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Biomedical subjects

F Nyberg

Publications and source records attributed to F Nyberg.

At least 127 records · Page 7Linked to original sources

Elevated cerebrospinal fluid substance P-like immunoreactivity in patients with painful osteoarthritis, but not in patients with rhizopatic pain from a herniated lumbar disc.

Cerebrospinal fluid (CSF) levels of substance P like immunoreactivity (SPLI) were determined in 11 patients with painful osteoarthritis in hip or knee, 9 patients with rhizopatic pain from a herniated lumbar disc, and in 9 healthy volunteers without pain. The patients with osteoarthritis had increased levels of SPLI in CSF (p < 0.001) compared to the controls. A positive correlation was also seen between the CSF SPLI and the degree of pain. At a second lumbar puncture 5 months after operation, SPLI had decreased, but was still significantly higher than in the controls. No difference in CSF SPLI was seen in the patients with herniated lumbar disc compared to the controls, neither before treatment, nor at follow up CSF postoperatively. The results suggest that nociceptive joint pain is consistent with increased SPLI in CSF. Differences in SPLI in CSF may be useful to differentiate pain from various origin, and may also increase our understanding of different pain mechanisms.

Chromatography, Gel↗

Occurrence of polymorphous light eruption in lupus erythematosus.

Photosensitivity is a well-known manifestation of lupus erythematosus (LE). Since there are no strict criteria for photosensitivity, varying prevalence figures have been reported. Also, distinction from polymorphous light eruption (PLE) can be difficult. The purpose of this study was to characterize photosensitivity in more detail and to determine the occurrence of PLE in a series of well-documented LE patients. A questionnaire was answered by 337 LE patients seen at dermatology departments in Finland and Sweden, and 63 of the patients were invited for interview. According to the questionnaire, LE lesions were made worse by sunlight in 242 (72%) patients. Symptoms consistent with PLE were reported by 165 (49%) patients. Detailed personal interviews supported the results from the questionnaire, and revealed that PLE had started 2-45 years before the onset of LE in 23 of 37 patients with both diagnoses, and more than 7 years before in 18 of 37 (49%). PLE proved to be common in patients with both systemic and cutaneous LE. The two conditions may often coexist and, in about half of the cases, PLE preceded LE. These two diseases may share pathogenic factors. PLE might predispose to LE in a subgroup of PLE patients.

Adolescent↗

Photosensitivity in lupus erythematosus, UV photoprovocation results compared with history of photosensitivity and clinical findings.

Photosensitivity, one of the presenting symptoms in lupus erythematosus (LE), is still poorly defined and varying prevalence figures have been reported. The possibility of a coexisting photodermatosis, especially polymorphous light eruption (PLE), has often not been taken into account. We report the results of ultraviolet A (UVA) and B (UVB) photoprovocation tests in 67 clinically photosensitive patients who had confirmed discoid LE (DLE), systemic LE (SLE) or subacute cutaneous LE (SCLE). The results are compared with a detailed history of photosensitivity and with clinical and serological findings. A pathological photoprovocation reaction, graded as weak, moderate or strong, was induced with either UVA or UVB in 69% of patients with LE, in 100% of those with SCLE, in 70% of those with SLE and in 64% of those with DLE, but in none of 14 controls. Only 16% of the pathological reactions were strong and long-lasting, resembling LE lesions, while 48% were moderate or weak and transient, clinically like PLE. Fifty-three per cent of the provocation reactions which were biopsied showed a PLE-like histology or a non-specific inflammatory reaction, and most of them were clinically moderate or weak reactions of short duration. In the remaining, mostly clinically strong or long-lasting reactions, the histology was consistent with LE. A history of sunlight sensitivity did not predict a pathological photoprovocation result but a positive association between the presence of SSA/Ro or SSB/La antibodies and a pathological photoprovocation reaction was found. We have shown that PLE coexists with LE and that both PLE- and LE-like lesions can be induced with UV radiation in LE patients.

