Grain count threshold dependence of FLM curve pattern and cell cycle parameters of hepatocytes in vivo

The continuous illumination of 2 months old Wistar rats during 1,2 and 6 months resulted in the appearance of permanent oestrus in 24, 61 and 100% of animals, resp. The weight of newborn rats from the females illuminated during pregnancy was by 7% higher than in the control. The continuous illumination during 1 month prior to mating did not affect the embryogenesis. The weight of 20 days old rats from the females illuminated during 1 month (prior to mating), 2 months (prior to mating + + pregnancy) and 6 months exceeded that of the control ones by 5, 18 and 30%, resp. The increase in the weight of rats persisted in the next reproductive cycle in spite of the standard conditions of light regime (14 hrs day: 10 hrs night).     

Skilled motor deficits in rats induced by ventrolateral striatal dopamine depletions: behavioral and pharmacological characterization

Rats were tested in an instrumental lever pressing procedure, in which a computer program recorded detailed parameters of responding such as response initiation and duration. Initially, rats with ventrolateral striatal dopamine depletions and control rats were tested on days 3-5 after surgery. Dopamine depletions produced by local injections of 6-hydroxydopamine substantially reduced the number of lever presses emitted. Dopamine depleted animals showed significant increases in average response initiation times, average length of fast initiation times, average length of pauses and total pause time. The distribution of initiation times was altered so that DA depleted rats showed significant reductions in the relative number of very high rate responses and also showed increases in the relative number of pauses. On day 7 after surgery, dopamine-depleted rats received one of three drug treatments: injections of ascorbate vehicle, injections of 20.0 mg/kg L-DOPA, and injections of 40.0 mg/kg L-DOPA. Injections of 40.0 mg/kg L-DOPA led to some improvement in several parameters of instrumental responding. Compared to the previous baseline day, the group that received 40.0 mg/kg L-DOPA showed a significant increase in number of responses on the drug treatment day, and also showed significant decreases in average response initiation time and total pause time. The group that received 40.0 mg/kg L-DOPA also showed significant increases in number of responses (expressed as a percent of the previous day) when compared to the control group that received injections of ascorbate vehicle. These results indicate that L-DOPA can partially reverse the skilled motor deficits produced by ventrolateral striatal dopamine depletions, and suggest that this test may be useful for the assessment of antiparkinsonian drugs.     

Muscle metabolism and quality (MQI) in prediabetic sedentary man

In the present study, we compared the basal local cerebral metabolic rates for glucose (LCMRglcs) both in Wistar rats with genetic absence epilepsy (GAERS: genetic absence epilepsy rats from Strasbourg) and in control non epileptic (NE) rats selected in our breeding colony. LCMRglc was measured both in immature rats at postnatal day 21 (P21) at which age no spontaneous spike-and-wave discharges can be recorded in GAERS and at the adult age (6 months) when GAERS fully express thalamo-cortical spike-and-wave discharges recorded on the EEG. LCMRglcs were measured in 24 structures by the quantitative [14C]2-deoxyglucose autoradiographic technique. In adults GAERS, LCMRglc underwent a widespread increase recorded in all brain structures except in mediodorsal and ventromedian thalamus, and in the nucleus accumbens. These metabolic increases ranged from 17 to 50% over control levels in adult NE rats. In P21 GAERS, LCMRglc was similar to that of P21 NE rats in 16 areas. It increased over control levels of NE rats in two groups of structures. Metabolic increases were recorded in four limbic structures (entorhinal and piriform cortices, hippocampus and basolateral amygdala) where no spike-and-wave discharges were recorded in adult GAERS. Increases in LCMRglcs were also located in the substantia nigra pars reticulata, superior colliculus and globus pallidus which are structures involved in the control of seizure activity. In conclusion, our data suggest that the consequences of the genetic mutation(s) underlying the cellular and molecular events responsible for the expression of spike-and-wave discharges in adult GAERS is (are) able to increase metabolic activity in both limbic structures and the nigral inhibitory system before the occurrence of spike-and-wave discharges.     

