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S Mathias

Publications and source records attributed to S Mathias.

At least 19 recordsLinked to original sources
PubMed2006

Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans.

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor. It is hypothesised to play a key role in energy balance stimulating food intake and body weight. Besides GH-releasing hormone (GHRH) and somatostatin, it is thought to be a regulating factor of GH release. Ghrelin also appears to be involved in sleep regulation. We showed recently that ghrelin promotes slow-wave sleep and the nocturnal release of GH, cortisol and prolactin in humans. Similarly, promotion of non-rapid-eye-movement (NREM) sleep was reported in mice after systemic ghrelin. If ghrelin is a factor that induces and/or maintains sleep, it should be enhanced after a period of sleep deprivation (SD). To clarify this issue, nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined and simultaneously sleep electroencephalogram (EEG) was recorded (2300-0700 h) during sleep before and after 1 night of total SD in 8 healthy subjects. Compared to baseline, ghrelin levels increased earlier by a non-significant trend, already before the beginning of recovery sleep. Further a non-significant trend occurred, suggesting higher ghrelin secretion in the first half of the night. The ghrelin maximum was found significantly earlier after SD than at baseline. GH secretion during the first half of the night and total night after SD were elevated. ACTH and cortisol were also elevated, which was most pronounced during the second half of the night. No effects of SD on the time of the maximum were found for GH, ACTH and cortisol. The increase in ACTH after SD is a novel finding. Whereas the effects of SD on ghrelin levels were relatively weak, our findings are in line with the hypothesis that ghrelin is a sleep-promoting factor in humans. Ghrelin may be involved in sleep promotion after SD.

Adrenocorticotropic Hormone↗
PubMed2005

Placentation in the African elephant, Loxodonta africanus: III. Ultrastructural and functional features of the placenta.

Successful transfer of nutrients to the elephant fetus during pregnancy relies on a variety of placental modifications. Our light and electron microscopical investigations show that the structure is endotheliochorial from implantation to term, with unicellular, never syncytial trophoblast. Light and electron microscope immunocytochemistry shows the restriction of the glucose transporter 1 isoform to the basolateral surfaces of the trophoblast, with the glucose transporter 3 restricted to the apical plasmalemma of the trophoblast. Glucose transport to the fetus therefore requires a sequential use of both isoforms. Light and electron microscope cytochemistry indicate the presence of iron deposits only in the haemophagous zones confirming their iron transport function. No trophoblast areas with high concentrations of Calcium binding protein, specialised for Calcium transport were found. In situ hybridisation demonstrated the presence of IGF-II mRNA in the trophoblast from the earliest stage, with TGFbeta1 and HGF-SF mRNA expressed subsequently but only IGF-II and HGF mRNA present in the second half of pregnancy. The results are briefly discussed in terms of placental growth and function and indicate that the elephant placenta is another example of a unique solution to the variety of problems posed by a resident fetus.

Animals↗
PubMed2005

Placentation in the African elephant, Loxodonta africana. IV. Growth and function of the fetal gonads.

The gonads, both ovaries and testes, of 44 elephant fetuses weighing 0.09-112 kg (6.1-21.3 months gestation) were examined grossly and histologically. As in equids, elephant fetal gonads undergo a phase of marked growth and enlargement during the second half of gestation, which is more pronounced in ovaries than testes due to growth and antrum formation of numerous follicles in the former. Stromal cells undergo hypertrophy and transformation to form zones of interstitial cells that are associated with the enlarged follicles in the ovaries and in which the primitive seminiferous tubules are embedded in the testes. The interstitial cells have the capacity to synthesize 5alpha-dihydroprogesterone and other 5alpha-reduced progestagens from cholesterol and pregnenelone and the hypothesis is raised that these fetal gonadal progestagens may supplement significantly the progestagens secreted by the multiple large corpora lutea of pregnancy in the elephant.

Animals↗
PubMed2003

Placentation in the African elephant (Loxodonta africana): II morphological changes in the uterus and placenta throughout gestation.

