Biomedical subjects

T V Persaud

Publications and source records attributed to T V Persaud.

At least 19 recordsLinked to original sources

PubMed2000

Histological observations of palatal malformations in rat embryos induced by retinoic acid treatment.

Malformations of the palate were induced in white rat embryos following maternal exposure to retinoic acid (tretinoin). Five experimental groups and the controls were treated by the following protocol: Group 1: pregnant rats received 100 mg retinoic acid (RA)/kg b.w. suspended in corn oil on gestational day (GD) 11.5; Group 2: 20 mg RA/kg b.w. from GD 8-12; Group 3: 20 mg RA/kg b.w. from GD 7.5-11.5; Group 4: 100 mg RA/kg b.w. on GD 10-11; Group 5: 100 mg RA/kg b.w. on GD 10 and 12; Group 6 received corn oil vehicle from GD 7-14.5; and Group 6: served as non-injected controls. In all retinoic acid treated groups, varying degrees of clefts with occasional attempts of fusion were noted. The severity and frequency of the malformations were dependent on dosage or gestational day of drug treatment. Our results indicate that RA, even at the lowest dose tested (20 mg/kg b.w.) severely affects the various tissues constituting the embryonic palatal shelves by altering cell interaction and possibly programmed cell death. These events would then result in lack of or inadequate differentiation with subsequent formation of aberrant craniofacial architecture.

Abnormalities, Drug-Induced↗

PubMed2000

Craniofacial abnormalities induced by retinoic acid: a preliminary histological and scanning electron microscopic (SEM) study.

Exogenous retinoic acid has been found to be teratogenic in animals and man. Craniofacial defects induced by retinoic acid have stimulated considerable research interest. The present report deals with scanning electron microscopical observations of the craniofacial region concurrent with histological examination of craniofacial dysmorphism induced in rat embryos following maternal treatment treated with varying dosages of all-trans-retinoic acid (tretinoin). Two groups of pregnant rats were treated with rat embryos exposed to retinoic acid suspended in corn oil (100 mg/kg b.w. on gestational day 11.5 and 50 mg/kg b.w. on gestational day 10, 11 and 12 respectively). A third group was treated with corn oil (vehicle) while a fourth group remained untreated. A wide spectrum of congenital abnormalities, including exophthalmos, microphthalmia and anophthalmia, maxillo-mandibular dysostosis, micrognathia of both maxilla and mandible, cleft palate, subdevelopment of ear lobe, preauricular tags and macroglossia, were observed in the offspring of retinoic acid treated animals. The abnormalities were both time and dosage dependent, and characteristic of Treacher Collins syndrome when retinoic-acid was administered on gestational day 11.5. In contrast, when retinoic acid was administered were on gestational days 10-12, the defects were similar to those seen in the first and second pharyngeal arch syndrome, as well as in the oculo-auriculo-vertebral spectrum. Whereas our data support the hypothesis that all-trans retinoic-acid disturbs growth and differentiation of several embryonic cell types essential for normal craniofacial development, its mechanism of action remains unclear.

Abnormalities, Drug-Induced↗

PubMed1999

Influence of rat placental lactogen-I on the development of whole rat embryos in culture.

Rat placental lactogen-I (rPL-I), the first prolactin-like hormone expressed in the placenta during pregnancy in the rat, is known to influence maternal functions. In the present study, we have investigated the effects of rPL-I on the growth and development of cultured whole rat embryos. Rat embryos, with or without ectoplacental cone (EPC) attached, were explanted at day 9 of gestation. After 48 h of culture, the embryos, enclosed by the yolk sacs, were assessed by the presence of visible heart contractions ('heart beats'), crown-rump length (CRL) and yolk sac diameter (YSD). When intact embryos with EPC were cultured, the concentrations of rPL-I and rPL-II (products of EPC) in the medium were 850+/-841 and 92+/-181 ng/ml respectively (means+/-s.e.m.). In embryo cultures with the EPC removed, rPL-I levels decreased to</=10 ng/ml, and only 70% of the embryos were viable, with visible heart beats. In the viable embryos, both CRL and embryonic DNA synthesis were reduced compared with controls, and the addition of rPL-I (1 microg/ml) did not prevent this reduction. YSD and yolk sac DNA synthesis were also reduced compared with control embryos, and the addition of rPL-I significantly prevented this decrease by 45%. In embryos cultured without EPC in the presence of neutralizing rabbit anti-rat prolactin serum (anti-rPRL), embryonic and yolk sac DNA synthesis were reduced by 35% compared with embryos exposed to normal rabbit serum. Addition of rPL-I significantly increased (P<0.05) embryonic and yolk sac growth. Thus the effects of rPL-I on embryo growth could only be seen in the absence of prolactin. The addition of human prolactin in the presence of anti-rPRL also resulted in significant increases (P<0.05) in embryonic DNA synthesis and CRL. These results suggest that rPL-I may substitute for prolactin to influence the growth of the rat embryo.

