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Biomedical subjects

Mads Rasmussen

Publications and source records attributed to Mads Rasmussen.

13 recordsLinked to original sources

Adiponectin receptors in human adipose tissue: effects of obesity, weight loss, and fat depots.

OBJECTIVE: To investigate the presence and regulatory properties of the adiponectin receptors, AdipoR1 and AdipoR2, in human adipose tissue (AT) and in isolated human adipocytes. RESEARCH METHODS AND PROCEDURES: The effect of obesity, weight loss, and gender on expression of AdipoR1 and AdipoR2 was investigated in subcutaneous AT. The influence of fat distribution on these receptors was investigated in paired samples of subcutaneous and omental AT. Gene expression of these receptors was quantified by reverse transcriptase-polymerase chain reaction. RESULTS: AdipoR1 mRNA levels were approximately 10-fold higher than adipoR2 in both AT fragments and in isolated adipocytes. AdipoR1 expression was lower in AT from obese subjects (p < 0.05) compared with that from normal-weight subjects, and AdipoR1 displayed a negative correlation with BMI (r = -0.53, p < 0.01). In obese subjects, weight loss (approximately 12 kg) increased AdipoR1 expression by 80% in AT (p < 0.01). Concerning regional differences, AdipoR1 showed significantly lower expression in omental AT than in subcutaneous AT (p < 0.01). No gender difference was observed in the expression of these receptors. In human preadipocyte cultures, AdipoR1 expression was not induced during the differentiation process, whereas AdipoR2 was induced by 5-fold (p < 0.05). DISCUSSION: AdipoR1 is highly expressed in human AT, indicating that adiponectin may have biological effects in AT in an autocrine/paracrine manner. AdipoR1 expression in AT is reduced in obese subjects and is increased after weight loss. Thus, it can be suggested that adiponectin might have reduced biological effects in AT due to low levels of adiponectin receptors in obese subjects and in omental adipocytes, which may further aggravate the negative metabolic effect of low levels of adiponectin characterizing the obese state.

Adipocytes↗

The effects of indomethacin on intracranial pressure and cerebral hemodynamics during isoflurane or propofol anesthesia in sheep with intracranial hypertension.

The effect of indomethacin in reducing intracranial pressure (ICP) may be dependent on the choice of anesthetic regimen. We studied the effects of indomethacin on ICP and cerebral blood flow (CBF) during isoflurane or propofol anesthesia in a sheep model of intracranial hypertension. A crossover design was applied in which six sheep were anesthetized with isoflurane and propofol in a random order. Anesthetic depth was measured with response and state entropy. Changes in CBF, ICP, mean arterial blood pressure, arterio-venous oxygen difference, and Paco2 were measured at specific times before and after an IV indomethacin bolus (0.2 mg/kg). Response and state entropy values during anesthesia were similar in both groups. Isoflurane and propofol reduced CBF by 11% and 34%, respectively. Indomethacin caused a reduction in ICP within 15 s during both anesthetic regimens, with the decrease in ICP being significantly more pronounced during isoflurane (P = 0.009). In both anesthetic groups, indomethacin caused a simultaneous increase in mean arterial blood pressure and a further 17% versus 14% decrease in CBF from predrug values for isoflurane and propofol, respectively. The reduction in CBF was significantly more pronounced for propofol (P = 0.02). The effect on ICP, however, was most pronounced during isoflurane anesthesia. We suggest that the effect of indomethacin is partly mediated by an autoregulatory response.

Anesthesia, Inhalation↗

Clonal spread of Staphylococcus aureus with reduced susceptibility to oxacillin in a dermatological hospital unit.

In November 2000, we became aware of isolates of Staphylococcus aureus with borderline resistance to oxacillin (BORSA) from patients in the Department of Dermatology, Aarhus University Hospital. The objective was to describe the isolates phenotypically and genotypically and to assess possible transmission routes in order to intervene and prevent further spread. Clonality of the isolates was confirmed by pulsed field gel electrophoresis. Several breaches in infection control procedures were revealed suggesting both direct and indirect transmission between patients. Defective skin barriers, high carrier rates of S. aureus in dermatological patients and high consumption rates of dicloxacillin in the department might facilitate transmission. Following improvement of the general infection control measures, and after reassessment of the antibiotic policy in the department, the outbreak has disappeared.

Adult↗

Human gliomas contain morphine.

BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous morphine via high pressure liquid chromatography (HPLC). The HPLC peak corresponding to an authentic morphine standard had its morphine level determined via radioimmune assay. The identity of this material was established by Q-TOF-MS analysis. RESULTS: Each glioma exhibited an endogenous morphine presence. Tumor extractions demonstrated a molecular mass of 286.14 da, identical to authentic morphine. Subsequent fragmentation analysis of this molecule revealed fragment masses of 129.01 da, 183.09 da and 201.07 da, corresponding to authentic morphine fragments. This material was not found in any of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.