Structural vascular changes in hypertension: role of angiotensin II, dietary sodium supplementation, blood pressure, and time

Previous studies have shown that a diet high in polyunsaturated fatty acids increases mammary tumor incidence in adult and pregnant mice and rats and in the female offspring. The present study investigated whether a high-fat diet alters the number of estrogen receptor (ER) binding sites and protein kinase C (PKC) activity in the mammary gland of these animals. In the female offspring, the effects of maternal exposure to a high-fat diet during pregnancy on development of the mammary epithelial tree were studied also. BALB/c mice were kept on a diet containing either 43% (high-fat) or 16% (low-fat) calories from corn oil, which consists mostly of n-6 polyunsaturated fatty acids, for 1 month. In adult female mice, a 6-fold increase in the number of ER binding sites and 2-fold increase in PKC activity were found in the mammary glands of the high-fat mice when compared with the low-fat mice. In pregnant mice, a high-fat diet increased ER binding sites by 61% and PKC activity by 51%. In contrast to adult and pregnant mice, females exposed to a high-fat diet only in utero through their pregnant mother exhibited a significantly reduced number of mammary ER binding sites by age 45 days (78% decrease) and a reduction in PKC activity by ages 30 and 100 days (44 and 20% decrease, respectively). The mammary epithelial tree of the high-fat offspring contained more terminal end buds and was less differentiated than that of the low-fat offspring. These findings show that consumption of a high-fat diet increases ER and PKC in the adult and pregnant mouse mammary gland, perhaps contributing to the fat-induced promotion of mammary tumorigenesis. In contrast, reduced ER and PKC following a high-fat exposure in utero may be associated with increased susceptibility to carcinogenesis, possibly due to an increased number of terminal end buds that are the sites of neoplastic transformation in the mammary gland.     

The synthesis and in vitro characterization of the mucoadhesion and swelling of poly(acrylic acid) hydrogels

Depression is a significant problem in epilepsy. Suicides occur in epileptic patients five times more often than in general population. Material included 34 epileptics with 76 suicidal attempts and 24 patients with no history of suicide. Psychical state was studied with Beck Depression Inventory and Hamilton Depression Rating Scale. In the group with suicidal attempts 65% of patients had depression (54.5% of them had major depression) and in group without suicide attempts depression was noted in 54% (23% with major depression). Patients with depression were divided into two groups: group I with suicidal attempts and group II without history of suicide. In group I more patients were alcohol abusers (50% vs 31%), more were treated because of epilepsy longer than 10 years (59% vs 46%) and more had tonic-clonic seizures (82% vs 46%). In group I, 54% of patients were on polytherapy (more than half of them with fenobarbital). In group II, 31% of epileptics were on polytherapy (no one with fenobarbital). Major depression was significantly more frequent in epileptics with suicidal attempts. The severity of depression may influence the risk of suicide. Major depression may be associated with late age of onset of epilepsy, longer treatment duration, tonic-clonic seizures, polytherapy (mainly with fenobarbital) and alcohol abuse.     

Prognostic value of plasma atrial natriuretic factor, norepinephrine and epinephrine in acute myocardial infarction

Case reports from the United Kingdom (UK) in 1989 have suggested that the introduction of human insulin in 1985 was associated with an increased risk of sudden death in insulin-treated diabetic patients. If human insulin increases the risk of sudden death, the number of these should have increased during the period where human insulin was introduced. We therefore identified all cases of sudden death in Denmark in younger insulin-treated diabetic patients, age at death below 50 years. During this period the consumption of human insulin went from 0.2% to 70% of the total consumption in Denmark. The total number of cases fulfilling the inclusion criteria was 226, and the annual number of sudden deaths did not change during the study period (p = 0.14). The number of deaths due to hypoglycaemia and cases with unexplained cause of death also remained constant (test for trend: p = 0.44). Chronic alcohol abuse or acute alcohol intoxication was found in 50% of the 135 patients dying from hypoglycaemia, ketoacidosis or unknown cause of death (including found dead in bed), while this was the case in only 16% of the remaining 91 cases dying from other natural causes. We conclude that introduction of human insulin in Denmark was not followed by an increase in sudden deaths among younger insulin-treated diabetic patients.     