The gross and microscopic development of the zonary endotheliochorial placenta in the African elephant was studied in 22 gravid uteri that ranged in gestational stage from 0.5 to 20.6 months. The conceptus only ever occupies one horn of the uterus and is associated with 2-5 large corpora lutea that persist in the ipsilateral ovary throughout gestation. Initially, the trophoblast in the equatorial region of the conceptus completely replaces the lumenal epithelium of the endometrium to which it is apposed. Blunt upgrowths of endometrial stroma then develop, each closely invested by trophoblast, and containing the capillaries that will vascularize this maternal component of the resulting placental band. With advancing gestation the lamellate stromal upgrowths increase markedly in length and become much thinner, thereby bringing the trophoblast into intimate contact with the endothelium of the maternal capillaries. They also become folded or pleated to increase the total area of intimate feto-maternal contact. At the lateral edges of the placental band the lamellae bend over towards the endometrium to form a blind cleft. Leakage of blood into this area creates haemophagous zones in which phenotypically specialized trophoblast cells phagocytose the blood components. The presence of large resorbing blood clots and circumferential scars in the uteri of three post parturient animals initiated the hypothesis that, when the standing elephant gives birth at term, the passage of the 120 kg fetus through the vagina may wrench the placenta off the endometrium by severing its very narrow maternal placental hilus. The resulting intrauterine haemorrhage may then play a role in preventing further conception for around 2 years.

Animals↗
PubMed2002

Ghrelin promotes slow-wave sleep in humans.

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor, stimulates GH release, appetite, and weight gain in humans and rodents. Synthetic GHSs modulate sleep electroencephalogram (EEG) and nocturnal hormone secretion. We studied the effect of 4 x 50 microg of ghrelin administered hourly as intravenous boluses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, ACTH, cortisol, prolactin, and leptin in humans (n = 7). After ghrelin administration, slow-wave sleep was increased during the total night and accumulated delta-wave activity was enhanced during the second half of the night. Rapid-eye-movement (REM) sleep was reduced during the second third of the night, whereas all other sleep EEG variables remained unchanged. Furthermore, GH and prolactin plasma levels were enhanced throughout the night, and cortisol levels increased during the first part of the night (2200-0300). The response of GH to ghrelin was most distinct after the first injection and lowest after the fourth injection. In contrast, cortisol showed an inverse pattern of response. Leptin levels did not differ between groups. Our data show a distinct action of exogenous ghrelin on sleep EEG and nocturnal hormone secretion. We suggest that ghrelin is an endogenous sleep-promoting factor. This role appears to be complementary to the already described effects of the peptide in the regulation of energy balance. Furthermore, ghrelin appears to be a common stimulus of the somatotropic and hypothalamo-pituitary-adrenocortical systems. It appears that ghrelin is a sleep-promoting factor in humans.

Adrenocorticotropic Hormone↗
PubMed2001

The GABA(A) agonist gaboxadol improves the quality of post-nap sleep.

RATIONALE: Previous studies demonstrated that gaboxadol, a selective GABA(A) agonist, increases both non-REM sleep and EEG delta activity within non-REM sleep in rats and slow wave sleep (SWS) as well as low-frequency activity in the EEG within non-REM sleep in healthy humans under normal conditions. OBJECTIVE: Because the hypnotic actions of drugs may be more readily demonstrated under conditions of poor sleep quality, we investigated the influence of gaboxadol on postnap sleep. METHODS: In a randomized, placebo-controlled cross-over study using a late afternoon nap model, we assessed the effects of a single oral dose of 20 mg gaboxadol on disturbed nighttime sleep in young, healthy subjects. RESULTS: Comparisons of visually scored sleep parameters between baseline and placebo postnap nights showed that the nap prolonged sleep latency, decreased total sleep time and SWS and attenuated delta, theta and alpha activity in the EEG within non-REM sleep. Compared with the placebo postnap night, gaboxadol tended to shorten sleep latency, significantly decreased intermittent wakefulness, increased total sleep time and SWS and enhanced delta and theta activity in the non-REM EEG. Furthermore, gaboxadol increased subjective sleep quality. CONCLUSIONS: These data show that gaboxadol counteracts the disrupting effects of a nap on subsequent sleep and suggest that, in addition to promoting deep sleep and sleep maintenance, gaboxadol is able to facilitate sleep initiation and thus, exhibits significant hypnotic actions under conditions in which sleep quality is experimentally reduced.

Adult↗
PubMed2001

Acute effects of melatonin on spontaneous and picrotoxin-evoked sleep-wake behaviour in the rat.

