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Biomedical subjects

J Westman

Publications and source records attributed to J Westman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antioxidant compounds EGB-761 and BN-520 21 attenuate heat shock protein (HSP 72 kD) response, edema and cell changes following hyperthermic brain injury. An experimental study using immunohistochemistry in the rat.

Influence of the extract of Gingko biloba (EGB-761) and one of its constituent Gingkolide B (BN-52021) on hyperthermia induced cellular damage and heat shock protein (HSP 72kD) response was examined in a rat model. Rats subjected to 4h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%, wind velocity 20-25cm/sec) resulted in profound edema and cell injury in many parts of the cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus and brain stem. Immunostaining of HSP 72 kD showed marked upregulation in the damaged and distorted neurons located within the edematous area. Pretreatment with EGB-761 (50mg/kg/day, p.o.) and BN-520 21 (2mg/kg, p.o.) per day for 5 days significantly reduced HSP expression and attenuated cell damage. Our results show that EGB-761 and its component Gingkolide B (BN-52021) has the capacity to reduce edema and cell injury following hyperthermia and this effect of the compound is somehow associated with a reduction in cellular stress response as evidenced with a reduction in HSP expression.

Animals↗
PubMed2000

Growth hormone attenuates alterations in spinal cord evoked potentials and cell injury following trauma to the rat spinal cord. An experimental study using topical application of rat growth hormone.

The influence of exogenous rat growth hormone on spinal cord injury induced alterations in spinal cord evoked potentials (SCEP) and edema formation was examined in a rat model. Repeated topical application of rat growth hormone (20microl of 1microg/ml solution) applied 30min before injury and at 0min (at the time of injury), 10min, 30min, 60min, 120min, 180min, and 240min, resulted in a marked preservation of SCEP amplitude after injury. In addition, the treated traumatised cord showed significantly less edema and cell changes. These observations suggest that growth hormone has the capacity to improve spinal cord conduction and attenuate edema formation and cell injury in the cord indicating a potential therapeutic implication of this peptide in spinal cord injuries.

Animals↗
PubMed2000

Spinal nerve lesion induces upregulation of constitutive isoform of heme oxygenase in the spinal cord. An immunohistochemical investigation in the rat.

The influence of carbon monoxide (CO) on chronic spinal nerve lesion induced spinal cord neurodegeneration was examined using immunohistochemical expression of the constitutive isoform of its synthesising enzyme, hemeoxygenase-2 (HO-2) in a rat model. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model of neuropathic pain and rats were allowed to survive for 8 weeks. Sham operated rats, in which the spinal nerves were exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of HO-2 expression which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, morphological investigations showed distorted neurons, membrane disruption, synaptic damage and myelin vesiculation. Sham operated rats did not show an upregulation of HO-2 expression and the structural changes in the spinal cord were absent. These observations strongly suggest that spinal nerve lesion is associated with an increased production of CO which is somehow contributing to the neurodegenerative changes in the spinal cord, not reported earlier.

Animals↗
PubMed2000

A new antioxidant compound H-290/51 attenuates nitric oxide synthase and heme oxygenase expression following hyperthermic brain injury. An experimental study using immunohistochemistry in the rat.

Influence of a new anti-oxidant compound H-290/51 on expression of nitric oxide synthase (NOS) and heme oxygenase (HO) enzymes responsible for nitric oxide (NO) and carbon monoxide (CO) production, respectively was examined in the CNS following heat stress in relation to cell injury. Exposure of rats to 4h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%, wind velocity 20-25cm/sec) resulted in profound edema and cell injury in many parts of the cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus and brain stem. Immunostaining of constitutive isoforms of neuronal NOS (nNOS) and HO-2 revealed marked upregulation in damaged and distorted neurons located within the edematous brain regions. Pretreatment with H-290/51 (50 mg/kg, p.o., 30 min before heat stress) significantly reduced the edematous swelling and cell injury and resulted in a marked attenuation of nNOS and HO-2 expression. These observations suggest that upregulation of NOS and HO is associated with cell injury, and the antioxidant compound H-290/51 is neuroprotective in heat stress.

