The influence of maternal nicotine exposure on neonatal lung carbohydrate metabolism.

The influence of maternal nicotine exposure (1 mg/kg body mass/day) during pregnancy and lactation on energy metabolism of lung tissue of neonatal rats were investigated. The glucose turnover of the lung tissue of the neonatal rats exposed to nicotine via the placenta and mother's milk was 86.4% higher than that of the controls. Glycolysis was however suppressed by 22.7% (P < 0.01). The adenine nucleotide pool (ATP+ADP+AMP) was 32.8% higher for the lungs of the 3 week old neonates exposed to nicotine than that of the control rat lung. After 4 weeks of nicotine withdrawal glycolysis of those animals exposed to nicotine were still inhibited to the same extent than during exposure. The adenine nucleotide pool was 69.95% higher than that of the controls. It is proposed that the inhibition of glycolysis was due to the high ATP/ADP ratio of the lungs of the nicotine exposed rats.     

Maternal nicotine exposure: reponse of type II pneumocytes of neonatal rat pups.

The influence of maternal nicotine exposure during pregnancy and lactation on the Type II cells of lung tissue of one day old neonatal rat pups was investigated. The results clearly show that maternal nicotine exposure resulted in an increase in the type II cell count in the lungs of the offspring. In addition the lamellar body content of the type II cells of the nicotine exposed rat pups were significantly (P< 0.01) higher than that of the control animals. The type II cell mitochondria of lung tissue of nicotine exposed rat pups were swollen and no microvilli occurred on the alveolar surface. This clearly illustrates that nicotine interfered with type II cell integrity of tlte neonatal lung and may subsequently interfere with the normal development of the alveolar region of the lung.     

Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Smoking during pregnancy is associated with deleterious physiological and cognitive effects on the offspring, which are likely due to nicotine‐induced alteration in the development of neurotransmitter systems. Prenatal nicotine exposure (PNE) in rodents is associated with changes in behaviors controlled in part by the pontine laterodorsal tegmentum (LDT), and LDT excitatory signaling is altered in a sex and age‐dependent manner by PNE. As effects on GABAergic LDT signaling are unknown, we used calcium imaging to evaluate GABA_A receptor‐ (GABA_AR as well as GABA_A‐_ρR) and GABA_B receptor (GABA_BR)‐mediated calcium responses in LDT brain slices from female and male PNE mice in two different age groups. Overall, in older PNE females, changes in calcium induced by stimulation of GABA_AR and GABA_BR, including GABA_A‐_ρR were shifted toward calcium rises. In both young and old males, PNE was associated with alterations in calcium mediated by all three receptors; however, the GABA_AR was the most affected. These results show for the first time that PNE is associated with alterations in GABAergic transmission in the LDT in a sex‐ and age‐dependent manner, and these data are the first to show PNE‐associated alterations in functionality of GABA receptors in any nucleus. PNE‐associated alterations in LDT GABAergic transmission within the LDT would be expected to alter output to target regions and could play a role in LDT‐implicated, negative behavioral outcomes following gestational exposure to smoking. Accordingly, our data provide further supportive evidence of the importance of eliminating the consumption of nicotine during pregnancy.     

Calcium rises induced by AMPA and nicotine receptors in the ventral tegmental area show differences in mouse brain slices prenatally exposed to nicotine

Nicotine exposure during gestation is associated with a higher risk of adverse behavioral outcomes including a heightened liability for dependency to drugs of abuse, which can exhibit drug‐specificity influenced by gender. This enhanced liability suggests that nicotine use during pregnancy alters neural development in circuits involved in motivation and reward‐based learning. The ventral tegmental area (VTA) is critical in motivated behaviors and we hypothesized that gestational exposure to nicotine alters the development of excitatory circuits in this nucleus. Accordingly, in VTA brain slices from male and female mice exposed to nicotine during the prenatal period (PNE) and controls, we compared cellular rises in calcium induced by AMPA receptor and nicotinic acetylcholine receptor (nAChR) stimulation by use of the ratiometric calcium binding dye, Fura‐2AM. We found that AMPA induced smaller amplitude calcium rises in the PNE VTA, which was an effect only detected in males. Further, while the amplitude did not vary between treatment and control in females, a greater number of cells responded with rises in calcium in the PNE. Conversely, the proportions of cells responding with calcium rises induced by nAChR stimulation did not change in either gender according to treatment. However, larger rises in calcium in PNE females were detected. When taken together our data show that excitatory signaling in the VTA is altered in a gender‐specific manner by PNE and suggest that alterations in signaling could play a role in drug‐specific differences in maladaptive, motivated behaviors exhibited by males and females born to mothers exposed to nicotine during pregnancy. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 2018     

