Biomedical subjects

M L Andersen

Publications and source records attributed to M L Andersen.

At least 19 recordsLinked to original sources

PubMed2006

Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in intact and ovariectomized rats compared with male rats.

The purpose of this study was to investigate the effects of paradoxical sleep deprivation (PSD) on circulating lipoproteins (total cholesterol, HDL, LDL and triglycerides) in males as well as in intact and ovariectomized (OVX) female rats. The intact female rat group was sub-distributed according to the phase of the estrous cycle (proestrus, estrus and diestrus) allowing for comparison of the lipid profile with males and OVX rats. The results indicate that PSD significantly reduced cholesterol in intact females compared to OVX and male rats; it reduced triglycerides in all groups except in diestrus rats and increased HDL levels in male rats compared with the respective controls. PSD also increased LDL levels in male and OVX rats when compared to intact females. Examinations of cholesterol fractions revealed significant increases in HDL in control-OVX animals when compared to the other groups, whereas HDL was significantly increased after PSD in male rats. Such results suggest that the cardiovascular response in intact, OVX females and male rats is differentially regulated especially when such are submitted to PSD. Similarities in blood parameters observed between OVX and male rats are likely due to the suppression of ovarian hormone release after ovariectomy.

Animals↗

PubMed2006

Association of paradoxical sleep deprivation and ecstasy (MDMA) enhances genital reflexes in male rats.

Ecstasy ((+/-)3,4-methylenedioxymethamphetamine, MDMA) is a psychostimulant and a synthetic derivative of amphetamine that, according to its consumers, promotes the enhancement of sexual pleasure. This study sought to investigate the effects of ecstasy in the genital reflexes of paradoxical sleep deprived (PSD) male rats. Distinct groups of PSD rats were administered with saline or different doses of ecstasy. The incidence of genital reflexes was verified for 100 min. The four doses that were used induced genital reflexes in PSD animals and these significantly differed from their respective treated control groups. Under the influence of two intermediary doses (2.5 and 5mg/kg), all animals displayed erection and ejaculation. The frequency of genital reflexes was also significantly greater than in relation to the PSD-saline group. The comparison between cocaine and ecstasy in PSD rats revealed that ecstasy induced more erections and ejaculations than cocaine. Thus, the present results showed a great enhancement of the genital reflexes of PSD rats that might have occurred due to serotoninergic alterations induced by this illicit substance when associated to sleep deprivation.

Adrenergic Uptake Inhibitors↗

PubMed2006

Effects of progesterone on sleep: a possible pharmacological treatment for sleep-breathing disorders?

Progesterone is present in a wide spectrum of biological activity within a variety of tissues. This hormone is also known to affect reproduction, sleep quality, respiration, mood, appetite, learning, memory and sexual activity. Progesterone exerts a sleep induction or hypnotic effect and is a potent respiratory stimulant that has been associated to a decrease in the number of central and obstructive sleep apnea episodes in men. The literature also contains a substantial amount of data on the effect of apnea in women with obesity-hypoventilation during menopause. This review attempts to outline the specific role of progesterone in normal sleep and breathing as well as its possible therapeutic effects in the treatment of sleep-disordered breathing.

Female↗

PubMed2005

Sleep pattern in rats under different stress modalities.

The present study was designed to evaluate the sleep pattern of rats submitted to chronic stressors (restraint, electrical footshock, swimming and cold) applied to male rats. After 48 h-baseline recording, rats were submitted to 4 days of chronic stress, and electrocorticogram recordings were carried out continuously. The stressors (footshock, swimming and cold) were applied twice a day for periods of 1 h at 9:00 and 16:00 h. Restrained animals were maintained in plastic cylinders for 22 h/day. The findings indicated that sleep efficiency, slow wave sleep (SWS) and paradoxical sleep (PS) were decreased on the third and fourth days of unpredictable shocks compared to baseline while immobilization and swimming presented reduced sleep efficiency in all 4-day recordings. Swimming led to decreased SWS, whereas augmented PS was observed on the first day compared to baseline. Immobilization produced drastic alterations in sleep patterns since it reduced SWS during the 4 days and PS at days 1 to 4 in relation to baseline. Of all stressors, cold was the only one that did not result in any statistical differences in sleep pattern during the light periods. Regarding the effect of stress compared to baseline on the dark recordings, PS was higher during cold stress periods, whereas footshock increased PS on days 2 to 4 and swimming only on day 2. Immobilization decreased PS throughout the 4 days of the stress sessions. Thus, the data suggest that different stress modalities result in distinct sleep responses, with immobilization producing the most dramatic alterations.

