[Do not forget the other half of the organ! Important to examine balance of deaf and hearing impaired persons].
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Adolescent↗
Biomedical subjects
C Möller
Publications and source records attributed to C Möller.
Decreased experimental anxiety and voluntary ethanol consumption in rats following central but not basolateral amygdala lesions.
A long-debated 'tension reduction' hypothesis postulates anti-anxiety effects to be important for ethanol reward, and states that elevated anxiety levels might predispose for ethanol consumption and addiction. Human data are contradictory, possibly due to heterogeneity of patient samples. In rats, baseline levels of experimental anxiety have been reported to correlate with voluntary ethanol consumption. Here, we addressed the possibility that mechanisms underlying experimental anxiety might be causally related to regulation of voluntary ethanol intake. Rats were bilaterally lesioned in central amygdala using microinjections of ibotenic acid. This resulted in a robust release of punished drinking in a modified Vogel conflict test, an effect typically seen with anxiety reducing drugs. This effect was specific, as unpunished drinking was unaffected by the lesion. On the elevated plus-maze, central amygdala lesions did not affect behaviour under baseline conditions, but attenuated the anxiogenic effect of restraint stress. Measures of locomotor activity were not affected. Voluntary ethanol consumption was examined in a two-bottle, free choice paradigm. Ethanol intake was markedly decreased in the lesion group. Total fluid intake was not affected. Basolateral amygdala lesions, which did not affect conflict behaviour, also left ethanol intake unaffected. These results are consistent with previous reports of an important role for central amygdala in anxiety related behaviours, and suggest that cell bodies located in central amygdala might be important in this context. Further, our results support a relation between experimental anxiety and voluntary ethanol consumption.
Alcohol Drinking↗
The lymphopenia (lyp) gene controls the intrathymic cytokine ratio in congenic BioBreeding rats.
The lymphopenia gene (lyp) on rat chromosome 4 is closely linked to autoimmune diabetes in the BioBreeding (BB) rat. Lyp controls the number of peripheral lymphocytes by reducing T cells of the RT6+ phenotype by almost 90%. Following nine cycle of marker-assisted cross-intercross breeding we have developed congenic lyp/lyp, lyp/+ and +/+ (wildtype) rats on the background of DR rats. Prediabetic and insulitis free lyp/lyp, lyp/+ and +/+ rats were used to determine the effect of lyp on cytokine expression in the thymus. In situ hybridization of thymus cryosections showed that the interferon gamma (IFN gamma) mRNA expression was highest in lyp/lyp rats and the hybridization signal was restricted to the medullary compartment. The frequency of IFN gamma and interleukin (IL)-10 mRNA expressing cells in isolated thymocytes determined by quantitative image analysis, demonstrated an increased IFN gamma: IL-10 ratio in thymocytes from lyp/lyp homozygotes compared to lyp/+ and +/+ rats. This confirmed a lyp gene dose-dependent segregation of the IFN gamma high phenotype. Recombinant human glutamic acid decarboxylase (GAD65) increased the number of IFN gamma and IL-10 mRNA expressing thymocytes after in vitro culture. We conclude that the quantitative ratio of cytokine producing thymocytes is associated with the lyp genotype. These potentially autoreactive thymocytes may explain the establishment of beta-cell directed autoimmunity in the BB rat despite peripheral lymphopenia.
Animals↗
B cells of aging rats: impaired stimulus-secretion coupling but normal susceptibility to adverse effects of a diabetic state.