Animals↗

PubMed1997

Ethanol effects on postimplantation rat embryos: influence of zinc and methionine.

Organic zinc salts and thiols, administered simultaneously, protect mice synergistically against ethanol toxicity. Moreover, chronic ethanol consumption could affect the bioavailability of zinc and amino acids such as methionine. This could result in impaired embryonic growth and development. The influence of zinc and methionine on ethanol-induced embryopathy was investigated by simultaneous administration of ethanol, zinc and methionine to pregnant rats from gestational day 6 through 12. Ethanol was given in the form of a liquid diet; zinc administered i.p., and methionine was given by gavage. The ethanol group received the liquid ethanol diet; the ethanol + zinc and methionine group received the ethanol diet, zinc and methionine; and the pair-fed control group was given an isocaloric control diet. On day 12 of gestation, embryos of ethanol alone treated rats revealed a significantly reduced embryonic protein content, number of somites, crown-rump length, and lower morphological score (embryological differentiation) compared to the pair-fed control embryos. However, embryonic growth and developmental parameters in the ethanol, zinc and methionine treated group were not significantly different from those exposed to ethanol alone.

Animals↗

PubMed1995

Protective influence of zinc against the deleterious effects of ethanol in postimplantation rat embryos in vivo.

Zinc is a cofactor for alcohol dehydrogenase, the ethanol metabolizing enzyme. Ethanol-induced zinc deficiency could decrease ethanol metabolism, resulting in an increase in circulating and tissue ethanol levels. This may cause retardation in embryonic growth and development. The influence of zinc supplementation on ethanol-induced embryopathy was studied by the simultaneous administration of ethanol and zinc to pregnant SD rats from gestational day 6 through 12. Ethanol was given in the form of a liquid diet and zinc was administered intraperitoneally. The ethanol group received the liquid ethanol diet, the ethanol+zinc group received the ethanol diet and zinc and the pair-fed control group was given an isocaloric control diet. Embryos were explanted from all groups on day 12 of gestation. Embryos of animals treated with ethanol alone exhibited a significantly higher rate of resorption and retarded embryonic growth and development compared to the pair-fed control group. The embryonic protein content, crown-rump length, the number of somites and embryonic morphological score were significantly reduced in the ethanol-treated group. In addition, serum zinc concentration also was lower. Compared to embryos from ethanol-treated animals, embryos from ethanol+zinc treated animals showed a significantly higher number of somites; cardiac development was more advanced and embryonic protein content was higher. These observations suggest that zinc supplementation of ethanol-treated pregnant rats may have some protective influence against the embryopathic effects of ethanol.

Animals↗

PubMed1995

Biotin influences palatal development of mouse embryos in organ culture.

Maternal biotin deficiency is strongly teratogenic in CD-1 mice. The most common malformations are craniofacial and limb defects such as cleft palate, micrognathia and micromelia. The effect of biotin deficiency on palatal development in mouse embryos on d 12 of gestation was studied by culturing mouse embryonic palates in serum-free medium using a suspension culture system. In control embryos palatal processes developed to the fused stage after 72 h in culture. The fusion of palatal processes was further increased by the addition of biotin (10(-8) mol/L) to the medium. The addition of organic acids such as propionic, beta-methyl crotonic or beta-hydroxy isovaleric acids as well as avidin to the medium did not affect the stage of palatal formation. Cycloheximide completely blocked the fusion of palatal shelves. In embryos from biotin-deficient mice, the incidence of fusion between the palatal shelves was < 7% and increased to > 30% when biotin (10(-8)-10(-6) mol/L) was added to the medium. The addition of fatty acids to the organ culture medium did not have any effect on the fusion of palatal processes. The incorporation of 35S-methionine into protein from biotin-deficient embryo explants was 88% of that in controls. The results indicate that biotin deficiency may interfere directly with synthesis of specific proteins and the formation of palatal processes.

Animals↗

PubMed1995

Effects of prenatal exposure to low dose ionizing radiation on the development of the cerebellar cortex in the rat.