Protein kinase C alterations in aortic vascular smooth muscle cells from rats with cirrhosis

It was found that the frequency of extreme situations (traumas, deaths, sudden diseases) in miners working in Spitsbergen mines (74 degree N) correlates well with heliogeomagnetic activity (local magnetic disturbances, solar proton flashes). It was shown that in winter, both an enhanced and an extremely low level of magnetic activity can affect the occurrence of extreme situations. The results obtained can be used for predicting and reducing the frequency of extreme events in the zone of the polar cap during geomagnetic disturbances.     

Effect of chronic amitriptyline administration on serotonergic receptors in rats with methylazoxymethanol-induced microencephaly

Biting density and biting cycle of Culex quinquefasciatus in Khon Kaen City were examined during November 1994 to October 1995. Biting activity of the mosquito was assessed by using the indoor human bait method. Trapped mosquitos were identified and carefully dissected to determine their parities. Climatory data ie temperature, relative humidity and rainfall were also recorded during the study. The densities of mosquito ranged from 1.6/man/hour in December to 9.2/man/hours in March with the average of 5.0/man/hours. The lowest biting density was observed in winter and higher densities were in summer and rainy seasons. The temperature was the most important variable that influenced the biting density in each month of the year (p<0.05). The biting cycle showed that the mosquito active throughout the night, with peak activity at 22.00-23.00 hours. Parous rate of the mosquito ranged from 33.3% in February to 71.9% in November with the average of 47.3%. The biting proportion of parous mosquitos was high during the early hours of the night and gradually decreased until 06.00 hours, whereas that of the nulliparous mosquitos showed an increasing trend from 18.00 to 06.00 hours. The biting cycle of the parous mosquito reached the peak activity at 21.00-22.00 hours, 1 hour ahead of the peak for nulliparous mosquito. These findings suggested that Cx. quinquefasciatus in Khon Kaen City may be able to transmit bancroftian filariasis if they were exposed to microfilaria carrier individuals.     

Clonidine and methohexital-induced epileptic magnetoencephalographic discharges in patients with focal epilepsies

PURPOSE: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings for focus localization. To increase the number of epileptic discharges required for MEG analysis, we administered methohexital (MHT), a short-acting barbiturate known to provoke epileptic activity. We also investigated the spike-provoking properties of clonidine in comparison with MHT. METHODS: Patients were briefly anesthetized with intravenously administered MHT after being premedicated orally with clonidine. Numbers and locations of epileptic MEG discharges were assessed after clonidine premedication as well as during MHT anesthesia. Results were compared with baseline MEG recordings. RESULTS: MHT increased the frequency of focal epileptic discharges in 8 of 13 patients ( of the 14 patients did not receive MHT after premedication with clonidine). Premedication with clonidine also increased focal epileptic discharges in 9 of 14 patients. The numbers of epileptic signals and numbers of spikes contributing to MEG source localizations were significantly increased in MEG recordings under both treatment conditions (clonidine premedication and MHT anesthesia) as compared with baseline MEG recordings. CONCLUSIONS: Our results confirmed the selective proconvulsive effects of MHT on the epileptic focus, as previously suggested by EEG and electrocorticographic (ECoG) investigations. However, our present data establish for the first time that clonidine increases epileptic activity in patients with seizure disorders and indicate that clonidine is suitable as an activating agent for localization of epileptogenic foci by MEG. This effect of clonidine on specific epileptic activity also indicates that specific care must be taken when clonidine is used as an antihypertensive drug in patients with seizure disorders.     

