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Biomedical subjects

L Persson

Publications and source records attributed to L Persson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Extracellular ischaemia markers in repeated global ischaemia and secondary hypoxaemia monitored by microdialysis in rat brain.

The aim of this study was to explore the usefulness of extracellular markers of cerebral ischaemia. Cortical microdialysate concentrations of the energy related metabolites lactate, pyruvate, glucose, adenosine, inosine, hypoxanthine and xanthine, were measured in rats subjected to repeated transient ischaemia. The animals were subjected to one or two 10-min periods of global ischaemia produced by induced intracranial hypertension, with a 2 h period of reperfusion after each insult. In addition, the effect of superimposed secondary hypoxaemia and hypotension was studied. In general, there was a good agreement between the extracellular markers and known intracellular energy disturbances under similar conditions, including marked transient increases of lactate, lactate/pyruvate ratio, inosine and hypoxanthine. Several new observations were made: (1) glucose appeared to be a useful marker of severe ischaemia and recirculation, (2) a marked post-ischaemic xanthine formation was observed implicating a substantial loss of salvageable hypoxanthine as well as increased production of superoxide radicals, (3) a blunted purine response was noted after the second insult, reflecting a reduced intracellular adenine nucleotide pool, and (4) a different pattern of ischaemia markers was observed during secondary hypoxia as compared to hypoxia with hypotension. In conclusion, extracellular lactate, pyruvate, glucose, adenosine, inosine hypoxanthine and xanthine all seem valuable as ischaemia markers. The results support the usefulness of intracerebral microdialysis for monitoring of energy metabolic disturbances caused by cerebral ischaemia/hypoxia. The pattern of extracellular ischaemia markers may help differentiate between various causes of energy perturbations, such as different degrees of ischaemia and hypoxia.

Animals↗
PubMed1998

Spermine affects intestinal in vitro permeability to different-sized molecules in rats.

The gut epithelial lining is normally an effective barrier to entry of luminal bacteria and macromolecules into the body and dietary polyamines may influence its function. Therefore, the effects of spermine on regional intestinal permeability to different-sized marker molecules in rats were investigated in Ussing diffusion chambers. Mucosal exposure to 1 mM spermine reduced the permeation of the marker Na-fluorescein in jejunum, expressed as the apparent permeability coefficient (Papp). In contrast, Papp for Na-fluorescein was increased by 10 mM spermine in ileum and by 50 mM spermine in both jejunum and ileum. No effects were observed on [51Cr]-EDTA permeability in any of the intestinal regions. For the larger marker molecules, bovine serum albumin (BSA) and FITC-dextran 71200 (FITC-D), mucosal exposure to 0.5 mM spermine reduced Papp in colon. Spermine (10 mM), increased Papp for FITC-D in all regions and for BSA only in ileum, while Papp for BSA was increased by 50 mM spermine in both jejunum and ileum. The effects of spermine on the intestinal permeability to different-sized molecules generally seemed to depend on the intestinal region and on the polyamine concentration; higher spermine concentrations (10-50 mM) enhanced, while lower (0.5-1 mM) decreased the permeability. These findings may be important when trying to modulate epithelial barrier functions, especially during barrier dysfunction.

Animals↗
PubMed1998

Recombinant expression of rat histidine decarboxylase: generation of antibodies useful for western blot analysis.

Histidine decarboxylase catalyses the formation of histamine, an important biological messenger. In spite of the essential biological functions exerted by histamine the knowledge about the mechanisms involved in the regulation of histidine decarboxylase is rather limited. This is most likely due to the limited supply of suitable tools, including highly specific antibodies. In the present study we describe the production and characterisation of specific antisera against rat histidine decarboxylase using recombinant protein synthesised in a bacterial expression system. The antisera were shown to effectively immunoprecipitate histidine decarboxylase activity in extracts of fetal rat liver as well as to detect the histidine decarboxylase protein by Western blot analysis of COS-7 cells expressing recombinant rat histidine decarboxylase. The results demonstrate the successful production of highly specific antisera to histidine decarboxylase which may become valuable tools in future studies of the structure and function of this enzyme.

Animals↗
PubMed1998

Smoking and vascular density of healthy marginal gingiva.