Animals↗
PubMed2000

Efficacy of a touchscreen computer based family cancer history questionnaire and subsequent cancer risk assessment.

OBJECTIVE: A computer based touchscreen family cancer history questionnaire was developed and implemented to facilitate the provision of cancer risk assessments for the ambulatory and outpatient populations of a free standing cancer hospital. METHODS: A questionnaire consisting of a series of branched point decision making screens was developed which enables the participant to enter demographic data, personal cancer history, and cancer histories for first and second degree relatives. A freestanding touchscreen computer kiosk system was used to place the questionnaire in public areas of the cancer hospital and clinic. Genetic professionals analysed the data received, using published criteria, and provided a basic cancer risk assessment and surveillance recommendations within 10 business days. A survey was completed by a small random group of users (n = 59) three to six months after receipt of their risk assessment. RESULTS: After 11 months, 1440 people had entered information and received a written communication. Only 2% of completed questionnaires contained insufficient information to provide a basic risk assessment. Of the small group of participants surveyed, almost all (95%) felt "very comfortable" using the system, 93% remembered receiving the risk assessment letter when queried three to six months later, 42% felt their perceptions about cancer risk had changed, and 20% had made changes in their or their family's cancer surveillance practices. CONCLUSION: The touchscreen computer family history questionnaire allows easy collection of family history information, provision of risk assessments to a broad population, and promotes increased awareness of familial risk and appropriate surveillance.

Cancer Care Facilities↗
PubMed2000

Neurotrophic factors influence upregulation of constitutive isoform of heme oxygenase and cellular stress response in the spinal cord following trauma. An experimental study using immunohistochemistry in the rat.

The influence of brain derived neurotrophic factor (BDNF) or insulin like growth factor-1 (IGF-1) on spinal cord trauma induced carbon monoxide (CO) production and cellular stress response was examined using immunostaining of the constitutive isoform of the hemeoxygenase (HO-2) enzyme and the heat shock protein (HSP 72kD) expression in a rat model. Subjection of rats to a 5 h spinal trauma inflicted by an incision into the right dorsal horn at T10-11 segment markedly upregulated the HO-2 and HSP expression in the adjacent spinal cord segments (T9 and T12). Pretreatment with BDNF or IGF-1 significantly attenuated the trauma induced HSP expression. The upregulation of HO-2 was also considerably reduced. These results show that BDNF and IGF-1 attenuate cellular stress response and production of CO following spinal cord injury which seems to be the key factors in neurotrophins induced neuroprotection.

Animals↗
PubMed1999

Ultrastructural analysis of the hippocampus of adult rats after long-term adrenalectomy.

Removal of adrenal steroids modulates various functions in the brain. However, adrenalectomy (ADX) induced cell death in the hippocampal formation of the adult rat is a recently described phenomenon. We undertook this ultrastructural study on long-term adrenalectomized (5 months) rats to investigate the mode of cell death in the hippocampus. Our results showed apoptotic changes in the hippocampus. In addition we have observed other types of degeneration in the hippocampal neurons. The novel finding in this study is that different morphological patterns of cell death were evident both in the dentate gyrus and in the pyramidal areas, which may reflect different stages of the same death process.

Adrenalectomy↗
PubMed1999

Anaphylactic response to factor IX replacement therapy in haemophilia B patients: complete gene deletions confer the highest risk.