Anticonvulsant-induced changes in tissue manganese, zinc, copper, and iron concentrations in Wistar rats

Human epileptics have been reported to have low blood manganese (Mn) concentrations in comparison to nonepileptics, an observation that is important because Mn deficiency can increase seizure susceptibility in experimental animals. Factors that have been suggested to contribute to the low blood Mn levels in epileptics include anticonvulsant use, seizure-induced tissue redistribution of Mn, and genetics; in the present study, the first of these possibilities was tested. Wistar rats were fed semipurified diets containing diphenylhydantoin ([DPH] 3 g/kg diet), phenobarbital ([PB] 2 g/kg diet), or primidone ([PRIM] 3 g/kg diet) for 7 weeks, at which time they were killed and tissues collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations. In comparison to pair-fed rats, DPH- and PRIM-fed rats had significantly elevated liver Mn concentrations, while Mn concentrations in blood, brain, heart, and kidney were unaffected by anticonvulsant exposure. Changes in the concentrations of Zn, Cu, and Fe in specific tissues were also found. Overall, these findings suggest that the anticonvulsants tested do not lead to significant derangements in the metabolism of Mn.     

Age- and sex-related differences in nuclear lipid content and nucleoside triphosphatase activity in the JCR:LA-cp corpulent rat

The putative role of the nuclear nucleoside triphosphatase (NTPase) is to provide energy to the nuclear pore complex for poly A(+) mRNA export. Previous work has demonstrated that liver nuclear NTPase activity is greater in 6 month old corpulent (cp/cp) female JCR:LA rats, a hyperlipidemic rat model, compared to lean (+/?) animals. This increase appeared to be related to increases in nuclear membrane cholesterol content. The current study extended these initial data to compare NTPase activity as a function of age and sex in isolated JCR:LA-cp rat liver nuclei, to further test the hypothesis that nuclear membrane cholesterol may modulate NTPase activity. NTPase activity was increased in cp/cp female animals compared to +/? females at all ages studied, with Vmax values increased by 60-176%. Membrane integrity of cp/cp female nuclei was reduced compared to +/? female nuclei. Nuclear membrane cholesterol levels increased linearly with age by 50, 150 and 250% in 3, 6 and 9 month old cp/cp females over leans. In contrast, nuclei from cp/cp males exhibited only minor, isolated changes in NTPase activity. Furthermore, there were no significant changes in nuclear cholesterol content or membrane integrity in the less hyperlipidemic male animals at any age. These data suggest that altered lipid metabolism may lead to changes in nuclear membrane structure, which in turn may alter NTPase activity and functioning of the nuclear pore complex.     

Epilepsy and the heart

The relations between epilepsy and heart are complex and expressed in two opposite sides. (1) Cardiac arrhythmias may provoke epileptic seizures but these seizures are, in this case, syncopal attacks. Nevertheless, in the past, these clinical features have been individualized as "cardiac epilepsy" or epilepsy in cardiacs. However, true epileptic seizures could be observed in the course of a syncopal attack and a syncope may complicate the issue of an epileptic seizure. (2) On the other hand, epileptic seizures may provoke severe cardiac arrhythmias. The incidence rate of sudden death in patients with epilepsy is estimated to be 1/1000 patients. The exact neural mechanisms in cardiac arrhythmias seizures could explain only some of the sudden unexpected deaths observed in epileptic patients. The role of antiepileptic drugs on cardiac conduction as well as the effects of seizures or status epilepticus on the myocardium are other enigmatic aspects of the relations between epilepsy and heart.     

Identification of plasminogen in Matrigel and its activation by reconstitution of this basement membrane extract

Cis-urocanic acid (cUCA) has been suggested as a mediator of impairment of contact hypersensitivity induction by ultraviolet B (UVB) irradiation. We ascertained whether topical cUCA influences local lymph node activation during induction of contact hypersensitivity. Topical cUCA or vehicle was applied during the local lymph node assay to oxazolone. Local lymph node weight and cell number were assessed in all animals. Additionally, cell proliferation rate was studied in Hartley guinea-pigs and CBA/Ca mice, whereas activation of antigen-presenting cells was quantified in NMRI mice and Wistar rats. Topical cUCA suppressed all parameters of local lymph node activation due to oxazolone application in guinea-pigs. No effect, with the exception of a suppression of antigen-presenting cell activity, was seen in mice. No effect was seen in rats. The study shows that topical cUCA may suppress local lymph node activation during contact sensitization and suggests that differences between the effect of cUCA in different animal species may exist.     

