the birthdays of cholinergic non-motor projection neurons of the pedunculopontine-laterodorsal tegmental nuclei (PPT-LDT) were contrasted to those of the cholinergic brainstem motor neurons. The peak birthdays of both rostrally and caudally located motor neurons were two days earlier than those of the PPT-LDT neurons. Thus, large cholinergic cells projecting to peripheral targets are born significantly earlier than those projecting within the CNS, even though the former are located more rostrally on the caudorostral neurogenetic gradient. This represents an apparent exception to the emerging rule that cholinergic neurons obey the general gradients of neurogenesis manifest in the regions of the central nervous system where they reside.

Animals↗

PubMed1986

Inhibition of suppressor cell generation by mouse serum in culture.

Normal C57BL/6 mouse spleen cells cultured for five days in the presence of fetal calf serum (FCS-induced suppressor generation culture) were shown, in mixing experiments, to suppress the primary humoral response of freshly explanted C57BL/6 spleen cells against sheep erythrocytes (SRBC). This suppressor cell generation was largely dependent on the FCS concentration in the suppressor generation culture. Ten or 5% FCS effectively supported the generation of suppressor cells, but 1% FCS only marginally supported it. When mouse serum (MS) from normal C57BL/6 mice was added to the suppressor generation culture, it inhibited the generation of the suppressor cells. Sera from allogeneic mice and athymic nude mice were also effective. The effect of MS was resistant to heat treatment (56 degrees C, 30 min). The inhibitory activity of MS was not dialyzable, and concentrated into the fraction which was not precipitated by 50% saturation of ammonium sulfate and which was eluted at a concentration of about 0.2 M NaCl from a DEAE-Sephadex A-50 column. The active fraction of MS also effectively inhibited the growth of Ehrlich tumor cells in culture. Further, MS also inhibited the generation of Con A-induced suppressor cells. The inhibition by MS of FCS-induced suppressor generation was eliminated by an interleukin 2-containing preparation.

Animals↗

PubMed1987

A three-generation reproduction study of Ponceau 4R in the rat.

Ponceau 4R was fed to three generations of rats, at dietary concentrations to provide 0, 50, 500 or 1250 mg/kg body weight/day. In each generation treated groups consisted of 36 rats of each sex while 60 females served as controls. Apart from the F0 generation, which started treatment as weanlings, treatment was continued throughout the study, providing in utero exposure of all offspring. The F0 generation was bred twice, on the first occasion to provide animals for the next generation and for a long-term study, and a second time to provide data on in utero and post-partum development. In each generation approximately one third of the females from each group were killed before parturition to provide data on in utero development. The foetuses from these animals were examined for skeletal abnormalities. Remaining animals were allowed to litter and the offspring were monitored for 21 days after birth for survival and development. All animals were killed and subjected to a post-mortem examination which, for a proportion of each group in each generation, included recording of organ weights. Although a few adult rats died during the study these deaths were not associated with treatment. Fur of the treated animals was coloured pink, and faeces and caecal contents of animals from the two highest dose groups were yellow, the faeces also being softer than those of the controls. Treatment had no observed effect on clinical observations, body weight or food and water intake at any stage of the study. Animals fed the two highest doses for prolonged periods had enlarged caeca, but this effect was not seen in weanling animals on the same treatment. Neither the caecal enlargement nor the liver weights seen in the F2 and F3 offspring were considered to be an adverse effect of treatment. No treatment-related effects were seen in the uterine contents of females at any generation, but the skeletons of treated foetuses showed a slightly more advanced development than those of the controls. Postnatal development of offspring was not affected by treatment at any stage of the study. Tissues from the F3 animals were examined by light microscopy and revealed no treatment-related effects. It is concluded that the no-adverse-effect level for Ponceau 4R is 1250 mg/kg body weight/day.

Abnormalities, Drug-Induced↗