A diabetic state impairs B-cell function and survival. We tested whether the negative effects are exacerbated by the aging process. Islets were isolated from old (63.3 +/- 2.3 weeks) and young (11.3 +/- 0.5 weeks) inbred Wistar rats. Age did not affect DNA and insulin content, yet both glucose-induced (27.8 mmol/L) and arginine-induced induced (10 mmol/L) insulin responses in old islets were significantly reduced. Islets were transplanted under the kidney capsule of recipients that were either nondiabetic or severely diabetic after streptozotocin (STZ) treatment (blood glucose > 20 mmol/L). Following 8 weeks' transplantation to nondiabetic recipients, perfused kidneys with grafts of old islets exhibited the same insulin responses to glucose as grafts of young islets. However, responses to arginine were reduced in grafts of old islets (28 +/- 4 microU/min) relative to grafts of young islets. (70 +/- 18 microU/min, P < .05). Insulin mRNA content was similar in grafts of old islets and grafts of young islets. Following 8 weeks' transplantation to diabetic recipients, 27.8 mmol/L glucose failed to induce insulin secretion in grafts of old islets and grafts of young islets alike, whereas arginine-induced insulin secretion was unaffected in grafts of old islets but reduced in grafts of young islets. Insulin mRNA content was reduced to a similar extent by the diabetic state (to 28% in grafts of old islets and to 27% in grafts of young islets grafts in nondiabetic recipients). We conclude that aging, although leading to impaired stimulus-secretion coupling, does not increase susceptibility to the negative effects of a diabetic state on B-cell function as presently tested.
Aging↗
Responses in skin microcirculation to vestibular stimulation before and during motion sickness.
BACKGROUND: Observation of physiological changes during motion sickness is required to quantify the degree of sickness. The review of the literature does not show unifying results. An objective symptom of motion sickness is facial pallor. It reflects changes in skin microcirculation which have not been measured so far. METHODS: Eleven healthy volunteers susceptible to motion sickness were subjected to eccentric vertical axis rotation. The dynamics and the correspondence of the changes in skin blood flow in two segments, forehead and finger, were measured by laser Doppler flowmeter. RESULTS AND CONCLUSIONS: The difference in the microcirculatory skin blood flow across the phases of motion sickness is significant for the forehead but not for the fingertip: the established dynamics of the forehead blood flow during motion sickness will be of benefit in quantifying the degree of sickness; there is no correlation between the blood flow changes in both measured areas; the rhythmic blood flow fluctuation increases during motion sickness; there is a difference between the blood flow responses to vestibular stimulation before the appearance of motion sickness and in the course of the sickness. Laser Doppler flowmetry is a reliable method in quantifying the degree of motion sickness.
Adult↗
Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium.
This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high-performance liquid chromatography. Sixteen patients were studied. On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58.8 +/- 7.1% and 47 +/- 3.2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in individual patients was significantly related (Spearman p = 0.65, P < 0.05). The unbound fraction of fentanyl rose from 0.23 to 0.34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman p = 0.85, P < 0.01). The estimated elimination half-life of fentanyl using the grouped data was 4.7 h. The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half-life of alcuronium using the grouped data was 234 min. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.
Adjuvants, Anesthesia↗
Nasal blockage in children with non-infectious rhinitis: consequences and treatment.
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Child↗
Long-term effects of aminoguanidine on insulin release and biosynthesis: evidence that the formation of advanced glycosylation end products inhibits B cell function.
Chronic hyperglycemia has adverse effects on B cell function. We investigated the possible role of advanced glycosylation end products (AGEs) in glucotoxicity. Rat islets were cultured at different glucose concentrations for 1-6 weeks in RPMI 1640. Culture was performed with or without aminoguanidine (AG), which is known to prevent AGE formation in other tissues. AGE-associated fluorescence (370 nm excitation and 440 nm emission) progressively increased during 6 weeks of culture at 38 nM, but not at 11 or 5.5 mM, glucose. The increase in fluorescence was significantly inhibited by AG. The effects of AG on insulin secretion were tested directly after the culture period as well as after a wash-out period of continued culture at 11 mM glucose in the absence of AG. The presence of AG during culture for 1 week at 38 mM glucose failed to affect basal release at 3.3 mM glucose or stimulated release at 27 mM glucose. AG was ineffective whether tested directly after the culture period or after wash-out. When the same culture conditions were prolonged for 6 weeks, culture with AG suppressed basal and stimulated insulin secretion after the culture period. However, after wash-out, previous AG treatment enhanced the insulin response to 27 mM glucose 2-fold compared to culture without AG (P < 0.01). Proinsulin and total protein biosyntheses in 38 mM glucose-cultured islets were increased 40-80% by AG after 6 weeks of culture, and this effect was similar after wash-out. Preproinsulin messenger RNA levels were significantly increased (P < 0.05) after 6 weeks of culture with AG. NG-Methyl-L-arginine, a nitric oxide synthase inhibitor, failed to mimic the effects of AG. The results indicate that the time-dependent beneficial effects of AG on insulin secretion and biosynthesis are related to inhibitory effects on AGE formation and that accumulation of islet AGEs could be important for glucotoxicity toward B cells.