Pediatric automotive restraints, pediatricians, and the academy

Behaviouristic and EEG-manifestations of pentylentetrazol convulsions were studied in unrestrained rats with preliminarily destroyed striatum. The operation caused no significant disturbance of the appearance of the spike-wave activity, but sharply inhibited provocation of myoclonic and their change into tonico-clonic convulsions. Besides, there was an increase in the threshold, the duration and the severity of the attack; an epileptic status was even observed in 50% of these rats. Striatectomy eliminated the action of catecholaminergic agents (apomorphine, DOPA, haloperidol, chlorpromazine) on the thresholds of myclonic jerks and the attack.     

The effect of pyrithioxine and pyridoxine on individual behavior, social interactions, and learning in rats malnourished in early postnatal life

Low protein (LP) or low calorie (LC) dietary regimens were applied in early postnatal life(1st-40th day of life) in male rats. After nutritional rehabilitation, open-field behavior in larger more illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), dyadic interactions, and learning ability were investigated in these animals as adults (between the 200th to 300th day of life). LP malnutrition induced an increase of open-field activity with features of sterotypy both in LI and HI situations, an increase number of intersignal reactions during learning procedures without changes in other registered criteria of learning ability (latency, number of correct responses), and an increase of aggressive behavior in pair interaction. LC rats revealed only significant inhibition in LI--open-field activity and a slightly increased number in intersignal reactions during avoidance learning. With the aim of preventing previously described long-term deviations in early malnourished rats, some groups of animals with the above-mentioned early calorie or protein deficits were treated with pyrithioxine (Encephabol Merck) or pyridoxine in 10 doses of 40 mg/kg i.p. administered in the period when nutritional rehabilitation was carried out (between the 40th--50th day of life). The treatment with pyrithioxine reduced significantly behavioral disturbances in adult LP rats except the increase of intersignal reactions which was even potentiated. Pyridoxine was less effective but normalized the increase number of intersignal reactions both in LP and LC rats. The effect of pyridoxine of adult LC rats was interesting. There was significant improvement in all registered parameters of avoidance learning and a significant increase of sexual acts was recorded.     

Enhanced sodium appetite in rats with lesions centered on nucleus medianus.

Recent experiments have demonstrated that rats with lesions of the ventral portion of nucleus medianus (VNM) frequently exhibit a chronic and robust hyperdipsia, which occurs only at night. The present study demonstrated that the same brain damage may produce a nocturnal appetite for sodium that is similarly pronounced and persistent. Of 68 male Sprague-Dawley rats with VNM lesions, 33 were observed to drink at least 15 ml of 0.51 M NaCl solution per day, and 11 of them consumed more than 30 ml daily. The basis for this high consumption of saline is uncertain; the brain-damaged Ss had normal sodium concentrations, renin activities, and aldosterone levels in plasma during basal maintenance conditions, and they conserved sodium in urine when maintained on a sodium-deficient diet. Nevertheless, the present results indicate that VNM and/or local fibers of passage may play an important role in the control of sodium appetite, as it does in the control of thirst. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypochord, an enigmatic embryonic structure: study of the axolotl embryo