The influence of smoking on the vascular characteristics in periodontally healthy individuals was studied over a period of 11 wk. Fourteen healthy female dental students, 7 smokers and 7 nonsmokers, aged 25 to 38 yr, volunteered for the experiment. Photodocumentation was performed on four occasions with the aid of a stereophotographic method. The characteristics of gingival vessels were evaluated according to a semi-quantitative vascular index. It was found that the vascular density was not statistically significantly different in smokers and nonsmokers. Furthermore, the vascular density remained stable in both smokers and nonsmokers. The results suggest that the vascular density of the marginal gingiva is uninfluenced by moderate smoking once healthy gingival conditions prevail.

Adult↗
PubMed1998

Long-term effects of a change from a mixed diet to a lacto-vegetarian diet on human urinary and faecal mutagenic activity.

This is an investigation of the long-term effects of a shift from a mixed diet to a lacto-vegetarian diet and of a return to a mixed diet on the mutagenic activity in urine and faeces. The participants were 20 normal weight, non-smoking subjects. Dietary surveys and urinary and faecal samples were collected before and 3, 6 and 12 months after the dietary shift as well as 3 years after termination of the lacto-vegetarian diet period. The faecal samples were assayed for direct acting mutagens with the fluctuation test for weak mutagens and the urinary samples were assayed with the same assay but with a metabolic activation system, the so-called S9 fraction. The dietary data showed an increase in consumption of fruits, vegetables and dairy products and a decrease in meat, fish, eggs, sweets and biscuits during the vegetarian diet period. These changes led to an increase in total carbohydrates, fibre, vitamin C and calcium and a decrease in fat and protein intake. Mutagenic activity in both urine and faeces decreased after shift to the vegetarian diet and mutagenic activity in faeces increased when the volunteers returned to a mixed diet (P = 0.025 and 0.035 respectively when comparing the diets). These data indicate that dietary factors may effect mutagenic activity in urine and faeces. However, it is still not clear whether a decrease in animal products, a change in other nutritional factors or a decrease in frying are the main contributors to this change.

Adult↗
PubMed1998

Spouses' view during their partners' illness and treatment.

Nine spouses of people who had suffered from acute leukemia or highly malignant lymphoma were interviewed about their everyday life experiences throughout their partner's illness and treatment, and concerning their view of the professional care provided. The transcribed texts were subjected to phenomenological-hermeneutic analysis. The spouses felt they were in a situation of overall severe crisis (i.e., experiencing feelings of distress, restrictions, and limited or lack of support). The analysis revealed three family types: the couple acting as a unit, the couple acting independently on equal terms, and the couple acting separately with the spouse in a subordinate position. The spouses' evaluation of the entire experience varied according to the family type and the spouses' personal resources, which influenced the availability and utilization of their social network as well as the support of health-care staff. Contentment was related to the couple acting as a unit or the couple acting independently on equal terms and taking control over the situation, actively asking for support and requiring the staff to meet their needs. Discontentment was related to subordination of the spouse to the partner or to health-care staff, and failure of the couple to obtain support between them or from others. Empowering the spouses may mean helping them develop their skills, providing them with opportunities and authority, and assisting them in gaining access to resources based on knowledge of the family type, the consent of the partner, and the spouse's freedom to make choices. This may well lead to increased efficiency and have positive effects for the patient, for the spouse, and for them both as a couple.

Acute Disease↗
PubMed1998

Interstitial glycerol as a marker for membrane phospholipid degradation in the acutely injured human brain.

OBJECTIVE: Brain interstitial glycerol was studied as a potential marker for membrane phospholipid degradation in acute human brain injury. METHODS: Glycerol was measured in microdialysis samples from the frontal lobe cortex in four patients in the neurointensive care unit, during the acute phase after severe aneurysmal subarachnoid haemorrhage. Microdialysis probes were inserted in conjunction with a ventriculostomy used for routine intracranial pressure monitoring. Clinical events involving hypoxia/ischaemia were diagnosed by neurological signs, neuroimaging (CT and PET), and neurochemical changes of the dialysate-for example, lactate/pyruvate ratios and hypoxanthine concentrations. RESULTS: Altogether 1554 chemical analyses on 518 microdialysis samples were performed. Clinical events involving secondary hypoxia/ischaemia were generally associated with pronounced increases (up to 15-fold) of the dialysate glycerol concentration. In a patient with a stable condition and no signs of secondary hypoxia/ischaemia the glycerol concentration remained low. Simultaneous determination of glycerol in arterial plasma samples showed that the changes in brain interstitial glycerol could not be attributed to systemic changes and an injured blood brain barrier. CONCLUSIONS: This study suggests that membrane phospholipid degradation occurs in human cerebral ischaemia. Interstitial glycerol harvested by microdialysis seems to be a promising tool for monitoring of membrane lipolysis in acute brain injury. The marker may be useful for studies on cell membrane injury mechanisms mediated by for example, Ca2+ disturbances, excitatory amino acids, and reactive oxygen species; and in the evaluation of new neuroprotective therapeutic strategies.

