Chemotoxicity and survival of tumor-bearing mice under exposure to randomized photoperiodic regimen

Although disruption of the circadian rhythm had been traditionally considered as a pathological sign, there is an increasing recognition that an existence of internal disorder (or chaos) in the organism's homeostasis is, to some degree, essential to the organism's well being. In this study we explored the effects of rhythm scrambling by exposure to random light/dark (RLD) alternation or by hydrocortisone administration. The variables measured were the toxicity of Adriamycin, Vincristin, Cisplatinum and Cyclophosphamide in C57Bl/6J mice and the survival of EL4 lymphoma-bearing mice, before and after chemotherapy. Rhythm alterations were determined by WBC counts and plasma Alkaline Phosphatase activity. Injections of Adriamycin, Cisplatinum and Vincristin in RLD conditions resulted in a better survival than in control groups of mice kept in LD illumination regimen, although the differences between the groups were significant only for injection of Adriamycin. RLD conditions imposed a "protective" effect on survival of tumor-bearing mice. On the 94th day, 20% of the injected mice in RLD conditions still survived while, there were no survivors beyond 38 days in control group. Chemotherapy had a more prominent beneficial effect on survival in RLD group, as compared to LD group. The injections of hydrocortisone had detrimental effect on survival in both illumination schedules. However, the survival in the RLD group was still better than in the LD group. These experiments indicate that temporal disorganization has beneficial effects on lymphoma-bearing mice and could be used for development of new therapeutic modalities.     

Inhibition of embryo implantation in mice through vaginal administration of a proprotein convertase 6 inhibitor

Uterine proprotein convertase 6 (PC6) plays a critical role in embryo implantation in both mice and women. It was hypothesized that inhibiting uterine PC6 could prevent pregnancy. Vaginal administration of a PC6 inhibitor presents the ideal route for local drug delivery. A peptide-based PC6 inhibitor, C-30k-PEG Poly R that was previously shown to have properties of increased vaginal absorption and penetration was tested for its contraceptive potential in mice following vaginal administration. The study demonstrated that this approach could inhibit embryo implantation in some mice (24% completely and 47% partially inhibited).     

Effects of time of l-ornithine administration on the diurnal rhythms of plasma growth hormone,melatonin, and corticosterone levels in mice

The synthesis and secretion of many hormones such as growth hormone (GH), melatonin, and corticosterone, exhibit temporal variations over each day and night. Oral administration of several nutritional factors, including l-ornithine, modulates these hormonal secretions and induces an acute increase in plasma GH levels. However, the impact of l-ornithine on the diurnal rhythms of hormone secretion remains unclear. In this study, we evaluated whether the diurnal rhythms of plasma GH, melatonin, and corticosterone secretion were altered by the daily administration of l-ornithine as well as the timing of the administration, in CBA/N mice. Our results showed that the plasma GH levels that peaked at light phase were amplified by l-ornithine (500?mg/kg) administered at Zeitgeber time (ZT) 22, but not at ZT10. Additionally, l-ornithine (1000?mg/kg) administered at ZT22 advanced the onset of the nocturnal rise of melatonin, which resulted in the elongation of the melatonin peak. On the other hand, l-ornithine (500 and 1000?mg/kg) administered at ZT10, but not at ZT22, suppressed the diurnal rhythm peaks of plasma corticosterone. The effects of l-ornithine on plasma GH rhythms lasted for at least 2 days after cessation of the daily administration. Running wheel activity during the active phase was slightly elevated by l-ornithine administration at ZT22, but the overall patterns were only slightly affected. l-Ornithine levels in the plasma and hypophysis after a single administration of l-ornithine at ZT22 were lower than those after administration at ZT10, suggesting that the metabolic rate of l-ornithine differs between day and night. In conclusion, our data suggest that a daily administration of l-ornithine regulates the diurnal rhythms of GH, melatonin, and corticosterone in a manner dependent on administration time, which might be related to the diurnal rhythms of l-ornithine metabolism.     

