PubMed Health⌕ Search

Biomedical subjects

F Nyberg

Publications and source records attributed to F Nyberg.

At least 109 records · Page 6Linked to original sources
PubMed1997

Rapid analysis of endogenous LVV-hemorphin-7 in cerebrospinal fluid by size-exclusion chromatography and electrospray ionization mass spectrometry.

LVV-hemorphin-7 is a peptide with opioid-like activity which is recognized by mu and sigma receptors. The sequence, derived from beta-, gamma-, delta- or epsilon- chains of human hemoglobin has been found in cerebrospinal fluid (CSF) of patients suffering from cerebrovascular bleedings, but not in CSF from healthy individuals. Procedures for isolation and identification of neuropeptides in body fluids and tissue extracts are often laborious and time-consuming. Additionally, extraction yield tends to be low after several chromatographic steps. In this study, we developed a rapid technique to analyze LVV-hemorphin-7 in CSF fluid from a patient with cerebrovascular bleedings using a combination of size-exclusion chromatography and electrospray ionization mass spectrometry. The methodology described utilizes small quantities of CSF (0.3-0.5 ml) and can be completed within a few hours. The proposed strategy opens possibilities for direct measurement of endogenous peptides in small volumes of body fluids.

Cerebral Hemorrhage↗
PubMed1997

Effects of an anabolic-androgenic steroid on the regulation of the NMDA receptor NR1, NR2A and NR2B subunit mRNAs in brain regions of the male rat.

The expression of the N-methyl-D-aspartate (NMDA) receptor subunits NR1, NR2A and NR2B mRNAs was examined in discrete areas of the male rat brain (including hippocampus, hypothalamus, nucleus accumbens and cortex) following 14 days daily intramuscular injections of high doses (5 and 15 mg/kg) of an anabolic-androgenic steroid (AAS) (nandrolone decanoate). The results indicated that the drug produced a significant decrease in the mRNA expression of the NR2A receptor subunit both in the hypothalamus and hippocampus. A decrease in the level of NR2B receptor mRNA was observed in hypothalamus at the lower dose of the AAS but in other areas examined, this receptor subunit mRNA was not affected. Except for a decreased expression in the nucleus accumbens at the higher dose of AAS the NR1 receptor subunit mRNA was not affected by the drug. The three subunit mRNAs in cortex were not significantly altered. The effects of the steroid on the mRNA expression for the NMDA receptor subunits in hippocampus and hypothalamus are suggested to be involved in the mechanism behind aggressive behaviour, a feature previously associated with AAS misuse. The downregulation of the mRNA for the NR1 receptor subunit in nucleus accumbens may relate to a mechanism involved in the recently suggested AAS-induced stimulation of the brain reward system.

Animals↗
PubMed1997

Involvement of nitric oxide in the pathophysiology of acute heat stress in the rat. Influence of a new antioxidant compound H-290/51.

The possibility that nitric oxide (NO) is involved in the pathophysiology of brain injury caused by heat stress (HS) was examined using immunohistochemistry of a constitutive isoform of neuronal nitric oxide synthase (c-NOS) in a rat model. In addition, to discover the role of oxidative stress in inducing c-NOS activity in HS, the effect of a new antioxidant H-290/51 on HS-induced expression of c-NOS immunoreactivity was examined. Subjection of conscious young animals to a 4-h HS in a biological oxygen demand (BOD) incubator at 38 degrees C resulted in marked upregulation of c-NOS in the cerebral cortex and hippocampus of stressed rats compared to normal rats kept at room temperature (21 +/- 1 degrees C). The c-NOS immunoreactivity was found in distorted neurons located in the edematous regions not normally showing c-NOS activity. Pretreatment with H-290/51 significantly attenuated the upregulation of c-NOS in animals subjected to HS, and the signs of neuronal distortion and edema were less pronounced. These results suggest that HS has the capacity to induce upregulation of c-NOS, and these effects can be reduced by prior treatment with H-290/51, indicating a possible neuroprotective effect of antioxidants in thermal brain injury.

Animals↗
PubMed1997

Design, synthesis, and biological activities of four angiotensin II receptor ligands with gamma-turn mimetics replacing amino acid residues 3-5.