The effects of maternal exposure to a single dose of whole body irradiation (0.5 Gy) on gestational days (GD) 17, 18, 19, or 20 on the development of the cerebellar cortex was examined in the offspring of Sprague Dawley rats at 21 and 28 days postnatally. No gross cerebellar anomalies were observed in the irradiated animals. However, compared to control animals, rat irradiated on each of GD-17, 18, 19 and 20 showed a significantly higher incidence (p < 0.05) of circumscribed cerebellar lesions (CL) distributed in the inner granular layer of the anterior and posterior lobes. These lesions were characterized by a loss of granule cells and atrophied and/or reduced number of Purkinje cells. In 21 days old rats, irradiation on GD-17 resulted in more CL anteriorly (75%) and in the vermis whereas on GD-20, the CL predominated posteriorly (100%) and in the lateral hemispheres. In 28 day old rats, following irradiation on each of GD-17 and GD-20, there was an equal distribution of CL in both the anterior and posterior lobes. However, with irradiation on both GD-17 and GD-20, these CL occurred more frequently in the lateral hemispheres of the anterior lobe, whereas in the posterior lobe they predominated in the vermis. These results suggest that a direct relationship exists between the proliferation, migration, development, and maturation of granule cells and their induction by Purkinje cells. The findings also support the view that both cell death and the regulation of granule cells by Purkinje cells maximize the effective development and organization of the cerebellum.

Animals↗

PubMed1995

Influence of zinc on ethanol-induced placental changes in the rat.

For normal fetal growth and development, an ample supply of nutrients and oxygen is essential. The placenta is the conduit for nutrient transfer and thus any factor that alters normal placental structure and function may adversely affect the nutritional status of the fetus. The effect of ethanol ingestion and zinc supplementation on placental structure was investigated by the simultaneous administration of ethanol and zinc to pregnant Sprague-Dawley rats from gestational day 6 through 12. One group of animals was given an ethanol liquid diet, a second group received the ethanol liquid diet plus zinc, and another group was pair-fed a control liquid diet. Placentas were recovered on day 20 of gestation. The mean placental weight in the ethanol group was significantly higher than that in either the pair-fed control or the ethanol plus zinc group. The ethanol-treated group revealed more stagnated blood in the basal-decidual and in the basal-labyrinthine junctions. Intervillous spaces in the labyrinthine zones were markedly dilated and filled with more blood corpuscles compared to the pair-fed control group. The giant cells of the basal zone were also larger in size in the ethanol-treated group. The frequency of occurrence of stagnated blood in either the labyrinthine zone and in the basal-labyrinthine junction was less in the ethanol plus zinc group compared to the ethanol group.

Animals↗

PubMed1994

Purkinje and granule cells distribution in the cerebellum of the rat following prenatal exposure to low dose ionizing radiation.

The effects of maternal exposure to a single dose of whole body irradiation (0.5 Gy) on gestational days (GD) 17, 18, 19, or 20 on the number of Purkinje and granule cells in the pyramis of the cerebellar cortex was examined in the offspring of Sprague Dawley rats at 21 and 28 days postnatally. The laterolateral distribution of both granule and Purkinje cells in the pyramis were significantly reduced (p < 0.001) from controls in rats irradiated on each of GD-17, 18, 19 and 20. There was a greater deficit in granule cell number with irradiation on GD-20 than on GD17 (p < 0.05). Purkinje cells were reduced in number with irradiation on GD-17 and GD-20; however, the decrease did not correspond to the degree of reduction in the number of granule cells. There was a greater reduction of both granule and Purkinje cells in the vermis with irradiation on GD-17, whereas on GD-20, both granule (p < 0.05) and Purkinje cells (p < 0.001) were more reduced in the lateral hemispheres. The GC/PC ratio was smaller in rats irradiated on GD-20 than on GD-17. The GC/PC ratio between the irradiated animals and the controls were relatively similar. The findings show that irradiation does not affect the population of granule cells directly, but rather indirectly. The reduction in the number of granule cells could be an indirect consequence of reduced critical interaction with Purkinje cells. These results suggest that a direct relationship exists between the proliferation, migration, development, and maturation of granule cells and their induction by Purkinje cells.

Animals↗

PubMed1994

In vitro effect of S-adenosyl methionine on ethanol embryopathy in the rat.