Effects of anandamide on embryo implantation in the mouse

Anandamide (N-arachidonoylethanolamine), an arachidonic acid derivative, is an endogenous ligand for both the brain-type (CB1-R) and spleen-type (CB2-R) cannabinoid receptors. To investigate the possible effects of anandamide on embryo implantation in the mouse, we used a co-culture system in which mouse embryos are cultured with a monolayer of uterine epithelial cells. Our results indicate that 14 nM anandamide significantly promotes the attachment and outgrowth of the blastocysts on the monolayer of uterine epithelial cells, and those effects could be blocked by CB1-R antagonists SR141716A, but not by SR144528, a CB2-R antagonist. It suggests that the effects of anandamide on embryo attachment and outgrowth are mediated by CB1-R. However, 56 nM anandamide is capable of inhibiting the blastocyst attachment and outgrowth, we, therefore, conclude that anandamide may play an essential role at the outset of implantation.     

Effects of day-time exposure to different light intensities on light-induced melatonin suppression at night

Background

Bright nocturnal light has been known to suppress melatonin secretion. However, bright light exposure during the day-time might reduce light-induced melatonin suppression (LIMS) at night. The effective proportion of day-time light to night-time light is unclear; however, only a few studies on accurately controlling both day- and night-time conditions have been conducted. This study aims to evaluate the effect of different day-time light intensities on LIMS.

Methods

Twelve male subjects between the ages of 19 and 23 years (mean ± S.D., 20.8 ± 1.1) gave informed consent to participate in this study. They were exposed to various light conditions (<10, 100, 300, 900 and 2700 lx) between the hours of 09:00 and 12:00 (day-time light conditions). They were then exposed to bright light (300 lx) again between 01:00 and 02:30 (night-time light exposure). They provided saliva samples before (00:55) and after night-time light exposure (02:30).

Results

A one-tailed paired t test yielded significant decrements of melatonin concentration after night-time light exposure under day-time dim, 100- and 300-lx light conditions. No significant differences exist in melatonin concentration between pre- and post-night-time light exposure under day-time 900- and 2700-lx light conditions.

Conclusions

Present findings suggest the amount of light exposure needed to prevent LIMS caused by ordinary nocturnal light in individuals who have a general life rhythm (sleep/wake schedule). These findings may be useful in implementing artificial light environments for humans in, for example, hospitals and underground shopping malls.     

Effects of different schedules of progesterone treatment on mammary tumorigenesis and uterine adenomyosis in SHN virgin mice

As a possible step to estimate the factors controlling the effects of progesterone on mammary tumorigenesis, 3 groups of SHN virgin female mice were treated as follows beginning 2.5–4 months of age: Group A received the subcutaneous implantation of silastic tube containing progesterone (low dose) during the initial 4 months followed by progesterone pellet implantation (high dose) every 2 months. Group B was implanted with progesterone pellet throughout the experiment. Group C was given the vehicle only. Whereas there was little difference among groups in mammary tumorigenesis during the initial 4 months of treatments, tumorigenesis was significantly stimulated in group B thereafter. On the contrary, group A was different little from group C even after progesterone pellet implantation. The results indicate that the effects of progesterone on mammary tumorigenesis are affected by the ‘preceding’ progesterone conditions and that there is a critical period for manifestation of the effects of progesterone on mammary tumorigenesis, which is before 8 months of age at most. While all mice developing mammary tumors developed uterine adenomyosis in each group, the progression was enhanced by both low and high doses of progesterone.     