Non-neurogenic stimulation of adrenomedullary secretion during endotoxicosis in the one day old rat

In both newborn and twenty day old rats, bacterial (S. enteritidis) endotoxin caused a marked decrease in adrenal epinephrine and norepinephrine. Catecholamine release was prevented by ganglionic blockade in 20 day old, but not 1 day old animals, indicating that the release in the neonatal rat is "non-neurogenic." The amount released was physiologically significant: equivalent to 20 micrograms/kg by i.v. administration. Two possible mechanism known to promote non-neurogenic secretion are hypoxia or histamine release, both of which can occur during endotoxicosis.     

Spermatogenesis in the golden hamster: the role of c-kit.

c-kit is related to the family of transmembrane tyrosine kinase receptors. Mutations in genes for either c-kit or its ligand, Steel factor, result in infertility, but the role of c-kit/SCF system in spermatogenesis is not well understood. In this study Western blot analysis together with confocal microscopy were used to follow c-kit expression in hamsters during the first spermatogenic wave in mature animals and in old age. Three antibodies raised against different domains of c-kit were tested on Western Blot. Confocal microscopy was performed after incubation of fixed seminiferous tubules with tested antibodies followed by binding of FITC-labeled secondary antibody. Longitudinal sections of seminiferous tubule were observed by confocal microscopy to determine in which stages of spermatogenesis and in which cell types c-kit was found. C-kit bands of 80,140, and 150 kDa were observed on Western blot, indicating that c-kit is a name related to several proteins sharing some common domains. Only the band of 150 kDa correlated with positive staining of c-kit in tubules using confocal microscopy. We term this protein c-kit150T (150 kDa, testis). We demonstrated that c-kit150T appeared in differentiating hamster spermatogonia at stages VII-VIII of adult spermatogenesis and at day 13-14 during the first spermatogenic wave. It remained attached to the cell until late pachytene. This suggests that c-kit may play a role in preparing the germinal cells to enter meiosis. In order to evaluate the effect of aging on the number of germ cells, B2 spermatogonia/Sertoli cell ratio was calculated in the group of young animals (5-7 months) compared to this ratio in older ones (20-26 months). A significant decrease (P < 0.01) in the number of B2 spermatogonia in the group of old hamsters as compared to young ones was seen. The calculated value for the B2 spermatogonia/Sertoli cell ratio was 5.6 +/- 0.7 in young animals and 3.8 +/- 1.2 in the 20-26 months ones. In addition, decrease in the intensity of staining for c-kit was detected in the old hamsters. These may be the reasons for subfertility in old age and in other cases of testicular disorders.     

Evidence for cigarette smoke-induced calcitonin secretion from lungs of man and hamster

In hamsters, acute cigarette smoke inhalation increased serum levels of the hormone calcitonin; and, in humans, smoking of two high-nicotine content cigarettes increased serum and urine levels of this hormone. The source of this immunoreactive calcitonin (iCT) does not appear to be the thyroid gland, since previously thyroidectomized patients demonstrated a similar response. In the hamster, the increased serum iCT levels were accompanied by a decreased lung tissue iCT content and hypocalcemia. It is suggested that the source of the cigarette smoke-induced hypercalcitonemia is the lung, possibly from the iCT-containing pulmonary neuroendocrine (PNE) cells. Moreover, this response appears to be dependent on the nicotine content of the cigarettes.     