Animals↗

PubMed2004

Different stress modalities result in distinct steroid hormone responses by male rats.

Since both paradoxical sleep deprivation (PSD) and stress alter male reproductive function, the purpose of the present study was to examine the influence of PSD and other stressors (restraint, electrical footshock, cold and forced swimming, N = 10 per group) on steroid hormones in adult Wistar male rats. Rats were submitted to chronic stress for four days. The stressors (footshock, cold and forced swimming) were applied twice a day, for periods of 1 h at 9:00 and 16:00 h. Restrained animals were maintained in plastic cylinders for 22 h/day whereas PSD was continuous. Hormone determination was measured by chemiluminescent enzyme immunoassay (testosterone), competitive immunoassay (progesterone) and by radioimmunoassay (corticosterone, estradiol, estrone). The findings indicate that PSD (13.7 ng/dl), footshock (31.7 ng/dl) and cold (35.2 ng/dl) led to lower testosterone levels compared to the swimming (370.4 ng/dl) and control (371.4 ng/dl) groups. However, progesterone levels were elevated in the footshock (4.5 ng/ml) and PSD (5.4 ng/ml) groups compared to control (1.6 ng/ml), swimming (1.1 ng/ml), cold (2.3 ng/ml), and restrained (1.2 ng/ml) animals. Estrone and estradiol levels were reduced in the PSD, footshock and restraint groups compared to the control, swimming and cold groups. A significant increase in corticosterone levels was found only in the PSD (299.8 ng/ml) and footshock (169.6 ng/ml) groups. These changes may be thought to be the full steroidal response to stress of significant intensity. Thus, the data suggest that different stress modalities result in distinct steroid hormone responses, with PSD and footshock being the most similar.

Animals↗

PubMed2004

Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats.

The effects of 96 h of paradoxical sleep deprivation (PSD) on blood parameters associated with cardiovascular risk were studied in young (3-month old) and aged (22-month old) rats. In general, aging was associated with an overall increase in most measures, irrespective of sleep deprivation condition. The latter manipulation also had significant effects on blood variables, but not in a consistent pattern. Thus, PSD significantly reduced triglyceride levels in both young and aged rats; it reduced blood viscosity in aged but not in young rats, and had no effect on the increased cholesterol levels observed in aged controls. Examinations of cholesterol fractions revealed significant increases in low density lipoprotein and high density lipoprotein in aged PSD rats compared to respective controls, whereas very low density lipoprotein was significant decreased after PSD in both young and aged animals. PSD increased vitamin B(12) levels in aged rats, and significantly decreased homocysteine levels in young but not in aged rats which in turn were already reduced. Folate levels were the only variable that was unaffected by aging and/or PSD. These results indicate that PSD has significant but heterogeneous physiological effects in aged rats and may intensify certain aging-related effects which contribute to cardiovascular disease risk while attenuating others.

Age Factors↗

PubMed2004

Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice.

Numerous animal and clinical studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Mice were sleep deprived for 72 h by the multiple platform method-groups of 4-6 animals were placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface. Mice kept in their home cage or placed onto larger platforms were used as control groups. The results showed that hippocampal oxidized/reduced glutathione ratio as well as lipid peroxidation of sleep-deprived mice was significantly increased compared to control groups. The same procedure of sleep deprivation led to a passive avoidance retention deficit. Both passive avoidance retention deficit and increased hippocampal lipid peroxidation were prevented by repeated treatment (15 consecutive days, i.p.) with the antioxidant agents melatonin (5 mg/kg), N-tert-butyl-alpha-phenylnitrone (200 mg/kg) or vitamin E (40 mg/kg). The results indicate an important role of hippocampal oxidative stress in passive avoidance memory deficits induced by sleep deprivation in mice.