Brain Neoplasms↗

Change in beta1-adrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss.

The aim of the present study was to examine gene expression and protein concentrations of beta(1)- and beta(2)-adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. Beta-adrenergic receptor mRNA levels were quantified by reverse transcription-PCR-HPLC. Beta-adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8+/-0.8 kg (mean+/-S.E.M.) during diet treatment. There was a 34% decrease in the beta(1)-adrenergic receptor mRNA level (0.92+/-0.09 compared with 0.61+/-0.06 amol/microg of DNA; P<0.002). Beta(2)-adrenergic receptor mRNA did not decrease significantly. Beta(2)-adrenergic receptor protein concentration decreased 37% (25.5+/-7.1 compared with 16.0+/-5.6 arbitrary units/ng of DNA; P=0.008), whereas beta(1)-adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of beta(1)-adrenergic receptor protein (r=0.65, P<0.003) and changes in receptor protein concentration (r=0.50, P=0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between beta(1)-adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation.

Adipose Tissue↗

Self-inflicted skin diseases. A retrospective analysis of 57 patients with dermatitis artefacta seen in a dermatology department.

We analysed clinical symptoms, gender, age and social relations among 57 patients for whom a final diagnosis of dermatitis artefacta was established. The study is retrospective and the patients were seen in our department from 1982 to 2002. We observed that the diagnosis was 2.8 times more common in females than males. Symptoms were most common in the age group 18-60 years, median age 39 years. The skin lesions were 'multiple' among 88% of the patients. When self-infliction was suggested as the cause, two-thirds of patients initially denied it and only one patient agreed to meet with a psychiatrist. Only one-quarter had a job, the rest were unemployed or on sick leave. Many patients (61%) received medical treatment with anxiolytica. Ten patients (18%) had a psychiatric diagnosis. Among our 57 patients, 11 were deceased at the time of our study, but none because of suicide. Four had died before the age of 70, of whom two suffered from alcoholism and two had diabetes mellitus. Therapy should include an optimal nursing relationship with the patient so that social problems can be discussed. Psychological or psychiatric intervention appeared unhelpful because of patient denial.

Adolescent↗

Indomethacin.

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Anti-Inflammatory Agents, Non-Steroidal↗

Endogenous morphinergic signaling and tumor growth.

The mu3 opiate receptor subtype has been characterized by various binding assays as opiate alkaloid selective (e.g. morphine) and opioid peptide (e.g. methionine enkephalin) insensitive. This opiate receptor subtype has been found on human, including cancer cell lines, and invertebrate tissues, demonstrating that it has been conserved during evolution. Furthermore, in numerous reports, this receptor is coupled to constitutive nitric oxide release. In this regard, for example, morphine immune down regulating activities parallels those actions formerly attributed to nitric oxide. We have now identified the mu3 receptor at the molecular level and sequence analysis of the isolated cDNA suggests that it is a novel, alternatively spliced variant of the mu opiate receptor gene (MOR). Furthermore, using Northern blot, reverse transcription coupled to polymerase chain reaction (RT-PCR) and sequence analysis, we have demonstrated the expression of this new mu variant in human vascular tissue, mononuclear cells, polymorphonuclear cells, and human neuroblastoma cells. The presence of this mu splice variant, adds to the growing body of evidence supporting the hypothesis that morphine is an endogenous signaling molecule in neural, immune and vascular systems. In addition to their use in the treatment of pain, opioid peptides appear to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of opiate alkaloids, e.g., morphine, on tumor growth, with emphasis on immuno-regulatory and antiproliferative mechanisms.

Alternative Splicing↗

Do indomethacin and propofol cause cerebral ischemic damage? Diffusion-weighted magnetic resonance imaging in patients undergoing craniotomy for brain tumors.

BACKGROUND: Diffusion-weighted magnetic resonance imaging was used to determine whether indomethacin and propofol induce cerebral ischemic damage in patients undergoing craniotomy for cerebral tumors. As a secondary aim, the authors investigated whether low jugular bulb oxygen saturation values were associated with brain parenchymal damage as evaluated by diffusion-weighted imaging. METHODS: Nine patients subjected to craniotomy for supratentorial brain tumors in propofol-fentanyl anesthesia were studied. Magnetic resonance imaging including diffusion- and perfusion-weighted and structural sequences were performed (1) on the day before surgery, (2) before and (3) 20 min after administration of indomethacin (bolus of 0.2 mg/kg followed by infusion of 0.2 mg.kg.h) in the propofol-fentanyl-anesthetized patient, and (4) 2 days after surgery. Apparent diffusion coefficient maps were calculated. Jugular bulb oxygen saturation, arteriovenous oxygen difference, mean arterial blood pressure, and arterial oxygen and carbon dioxide tensions were measured simultaneously with the magnetic resonance examinations performed during anesthesia. RESULTS: No ischemic lesions were detected in the diffusion-weighted or apparent diffusion coefficient images. A nonsignificant decrease in jugular bulb oxygen saturation from 51% (range, 40-61%) to 43% (range, 37-63%) and increase in arteriovenous oxygen difference from 4.4 mm (range, 2.7-4.6 mm) to 4.7 mm (range, 2.9-5.2 mm) was observed after indomethacin administration. CONCLUSION: Administration of indomethacin during propofol anesthesia is not associated with evidence of ischemic damage in patients with brain tumors, as evaluated by diffusion-weighted imaging.