Haemophilia B is an X-linked recessive coagulopathy due to mutations in the factor IX gene. Occasionally, patients receiving factor IX replacement therapy develop inhibiting antibodies to the factor IX protein, and it has been recently documented that a subset of these patients have had anaphylactic responses to factor IX replacement therapy in association with the development of inhibiting antibodies. To determine the relationship between mutation type and the risk of anaphylaxis, eight unrelated patients from families in whom anaphylaxis had occurred were genotyped. The mutations were compared to those in 550 haemophilia B patients and to those in 276 patients with clinically severe disease. Individuals with complete gene deletions were found to be at greatest risk for anaphylaxis, with an estimated risk of 26% or greater. Anaphylaxis was less likely to occur in patients with protein truncation mutations or partial gene deletions and least likely to occur with missense mutations. Genotypes can help physicians and patients anticipate the likelihood of anaphylaxis, a potentially life-threatening complication of factor IX replacement therapy. The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anaphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphylactic immune response.

Anaphylaxis↗
PubMed1998

Nitric oxide in the pathophysiology of hyperthermic brain injury. Influence of a new anti-oxidant compound H-290/51. A pharmacological study using immunohistochemistry in the rat.

The possibility that nitric oxide (NO) is involved in the pathophysiology of brain injury caused by heat stress (HS) was examined using neuronal nitric oxide synthase (NOS) immunohistochemistry in a rat model. In addition, to find out a role of oxidative stress in NOS upregulation and cell injury, the effect of a new antioxidant compound H-290/51 (Astra Hässle, Mölndal, Sweden) was examined in this model. Subjection of conscious young rats to 4 h HS in a biological oxygen demand (BOD) incubator at 38 degrees C resulted in a marked upregulation of NOS in many brain regions compared to control rats kept at room temperature (21 +/- 1 degree C). This NOS immunoreactivity was found mainly in distorted neurons located in the edematous regions not normally showing NOS activity. Breakdown of the blood-brain barrier (BBB) permeability, increase in brain water content and marked neuronal, glial and myelin reaction were common findings in several brain regions exhibiting upregulation of NOS activity. Pretreatment with H-290/51 significantly attenuated the upregulation of NOS in rats subjected to HS. In these animals breakdown of the BBB permeability, edema and cell changes were considerably reduced. Our results suggest that hyperthermic brain injury is associated with a marked upregulation of NOS activity in the CNS and this upregulation of NOS and concomitant cell injury can be reduced by prior treatment with an antioxidant compound H 290/51. These observations indicate that oxidative stress seems to be an important endogenous signals for NOS upregulation and cell reaction in hyperthermic brain injury.

Animals↗
PubMed1998

Spinal nerve lesion induces upregulation of neuronal nitric oxide synthase in the spinal cord. An immunohistochemical investigation in the rat.

The possibility nitric oxide (NO) is involved the neurodegenrative mechanisms in the spinal cord following a chronic peripheral nerve lesion was examined using NOS immunohistochemistry. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model, a model of neuropathic pain and rats were allowed to survive for 8 weeks. In one group of animals L-NAME was given intraperitoneally (1-2 mg/kg, i.p. daily) for 6 weeks. Sham operated rats, in which the spinal nerve was exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of NOS which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, ultrastructural investigations showed distorted neurons, membrane disruption and myelin vesiculation. Sham operated rats did not show either NOS upregulation or structural changes in the spinal cord. Pretreatment with L-NAME significantly reduced NOS upregulation and the structural changes in the spinal cord were less pronounced. These observations strongly indicate a putative role of NOS in the pathophysiology of chronic nerve lesion. Our results may provide a new strategy to treat chronic neuropathic pain or to minimise neurodegeneration in the patients suffering from such diseases of the nervous system.

Animals↗
PubMed1998

Brain derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord. An immunohistochemical study in the rat.