Disulfide cyclization is a powerful method for reducing the conformational space of a peptide. This in turn may enable the study of its bioactive conformation. Several analogues of angiotensin II (Ang II) containing a disulfide bridge between amino acids 3 and 5 have been reported. Among these the cyclic octapeptides c[Hcy3,5]-Ang II, c[Cys3,5]-Ang II, and c[Pen 3,5]-Ang II showed significant activity at Ang II receptors. We have performed conformational analysis studies using theoretical calculations and 1H-NMR spectroscopy on tripeptide model compounds of these cyclic octapeptides which show that the cyclic moieties of c[Cys3,5]-Ang II and c[Pen3,5]-Ang II preferentially assume an inverse gamma-turn conformation. On the basis of these results, we substituted amino acid residues 3-5 in Ang II with two different gamma-turn mimetics giving four diastereomeric Ang II analogues. Interestingly, two of these are equipotent to Ang II in binding to AT1 receptors. In the contractile test using rabbit aorta rings, one of the analogues is an agonist with full contractile activity approximately equipotent to c[Pen3,5]-Ang II but 300-fold less potent than Ang II. This low potency may suggest that Ang II does not adopt a gamma-turn in the 3-5 region when interacting with the receptor.

Angiotensin II↗
PubMed1997

Increased cerebrospinal fluid concentration of aspartate but decreased concentration of nitric oxide breakdown products in women experiencing visceral pain during active labour.

The aim of the present study was to investigate some putative neurotransmitters involved in nociception and pain in parturients during active labour experiencing intense visceral pain. The concentration of the excitatory amino acid aspartate was significantly increased, and there was a tendency for an increase in glutamate, in lumbar cerebrospinal fluid (CSF) of parturients in active vaginal labour compared with control patients without pain subjected to elective caesarean section. The CSF concentration of the nitric oxide breakdown product nitrate was significantly decreased in parturients compared with control patients and healthy volunteers. No significant differences in the concentrations of substance P, substance P-endopeptidase or met-enkephalin were detected between parturients and controls. Our data suggest a paradoxical negative relationship between CSF concentrations of excitatory amino acids and nitric oxide in labour pain. The mechanisms behind this finding is unclear at present.

Adult↗
PubMed1997

The hemorphins: a new class of opioid peptides derived from the blood protein hemoglobin.

Hemorphins are endogenous peptides belonging to the family of "nonclassical" or "atypical" opioid peptides. They are generated by enzymatic hydrolysis of the beta-, kappa-, delta-, or epsilon-chain of the blood protein hemoglobin. Originally, the hemorphins were isolated from enzymatically treated bovine blood. In recent years hemorphin structures have been identified as naturally occurring peptides in brain, plasma, and cerebrospinal fluid. This article will review recent studies of the hemorphins regarding their structures, mechanisms for their release, and their biological actions. A particular emphasis will be directed to their role in exercising human and their clinical relevance.

Amino Acid Sequence↗
PubMed1997

Topical application of insulin like growth factor-1 reduces edema and upregulation of neuronal nitric oxide synthase following trauma to the rat spinal cord.

The neuroprotective effects of insulin like growth factor-1 (IGF-1) on spinal cord injury induced edema formation, cell changes and profound upregulation of constitutive isoform of neuronal nitric oxide synthase (cNOS) was examined in a rat model. A focal spinal cord injury produced by making a lesion (about 2 mm deep and 5 mm long) of the right dorsal horn of the T10-11 segment resulted in a marked edema formation, cell injury and upregulation of cNOS following 5 h after trauma. In separate groups application of IGF-1 (0.1 microgram/microliter) topically on the exposed spinal cord (T10-11) starting from 30 min before injury (20 microliter), immediately before injury followed by 30 min, 60 min and thereafter every 1 h after injury until sacrifice resulted in significant attenuation of edema formation and cell changes. Immunohistochemistry showed a less pronounced expression of cNOS in the T9 and T12 segments of the cord in IGF treated rats compared to untreated traumatised controls. These results for the first time show that IGF treatment is neuroprotective and this effects of the IGF appears to be mediated via inhibition of NOS upregulation.