Adult↗

Craniotomy for supratentorial brain tumors: risk factors for brain swelling after opening the dura mater.

OBJECT: Cerebral swelling often occurs during craniotomy for cerebral tumors. The primary aim in this study was to determine risk factors (intracranial pressure [ICP], patient characteristics, histopathological features, neuroimaging characteristics, anesthetic regimen, and perioperative physiological data) predictive of brain swelling through the dural opening. As a secondary aim the authors attempted to define subdural ICP thresholds associated with brain swelling. METHODS: The study population consisted of 692 patients (mean age 50+/-15 years) scheduled for elective craniotomy for supratentorial brain tumors. Brain swelling through the dural opening was estimated according to a four-point scale. The patients were dichotomized as those without cerebral swelling (that is, brain below the dura mater [59 patients] or brain at the level of the dura mater [386 patients]) and those with cerebral swelling (that is, moderate brain swelling [205 patients] or pronounced brain swelling [42 patients]). Logistic regression analysis was used to identify subdural ICP (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.72-2.1, p < 0.0001), midline shift (OR 1.06, 95% CI 1.02-1.11, p = 0.008), a diagnosis of glioblastoma multiforme (OR 2.1, 95% CI 1.01-4.3, p = 0.047), and metastasis (OR 2.9, 95% CI 1.3-6.9, p = 0.01) as independent risk factors of intraoperative brain swelling. Thresholds for ICP associated with brain swelling were defined as follows: at an ICP less than 5 mm Hg, brain swelling rarely occurred (5% probability); at an ICP greater than 13 mm Hg, brain swelling occurred with 95% probability; and at an ICP greater than 26 mm Hg, severe brain swelling occurred with 95% probability. CONCLUSIONS: Subdural ICP is the strongest predictor of intraoperative brain swelling. It is possible to define thresholds of cerebral swelling and the authors recommend subdural ICP measurement as a tool to initiate preventive measures to reduce ICP before opening the dura mater.

Adult↗

Elevated beta2-adrenoceptor protein concentration in adipose tissue from obese subjects is closely related to the body mass index and waist/hip ratio.

The aim of the present study was to quantify beta(2)-adrenoceptor protein content in adipose tissue during fasting, and to study the relationships between beta(2)-adrenoceptor protein and mRNA levels and changes in metabolites related to lipolysis. Groups of male subjects with a body mass index of <25 kg/m(2) or >30 kg/m(2) fasted for 60 h. Abdominal subcutaneous fat biopsies were analysed for receptor mRNA levels by reverse transcription-PCR-HPLC. The beta(2)-adrenoceptor protein concentration was measured by Western blotting using fluorescence laser scanning for detection. The beta(2)-adrenoceptor protein concentration per cell (on a DNA basis) was higher in obese subjects ( P <0.03). There were highly significant relationships between beta(2)-adrenoceptor protein concentration and both body mass index and waist/hip ratio ( P <0.001 for both). Furthermore, there was an inverse relationship between the receptor protein concentration and the serum beta-hydroxybutyrate level during fasting ( P <0.005). beta(2)-Adrenoceptor protein levels decreased in both groups during fasting, to a similar degree. Basal beta(2)-adrenoceptor mRNA levels were similar in the two groups, but there was a smaller increase in the obese group during fasting ( P <0.03). The increased beta(2)-adrenoceptor protein level in obese subjects is likely to be related to the greater plasma membrane area of their adipocytes. The decrease during fasting may be due to increased binding of noradrenaline and subsequent internalization and degradation of the receptor. Elevated levels of less responsive beta(2)-adrenoceptor protein in obese subjects may contribute to the development of obesity.

Adipose Tissue↗

Effects of morphine on tumour growth.

Endogenous opiate alkaloids, such as morphine, and their peptide counterparts have been implicated in a wide variety of pharmacological and physiological functions. In addition to their use in the treatment of pain, opioids, appears to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of endogenous and exogenous opioids on tumour growth, with emphasis on immunoregulatory and antiproliferative mechanisms.

Analgesics, Opioid↗