Acute Disease↗
PubMed1998

A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury.

OBJECT: The authors prospectively studied the efficacy of tirilazad mesylate, a novel aminosteroid, in humans with head injuries. METHODS: A cohort of 1120 head-injured patients received at least one dose of study medication (tirilazad or placebo). Eighty-five percent (957) of the patients had suffered a severe head injury (Glasgow Coma Scale [GCS] score 4-8) and 15% (163) had sustained a moderate head injury (GCS score 9-12). Six-month outcomes for the tirilazad- and placebo-treated groups for the Glasgow Outcome Scale categories of both good recovery and death showed no significant difference (good recovery in the tirilazad-treated group was 39% compared with the placebo group in which it was 42% [p=0.461]; death in the tirilazad-treated group occurred in 26% of patients compared with the placebo group, in which it occurred in 25% [p=0.750]). Subgroup analysis suggested that tirilazad mesylate may be effective in reducing mortality rates in males suffering from severe head injury with accompanying traumatic subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of patients; in the placebo group it occurred in 43% [p=0.026]). No significant differences in frequency or types of serious adverse events were shown between the treatment and placebo groups. CONCLUSIONS: Striking problems with imbalance concerning basic prognostic variables were observed in spite of the large population studied. These imbalances concerned pretreatment hypotension, pretreatment hypoxia, and the incidence of epidural hematomas. In future trials of pharmacological therapy for severe head injury, serious consideration must be given to alternative randomization strategies. Given the heterogeneous nature of head injury and the identification of populations that do relatively well with standard therapy, target populations with a higher risk for mortality and morbidity may be more suitable for clinical trials of such agents.

Adult↗
PubMed1998

[PET scan in neuro-intensive care and research].

The main objective of neurointensive care is to counteract the development of secondary brain ischemia. The management is focused on preventing, detecting and correcting secondary insults that are likely to produce ischemic brain damage. This requires intensive multimodality monitoring of the brain. There is no reliable technique available for continuous monitoring of cerebral blood flow and therefore intermittent methods have to be used in some cases for objective measurement of cerebral perfusion. PET allows measurements of both cerebral blood flow and metabolism, which is essential for the assessment of the energy metabolic state of the brain tissue. PET may be used to guide therapeutic intervention, to evaluate the effect of treatment, to validate new techniques for monitoring of the brain and to determine the efficacy of potential neuroprotective drugs. The possibilities that PET offers in neurointensive care and research are illustrated. The experiences from the application of PET in the evaluation of pharmacological treatment of increased intracranial pressure in head injured patients and the use of PET in combination with intracerebral microdialys, in an MCA-occlusion-reperfusion primate model and in patients with subarachnoid hemorrhage, to validate intracerebral microdialysis as an instrument for chemical monitoring of the brain during neurointensive care, are reported.

Critical Care↗
PubMed1998

Neck support pillows: a comparative study.

BACKGROUND: Special neck support pillows claiming to improve rest and reduce neck pain are currently being advertised. OBJECTIVE: To test whether neck pillows have any positive effect on neck pain and quality of sleep compared with usual pillows and, if so, to find the optimal characteristics of such a pillow. METHODS: Thirty-seven hospital employees and 18 neck patients were asked to test six neck pillows with different shapes and consistency randomly over the course of 3 wk, to grade them according to comfort and to describe the characteristics of an ideal pillow. RESULTS: Thirty-six of 55 persons found the pillows positively affected sleep and 27 of 42 found that they positively affected neck pain. The ideal pillow should be soft and not too high, should provide neck support and should be allergy-tested and washable. The pillow that included two firmer supporting cores for neck lordosis received the best rating. CONCLUSION: A neck pillow with good shape and consistency and with firm support for cervical lordosis can be recommended as a part of treatment for neck pain.