Animals↗
When and how to use gentamicin in the treatment of Menière's disease.
Gentamicin given as local therapy for severe Menière's disease is of considerable value in the control of vertigo. The ototoxic antibiotic is instilled through the tympanic membrane causing a peripheral vestibular loss and possibly also diminished endolymph production. In order to achieve the best results with gentamicin treatment it is of utmost importance that the diagnosis is correct. Given to a patient with vertigo of other than peripheral origin, the outcome would be worsening of the existing symptoms and addition of new ones. The method should be used only by physicians who are very familiar with vertigo and otology, and only in patients with such a disturbing degree of vertigo that they are well motivated to receive treatment. Thorough information regarding the disease, the treatment procedure and the symptoms caused by a unilateral peripheral vestibular loss should be given to the patient. Vestibular rehabilitation, including movement therapy, should be given by the physician or preferably, a well trained physiotherapist on an individual basis or in patient groups together with written practice programmes for use at home. Vertigo attacks are usually relieved in 95% of patients. Twenty percent of patients experience an added hearing loss in the treated ear, although this number is reduced if the treatment is given as a single installment on consecutive days with extra installments given one month later if the vertigo remains.
Anti-Bacterial Agents↗
Are deficits in the equilibrium system relevant to the clinical investigation of solvent-induced neurotoxicity?
OBJECTIVES: The diagnosis of solvent-induced chronic toxic encephalopathy is commonly based on case histories of exposure to solvents, symptoms, and deficits on psychometric tests. It has previously been demonstrated that long-term solvent-exposed workers have disturbances of the equilibrium system. The correlation between these disturbances and the diagnosis of chronic toxic encephalopathy has been analyzed in the present study. MATERIAL AND METHODS: Sixty men, consecutively admitted due to the suspicion of this syndrome, were investigated and classified into 3 groups--solvent-induced chronic toxic encephalopathy, incipient chronic toxic encephalopathy and nonchronic toxic encephalopathy. They were all examined using an otoneurological test battery, including analysis of saccades, smooth pursuit, visual suppression of the vestibular ocular reflex, and dynamic posturography. RESULTS: Compared with healthy referents several of the subjects, even in the nonchronic toxic encephalopathy group, showed a reduced visual suppression ability, a prolonged latency of saccades, and pathological posturographic results. Some otoneurological tests correlated with the duration of exposure and the results of psychometric tests representing memory and perceptual skills. Nevertheless, there was no significant group correlation between the otoneurological findings and the diagnosis of chronic toxic encephalopathy. CONCLUSION: Disturbances revealed by an otoneurological investigation have so far not been considered in the diagnosis of chronic toxic encephalopathy. Our results indicate that an otoneurological test battery adds worthwhile information about lesions within the brainstem-cerebellar complex not revealed by a psychometric investigation.
Adult↗
Decreased measures of experimental anxiety in rats bred for high alcohol preference.