Effects of prenatal administration of nicotine on amino acid pools,protein metabolism,and nicotine binding in the brain

The effects of nicotine on brain protein metabolism and on the properties of the nicotine binding site were investigated in newborn animals exposed to nicotine during gestation. Brain protein synthesis rates measured in vivo were lower by 18% in newborn of treated animals. Protein degradation rates measured in vitro in the presence of nicotine were lower by 13%. The effect was specific forl-(-) nicotine, sinced-(+)nicotine, nicotinic acid, or nicotinamide had no effect on degradation rates. Newborn brain amino acid levels, mainly nonessential amino acids and amino acids of putative neurotrans nitter function, were changed some-what; an increase in the level of taurine (13%), threonine (21%), serine (35%) and glycine (35%), and a decrease in lysine (14%) was observed in the offspring of nicotine treated animals (0.5 mg/kg, s.c., 2×daily throughout gestation). These changes could not account for the decrease in protein metabolism. Nicotine binding was higher by 25% in the offspring of animals exposed to nicotine during gestation. No such increase was found after treatment of adult rats with nicotine, indicating that the properties of the nicotine binding site change with age.     

The influence of maternal nicotine exposure on neonatal lung alveolar epithelial status: an electron microscope study.

The aim of the present study was to investigate the effect of maternal nicotine exposure (1 mg nicotine/kg body mass/day) on neonatal lung alveolar epithelial cells. Rats (Wistar descendants) were used. The data illustrate that maternal nicotine exposure during pregnancy and lactation resulted in alveolar fenestrations, blebbing and rupturing of the blood-air barrier. The type I pneumocyte appears to be more sensitive to the effect of nicotine than the type II pneumocytes.     

The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid.

The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism.     

Photodynamic therapy for American cutaneous leishmaniasis: the efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis

The aim of this study was to investigate the effectiveness of Photodynamic Therapy (PDT) using Methylene Blue (MB) as the photosensitizing compound and a Light-Emitting Diode (LED) in American cutaneous leishmaniasis (ACL). Hamsters were experimentally infected with Leishmania (Leishmania) amazonensis. After the development of the lesions in the footpad, the animals were treated with MB three times a week for 3 months. Ten minutes after each application of MB, the lesions were irradiated with LED for 1 h. The lesions were evaluated weekly by the measurement of the hamster footpad thickness. At the end of the treatment the parasitic load was quantified in the regional lymph node of the hamsters. The treatment promoted a decrease in the thickness of infected footpad (P = 0.0001) and reduction in the parasitic load in the regional lymph node (P = 0.0007) of the animals from group treated with MB + LED. PDT using MB + LED in ACL caused by L. amazonensis shows a strong photodynamic effect. This therapy is very promising, once it is an inexpensive system and the own patient can apply it in their wound and in their house without the need of technical assistance.     

The Syrian golden hamster strain LPN: a useful animal model for human cholelithiasis