Adolescent↗

In vitro metabolism of LVV-hemorphin-7 in human plasma studied by reversed-phase high-performance liquid chromatography and micro-electrospray mass spectrometry.

In these experiments we have studied the in vitro metabolism of LVV-hemorphin-7 in human plasma by using reversed-phase high-performance liquid chromatography (RP-HPLC) in combination with micro-electrospray mass spectrometry (micro-ES-MS). Tandem mass spectrometry (MS-MS) was performed in order to verify the structure of the peptide fragments found. Incubations were performed with and without different protease inhibitors. Results showed that LVV-hemorphin-7 was metabolized from the N-terminal end of the peptide, probably by an amastatin-sensitive exopeptidase.

Amino Acid Sequence↗

Reversed-phase high-performance liquid chromatography combined with tandem mass spectrometry in studies of a substance P-converting enzyme from human cerebrospinal fluid.

The application of reversed-phase HPLC in combination with micro-electrospray mass spectrometry to study a substance P (SP)-hydrolysing endoprotease in human cerebrospinal fluid (hCSF) is reported. The enzyme was partially purified from the hCSF specimens by ion-exchange chromatography and molecular sieving. During the purification procedure the enzyme activity was monitored by measuring the formation of the SP-fragment 1-7 from SP by radioimmunoassay. Regarding its behaviour upon molecular sieve chromatography, the enzyme was suggested to be associated with an apparent molecular mass of around 100 x 10(3). In subsequent experiments using the partially purified endopeptidase, the hydrolysis of SP was demonstrated by HPLC. The reaction product mixture was resolved in several components including the N-terminal fragments 1-8, 1-7 and 1-6 and the C-terminal fragment 8-11. The identity of these fragments were confirmed by tandem mass spectrometry. It was concluded that the present SP-degrading enzyme is different from those previously identified and purified from hCSF. The applied techniques were proven to be highly efficient for the recovery and identification of the released peptide products.

Animals↗

Isolation of haemorphin-related peptides from filter membranes collected in connection with haemofiltration of human subjects.

This paper describes the extraction and isolation from dialysis filters of two peptides containing the opioid active sequence haemorphin-7. The filter devices were obtained from uraemic patients subjected to haemofiltration. Following acidic extraction of the filter membranes the peptides were purified by size-exclusion, ion-exchange chromatography and finally by reversed-phase chromatography using different columns and different chromatographic systems. The purification was guided by radioimmunoassay and the structure of the final products was elucidated by N-terminal sequencing and fast-atom bombardment mass spectrometry as well as micro-electrospray mass spectrometry. The isolated peptides were suggested to be identical to fragments 1-41 and 32-41 of the beta-chain of human haemoglobin.

Amino Acid Sequence↗

Effects of insulin-like growth factor I (IGF-I) on the porto-arterial concentration differences of amino acids and glucose: a comparison between oral and intraperitoneal administration in the newborn piglet.

It is established that insulin-like growth factor I (IGF-I) influences cell differentiation and proliferation. Less is known, however, if such changes also influence the flow of nutrients from the intestinal lumen to the portal circulation. In the present study, we tested if IGF-I treatment (0.3 mg IGF-I/24 hr and kg) during 7 days affects the porto-arterial concentration differences of amino acids and glucose in piglets. Two routes of administration, oral and intraperitoneal, were compared. Following the IGF-I treatment, a bolus of nutrients was administered to the proximal duodenum and the porto-arterial concentration differences of amino acids and glucose were determined. We found that intraperitoneal administration of IGF-I significantly increased the difference in concentration between portal and arterial plasma for amino acids, whereas no such effect was seen with glucose. This might suggest that IGF-I has a specific effect on amino acid transporters in the intestinal wall. The same dose of IGF-I given orally did not exhibit the same effect on the absorption of amino acid as the animals which were given the peptide intraperitoneally.

Administration, Oral↗

Growth hormone and its receptors in the central nervous system--location and functional significance.