Adult↗
PubMed1997

CGP 48664, a potent and specific S-adenosylmethionine decarboxylase inhibitor: effects on regulation and stability of the enzyme.

Mammalian S-adenosylmethionine decarboxylase (AdoMetDC) catalyses a regulatory important step in the biosynthesis of polyamines and is a potential target for therapeutic agents against various parasitic diseases and proliferative disorders. In the present study we examined the effects of a newly synthesized AdoMetDC inhibitor. 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664), on polyamine metabolism in the mouse leukaemia cell line L1210. Treatment of the cells with 2 microM CGP 48664 led to a depletion of cellular spermidine and spermine. The putrescine content, in contrast, was markedly increased. Cells seeded in the presence of the inhibitor showed a significant decrease in growth rate, which was fully reversed by the addition of 2 microM spermidine or 1 microM spermine. The syntheses of ornithine decarboxylase and AdoMetDC were greatly increased in cells treated with CGP 48664. These increases were not correlated with similar changes in the mRNA levels, indicating the involvement of a translational mechanism. CGP 48664 was demonstrated to be a very poor competitor of spermidine uptake in the L1210 cells. L1210 cells deficient in polyamine transport were as sensitive to the antiproliferative effect of the inhibitor as were the parental cells, indicating that CGP 48664 did not enter the cells by the polyamine transport system. In addition to inhibiting AdoMetDC, CGP 48664 stabilized the enzyme against degradation. In the present study we also demonstrated that aminoguanidine (AMG), which is frequently used in cellular systems to inhibit any action of serum polyamine oxidase, apparently inhibits AdoMetDC by an irreversible mechanism that markedly stabilizes the enzyme against proteolytic degradation. CGP 48664 and the parental compound methylglyoxal bis(guanylhydrazone), which is also a potent inhibitor of AdoMetDC, contain one or two AMG-like moieties; the importance of these residues in the inhibition of AdoMetDC is discussed.

Adenosylmethionine Decarboxylase↗
PubMed1997

Cloning of a trypanosomatid gene coding for an ornithine decarboxylase that is metabolically unstable even though it lacks the C-terminal degradation domain.

Mammalian ornithine decarboxylase (ODC) is among the most labile of cellular proteins, with a half-life of usually less than an hour. Like other short-lived proteins ODC is degraded by the 26S proteasome. Its degradation is not triggered by ubiquitination, but is stimulated by the binding of an inducible protein, antizyme. Truncations and mutations in the C terminus of mammalian ODC have been shown to prevent the rapid turnover of the enzyme, demonstrating the presence of a degradation signal in this region. Moreover, ODCs from the trypanosomatid parasites Trypanosoma brucei and Leishmania donovani, which lack this C-terminal domain, are metabolically stable, and recombination of T. brucei ODC with the C terminus of mammalian ODC confers a short half-life to the fusion protein when expressed in mammalian cells. In the present study we have cloned and sequenced the ODC gene from the trypanosomatid Crithidia fasciculata. To our knowledge, this is the first protozoan shown to have an ODC with a rapid turnover. The sequence analysis revealed a high homology between C. fasciculata ODC and L. donovani ODC, despite the difference in stability. We demonstrate that C. fasciculata ODC has a very rapid turnover even when expressed in mammalian cells. Moreover, ODC from C. fasciculata is shown to lack the C-terminal degradation domain of mammalian ODC. Our findings indicate that C. fasciculata ODC contains unique signals, targeting the enzyme for rapid degradation not only in the parasite but also in mammalian cells.

Amino Acid Sequence↗
PubMed1997

Fusion or stabilization alone for acute distractive flexion injuries in the mid to lower cervical spine?

Long-term pain problems and residual restricted mobility were evaluated for patients sustaining acute distractive flexion injuries to the cervical spine. To assess which of two alternative surgical approaches gives better long-term outcomes, 58 patients were studied, 29 in each group. The results of posterior wire stabilization without fusion according to Brandt were contrasted with those of the Cloward technique. We found significantly more late pain problems and restricted neck mobility in the group treated with wiring without fusion than in those managed with anterior fusion. We conclude that this continuing pain may be due to residual mobility in the damaged degenerated non-fused motion segment, and that the difference between the two groups may reflect the difference in the quality and rate of fusion achieved by the two surgical approaches.

Adolescent↗