Animals↗

PubMed2004

Cholinergic mechanisms in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats.

In view of the fact that paradoxical sleep deprivation (PSD) modifies cocaine-induced genital reflexes (penile erection [PE] and ejaculation [EJ]), the aim of this study was to address the interaction of cholinergic agents with the action of cocaine on the genital reflexes of PSD male rats. After a 4-day period of PSD, each group was administered with cholinergic drugs 1 h prior to cocaine and was placed in observation cages. The administration of nicotine (0.12, 0.25, 0.5 and 1 mg/kg sc) reduced the frequency and number of animals displaying PE and increased PE latency. Pretreatment with mecamylamine (1.25, 5, 10 and 20 mg/kg sc) also significantly reduced PE frequency for all doses used. The percentage of rats showing EJ was significantly reduced in the group pretreated with 1 mg/kg of nicotine compared with the saline group. The administration of pilocarpine (1.25, 2.5, 5 and 10 mg/kg sc) and atropine (1.25, 5, 10 and 20 mg/kg sc) led to a reduction in the frequency of PE displayed by the rats. These data show that agonist and antagonist cholinergic drugs inhibit genital reflexes in PSD male rats injected with cocaine. The data also suggest that the stimulating action of cocaine in potentiating the sexual effects in PSD rats does not override the effects of the cholinergic mechanisms of sexual behavior.

Animals↗

PubMed2004

Inhibitory effect of GABAergic drugs in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats.

The aim of this study was to seek whether GABAergic drugs were involved in the action of cocaine on spontaneous genital reflexes (penile erection-PE, and ejaculation-EJ) of paradoxical sleep-deprived (PSD) male rats. After a 4-day period of PSD, each group was administered with GABAergic drugs 1 h prior to cocaine and placed in observation cages. The administration of gamma-aminobutyric acid (GABA)-A agonist (muscimol, 2 and 3 mg/kg sc) reduced the number of animals displaying PE, whereas all doses tested of muscimol and bicuculline significantly reduced the frequency of PE. Pretreatment with the lower doses of GABA-B antagonist, phaclofen (1 and 2 mg/kg sc), also significantly reduced the percentage of rats showing PE; however, after the higher dose injection, the proportion of animals with PE was similar to those seen after vehicle pretreatment. Both GABA-B agonist and antagonist significantly reduced the PE frequency for all doses used compared with the vehicle group. There were no significant differences between control and GABA-A drugs in EJ behavior, whereas phaclofen 2 mg/kg pretreatment increased the ejaculatory latency. These data show that GABAergic compounds inhibited PE in male PSD rats suggesting that this inhibition points to a differential role of GABA receptor subtypes.

Animals↗

PubMed2004

Effects of morphine or naloxone on cocaine-induced genital reflexes in paradoxical sleep-deprived rats.

The involvement of opioidergic neurotransmission in the modulation of genital reflexes induced by paradoxical sleep deprivation (PSD) and cocaine in rats was the aim of the present study. Morphine (0, 1, 5 and 10 mg/kg) and naloxone (0, 0.3, 3 and 30 mg/kg) were administered prior to saline or cocaine to rats that had been deprived of sleep and the incidence of penile erections (PE) and ejaculations (EJ) was measured. PSD alone induced PE in 50% and EJ in 20% of the rats, but these behaviors were not influenced by morphine or naloxone. Cocaine potentiated the incidence of genital reflexes in PSD rats to 90% (PE) and 70% (EJ). Morphine and not naloxone significantly reduced the percentage of rats displaying this response at the highest doses. Morphine also significantly reduced PE and EJ frequencies at 10 mg/kg. Furthermore, this inhibitory effect of morphine on genital reflexes was prevented by the prior injection of naloxone. Although a number of factors are involved in such a complex phenomenon as PE and EJ, our data show that activation of the opioidergic systems by the agonist morphine reduces genital reflexes-induced by cocaine in PSD males while the antagonist, naloxone, did not have any significant effect. The findings suggest that the stimulating effects of cocaine in potentiating genital reflexes in PSD rats can be unidirectionally modified by opioidergic systems.