Administration, Topical↗
PubMed1997

Topical application of 5-HT antibodies reduces edema and cell changes following trauma of the rat spinal cord.

Involvement of serotonin in the early microvascular reactions and cell changes following trauma of the spinal cord was examined using topical application of serotonin antibodies to the traumatised cord in a rat model. A focal trauma of the spinal cord was produced by making an incision into the right dorsal horn of the T10-11 segments (about 2 mm deep and 5 mm long); the animals were allowed to survive 5 h after injury. Monoclonal 5-HT antibodies (1:20) were applied (25 microliters in 10 sec) to the traumatised spinal cord 2 min after injury. There was a significant reduction in the breakdown of the blood-spinal cord barrier, edema formation, and cell changes in the traumatised rats which received 5-HT antiserum compared to the injured rats given saline. These results show that 5-HT is an important mediator involved in the early pathophysiological responses of spinal cord injury.

Administration, Topical↗
PubMed1997

Substance P endopeptidase activity in the rat spinal cord following injury: influence of the new anti-oxidant compound H 290/51.

The influence of the new antioxidant compound H-290/51 was examined on the substance P endopeptidase (SPE) activity in a rat model of spinal cord injury. This compound (H-290/51) has neuro-protective effects on edema and cell changes in this model. Infliction of trauma to the cord by making an incision into the right dorsal horn of the T10-11 segment resulted in a marked upregulation of SPE in the segments rostral to the lesion. On the other hand, the injured and adjacent caudal segments exhibited a marked down-regulation of the enzyme activity. Pretreatment with H 290/51 increased the SPE activity in the T9 segment but downregulated the enzyme activity in the T10-11 and T12 segments. The drug induced enzyme activity change was not further influenced by the trauma of the cord. The results indicate that a focal trauma induces widespread alterations in spinal cord SPE activity which can be influenced by the anti-oxidant drug H 290/51, suggesting that SPE is somehow involved in cell injury.

Animals↗
PubMed1997

Role of neurochemicals in brain edema and cell changes following hyperthermic brain injury in the rat.

The involvement of three potent neurochemical mediators of the edema formation such as serotonin, prostaglandins and opioids in the pathophysiology of hyperthermic brain injury was examined in a rat model using a pharmacological approach. Hyperthermic brain injury was induced in conscious young rats by exposing them to heat stress at 38 degrees C for 4 h. In these rats the blood-brain barrier (BBB) permeability, brain edema, cerebral blood flow (CBF), heat shock protein 72 kD (HSP) response and cell changes were examined. Pretreatment with ketanserin (a serotonin-2 receptor antagonist), indomethacin (prostaglandin synthesis inhibitor) and naloxone (opioid receptor antagonist) in separate groups of rats reduced hyperthermia and HSP response following heat stress and significantly attenuated changes in the BBB permeability, brain edema, CBF and cell reaction. These results suggest that the pathophysiology of hyperthermic brain injury is a complex mechanisms and several neurochemicals are involved in the brain pathology caused by heat stress.

Animals↗
PubMed1997

Acute heat stress induces edema and nitric oxide synthase upregulation and down-regulates mRNA levels of the NMDAR1, NMDAR2A and NMDAR2B subunits in the rat hippocampus.

The influence of heat stress on constitutive isoform of neuronal nitric oxide synthase (cNOS) and NMDA receptor gene expression in hippocampus was examined in a rat model. Subjection of animals to 4 h heat stress at 38 degrees C resulted in a marked upregulation of cNOS in the hippocampus accompanied with a marked general expansion and edematous cell changes. On the other hand NMDA receptor messenger RNA encoding NMDAR1, NMDAR2A and NMDAR2B subunits showed a marked downregulation in the hippocampus of heat stressed rats compared to the controls. Our results show that upregulation of cNOS is instrumental in heat stress associated edema and cell injury. Furthermore, an increased production of NO as evident with upregulation of cNOS appears to be a key factor in the downregulation of NMDA receptor gene expression in heat stress.

Acute Disease↗
PubMed1997

Elevated cerebrospinal fluid level of substance P and decreased undecapeptidase activity at term pregnancy.