Various studies indicate that exogenous melatonin has hypnotic properties in humans, which may be mediated by its influence on the circadian timing system or direct sleep-promoting actions, e.g. through a modulation of GABAergic transmission. The aim of the present placebo-controlled study was to examine the effects of melatonin on sleep in rats and the contribution of gamma-aminobutyric acid (GABA)A receptors. Sleep-wake behaviour was assessed in nine rats after intraperitoneal (i.p.) administration of pharmacological doses of melatonin (5 and 10 mg kg(-1)) and after combined administration of the GABAA receptor antagonist picrotoxin (1.5 mg kg(-1)) and melatonin (10 mg kg(-1)). To prevent chronobiotic effects, melatonin was delivered in the middle of the light period. Neither doses of melatonin exerted significant effects on brain temperature, sleep architecture or sleep electroencephalogram (EEG). Moreover, melatonin failed to attenuate the picrotoxin-induced promotion of wakefulness. These observations indicate that melatonin hardly influences sleep-wake behaviour in rats.

Animals↗
PubMed2001

Effect of the GABAA agonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects.

Aging is associated with a dramatic decrease in sleep intensity and continuity. The selective GABA(A) receptor agonist gaboxadol has been shown to increase non-REM sleep and the duration of the non-REM episodes in rats and sleep efficiency in young subjects and to enhance low-frequency activity in the electroencephalogram (EEG) within non-REM sleep in both rats and humans. In this double-blind, placebo-controlled study, we investigated the influence of an oral dose of 15 mg of gaboxadol on nocturnal sleep and hormone secretion (ACTH, cortisol, prolactin, growth hormone) in 10 healthy elderly subjects (6 women). Compared with placebo, gaboxadol did not affect endocrine activity but significantly reduced perceived sleep latency, elevated self-estimated total sleep time, and increased sleep efficiency by decreasing intermittent wakefulness and powerfully augmented low-frequency activity in the EEG within non-REM sleep. These findings indicate that gaboxadol is able to increase sleep consolidation and non-REM sleep intensity, without disrupting REM sleep, in elderly individuals and that these effects are not mediated by a modulation of hormone secretion.

Aged↗
PubMed2000

Diurnal variations in lipopolysaccharide-induced sleep, sickness behavior and changes in corticosterone levels in the rat.

Inoculation of rats with microorganisms or microbial constituents that activate host defense promotes non-rapid eye movement sleep (non-REMS) and suppresses REMS. In this study, we evaluated circadian influences on the effects of lipopolysaccharide (LPS) on sleep, sickness behavior and plasma corticosterone levels in the rat. Three sets of experiments were performed. In each, the animals were intraperitoneally injected with vehicle for LPS (30 microg/kg) during 2 consecutive days, at the beginning of either the circadian rest or the activity phase. In experiment 1, sleep-wake behavior and brain temperature were recorded, and in experiment 2, core body temperature, locomotor activity as well as food and water intake. In experiment 3, corticosterone blood levels were measured. The results show that LPS-evoked changes in temperature, sleep and other behavioral parameters depend markedly on the time of day LPS is administered. However, a direct comparison of the LPS data demonstrates that, except for sleep parameters, the absolute time course of the assessed parameters was rather similar between the rest and activity phases. These findings suggest that LPS evokes a state characterized by high temperature and low vigilance, which is reached independently of the circadian phase.

Animals↗
PubMed1998

Signal transduction of stress via ceramide.

The sphingomyelin (SM) pathway is a ubiquitous, evolutionarily conserved signalling system analogous to conventional systems such as the cAMP and phosphoinositide pathways. Ceramide, which serves as second messenger in this pathway, is generated from SM by the action of a neutral or acidic SMase, or by de novo synthesis co-ordinated through the enzyme ceramide synthase. A number of direct targets for ceramide action have now been identified, including ceramide-activated protein kinase, ceramide-activated protein phosphatase and protein kinase Czeta, which couple the SM pathway to well defined intracellular signalling cascades. The SM pathway induces differentiation, proliferation or growth arrest, depending on the cell type. Very often, however, the outcome of signalling through this pathway is apoptosis. Mammalian systems respond to diverse stresses with ceramide generation, and recent studies show that yeast manifest a form of this response. Thus ceramide signalling is an older stress response system than the caspase/apoptotic death pathway, and hence these two pathways must have become linked later in evolution. Signalling of the stress response through ceramide appears to play a role in the development of human diseases, including ischaemia/reperfusion injury, insulin resistance and diabetes, atherogenesis, septic shock and ovarian failure. Further, ceramide signalling mediates the therapeutic effects of chemotherapy and radiation in some cells. An understanding of the mechanisms by which ceramide regulates physiological and pathological events in specific cells may provide new targets for pharmacological intervention.

Animals↗
PubMed1998

Multicenter comparison of two clinical decision rules for the use of radiography in acute, high-risk knee injuries.