Animals↗

PubMed2004

Influence of temporomandibular joint pain on sleep patterns: role of nitric oxide.

Since nitric oxide is related to nociception and the sleep-wake cycle, this study sought to determine its involvement in the altered sleep pattern in a temporomandibular joint pain model by investigating the effect of the inhibitor of nitric oxide synthase (L-NAME) and that of its precursor (L-arginine). The temporomandibular joints of test animals were injected with Freund's adjuvant or saline, and their sleep was recorded. The procedure was repeated after the administration of L-NAME and L-arginine. L-NAME increased rapid eye movement (REM) sleep in the control group. The orofacial pain group showed a reduction in total sleep time and an increase in sleep latency compared with the SHAM group. L-NAME increased sleep time, non-rapid eye movement (NREM), and REM sleep and reduced sleep latency in the orofacial pain group. L-arginine did not alter sleep parameters. Thus, L-NAME improved sleep efficiency, whereas L-arginine did not modify it, suggesting the involvement of nitric oxide in painful temporomandibular joint conditions.

Animals↗

PubMed2003

Sleep alterations in an experimental orofacial pain model in rats.

This study sought to assess sleep patterns in rats injected with Freund's adjuvant (FA) in the temporomandibular joint (TMJ) as a potential experimental orofacial pain model. Pain response to indomethacin was also assessed. Rats were implanted with electrodes to record electrocorticogram and eletromyogram signals. After a baseline (B) recording, they were injected with Freund's adjuvant (orofacial pain group, n=8) or saline (sham group, n=8) in the temporomandibular joint, and their sleep was monitored over two 12-h light periods. In the second phase of the study, after injecting Freund's adjuvant, indomethacin was administered (1 mg/kg p.o.) at 12- intervals, and sleep patterns were recorded for two additional light periods. The orofacial pain group showed a reduction in sleep efficiency during the two light periods compared with the baseline recording and with the sham group (p<0.001). Increases in sleep and paradoxical sleep (PS) latencies of approximately 200% and 420%, respectively, were observed, as well as an increase in the number of awakenings during both periods (p<0.001). Treatment with indomethacin increased sleep efficiency (p<0.001) and paradoxical sleep time (p<0.001). The number of awakenings (p<0.001) and sleep (p<0.001) and paradoxical sleep latencies (p<0.001) were reduced reestablishing the normal sleep pattern. The results showed the reliability and usefulness of the temporomandibular joint pain model to characterize sleep disturbances related to pain and its response to indomethacin.

Analysis of Variance↗

PubMed2001

Modification of the levels of polyphenols in wort and beer by addition of hexamethylenetetramine or sulfite during mashing.

The effects of addition of hexamethylenetetramine (HMT) or sulfite during mashing on the polyphenol content and oxidative stability of wort and beer have been evaluated in a series of laboratory mashings and pilot brews. HMT reduced the concentration of catechin, prodelphinidin B-3, and procyanidin B-3 in wort and beer, whereas the concentration of ferulic acid was unaffected. Sulfite had only a minor effect on the concentration of phenolics in wort and beer. Addition of HMT or sulfite during mashing increased the oxidative stability of the beer slightly as judged by the tendency of formation of radicals (ESR spin trapping technique), although sensory analysis gave identical flavor acceptance scores to beers produced from untreated and HMT-treated wort and lower scores to beer from sulfite-treated wort. No difference in the oxidative stability of the differently treated sweet worts could be detected as judged by the rate of formation of radicals. HMT addition during mashing has thus been demonstrated to be a valuable experimental tool to control the level of polyphenols in wort and for producing brews with various levels of polyphenols from a single malt.

Beer↗

PubMed2001

Physiology and pathophysiology of renal aquaporins.

The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have shown that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells and AQP8 are present intracellularly at low abundance in proximal tubules and collecting duct principal cells but the physiological function of these 2 channels remain undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. A series of studies have underscored crucial roles of aquaporins for regulation of renal water metabolism and hence body water balance. Moreover it has become clear that dysregulation of aquaporins, and especially AQP2 is critically involved in many water balance disorders. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.