This paper reports a study of substance P and its converting enzyme substance P endopeptidase (SPE) in cerebrospinal fluid (CSF) collected from women at term pregnancy. A method was developed to assess the CSF levels of substance P itself with minimum contribution from prestages or fragments of the undecapetide. The measured activity was compared with that detected in CSF from control, non-pregnant, non-puerperal women. The result indicates a significant increase in substance P-like immunoreactivity at term pregnancy (19.9 +/- 3.9 fmol/ml, n = 10) compared with that of control subjects (12.3 +/- 2.8 fmol/ml, n = 9; P < 0.001). This elevation was suggested to reflect an increased activity in spinal sensory neurons at this stage of pregnancy. The activity of SPE was assessed by measuring the product substance P1-7 by a radioimmunoassay specific for this fragment. It was found that the enzyme activity was significantly decreased in CSF from pregnant women (11.2 +/- 0.71 pmol/h.ml), compared with control samples (18.4 +/- 0.73 pmol/h.ml; P < 0.05). Moreover, a significant negative correlation was found to exist between the level of substance P and the activity of SPE (P < 0.05, r2 = 0.65), suggesting that the enzyme may be involved in a mechanism regulating the level of substance P concentration.

Case-Control Studies↗
PubMed1997

Anabolic androgenic steroids increase beta-endorphin levels in the ventral tegmental area in the male rat brain.

The levels of beta-endorphin and Met-enkephalin-Arg-Phe (MEAP) immunoreactivity in various brain regions (including amygdala, cortex, hippocampus, hypothalmus, nucleus accumbens, pituitary and ventral tegmental area) were studied in male rats subjected to daily intramuscular injections during 14 days of high doses (5 and 15 mg/kg) of the anabolic androgenic steroid (AAS), nandrolone decanoate. At the nandrolone dose of 15 mg/kg a significant (about 20-fold) increase in beta-endorphin levels in the ventral tegmental area (VTA) was observed. The steroid did not significantly affect the concentration of the peptide at any dose in other brain areas examined. The levels of MEAP remained unaltered in all studied regions. A slight increase in serum concentrations of both peptides was also found but this elevation was not statistically significant. The observed increase in beta-endorphin in VTA was suggested to be involved in a mechanism by which the steroid may influence the reward system in the brain. An opioid mediated stimulation of the reward system following injection of AAS supports a previous hypothesis that AAS may induce psychological dependence.

Anabolic Agents↗
PubMed1997

Purification and characterization of substance P endopeptidase activities in the rat spinal cord.

Two enzymes with substance P degrading activity were purified from the membrane bound fraction of the rat spinal cord. The purified enzymes were characterized with regard to biochemical and kinetic properties. One of the enzymes exhibited close similarity to neutral endopeptidase 24.11 (NEP, EC 3.4.24.11), while the other resembled a substance P converting endopeptidase (SPE), which has previously been identified and purified from human cerebrospinal fluid (CSF). Detergent treated spinal cord homogenates from male Sprague Dawley rats were purified by anion-exchange chromatography (DEAE-sepharose CL-6B), hydrophobic-interaction chromatography (phenyl-sepharose CL-4B) and molecular sieving (Sephadex G-50). Two fractions with enzymes differing in size were recovered and allowed for further purification to apparent homogeneity by ion-exchange chromatography and molecular sieving on a micro-purification system (SMART). The enzyme activities were monitored by following the conversion of synthetic substance P using a radioimmunoassay specific for the heptapeptide product, substance P (1-7). By SDS-polyacrylamide gel electrophoresis of the purified enzymes molecular weights of 43 and 70 kDa were estimated for the SPE-like and NEP-like activity, respectively. A K(m) of 5 microM was determined for the conversion of substance P to its (1-7) fragment by the SPE-like activity. Reversed-phase HPLC together with mass spectrometry permitted identification of all fragments released from substance P by the peptidases. The released fragments were for both enzymes identified as substance P (1-7), substance P (8-11), substance P (1-8), substance P (9-11). The NEP-like enzyme preparation also gave substance P (1-6) as a major product.

Animals↗
PubMed1997

Misclassification of smoking status and lung cancer risk from environmental tobacco smoke in never-smokers.