STUDY OBJECTIVE: Two separate clinical decision rules, one developed in Ottawa and the other in Pittsburgh, for the use of radiography in acute knee injuries have been previously validated and published. In this study, the rules were prospectively validated and compared in a new set of patients. METHODS: A prospective, blinded, multicenter trial was conducted in the emergency departments of three urban teaching hospitals. A convenience sample of 934 patients with knee pain requiring radiographs was enrolled. A standardized data form was completed for each patient, comprising the 10 clinical variables included in the two rules. Standard knee radiographs were then taken in each patient. The rules were interpreted by the primary investigator on the basis of the data sheet and the final radiologist radiograph reading. RESULTS: In the 745 patients in whom the Pittsburgh rules could be applied there were 91 fractures (12.2%). The use of the Pittsburgh rule missed one fracture, yielding a sensitivity of 99% (95% confidence interval [CI], 94% to 100%); the specificity was 60% (95% CI, 56% to 64%). The Ottawa inclusion criteria were met by 750 patients, with 87 fractures (11.6%). The Ottawa rule missed three fractures, for a sensitivity of 97% (95% CI, 90% to 99%); specificity was 27% (95% CI, 23% to 30%). CONCLUSION: Prospective validation and comparison found the Pittsburgh rule for knee radiographs to be more specific without loss of sensitivity compared with the Ottawa rule.

Acute Disease↗
PubMed1997

Soluble tumor necrosis factor receptor (p75) does not attenuate the sleep changes induced by lipopolysaccharide in the rat during the dark period.

Sleep is generally enhanced during the early phase of infection. The cytokine tumor necrosis factor (TNF) has been postulated to play an important role in the acute phase sleep response. After demonstrating the ability of a soluble p75 TNF receptor (TNFR) to inhibit TNF activity in vitro, we assessed the influence of TNFR on the sleep changes evoked by lipopolysaccharide (LPS). In this vehicle-controlled experiment, 24 rats received either an intracerebroventricular injection of 10 micrograms TNFR, an intraperitoneal injection of 30 micrograms/kg LPS, or both, at the beginning of the dark period. EEG, EMG and brain temperature (Tbr) were recorded during the first 12 h post injection. Compared with vehicle, LPS had minimal effects on Tbr, but promoted non-rapid eye movement sleep (non-REMS), suppressed REMS, shortened the sleep episodes and decreased high-frequency (> or = 8 Hz) EEG activity during non-REMS. TNFR alone had no significant effects and did not attenuate any of the LPS-induced sleep changes. These results may either indicate that TNF is not critically involved in the sleep response to a low level LPS challenge during the activity phase or that the soluble p75 TNFR does not effectively antagonize the sleep changes evoked by TNF.

Animals↗
PubMed1997

Resurgence of tuberculosis: implications for emergency nurses.

An emergency nurse is often the first person with contact with patients with suspected or known TB when they come to the emergency department. With rapid recognition of signs and symptoms of active TB and prompt implementation of precautions, emergency nurses can reduce the transmission of the "greatest killer of mankind" to other patients, visitors, health care workers, and ourselves.

Emergency Nursing↗
PubMed1997

Maternal response to paternal trophoblast antigens.

PROBLEM: What is the function of the immunoglobulin (Ig) G antibody bound to trophoblast in normal pregnancy, and what is the antigen? METHOD: IgG was acid eluted from term human placental microvesicles and reacted with the antigen, R80K, left on the vesicles. The eluted antibody was used to detect the antigen on monocytes, lymphocytes, and lymphoblastoid cell lines. The eluted antibody is highly polymorphic, but monoclonal antibodies (mAbs) were made against conserved regions of the molecule. These also reacted with the murine equivalent of the human R80K and were used in inhibition studies of natural killer (NK) cell killing and the mouse abortion models, CBA x DBA2 F1 resorption in CBA females, the endotoxin-induced resorption model, and a sonic stress-induced murine resorption model. RESULTS: All 600 syncytiotrophoblast microvesicle preparations of human term placenta had IgG antibody bound, elutable at pH 3.0. The eluted antibody reacted with about 15% of unrelated human placentae. In horses mares make detectable antibody early in pregnancy, at about the time of implantation. The IgG antibody was bound to an 80-kDa protein (R80K) also detected on B lymphocytes and monocytes. In HLA homozygous lymphoblastoid B cell lines, which reacted with one or more eluted antibodies, had a pattern of cytotoxicity independent of HLA Class I; and as a single 80-kDa peptide chain, R80K did not resemble HLA molecules. Genetic studies in horses show that of the two paternal allotypes of R80K detectable by placental alloantibodies, only one, usually the grandpaternal one, is present in all the placentae of a sibship. Two of 26 eluted human antibodies had affinity for K562 and inhibited killing by human peripheral blood NK cells. One mAb, BA11, against a conserved site on R80K inhibited killing of K562, and also reacted with the murine R80K homologue. BA11 inhibited murine NK cell killing and virtually completely inhibited three NK cell-dependent mouse resorption models. CONCLUSION: R80K protein is a target molecule for NK cell activity expressed on all placentae. It has a polymorphic alloantigenic determinant completely covered with maternal antibody in all successful term pregnancies. In murine NK cell-dependent models of abortion, a mAb against a monomorphic determinant present in human and murine R80K prevents abortion very effectively. It seems that the R80K molecule must be covered with antibody to prevent NK attacks on trophoblast.