Effects of perinatal exposure to Zamzam water on the teratological studies of the mice offspring

Zamzam water is well documented for plenty of medicinal value for curing illness. In the present study, the effects of perinatal consumption of Zamzam and normal drinking water by the pregnant mice on their offspring’s physical parameters, early sensory motor reflexes, locomotor activities, acetylcholinesterase (AChE) activity in the homogenize brain tissue and blood parameters were compared. To achieve that; Zamzam water was given to female Swiss-Webster strain mice as the only source of drinking fluid and the control animals were administered plain tap water. Treatment started from the first day of pregnancy and continued until the postnatal day fifteen of delivery. All offspring were subjected to various tests. The rate of body weight gain remained relatively unaffected until the second week of weaning period, however; in the last week the offspring exposed to Zamzam water gained significant body weight as compared to their control offspring. Furthermore, the opening of eyes and appearance of body hairs in Zamzam exposed pups remained unaffected as compared to the controls. The sensory motor reflexes in Zamzam exposed pups after birth and during the first two weeks of weaning period were significantly increased. Locomotor Activity Test performed in the male and female offspring after weaning period showed a significant decrease in the male and increase in the female on most of the elements of this test due to Zamzam exposure. AChE activity in the homogenized brain tissue and blood parameters were unaffected as compared to the controls, the present Zamzam effects in the offspring are possibly via in utero action and/or via mother’s milk.     

Maternal diazepam exposure on brain ornithine decarboxylase and growth of offspring

The prenatal treatment of diazepam on the developmental pattern of brain ornithine decarboxylase and the general growth of offspring were studied. Diazepam (120 mg/kg/day) was administered orally to pregnant Sprague-Dawley rats from day 14 to day 20 of gestation. The activity of brain ornithine decarboxylase and body weight of the offspring were measured from the late fetal stage to the early postnatal stage. It was found that diazepam inhibited both the prenatal and 4-hour postnatal ornithine decarboxylase activities, though the general maturation pattern of the enzyme in the brain was not much altered. It may indicate that diazepam inhibits early brain development. The enzyme activity fell off as it reached maturation. Prenatal treated neonates of 6-hour or older age group had the normal activities of brain ornithine decarboxylase. The general growth of the treated offspring was substantially retarded. Their body weights were very much lower than the control offspring. The results of the present study is an additional evidence that diazepam and other benzodiazepines should be used with great care in pregnant women.     

Effect of melatonin on hyperlipidemic nephropathy under constant light exposure

Studies have shown anti-hyperlipidemic actions of melatonin, with pharmacological doses inducing changes in cholesterol levels. This study was designed to evaluate the effect of melatonin on adriamycin-induced (25mg/kg b.w., i.p.) hyperlipidemia under constant light exposure. Melatonin was injected i.p. (1,000 microg/kg b.w./day). Triglycerides, total cholesterol, high-density lipoprotein cholesterol, light-density lipoprotein cholesterol, non-proteic nitrogen compounds (urea and creatinine levels), total protein in serum, proteins eliminated in the urine and melatonin levels in serum and kidney were determined. Results show a decrease in melatonin levels induced by both adriamycin and constant light. Likewise, adriamycin induced significant increases in triglycerides, total cholesterol and light-density lipoprotein cholesterol, and lowered high-density lipoprotein cholesterol levels. Constant light exposure also prompted an increase in LDL-c levels and a decrease in HDL-c values, and intensified the effects of adriamycin on these two lipoproteins. All changes induced by adriamycin and constant light were reverted toward normality by melatonin administration.     

Immunomodulating effect of cyclophosphane under different modes of administration to mice

A study was made of the effect of injection of cyclophosphamide (CP) immunomodulating to BALB/c mice, according to 3 schemes of injection with the whole dose being 200 mg/kg. In all, the state of peripheral blood and spleen, the cellular content of lymph nodes and the number of DNA-synthesizing cells in them were studied, in addition to the ability of lymph node lymphocytes to proliferative reaction on T and B cells mitogens in vivo. It was determined that a 2-fold injection of CP, in contrast to 10- and 5-fold injections, resulted in splenomegaly and leukocytosis in the experimental animals. By means of quantitative tests in vivo, in was demonstrated that the dynamics of restoration of proliferative responses to mitogens depends on the CP injection scheme. These tests proved to be more informative for registration of immunomodulating effect of CP, than the study of cellular content of lymph nodes and the number of DNA-synthesizing cells in them.     