The purpose of this study was to specify the main mechanisms at the origin of gallstone formation in very young (5-week old) or young adult (9-week old) LPN hamsters fed a sucrose-rich (normal lipid) lithogenic diet for one and four weeks, respectively. It was also to compare these mechanisms in the two strains of hamsters (LPN and Janvier) or when an anti-lithiasic diet was given by substituting 10% of the sucrose by beta cyclodextrin. The LPN strain of hamsters showed a very high incidence of cholesterol gallstones (73%) after receiving the lithogenic diet. The gallstone formation is very rapid and occurs in less than one week in very young hamsters which show a high cholesterol synthesis rate in the liver. The cholesterol and phospholipid concentrations in the bile, cholesterol saturation index (CSI) and hydrophobic index (HI) increased significantly, concomitantly with a higher liver cholesterol synthesis in very young hamsters and with a lower bile acid synthesis (neutral pathway: cholesterol 7alpha-hydroxylase, CYP7A1 and acidic pathway: sterol 27 hydroxylase, CYP27A1) in young adult hamsters. No significant changes in the lipoprotein receptor expression (LDLr, SR-BI) were observed after feeding the lithogenic diet. Adding ten per cent beta-cyclodextrin, a cyclic oligosaccharide that binds cholesterol and bile acids to the lithogenic diet at the expense of sucrose, induced a decrease in cholesterol bile secretion and in the CSI and HI and prevented cholesterol gallstone formation. Similarly, another strain of Syrian Golden hamsters (" Janvier ") which originally exhibited a smaller bile cholesterol concentration, lower liver cholesterol synthesis and higher CYP7A1/CYP27A1 activity ratio did not carry cholesterol gallstones when fed the lithogenic diet. The main parameters always found at the origin of cholelithiasis in the Hamster are discussed: a higher hepatic cholesterogenesis (HMGCoAR), a higher HMGCoAR/CYP7A1 activity ratio, a lower cholesterol ester storage capacity, a higher CYP27A1/CYP7A1 activity ratio correlated to a higher cholesterol secretion in the bile and higher CSI and HI. In LPN hamsters, the incidence of cholesterol gallstones is nil when CSI + HI < 0.8 and positive for CSI + HI > 0.9. An overall comparison of the data obtained in LPN Hamsters and in Man suggests that this hamster strain appears to be an interesting model for human cholelithiasis.     

Observations on circulatory adjustment in newborn reindeer and elk

Haemodynamics of two reindeer (18 h and 4 days old) and one elk (1 week old) calves were studied by catheterization and angiography. Early closure of foetal shunts, high cardiac output and large ejection fractions were observed in all three animals. Pulmonary arterial blood pressure decreased to the full-grown level during the first days of life in the reindeer. Electrocardiography showed cranial-orientated QRS vector in both species. The cardiovascular system of the Cervidae is well developed at birth and adapts rapidly during the neonatal period.     

Nicotine and lung development

Nicotine is found in tobacco smoke. It is a habit forming substance and is prescribed by health professionals to assist smokers to quit smoking. It is rapidly absorbed from the lungs of smokers. It crosses the placenta and accumulates in the developing fetus. Nicotine induces formation of oxygen radicals and at the same time also reduces the antioxidant capacity of the lungs. Nicotine and the oxidants cause point mutations in the DNA molecule, thereby changing the program that controls lung growth and maintenance of lung structure. The data available indicate that maternal nicotine exposure induces a persistent inhibition of glycolysis and a drastically increased cAMP level. These metabolic changes are thought to contribute to the faster aging of the lungs of the offspring of mothers that are exposed to nicotine via the placenta and mother's milk. The lungs of these animals are more susceptible to damage as shown by the gradual deterioration of the lung parenchyma. The rapid metabolic and structural aging of the lungs of the animals that were exposed to nicotine via the placenta and mother's milk, and thus during phases of lung development characterized by rapid cell division, is likely due to "programming" induced by nicotine. It is, therefore, not advisable to use nicotine during gestation and lactation.     

Chronic exposure to nicotine alters endothelium-dependent arteriolar dilatation: effect of superoxide dismutase.

The first goal of this study was to determine whether chronic injection of nicotine alters endothelium-dependent arteriolar dilatation. We measured the diameter of cheek pouch resistance arterioles (approximately 50 microm in diameter) in response to endothelium-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in control hamsters and hamsters treated with nicotine (2 microg. kg-1. day-1 for 2-3 wk). In control hamsters, acetylcholine (0.1 and 1.0 microM) dilated arterioles by 13 +/- 2 and 31 +/- 3%, respectively, and ADP (1.0 and 10 microM) dilated arterioles by 18 +/- 1 and 30 +/- 1%, respectively. In contrast, acetylcholine (0.1 and 1.0 microM) dilated arterioles by only 5 +/- 2 and 12 +/- 3%, respectively, and ADP (1.0 and 10 microM) dilated arterioles by only 7 +/- 2 and 13 +/- 3%, respectively, in animals treated with nicotine (P < 0.05 vs. response in control hamsters). Nitroglycerin produced similar dose-related dilatation of cheek pouch arterioles in control and nicotine-treated hamsters. Our second goal was to examine a possible mechanism for impaired endothelium-dependent arteriolar dilatation during chronic treatment with nicotine. We found that superfusion of the cheek pouch microcirculation with superoxide dismutase (150 U/ml) restored impaired endothelium-dependent, but did not alter endothelium-independent, arteriolar dilatation in hamsters treated with nicotine. Superfusion with superoxide dismutase did not alter endothelium-dependent or -independent arteriolar dilatation in control hamsters. We suggest that chronic exposure to nicotine produces selective impairment of endothelium-dependent arteriolar dilatation via a mechanism related to the synthesis/release of oxygen-derived free radicals.     