Age-dependent alterations in behavioral and neuronal functioning were assessed in young (2-3 month), middle-aged (12 month), and aged (24 month) Fischer 344 rats treated with the indirect dopamine agonist amphetamine (2.25 or 5 mg/kg), the D1 agonist SKF 38393 (7.5, 15, 30 mg/kg), or the D2 agonist quinpirole (0.3, 1.0, 3.0 mg/kg). Drug-induced changes in activity and stereotypy were measured during a 90-min testing session, with Fos immunohistochemistry being used to assess the neuronal response to dopamine agonist treatment. As expected, aged rats given amphetamine (5 mg/kg) had fewer activity counts and higher stereotypy scores than young rats. Middle-aged rats also had fewer activity counts but were similar in stereotypy scores to young rats. Amphetamine also induced different patterns of Fos immunoreactivity in the neostriatum and nucleus accumbens of young and aged rats, as Fos expression in aged rats exhibited a distinctive dorsal to ventral pattern of decline. In general, SKF 38393 had few age-related actions, although aged rats did show a slight relative increase in stereotypy. In contrast, the D2 agonist quinpirole substantially enhanced the motor activity and Fos expression of young rats, while only modestly affecting aged rats. Hence, these results suggest that the D2 receptor is more vulnerable to the effects of aging than the D1 receptor.     

Effects of p,p'-DDE on male reproductive organs in peripubertal Wistar rats following a single intraperitoneal injection

The effects of p,p'-DDE on male reproductive organs were investigated in detail in peripubertal Wistar rats following a single intraperitoneal injection. 220 mg/kg of p,p'-DDE (1/4 of LD50) were injected once into prepubertal and postpubertal Wistar rats and its effects were observed until 20 weeks of age. Weights of the body and reproductive organs in p,p'-DDE-injected rats were similar to those in control rats, who were injected with corn oil only. Sperm profile parameters such as spermatid number within the testis, sperm number within the epididymis, sperm motility and its morphology were not different between the prepubertal or postpubertal p,p'-DDE-exposed group and the control group. Like-wise, the histopathological examination at stage VII of the seminiferous epithelium cycle, when the germ cells are sensitive to testosterone, was similar in all three groups during the observation period. Serum levels of testosterone also showed no significant changes by exposure to p,p'-DDE under the conditions of this study. From these results, the antiandrogenic or estrogenic activity attributed to p,p'-DDE was not confirmed in male reproductive organs and no impairment of sperm profile was observed. This study confirmed that the reproductive functions of matured animals are scarcely affected by p,p'-DDE exposure during the peripubertal period and revealed that they might be relatively resistant to exogenous endocrine-disrupting chemicals. p,p'-DDE may threaten the hormonal equilibrium required for normal gonadal development during the organogenesis period, at an earlier stage of life. Further studies are necessary to fully reveal all the effects of p,p'-DDE on male reproductive organs and sperm profile.     

Effect of GABA on motor activity in the rat during the early postnatal period

Effect of GABA on the motor activity of rats of the first month of life was studied in conditions of free behaviour in the maternal cage. It has been found that at the age of 1-10 days the injection of GABA increases, and at the age of 11-30 days decreases both the general motor activity and the grooming activity. It is suggested that a possible mechanism of the observed effect of GABA consists in the deepening of presynaptic inhibition, which results, during the earlier stages of postnatal ontogeny, in intensifying the autorhythmical activity of spinal motor centres, whereas during the later stages, when the autorhythmical activity of the spinal cord is replaced by reflex excitatory mechanisms, in depressing the latter.     

Role of intrahypothalamic insulin in circadian patterns of food intake, activity, and body temperature.

Examined the extent to which chronic intrahypothalamic (IH) insulin infusions that alter circadian patterns of food intake (FIN) affect the regulation of other diurnally varying behavior in the rat. One-week IH insulin infusion (1.5 μU/hr) significantly decreases rats' night FIN and increases day FIN but does not alter the diurnal pattern of activity. Mean daily core temperature increased slightly but significantly during insulin infusion, the daily peak of the body temperature rhythm did not shift significantly, and the daily range of body temperature increased. IH insulin infusion in rats living in constant light and thus without circadian rhythm of FIN led to significant decreases in FIN and body weight. These data support the conclusion that IH insulin infusion alters FIN and body weight through a specific effect on a neural system that regulates FIN and body weight, and not by altering circadian rhythms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)