Influence of photoperiod and melatonin administration on growth and metamorphosis in Discoglossus pictus larvae

• 1.1. The participation of an environmental factor such as photoperiod in the metamorphic development of Discoglossus pictus has been studied.
• 2.2. Short photoperiods were more effective in accelerating the rate of growth and the stages of development of tadpoles than were long photoperiods.
• 3.3. Daily melatonin injections to tadpoles during larval development showed different effects depending on the artificial photoperiod in which the tadpoles were maintained.

     

Effects of daily melatonin injections on the photoperiodic gonadal response of the female frog Rana ridibunda

The effects of daily melatonin injections on female gonads in Rana ridibunda were examined. Melatonin-treated R. ridibunda maintained on a long photoperiod (18L:6D) had significantly smaller gonads than control animals. Thus, frogs injected daily with melatonin exhibited a substantial decrease in ovary weight when compared to saline-injected animals. Our findings suggest that melatonin exerts antigonadal effects in female Rana ridibunda.     

Effects of leukaemia inhibitory factor on embryo implantation in the mouse

Leukaemia inhibitory factor (LIF) is a pleiotrophic cytokine. Recent reports indicate that LIF is relevant to murine embryo implantation. In this work, results of indirect immunofluorescence under a confocal microscope illustrated that LIF was mainly located in the uterine lumen and uterine epithelial cells in pregnant mice on day 4. The number of embryos implanted in pregnant mice on day 8 decreased significantly after injection of 3 microg LIF antibodies into a uterine horn (P<0.001), which demonstrated again that LIF is a critical factor for embryo implantation. In a co-culture system, LIF (0.1 ng/ml, 1 ng/ml, 10 ng/ml and 100 ng/ml) significantly enhanced the blastocyst outgrowth after 24, 48 or 72 h of co-culture, and outgrowth areas after 72 h of co-culture. Conversely, 5 microg/ml and 10 microg/ml, but not 1 microg/ml, LIF antibodies decreased the percentage of blastocysts with outgrowth; only 10 microg/ml LIF antibody inhibited blastocyst outgrowth area significantly (P<0.001). However, neither LIF nor its antibodies changed embryo attachment. Analysis of correlation showed that the effects of LIF or its antibodies on the blastocyst outgrowth were dose-dependent. In summary, different pathways may exist to regulate the blastocyst attachment and outgrowth on a monolayer of uterine epithelial cells. LIF protein from the maternal uterus exerts an essential role in embryo implantation in the mouse, which is mediated by stimulating trophoblast outgrowth, but not by promoting the attachment.     

Effect of different photoperiodic regimes on growth, flowering and essential oil in Mentha species

Three major cultivated Mentha spp. (M. arvensis, M. citrata and M. cardiaca) were grown under short-days, normal-days or long-days for 60 cycles. Subsequent to photoperiodic treatment, the plants were assessed for growth behaviour, essential oil content, oil composition and essential oil biosynthesis. The species grew better under long-day conditions. The long-day treatment resulted in flowering in M. citrata, which normally does not flower under our conditions. The oil concentration and biogenesis was maximal in short-day plants. The photoperiodic treatment also affected the oil composition. The observations are discussed in relation to physiology of the oil biogenesis.     