A prevalent notion holds that acute anti-anxiety actions of ethanol are important for the reinforcing properties of this drug, and might predispose individuals with pre-existing anxiety disorders for developing ethanol dependence. This notion remains controversial, and human studies have yielded conflicting results. Ethanol dependence is likely a heterogenous disorder, and the discrepancies might be explained by a different relationship between anxiety and alcohol reinforcement in different subtypes of alcoholism. Recent results in experimental animals suggest that antianxiety actions of ethanol are important reinforcers of voluntary ethanol consumption in heterogeneous rats. Here, we examined whether the relationship is different in the AA line of rats bred for high voluntary ethanol intake. Behavior was studied in two established animal models of anxiety, a punished drinking conflict test, and the elevated plus maze. In the conflict test, the AA line displayed a markedly disinhibited behavior over a range of shock intensities, compared both with their counterpart, the ANA line, and with regular Wistar rats. On the plus maze, both AA and Wistar rats showed lower measures of experimental anxiety than ANA subjects. The phenotype of the animals was confirmed using a two-bottle free choice alcohol drinking procedure. The disinhibited behavior and spontaneous ethanol preference of the AA line differs from what has been found in heterogeneous rats, and displays similarities to genetically transmitted type II alcoholism according to the nomenclature of Cloninger.
Alcohol Drinking↗
[Changes in regional CNS perfusion in obstructive sleep apnea syndrome: initial SPECT studies with injected nocturnal 99mTc-HMPAO].
Some of the clinical features of obstructive sleep apnoea syndrome (OSA) are suggestive of impaired cerebral blood flow. Cerebral blood flow alterations might, for example, be responsible for headaches, which are frequent complaints in patients with OSA. Even the high frequency of ischaemic cerebral complications in patients with OSA might be caused in part by sleep apnoea-associated impairment of cerebral perfusion. Previous studies have demonstrated reduced total cerebral blood flow in patients with OSA, but regional changes of cerebral perfusion have not been studied up to now. We performed SPECT studies using 99mTc-(d,l)-hexamethyl-propylenaminoxim (HMPAO) as a tracer in 14 adult patients with moderate to severe OSA (AHI > 30/h; mean AHI 59.2 +/- 4.3). The injection of the tracer took place between 2:00 and 4:00 a.m. while repeated episodes of obstructive apnoea were detected by polysomnography during stage II sleep. Data acquisition took place at 7:30 a.m. All measurements were repeated some nights later under effective treatment with nCPAP. Visual analysis showed marked frontal hyperperfusion in 5 patients. When regional perfusion indices were calculated for 32 regions of interest statistical analysis showed reduced perfusion of the left parietal region. These changes were completely reversed by effective nCPAP therapy. These data suggest that OSA is associated with reversible changes of regional cerebral perfusion. The underlying pathophysiologic mechanisms are matter of speculation so far. There might be an apnoea-associated effect of local vascular autoregulation mechanisms acting to compensate systemic blood flow alterations or blood gas changes in OSA. The observed frontal hyperperfusion might be caused by activation of the frontal lobe by repetitive cortical arousals.
Adult↗
Cockroach and Dermatophagoides pteronyssinus cross-react.
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Allergens↗
Childhood asthma and exposure to indoor allergens: low mite levels are associated with sensitivity.
The prevalence and level of sensitivity to indoor allergens were studied in relation to current exposure at home in 124 children with perennial asthma living in three climatic zones of Sweden. The house dust mite (HDM) allergen levels were higher in the South than in the North (p < 0.001), while cat and dog allergen levels tended to be higher in the North than the South (n.s.). Thirty-four percent of the children were sensitive to the HDM Dermatophagoides pteronyssinus, as determined by IgE antibodies in vitro, 27% were sensitive to D. farinae, 57% to cat and 55% to dog. Sensitivity to HDM was significantly more prevalent in Southern, than in Central and Northern Sweden (p = 0.001) where the children were more often sensitive to pets (cat p = 0.005, dog p = 0.002). A significant association between the concentration of Der p I and Der fI in the house dust and both the prevalence of sensitivity to HDM and the IgE antibody levels against mites was found even at concentrations well below the commonly suggested risk level for sensitisation of 2 micrograms/g dust. No relationship was found between pet allergen concentration in the home dust and sensitivity to pets, possibly because of exposure outside home, e.g. in schools and meeting places for leisure activities. Similarly, there was no consistent association between the level of mite or pet allergen exposure at home and asthma severity as judged by symptom and medication score. The study indicates that there is no threshold value for sensitisation to mite allergens in asthmatic children, and therefore, dust allergen levels at home should be kept as low as possible in homes of children at risk for asthma.
Adolescent↗
Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers.