During the past few years, there has been increasing interest in functions that growth hormone (GH) may play in the central nervous system. Accumulating evidence that the hormone may pass the blood-brain barrier and the psychological improvements seen in adults following GH therapy have received particular attention. This paper will review our recent studies on GH receptors in the human and rat brain. A recent study on the effects of GH treatment in adult growth hormone-deficient patients on quality of life and cerebrospinal fluid levels of various hormones and neurotransmitters is also included.

Adult↗

Neuropeptide-converting enzymes in cerebrospinal fluid: activities increased in pain from herniated lumbar dis, but not from coxarthrosis.

We measured activities of dynorphin-converting enzyme (DCE), substance P endopeptidase (SPE) and angiotensin-converting enzyme (ACE) in cerebrospinal fluid (CSF) in 13 patients with rhizopathic pain from an herniated lumbar disc, in 9 patients with pain from coxarthrosis and in 11 control patients without pain. In the patients with disc hernia and coxarthrosis, another sample of CSF was analyzed 3-12 months after treatment, when pain had subsided. The DCE activity in the patients was higher than that in both the control patients and the patients with pain from coxarthrosis (nociceptive pain). Similarly, the activity of SPE was lower in the patients with herniated lumbar disc than in controls and in the patients with coxarthrosis. After treatment, the difference in activity compared to controls was lower, but still significant in patients with herniated discs. The ACE activity did not differ from controls in patients with ischialgia, while it was increased in patients with coxarthrosis. This increase also remained after arthroplasty with pain relief. In conclusion, measurements of neuropeptides may be useful for evaluating neuropathic pain.

Adult↗

Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131I-sodium tracers in the rat.

The possibility that endogenous serotonin (5-hydroxytryptamine, 5-HT) participates in alteration of the blood-brain barrier (BBB) following short-term forced swimming (FS) exercise was examined in a rat model. Subjection of conscious young (age 8-9 weeks, 80-90 g) animals to continuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in six and nine brain regions, respectively. The EBA staining was noted in posterior cingulate cortex, parietal, occipital cortices, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB permeability to 131I-sodium was further extended to caudate nucleus, thalamus and hypothalamus. This effect of FS on the BBB permeability was absent in adult (age 24-30 weeks, 300-400 g) animals. Measurement of 5-HT showed a profound increase of plasma and brain in young rats by 180% and 250%, respectively, from the control group. Adult animals showed only a minor increase in brain and plasma 5-HT levels. In young animals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomethacin (a prostaglandin synthesis inhibitor) prevented the FS induced increase in BBB permeability and 5-HT levels. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdown of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increased permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an important role in the breakdown of BBB permeability in FS, (ii) this effect of 5-HT on BBB permeability is mediated by 5-HT2 receptors, and (iii) FS induced increase in BBB permeability is age dependent.

5,7-Dihydroxytryptamine↗

Detection of growth hormone receptor mRNA in an ovine choroid plexus epithelium cell line.

The expression of growth hormone receptor (GHR) mRNA in an ovine choroid plexus cell line (SCP) was studied. RNA isolated from SCP cells was subjected to reverse transcription followed by PCR using a set of primers, designed on the basis of the ovine liver GHR sequence. A specific product with expected size of 1204 bp was obtained and the nucleotide sequence was found to be identical to that of ovine liver GHR. When the PCR product was used as a probe for Northern blot analysis, a transcript of 4.4 kb was detected in mRNA isolated from the SCP cells. This is the first report demonstrating the presence of mRNA for GHR in the choroid plexus.

Animals↗

Prolactin binding sites in rat brain and liver: effects of long-term ovariectomy and ovarian steroids.

The effects of long-term ovariectomy on the levels of brain and liver lactogenic binding sites as well as plasma and liver prolactin (PRL) have been investigated in sham-operated and ovariectomized rats receiving either 17 beta estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX-V). The levels of lactogenic binding sites in the parietal and piriform cortices, amygdala, thalamus, hypothalamus, as well as in the liver were significantly decreased after long-term ovariectomy. Moreover, the levels of plasma and liver PRL were also significantly decreased. Exogenous estradiol and progesterone replacement restored the levels of lactogenic binding sites in the parietal cortex and hypothalamus as well as in the liver. However, plasma and liver PRL levels were significantly increased by estradiol but only restored by progesterone. These results suggest that ovarian steroids influence the levels of lactogenic binding sites and prolactin.