Effects of different photoperiodic treatments on flowering in two cultivars of American cotton

The photoperiodic behaviour of two cotton cultivars, H-14 andJ-34, was reinvestigated under more elaborate photoperiodictreatments, including combinations of photoperiodic regimesin different successions. When the plants were continually retainedunder a constant photoperiod, both cultivars seemed to behaveas quantitative LDP. More truly, however, they turned out tobe LSDP. SDs following 35 LDs brought about floral initiationearlier and at a lower node. The number of squares and flowerswas also larger with this treatment. Continuous SD or SDs precedingLDs depressed flowering. (Received November 16, 1971; )     

Effect of exposure to high isoflavone-containing diets on prenatal and postnatal offspring mice

Isoflavone (IF), a type of phytoestrogen, has multiple beneficial effects, but too much phytoestrogen can have adverse effects on offspring. To examine whether chronic exposure to high IF has adverse effects on reproductive development, mice offspring were exposed to IF through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning until sacrifice. In male offspring, there was no difference between the IF group and controls; however, in female offspring in the IF group, remarkably earlier puberty and induction of multioocyte follicles on postnatal day (PND) 21 were observed. Gene expression levels of estrogen receptor beta decreased in the ovary and vagina on PND 21. These results suggest that chronic exposure to higher than normal levels of IF induces alterations in the reproductive development of female mice through an estrogenic effect.     

Effects of acute cold exposure at night on pineal N-acetyltransferase activity and melatonin content in white-footed mice, Peromyscus leucopus

1. Pineal N-acetyltransferase (NAT) activity in long-day white-footed mice (Peromyscus leucopus) exposed to cold soon after onset of darkness was depressed relative to controls, whereas mice exposed to cold later at night had slightly elevated enzyme activity. 2. NAT activity in short-day mice exposed to cold soon after lights off did not differ from controls. Pineal melatonin in these mice, however, did not rise, as it did in controls. 3. These results suggest that acute cold exposure may modulate NAT activity, which is controlled primarily by the L:D cycle.     

Effects of the perinatal exposure of Gum Arabic on the development,behavior and biochemical parameters of mice offspring

The effects of the perinatal oral exposure to Gum Arabic (GA) on mice offspring was examined. GA was added to the drinking water of pregnant female Swiss–Webster strain mice at doses of 1 and 4 g/kg body weight, starting from the first day of pregnancy. The treatment continued until the fifteenth day after delivery, after which mothers were switched to plain tap water. A number of tests were carried out on offspring starting one day after birth and extending up to postnatal day 30 (PD30). Pups showed a reduced gain of body weight and delayed opening of the eyes in comparison to the control group and only pups exposed to 1 g/kg body weight GA had a faster appearance of hair. Sensory motor reflex tests carried out during the weaning period (from day of birth to PD21) showed enhanced motor reflexes in pups exposed to GA. During the adolescent period (from PD22 to PD30), offspring showed dose-dependent enhanced motor activity (on PD22), reduced anxiety and fear (on PD27) and slightly enhanced memory and learning abilities (on PD30). Biochemical tests of a number of blood parameters were conducted during and after the weaning period (on PD15 and PD30, respectively). Our results indicated that GA might have a hypoglycemic and a beneficial effect on red and white blood cell counts. This study gives a first insight on the effect of GA consumption on offspring, providing a starting point for further studies.     

Effect of melatonin on cholestatic oxidative stress under constant light exposure

This study was designed to evaluate the effect of melatonin on cholestatic oxidative stress under constant light exposure. Cholestasis was induced by double ligature and section of the extra-hepatic bile duct. Melatonin was injected i.p.(1000 microg kg(-1) day(-1)). Malondialdehyde, reduced glutathione, catalase, superoxide dismutase, glutathione reductase, peroxidase and transferase were determined in liver. After bile-duct obstruction and under constant light exposure, an increase in malondialdehyde (p < 0.05) and a slight decrease in reduced glutathione were seen. Enzyme activity, with the exception of glutathione reductase, had significantly diminished. After melatonin administration, malondialdehyde fell (p < 0.001), whereas there was an increase in reduced glutathione (p < 0.0001) compared with untreated controls. Constant light exposure was associated with an increase in hepatic oxidative stress. Treatment with melatonin decreased lipid peroxide synthesis, and permitted a recovery of both reduced glutathione and scavenger enzyme activity.