Lung cancer risk estimates for exposure to environmental tobacco smoke remain controversial, a major unresolved issue being misclassification of smokers. We studied misclassification rates in two large cohorts using information on smoking obtained several years apart. Cohort I included Swedish twins born between 1886 and 1925 who answered questionnaires in 1961 and again in 1967 or 1970. Cohort II was a random stratified population sample of individuals born between 1894 and 1945 who responded to postal smoking surveys in 1963 and 1969. We considered those who stated that they had never smoked in the second questionnaire, but who reported smoking or former smoking in the first questionnaire, to be misclassified. In cohort I, 4.9% of male and 4.5% of female ever-smokers were misclassified, corresponding to 11.1% and 1.3% of reported never-smokers, respectively. Cohort II yielded similar results. A follow-up through 1992 of cohort I showed a relative risk for lung cancer among misclassified men of 1.9 [95% confidence interval (CI) = 0.4-9.1], as compared with 4.5 (95% CI = 2.0-9.9) and 13.3 (95% CI = 6.5-27.0) for former and current smokers, respectively. No case occurred among misclassified women. Although misclassification of smokers exists, our results indicate that it mainly concerns light smokers or long-time ex-smokers, who have only a very moderately elevated risk of lung cancer. It therefore appears unlikely that confounding by smoking explains the increased risk for lung cancer related to environmental tobacco smoke exposure.

Bias↗
PubMed1997

Different patterns of soluble adhesion molecules in systemic and cutaneous lupus erythematosus.

Circulating isoforms of cellular adhesion molecules (CAMs) have been described recently, and elevated levels of certain sCAMs have been reported in various inflammatory diseases such as systemic lupus erythematosus (SLE). There are previously no reports on sCAMs in cutaneous LE. Sera from 61 patients with LE: systemic (SLE: n=24), chronic cutaneous (discoid LE, DLE: n= 19) or subacute cutaneous (SCLE: n=8), chronic biologically false positive (CBFP) reactors for syphilis (n= 10) and 32 controls were examined for sICAM-1, sVCAM-1 and sE-Selectin with specific ELISA kits. Protocol forms were reviewed. We found significantly elevated levels of sE-Selectin in patients with DLE and widespread cutaneous symptoms, and a correlation between active cutaneous disease as well as polymorphous light eruption (PLE) and elevated levels of sE-Selectin. In contrast, patients with systemic LE did not have elevated levels of sE-Selectin, but in concordance with earlier reports, sICAM-1 and sVCAM-1 levels were elevated compared to controls in SLE, as well as in SCLE patients, which has not been reported previously. Since activated endothelial cells are the only source for E-Selectin, the elevated sE-Selectin level in patients with widespread and active cutaneous disease suggests a more important role for endothelial cells in the pathogenesis of cutaneous LE than previously assumed.

Adult↗
PubMed1997

Growth hormone stimulates production of interferon-gamma by human peripheral mononuclear cells.

There is substantial evidence for interactions between the immune and endocrine systems at different levels. In the present study we investigated whether human growth hormone (hGH) could stimulate proliferation of interferon-gamma-secreting cells (IFN-gamma-SC), and production of IFN-gamma. Human peripheral blood mononuclear cells (PBMC) taken from 15 normal subjects were incubated with varying doses (200,400,600 and 800 ng/ml) of recombinant hGH. Samples of cells were also incubated with PBS buffer (without hGH) to serve as controls. Effects of hGH were studied by enumerating IFN-gamma-SC and by measuring the concentration of IFN-gamma using an Immunospot assay and an enzyme-linked immunosorbent assay, respectively. The results showed that hGH significantly increased both the number of IFN-gamma-SC and the concentration of IFN-gamma in a dose-dependent manner. The maximum effects were obtained in the presence of (400 ng/ml) hGH (15 +/- .5 IFN-gamma-SC/10(6) PBMC and 300 +/- 55 U/ml IFN-gamma) compared to controls (4 +/- 2 IFN-gamma-SC/10(6) PBMC and 50 +/- 10 U/ml IFN-gamma). The results of the present study suggest that hGH might influence the immune system by stimulating the proliferation of IFN-gamma-SC and the production of IFN-gamma.

Human Growth Hormone↗