Animals↗

Effects of long-term ovariectomy and ovarian steroids on somatogenic binding sites in rat brain and liver.

The effects of long-term ovariectomy and replacement with ovarian steroids on the levels of brain and liver somatogenic binding sites as well as plasma and liver growth hormone (GH) were studied in sham-operated (Sham) and ovariectomized female rats receiving either, 17 beta-estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX). Long-term ovariectomy decreased the levels of somatogenic binding sites in the choroid plexus and liver as well as GH in plasma and liver. The levels of these sites in the choroid plexus were partially restored only by estradiol replacement. Moreover, exogenous estradiol but not progesterone restored the levels of plasma and liver GH as well as liver somatogenic binding sites. Our results suggest that estrogens regulate the levels of somatogenic binding sites in the liver and choroid plexus.

Animals↗

Capillary liquid chromatography-fast atom bombardment mass spectrometry using a high-resolving cation exchanger, based on a continuous chromatographic matrix. Application to studies on neuropeptide peptidases.

Hyphenated mass spectrometric techniques such as LC-MS are advantageous over standard MS methods, because they provide increased sensitivity and minimize signal suppression by other compounds present in the reaction mixture. Recently, we have introduced so-called continuous beds, and applied this technique to prepare a 0.32 mm I.D. cation-exchange capillary column, in order to separate the reaction product substance P(1-7) after proteolytic cleavage of substance P by an endopeptidase recovered from human cerebrospinal fluid. The use of a volatile buffer for elution provides very good flow stability. Ion-exchange microcolumns may be particularly useful for the separation of those peptides that co-elute in reversed-phase chromatography because the separation mechanisms of these two methods are different.

Cation Exchange Resins↗

Decreased binding of growth hormone in the rat hypothalamus and choroid plexus following morphine treatment.

Male Sprague-Dawley rats were continuously infused with morphine through subcutaneously implanted mini-osmotic pumps over a period of 5 days. The binding of rat growth hormone (rGH) to specific sites in choroid plexus, cortex, hypothalamus, hippocampus and striatum was determined. It was found that in the acute phase of morphine administration the density of growth hormone-binding sites was significantly decreased in choroid plexus and in hypothalamus, but not in any other of the tissues studied. When tolerance to morphine was developed, the level of growth hormone-binding was restored to control level. In the acute phase, the plasma levels of GH, as measured by radioimmunoassay, correlated negatively with the density of the binding sites in choroid plexus and hypothalamus. The decrease in growth hormone-binding in these regions of the rat brain was also confirmed by SDS-polyacrylamide gel electrophoresis of cross-linked complexes of the binding entities to 125I-labelled rGH as visualized by autoradiography. In experiments, where morphine was administrated by intermittent injections, a similar decrease in rGH-binding was observed. However, the time-course of this decrease seemed to be dependent upon the route of administration. Following intracerebroventricular (i.c.v.) injections, the binding of the hormone was already affected after 30 min, whereas the binding of rGH in brain areas after subcutaneous (s.c.) injections was affected at a later stage.

Animals↗

Distribution of tripeptidyl-peptidase II in the central nervous system of rat.

Tripeptidyl-peptidase II (TPP II) is a high molecular weight serine peptidase which removes tripeptides from a free N-terminus of longer peptides. Since it had previously been demonstrated that the enzyme can inactivate enkephalins and dynorphins in vitro by removing the N-terminal Tyr-Gly-Gly peptide, we wanted to see whether TPP II could be involved in this process also in vivo. Therefore, the localization of TPP II in different cerebral regions of rat was investigated by immunoblot analysis and activity measurements. It could be shown that TPP II is relatively evenly distributed in the central nervous system of rat. This indicates that the physiological role of the enzyme is probably not a specific degradation of enkephalins, but rather pertains to the general turnover of proteins.

Amino Acid Sequence↗