Animals↗

PubMed2001

Expression and immunolocalization of aquaporin water channels in rat exocrine pancreas.

Both the acinar and ductal cells of the pancreas secrete a near-isotonic fluid and may thus be sites of aquaporin (AQP) water channel expression. Northern blot analysis of mRNA from whole rat pancreas revealed high levels of AQP1 and AQP8 expression, whereas lower levels of AQP4 and AQP5 expression were just detectable by RT-PCR Southern blot analysis. Immunohistochemistry showed that AQP1 is localized in the microvasculature, whereas AQP8 is confined to the apical pole of the acinar cells. No labeling of acinar, ductal, or vascular tissue was detected with antibodies to AQP2-7. With immunoelectron microscopy, AQP8 labeling was observed not only at the apical membrane of the acinar cells but also among small intracellular vesicles in the subapical cytoplasm, suggesting that there may be regulated trafficking of AQP8 to the apical plasma membrane. To evaluate the contribution of AQPs to the membrane water permeability, video microscopy was used to measure the swelling of acinar cells in response to hypotonic stress. Osmotic water permeability was reduced by 90% following exposure to Hg(2+). Since AQP8 is confined to the apical membrane, the marked effect of Hg(2+) suggests that other water channels may be expressed in the basolateral membrane.

Algorithms↗

PubMed2000

[How do patients evaluate the newly introduced system of substituting prescriptions?].

In 1997 a new prescription system was introduced in Denmark. The pharmacist must now substitute the prescribed drug with a cheaper version either by a generic prescription (G-substitution) or by an original prescription (O-substitution) unless the prescribing doctor indicates that substitution is not allowed in the specific case. The purpose of this study was to obtain the patients' view on the new prescription system and to identify any related problems. The investigation was based on structured interviews. The interview guide was designed as a questionnaire, which was validated and tested before use. The response rate was 82%. The study showed that 84% of the patients were satisfied with the system and 85% of the patients thought that it should continue. Eighty-three percent of the patients had tried another version of the substituted medicine earlier. Out of these, 6% had experienced more side-effects from the substituted medicine, and 10% felt that the substituted medicine had a weaker effect. There was one case of erroneous medical treatment as a consequence of the substitution system. Only few problems such as more side-effects or less effect of the substituted medicine was experienced by the patients. It can be concluded that the patients in general are satisfied with the new prescription system.

Adult↗

PubMed2000

[How do practitioners evaluate the newly introduced system of substituting prescriptions?].

AIMS: In 1997 a new prescription system was introduced in the Danish health care system. The pharmacist must now substitute a prescribed drug with a cheaper version, either generic (G-substitution) or original (O-substitution) unless the general practitioner (GP) indicates that substitution is not allowed. The purpose of this study was to obtain the GPs' views on the system and evaluate the problems related to the system. METHODS: The study was based on questionnaires to GPs developed via qualitative interviews with the GPs and afterwards pilot tested. RESULTS: Out of 300 GPs the response rate was 80%. The study showed that 61% of the GPs were dissatisfied with the system and thought that it should be removed. There were several reasons for this: the system was incomprehensible, the introduction and information about the system was insufficient and the extra workload was too heavy. All the GPs agreed that analogue substitution (substitution between drugs with the same effect obtained by different means) was medically unjustifiable and should not be introduced.

Adult↗

PubMed2000

[How do pharmacists evaluate the newly introduced system of substituting prescriptions?].

In 1997 a new prescription system was introduced in the Danish health care system. The pharmacist must now substitute a prescription with a cheaper version of the drug (either generic or original) unless the prescribing doctor indicates that substitution is not allowed in the specific case. The purpose of this study was to evaluate problems of the system and obtain the pharmacists' views on the system. The study was based on questionnaires to a representative sample of 75 pharmacists (a quarter of Denmark's pharmacists). The response rate was 72%. Half of the pharmacists were dissatisfied with the system, which primarily was due to the excessive workload imposed. In spite of this, about half the pharmacists wanted the system to be continued, because the overall purpose of finding the cheapest drug for the patient is good. Nearly all pharmacists thought that analogue substitution (substitution between drugs with the same overall effects but obtained by different means) should not be introduced.

Adult↗