S-adenosyl methionine (SAM) is a universal methyl donor for biological systems. Chronic consumption of ethanol results in depletion of available SAM and reduces its biosynthesis in the transmethylation pathway. Administration of excess SAM may reduce the embryopathic effects of ethanol. The in-vitro effects of SAM on ethanol embryopathy was investigated by culturing 9.5 day old whole rat embryos for 48 hours in ethanol alone (Group II), 0.05 mM SAM (Group III), ethanol + 0.05 mM SAM (Group IV), ethanol + 0.1 mM SAM (Group V), ethanol + 1 mM SAM (Group VI), and in ethanol + 3 mM SAM (Group VII). In Group VII embryos, cardiovascular, nervous, auditory, visual, craniofacial and musculoskeletal systems were retarded in development; crown-rump length, yolk-sac diameter, as well as morphological scores, were reduced compared to those in embryos treated with ethanol alone (Group II). There were, however, significant differences between Group II and Group IV embryos with respect to crown-rump length, yolk sac diameter and somite number. The mean crown-rump length, yolk sac diameter and somite number in Group II were 2.3 +/- 0.2, 2.8 +/- 0.3 and 22.4 +/- 3.5 respectively, compared to 2.6 +/- 0.2, 3.1 +/- 0.2 and 25.3 +/- 3.1 in Group IV. These results suggest that simultaneous administration of S-adenosyl methionine and ethanol may protect against the embryopathic effects of ethanol.

Animals↗

PubMed1994

Effects of in utero exposure to low dose ionizing radiation on development in the rat.

Most studies of in utero effects of ionizing irradiation involve high doses and examination at postnatal intervals. Little information is available on the effects of low levels of ionizing radiation on embryogenesis. The developmental effects of in utero exposure to 50 cGy gamma radiation on gestational day-9.5 was investigated using Sprague-Dawley rats. Irradiated rats and appropriate controls were killed at prenatal intervals of 4h, 48h and 10 days after exposure. Fetuses were examined for abnormalities and random samples of tissues were prepared for microscopic study. With the exception of the neuroepithelium, no histopathological changes were observed in embryos 4h after exposure to 50 cGy. In irradiated embryos, mitoses were reduced within the neuro-epithelium; pyknosis and some necrosis of cells were apparent at this gestational interval. Among the gross developmental abnormalities observed in embryos 48h after irradiation, excessive flexion of the embryo and abnormal flexion of the head were the only ones that appeared to be radiation-induced. The mean numerical score (42.3 +/- 0.2, controls; 42.4 +/- 0.1, irradiated) for 17 morphological parameters examined in fetuses at this gestational period compares favorably with other studies. Controls, however, showed greater variability in the extent of development of their forebrain, olfactory system, midbrain, hindbrain, and caudal neural tube. In all cases, there was evidence of slower development in these regions compared to their irradiated counterparts. At term, no significant differences in litter size or resorption rates were observed in irradiated animals compared to the controls, but there was a higher incidence of defective eye development, spinal curvature and visceral anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Radiation-Induced↗

PubMed1993

Postnatal development of the rat CNS following in utero exposure to a low dose of ionizing radiation.

In utero exposure to ionizing radiation is of importance because of its potential health risks. The developing nervous system is particularly vulnerable and the consequences of exposure to low levels of radiation (< or = 1 Gy) are not well established. The developmental effects of maternal exposure to 50 cGy gamma-radiation on gestational days (GD) 9.5, 15, and 18 were investigated in Sprague Dawley rats. Rats exposed on GD-9.5 along with appropriate controls were killed at 4 h, 48 h, and 10 days post-irradiation while those irradiated on GD-15 and GD-18 were killed postnatally (PN) on days 7 and 26. All were examined for developmental anomalies and representative samples of brains were processed for microscopic study. No significant developmental differences were observed between irradiated and control embryos killed 48 h after irradiation on GD 9.5. However, in irradiated fetuses a larger number of developmental anomalies were observed at term. Defects of the eye and of spinal curvature were the most common malformations encountered. Mitoses were reduced within the neuroepithelium of embryos irradiated on GD-9.5 and evidence of pyknosis and necrosis was seen 4 h after irradiation. The capacity of surviving primitive neural cells for repair, however, was such that by 48 h after exposure the irradiated nervous system no longer differed from controls. Rats irradiated on GD-15 and GD-18 and examined on PN-26 exhibited clusters of small, dark, pyknotic neurons within the hippocampal and dentate gyri, often bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Radiation-Induced↗

PubMed1993

Ossification of the vertebral column in the offspring of rats exposed to alcohol, acetaldehyde and caffeine.