Animals↗
PubMed1997

Muscimol and midazolam do not potentiate each other's effects on sleep EEG in the rat.

The interaction of a gamma-aminobutyric acid-A (GABAA) receptor agonist and a benzodiazepine-type modulator of GABAA receptors on sleep was investigated. Low doses of muscimol (0.3 mg/kg) and the benzodiazepine midazolam (1.5 mg/kg) were administered alone and in combination, in random order, to eight rats. All injections were given intraperitoneally at light onset. Electroencephalogram (EEG) and electromyogram were recorded during the first 6 h post injection. Compared with vehicle, muscimol hardly affected the time spent in non-rapid eye movement sleep (non-REMS) and REMS, but significantly enhanced EEG activity in the frequency range between 2 and 6 Hz during non-REMS. Midazolam significantly increased the time spent in non-REMS, reduced EEG activity at frequencies < 12 Hz, and elevated EEG activity in most higher frequencies during this state. The combined administration of muscimol and midazolam affected non-REMS-specific EEG activity in an unexpected fashion: the effects were intermediate between those of muscimol and midazolam. These results indicate that muscimol and midazolam have dissimilar effects on EEG within non-REMS and demonstrate that midazolam does not augment but attenuates the muscimol-induced changes in sleep EEG. Our data are at variance with established mechanisms, according to which agonistic modulators would have similar effects and should potentiate the effects of GABAA agonists. The present data suggest that application of agonists and agonistic modulators of GABAA receptors causes differential net effects on sleep parameters.

Animals↗
PubMed1996

The use of propofol for sedation in the emergency department.

OBJECTIVE: To evaluate the effectiveness of propofol and fentanyl when used by emergency physicians (EPs) for systemic sedation and analgesia in the ED. METHODS: Over an eight-month period, a convenience sample of consenting patients at an urban teaching hospital ED who required sedation for painful procedures were enrolled in a descriptive study of therapeutic propofol sedation. After receiving 2 micrograms/kg of fentanyl i.v. the patients received a continuous infusion of propofol at 0.21 mg/kg/min i.v. to the desired level of sedation. A maintenance infusion of 3-6 mg/kg/hr was administered during the remainder of the procedure. Sedation time, total procedure time, and recovery time were recorded and the presence of side effects was noted. The patients and the physicians rated their satisfaction with the technique on a 100-mm visual analog scale. The patients were contacted at 24 hours for follow-up information. RESULTS: Twenty patients (aged 19-62 years) received propofol infusion for procedures that included ten abscess incision and drainages, eight orthopedic reductions, one chest tube placement, and one wound exploration. The mean (+/- SD) total dose of propofol was 200 +/- 160 mg. The mean time to onset of sedation was 6.6 +/- 3.2 min, the mean procedure interval was 9.6 +/- 6.3 min, and the mean interval until recovery was 6.1 +/- 4.1 min. The median patient satisfaction score was 97 mm (range 40-100 mm); the median rating by physicians was 88 mm (range 4-100 mm). Side effects were noted in six patients: three had pain on injection, one had pain on injection and brief (< 1 min) hypotension (systolic blood pressure = 80 mm Hg), and two had apnea (< 30 sec). Seven patients had some recall of the procedure immediately afterwards, but only five had any recall at 24 hours. All 20 patients stated they would be willing to receive the same sedation again for a future procedure. CONCLUSION: Propofol appears to be an effective agent to provide systemic sedation and analgesia when used in conjunction with fentanyl for procedures in the ED. Given its rapidity of onset and elimination, it may become a useful agent to EPs for i.v. sedation in the ED.

Adult↗