Influence of maternal nicotine exposure on neonatal rat bone: protective effect of pentoxifylline

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. The aim of this study was to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on neonatal rat bone development, and to determine a protective effect of pentoxifylline (PTX). Gravid rats were assigned into four groups, one control (group I) and three experimental (groups II, III, and IV). In group II, pregnant rats received 3 mg/kg/day nicotine alone, subcutaneously, until 21 days postnatal. In group III, pregnant rats received nicotine (3 mg/kg/day) and PTX (60 mg/kg/day). In group IV, pregnant rats received PTX alone (60 mg/kg/day). Whole body mineral density (BMD), content (BMC), area (BA), and histopathologic and morphologic findings of the femur were determined at 21 days of age. The study revealed that nicotine exposure (group II) decreased birth weight, pregnancy weight gain, and length of femur compared with other groups (P < 0.01). Birth weight was higher in groups III (PTX + nicotine) and IV (PTX) than in group II (nicotine). Body weight at 21 days of age was higher (P = 0.009) in the PTX alone group (group IV) compared with the other groups. BMD was higher (P < 0.001) in the PTX-treated groups (group III and IV) compared with other groups. In addition, there were more apoptotic chondrocytes in the hypertrophic zone of rats exposed to nicotine alone (group II) compared with the other groups (P < 0.001). In conclusion, maternal nicotine exposure resulted in decreased birth weight, pregnancy weight gain, and bone lengthening, and increased apoptosis. Pentoxifylline supplementation was found to prevent the adverse effects of maternal nicotine exposure on BMD and birth weight.     

Evaluation of chemopreventive effects of Thymoquinone on cell surface glycoconjugates and cytokeratin expression during DMBA induced hamster buccal pouch carcinogenesis

The present study aimed to investigate the membrane stabilizing effect of Thymoquinone (TQ) on cell surface glycoconjugates and cytokeratin expression against DMBA induced hamster buccal pouch carcinogenesis. 0.5% DMBA painting (three times per week) in hamster buccal pouches for 14 weeks resulted in the formation of well developed oral squamous cell carcinoma. We observed 100% tumor formation with marked abnormalities of glycoconjugates status in tumor bearing hamsters as compared to control animals. Oral administration of TQ at a dose of 30 mg/kg body weight, to DMBA painted hamsters on alternate days for 14 weeks, reduced the tumor formation as well as protected the levels of cell surface glycoconjugates in DMBA painted hamsters. The present study thus suggests that TQ has potent chemopreventive efficacy as well as protected the abnormalities on cell surface glycoconjugates during DMBA induced hamster buccal pouch carcinogenesis.     

Effects of chronic exercise on the kidneys at different ages

In order to determine the effects of chronic exercise on the kidneys at different ages, young, adult, and old rats swam 1 hour either daily or twice a week for 10 weeks and then were killed along with unexercised controls. The kidneys were removed and sections were prepared for histometric analysis including planimetric measurements on camera lucida drawings of renal components and line sampling. With both degrees of exercise young rats showed lower kidney weight, fewer glomeruli and less medullary tissue than unexercised controls. In the adult group no significant differences were noted between exercised and unexercised rats. In old rats both degrees of exercise resulted in a loss of kidney weight and medullary and cortical mass, and a decrease in size of glomeruli while total number of glomeruli remained unchanged. Thus the effects of chronic exercise on the kidneys varied with age. Retarded kidney development occurred in young animals; a loss of renal tissue in old animals; and no change in adult animals.     