The embryopathic effects of alcohol have been widely studied in humans and laboratory animals. However, the role of risk factors remains largely unknown. Whereas skeletal abnormalities are often present in the offspring of alcoholic mothers, these have not been fully documented. This report is concerned specifically with the development of the vertebral column in rats exposed in utero to ethanol, its primary metabolite acetaldehyde, and caffeine. Our results indicate a possible causal association between alcohol abuse and ossification anomalies of the vertebral column. Maternal treatment with caffeine accelerated ossification in the sacro-caudal vertebrae. Caffeine combined with ethanol only moderately affected the development of the centra and arches.

Acetaldehyde↗

PubMed1992

New familial syndrome of unilateral upper eyelid coloboma, aberrant anterior hairline pattern, and anal anomalies in Manitoba Indians.

We report on 6 (3 male, 3 female) Manitoba Indian children with hypertelorism and variable combinations of unilateral eye malformations, aberrant anterolateral scalp hairline, and nasal and anal anomalies. These children belong to 4 related families. The parents and 7 other sibs are clinically unaffected. The family histories are otherwise unremarkable. The presence of 2 major malformations in sibs and related individuals (with unaffected parents) suggests that this is a newly described pleiotropic autosomal recessive syndrome. The differential diagnosis includes cryptophthalmos syndrome and several other related malformation syndromes. Although multifactorial determination cannot be excluded, the inbred, isolated population and distribution make autosomal recessive inheritance more likely.

Anal Canal↗

PubMed1992

Prenatal influence of alcohol following a single exposure in two inbred strains of mice.

The effect of a single dose of ethanol on embryonic development was investigated in two inbred strains of mice. Ethanol (25% v/v solution, 0.02 ml/g body weight) was administered intraperitoneally on either gestational day 6, 9 or 12 to C57BL/6J and DBA/2J mice. All fetuses recovered near term were alive and appeared normal. The incidence of fetal death was not affected. Fetal weight was significantly reduced in the C57BL/6J strain of mice. Maternal exposure to a single and moderate dose of ethanol did not have any profound effect on the conceptus. For the development of laboratory models to mimic fetal alcohol effects in humans, the selection of appropriate genotype is important.

Animals↗

PubMed1992

Embryonic development in the chick following exposure to ethanol, acetaldehyde and cyanamide.

The influence of cyanamide, an inhibitor of aldehyde dehydrogenase, on the embryopathic effects of ethanol and acetaldehyde, was investigated in the chick embryo. Both ethanol and cyanamide significantly increased embryonic mortality, but did not affect embryonic growth, compared to treatment with either ethanol or cyanamide. Acetaldehyde combined with cyanamide increased embryonic mortality and retarded embryonic growth. Cyanamide influence on embryonic development was minimal. The extent of acetaldehyde involvement in ethanol teratogenicity remains unclear from the present findings.

Acetaldehyde↗

PubMed1992

Effects of alcohol and caffeine on cultured whole rat embryos.

The direct effects of ethanol and caffeine on embryogenesis were investigated using the whole rat embryo culture system. Compared to control embryos, the crown-rump length, number of somites, branchial bars, and morphological score were significantly reduced in embryos exposed to ethanol, caffeine, or both substances. Development of the craniofacial region, cardiac primordium and forelimb was delayed following ethanol treatment. Compared to the controls, the anterior neuropore lagged in development following caffeine treatment; closure of the posterior neuropore was significantly delayed in each of the treatment groups. The optic and olfactory primordia were not affected. The results indicate that alcohol and caffeine independently affect the embryo, but when combined their effects were not potentiated.

Abnormalities, Drug-Induced↗

PubMed1991

Can methionine and zinc prevent the embryopathic effects of alcohol?

Alcoholism is a major and world-wide health problem. A characteristic pattern of congenital defects, known as the fetal alcohol syndrome, has been detected in the offspring of mothers who are chronic alcoholics. The mechanism underlying the teratogenic effects of ethanol is not known. An important hypothesis is that ethanol becomes teratogenic by inducing maternal/fetal nutritional deficiencies. Nutrients affected by ethanol consumption include methionine and zinc. Epidemiological and experimental studies have shown that zinc deficiency is associated with both fetal growth retardation and developmental defects. Furthermore, the ethanol metabolizing enzyme, alcohol dehydrogenase, is a zinc metalloenzyme. Zinc deficiency decreases alcohol dehydrogenase activity and thus slows down elimination of ethanol. Methionine, an essential amino acid, is a lipotrope, as well as a universal methyl donor. It is involved in hepatic detoxification. Studies on the effects of methionine and zinc might lead to appropriate therapeutic intervention in pregnancies of alcoholic mothers who are at a risk of giving birth to an impaired offspring. Furthermore, the results of such investigations will provide a better understanding of the mechanism of action of ethanol on the embryo.

Animals↗