The possibility that brain derived neurotrophic factor (BDNF) and insulin like growth factor-1 (IGF) induced neuroprotection is influenced by mechanisms involving nitric oxide was examined in a rat model of focal spinal cord injury. BDNF or IGF-I (0.1 microgram/10 microliters in phosphate buffer saline) was applied topically 30 min before injury on the exposed spinal cord followed by repeated doses of growth factors immediately before and 30 min after injury. Thereafter application of BDNF or IGF was carried out at every 1 h interval until sacrifice. Five hours after injury, the tissue pieces from the T9 segment were processed for nNOS immunostaining, edema and cell injury. Untreated injured rats showed a profound upregulation of nNOS which was most pronounced in the nerve cells of the ipsilateral side. A marked increase in the blood-spinal cord barrier (BSCB) permeability to 125I-albumin, water content and cell injury in these perifocal segments was also found. Pretreatment with BDNF and IGF significantly reduced the upregulation of nNOS in the spinal cord. This effect of the growth factors was most pronounced in the contralateral side. Rats treated with these neurotrophic factors showed much less signs of BSCB damage, edema and cell injury. These results suggest that BDNF and IGF pretreatment is neuroprotective in spinal cord injury and that these neurotrophic factors have the capacity to down regulate nNOS expression following trauma to the spinal cord. Our data provide new experimental evidences which suggest that BDNF and IGF may exert their potential neuroprotective effects probably via regulation of NOS activity.

Animals↗
PubMed1998

Spinal cord evoked potentials and edema in the pathophysiology of rat spinal cord injury. Involvement of nitric oxide.

The possibility that nitric oxide is somehow involved in the early bioelectrical disturbances following spinal cord injury in relation to the later pathophysiology of the spinal cord was examined in a rat model of spinal cord trauma. A focal trauma to the rat spinal cord was produced by an incision of the right dorsal horn of the T 10-11 segments under urethane anaesthesia. The spinal cord evoked potentials (SCEP) were recorded using epidural electrodes placed over the T9 and T12 segments of the cord following supramaximal stimulation of the right tibial and sural nerves in the hind leg. Trauma to the spinal cord significantly attenuated the SCEP amplitude (about 60%) immediately after injury which persisted up to 1 h. However, a significant increase in SCEP latency was seen at the end of 5 h after trauma. These spinal cord segments exhibited profound upregulation of neuronal nitric oxide synthase (NOS) immunoreactivity, and the development of edema and cell injury. Pretreatment with a serotonin synthesis inhibitor drug p-chlorophenylalanine (p-CPA) or an anxiolytic drug diazepam significantly attenuated the decrease in SCEP amplitude, upregulation of NOS, edema and cell injury. On the other hand, no significant reduction in SCEP amplitude, NOS immunolabelling, edema or cell changes were seen after injury in rats pretreated with L-NAME. These observations suggest that nitric oxide is somehow involved in the early disturbances of SCEP and contribute to the later pathophysiology of spinal cord injury.

Animals↗
PubMed1998

Lipoprotein-like phospholipid particles inhibit the smooth muscle cell cytotoxicity of lysophosphatidylcholine and platelet-activating factor.

Oxidation of LDL is associated with degradation of phosphatidylcholine into platelet-activating factor (PAF)-like phospholipids and lysophosphatidylcholine (LPC). Exposure of cultured human smooth muscle cells to PAF and LPC in a concentration of 25 micromol/L was found to result in complete cell death, as assessed by the MTT cytotoxicity assay and cell counting. Addition of 50 microg/mL apolipoprotein A-I- and apolipoprotein A-I(Milano)-containing phospholipid particles completely inhibited this cytotoxicity. Phospholipid complexes alone were almost as effective, whereas free apolipoprotein A-I(Milano) and albumin were without effect, suggesting that the effect was phospholipid dependent. Experiments using [14C]LPC demonstrated that apolipoprotein A-I- and apolipoprotein A-I(Milano)-containing phospholipid particles effectively bind LPC. The results show that HDL-like phospholipid particles effectively inhibit the toxic effect of phospholipids and other lipid-soluble factors. The ability of HDL to inhibit the proinflammatory and toxic effects of phospholipids generated during oxidation of LDL may be responsible for part of the antiatherogenic properties of HDL.

Apolipoprotein A-I↗