Maintenance treatment with nebulized budesonide was studied in young children with asthma not controlled without steroids. In a blind parallel-group study for 18 weeks, 102 children, mean age 22 (5- 47) months, were randomized for treatment starting with 0.25 or 1 mg b.i.d. The patients were reviewed every 3 weeks, and if symptom control had been achieved the dose was reduced, otherwise it was kept. The clinical effect was very good with both dose regimens. The median time to 7 consecutive days without any asthma symptoms was about 1 month with both, highlighting the importance of the duration of therapy rather than the benefits of a high starting dose. In 18 of 24 children who attained the placebo stage, symptoms had reappeared at the last visit. Although an overall minimal effective maintenance dose could not be demonstrated, 47% achieved symptom control on 0.25 mg b.i.d., i.e. fulfilled criteria for further dose reduction. No significant side effects were seen. On average, 25% of the nominal dose reached the patients.
Administration, Inhalation↗
MR imaging in solvent-induced chronic toxic encephalopathy.
PURPOSE: To use MR to examine patients with CNS symptoms indicating +chronic intoxication. MATERIAL AND METHODS: Thirty-two subjects exposed to industrial solvents for 5 to 28 years and 40 age-matched, healthy controls were examined. RESULTS: All patients showed decreased signal in the basal ganglia on T2-weighted images. In 11 of the patients the white matter showed diffuse hyperintensity with loss of the grey-white matter discrimination and with distinct periventricular hyperintensities in 5 of the patients. The controls had no pathological changes in the brain. CONCLUSION: Although the relatively small number of patients may obscure the significance, findings observed on T2-weighted images were patchy periventricular hyperintensities and hypointensities in the basal ganglia. Fast spin-echo is a good technique with fast acquisition of images with true spin-echo contrast features.
Adult↗
Modulation of carbon monoxide production and enhanced spatial learning by tin protoporphyrin.
Endogenous carbon monoxide (CO), produced by haem oxygenase (HO), may play a role in hippocampal long-term potentiation (LTP). Its role in learning and memory in intact animals is less well known. Tin protoporphyrin (Sn-PP; 25 mg kg-1, i.p.) effectively but transiently inhibited HO activity in brain homogenates, and improved acquisition in the Morris water maze. Locomotor activity was unaffected, indicating a behavioural specificity of the learning effect. The analogue zinc protoporphyrin (25 mg kg-1, i.p.), which does not pass the blood-brain barrier, did not affect learning. If the observed memory effect is related to inhibition of HO, the role of CO in spatial learning may be different from that suggested by LTP studies.
Animals↗
Progress in identifying clinical relevance of inhibition, stimulation and measurements of poly ADP-ribosylation.
Our laboratory, in collaboration with Oxigene Inc, has been involved in identifying commercially feasible clinical applications of measurement or modulation of ADP-ribosylation as a core technology. For this purpose a pivotal regulatory role for ADP-ribosylation in the repair of DNA lesions leading to cytotoxic as well as mutagenic events has been hypothesized. A new class of DNA repair inhibitors, the N-substituted benzamides, has been identified which can react with radiation to produce reactive intermediates that oxidize thiol amino acids. Their proposed mechanisms of action are two-fold: ie they can interact with radiation: i) to directly enhance DNA damage; and ii) to react with thiols in the zinc finger DNA binding domain of poly ADP-ribosyl transferase to inhibit DNA repair and thereby increase DNA damage. Sensamide, a clinically relevant formulation of metoclopramide which is an N-substituted benzamide, has indicated enhancement of tumor response and survival in patients with inoperable squamous cell carcinoma of the lung when it was administered as a radiosensitizer in a phase I/II trial and compared to historical controls. A mechanism of endogenous regulation of human mononuclear leucocyte ADP-ribosylation has been identified to be HOCl/N-chloramine production via the oxidative burst of phagocytes. HOCl/N-chloramines are potent oxidants of thiol-containing proteins. Quantitative estimation of N-chloramine sensitive plasma thiols has been identified as an effective surrogate measure of leucocyte poly ADPRT.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