Vitamin A deprivation in hamsters. Correlations between tracheal epithelial morphology and serum/tissue levels of vitamin A

The effects of vitamin A deprivation on the tracheal epithelium of young hamsters were investigated. Colchicine was administered 6 h prior to death to induce metaphase arrest, thus making it possible to quantify the mitotic rates of basal cells and secretory (mucous) cells in the epithelium. Blood samples were taken from all hamsters, and liver samples from some, in order to measure serum and tissue levels of vitamin A. Age-matched controls were compared with the following groups of hamsters maintained on a vitamin A deficient diet: pre weight plateau animals (those gaining weight), weight plateau-early weight loss animals (those maintaining approximately the same weight for 3 or 4 days, followed in some cases by a loss of weight for 3 or 4 days), and prolonged weight loss animals (those showing a loss of weight for 5 or more days). Four week old hamsters in a pre weight plateau had undetectable amounts of vitamin A in their livers and declining levels in their serum, whereas 4 1/2 week old hamsters still gaining weight had barely detectable levels of vitamin A in their serum. Nevertheless, the tracheal epithelium of these animals was not different from controls in appearance, proportions of different cell types, mitotic rates of secretory and basal cells, or in the number of cells per millimeter of basement membrane (cell density). Vitamin A was undetectable in the serum and livers of hamsters in the weight plateau-early weight loss stage. At this time the tracheal epithelium showed minimal morphological change, with small focal areas of epidermoid metaplasia in some animals. The tracheas of animals in early weight loss were smaller than tracheas in the control group, and there was a trend towards an increase in the number of epithelial cells per millimeter basement membrane. Cell types in the minimally changed epithelium appeared nearly normal, but there was an increase in the proportion of basal cells, and an absence (or near absence) of division in both basal and secretory cells. Tracheal rings from hamsters in the prolonged weight loss stage were lined by a cornifying metaplastic epidermoid epithelium. Our findings demonstrate that barely detectable levels of vitamin A in the serum are sufficient to maintain normal growth and differentiation of hamster tracheal epithelium (late pre weight plateau stage). When vitamin A serum levels fall below detectable limits the animals enter the weight plateau-early weight loss stage. This stage is accompanied by an inhibition of tracheal epithelial cell growth, although nearly normal cellular differentiation is maintained.(ABSTRACT TRUNCATED AT 400 WORDS)     

Energetics of offspring production: a comparison of a marsupial (Monodelphis domestica) and a eutherian (Mesocricetus auratus)

This study compares the energetic cost of reproduction during gestation and lactation of a eutherian, the golden hamster (Mesocricetus auratus), and a similar-sized (60–120 g) marsupial, the gray short-tailed opossum (Monodelphis domestica). Food consumption was monitored in 20 reproductively active (RA) opossums and 16 RA hamsters from conception to weaning and at equivalent intervals in 19 non-reproductive (NR) opossums and 21 NR hamsters, all maintained within their zone of thermoneutrality (30 °C). Total energy assimilated from conception to weaning [opossums: 1261.3 ± 28.0 Kcal (1 Kcal = 4.1868 J) and hamsters: 1647.5 ± 60.6 Kcal] was positively correlated with litter size and mass per young in both species. Maternal mass-specific assimilated energy was significantly greater in hamsters than in opossums during gestation (P < 0.001), but not during lactation or from conception to weaning (P > 0.05). Efficiency of offspring production (energy stored in young/incremental energy in RA females) was higher in hamsters than in opossums and, in both species, it was higher during lactation than in gestation. The energetic cost of reproduction (per young per day) was higher in hamsters than in opossums. The marsupial mode of reproduction, as seen in opossums, yields young at lower cost but requires a longer reproductive period than is the case for a similar-sized eutherian. Accepted: 8 September 1998