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Biomedical subjects

L Jansson

Publications and source records attributed to L Jansson.

At least 199 records · Page 11Linked to original sources
PubMed1989

Terbutaline decreases the blood flow of the pancreatic islets but does not reduce the diabetogenic action of streptozotocin in the rat.

Male Sprague-Dawley rats were injected i.v. with either 0.5 ml saline or terbutaline (1 mg/kg body weight) and 5 min later the whole pancreatic blood flow (PBF) and the islet blood flow (IBF) were measured with a microsphere technique. Injection of terbutaline increased the serum insulin concentrations, but had no effect on the serum glucose concentration of the animals. The IBF was decreased by terbutaline by approximately 40%, while the PBF remained unchanged. Furthermore, the diabetogenic action of streptozotocin (SZ; 35 mg/kg bodyweight; i.v.) was not affected by the administration of terbutaline 5 min before the SZ injection. It is concluded that the beta 2-selective adrenoceptor agonist terbutaline selectively decreases the blood flow of the pancreatic islets in spite of its stimulatory effects on the release of insulin. This confirms our previous findings that the IBF and the release of insulin can be dissociated. Moreover, the hyperglycemic action of a single diabetogenic dose of SZ could not be reduced by terbutaline administration despite the reduction in the IBF. This suggests that a decrease in the islet blood flow is not sufficient to prevent the cytotoxicity of SZ.

Animals↗
PubMed1989

Age-dependent changes of pancreatic islet blood flow in the rat.

Whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured in anesthetized Sprague-Dawley rats aged 5, 20, 52, or 104 wk. PBF decreased progressively with age, from approximately 0.55 mL x min-1 x g pancreas-1 in 5- and 20-wk-old rats to 0.30 mL x min-x g pancreas-1 in 52- and 104-wk-old rats. In animals aged 5 wk, the IBF was approximately 25 microL x min-1 x g pancreas-1 but increased to about 60 microL x min-1 x g pancreas-1 (p less than 0.001) in animals aged 20-104 wks. When IBF was expressed as a fraction of PBF, a different pattern was observed. In the 5-wk-old animals only 5% (p less than 0.001) of the PBF flowed through the islets, whereas the rats aged 20 wk had a fractional IBF of about 10%. A significantly larger fraction, of approximately 20%, was diverted through the islets in the 52- and 104-wk-old rats. Glucose administration to animals aged 5, 20, and 52 wk significantly increased both PBF and IBF, but had a more marked effect in the older animals. The fractional IBF was also increased by glucose in the two latter groups, indicating a preferential increase in IBF. In the animals aged 5 wk, however, PBF and IBF increased in concert. We conclude that the previously described age-dependent changes in islet volume and functional capacity of the islet organ is also accompanied by changes in the IBF.

Aging↗
PubMed1989

Oestrogen induced suppression of collagen arthritis. IV: Progesterone alone does not affect the course of arthritis but enhances the oestrogen-mediated therapeutic effect.

The effects of 17 beta-oestradiol and progesterone on the development of type II collagen-induced arthritis (CIA) and the anti-type II collagen (CII) autoantibody response were investigated. Treatment with physiological doses of 17 beta-oestradiol, inducing serum levels below the estradiol peak at the end of pregnancy, abrogated the development of arthritis and suppressed the anti-CII autoantibody response. Treatment with progesterone alone did not have significant effects on the development of arthritis or on the anti-CII autoantibody response. However, a combined treatment with both progesterone and oestrogen in physiological doses induced a more pronounced suppression of CIA than the suppression induced with oestrogen treatment alone. These findings suggest that oestrogen, but not progesterone, may be the critical factor to explain the pregnancy-related down-regulation of CIA.

Animals↗
PubMed1989

Aspects of pancreatic islet transplantation in diabetes mellitus.

The justification for pancreatic or islet transplantation in diabetes mellitus is to halt progression of diabetic vascular complications. Although this goal has so far not been achieved, technical progress in transplanting the whole or segmental, vascularized pancreas has been remarkable. However, the operation is complicated and not without risk; immune rejection is furthermore a major problem, and the availability of suitable organs is limited. Transplantation of isolated pancreatic islet grafts, i.e. isolated islets or fetal pancreas, has therefore emerged as an attractive alternative. Iso-, allo- or xenografts of such preparations have been found to reverse diabetes in experimental animals. Only a minor operation is required and islets, although highly immunogenic, may be accessible to immunomodulation in vitro in order to decrease or abolish the allograft rejection and prevent cells from becoming targets for the autoimmune assault. However, problems and difficulties have emerged in this context also. Thus, islets are extremely difficult to isolate from the adult human pancreas. Such glands, be they adult or fetal, are not easily available, and clinical trials have so far remained without documented success. Considerable efforts are being made to overcome the difficulties encountered in islet transplantation. Attempts are being made to improve the techniques for preparation of clean and viable islets and to understand critical factors in the cellular interactions between the graft and the host after transplantation. Factors of importance in this context are the nutritional requirements of the graft and the vascularization process at the site of implantation. In order to provide unlimited access to cells with a high potential for insulin production and adaptive growth in the diabetic recipient, ongoing research is also directed towards methods for preparation of porcine fetal and adult islets suitable for xenotransplantation. The obvious problems involved in immune rejection of the grafted tissue are being investigated with respect both to the possibility of immunomodulation of the graft in vitro, the design of new immunosuppressive drugs, and the possibility of immuno-isolation of the insulin-producing cells with the aid of artificial membranes.

Diabetes Mellitus↗
PubMed1989

Oestrogen is a potent immunomodulator of murine experimental rheumatoid disease.

Oestrogen has important modulatory effects on autoimmune diseases. Earlier studies, both in humans and in experimental models, have convincingly suggested that oestrogen exaggerates lupus disease and enhances autoantibody production in lupus. However, a general effect by oestrogen to stimulate auto-immune disease does not fit with recent findings in human rheumatoid arthritis and in certain experimental autoimmune models. Here it is shown that oestrogen treatment suppresses development of type II collagen induced arthritis in mice and rats, which is a T-cell dependent experimental model for human RA. The oestrogen-mediated effects are obtainable in physiological levels and both incidence and severity of disease can be suppressed. It is demonstrated that oestrogen has a dualistic effect on the immune system by suppressing antigen-specific T-cell dependent immune reactions while enhancing B-cell activities. On these grounds, we suggest that autoimmune diseases should be divided into two groups, one in which oestrogen accelerates disease progression and another in which oestrogen is beneficial.

Animals↗
PubMed1989

Feeding problems in severely demented patients seen from task and relationship aspects.

This study aimed at increasing the understanding of feeding problems in severely demented patients cared for in a task assignment system. Twenty-three video-recordings made during the feeding of 15 severely demented patients and 55 focused interviews with 45 caregivers, who fed the 15 patients during that period were analysed regarding the feeding problems seen from a task aspect and from a relationship aspect. The result indicated that the problems were partly of a more constant nature and partly fluctuated from meal to meal. Feeding problems regarding the task aspect were mentioned first by the caregivers in the interviews in spite of the fact that the patients had severe communication problems which could be expected to cause great problems in the relationship between the patient and his caregiver. Reasons for these findings are suggested.

Aged↗
PubMed1989

Collagen induced arthritis as an experimental model for rheumatoid arthritis. Immunogenetics, pathogenesis and autoimmunity.

The type II collagen (CII) induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and may be used as a model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA model, when induced with autologous CII, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases are autoantibodies to CII and rheumatoid factors produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells and an infiltration of granulocytes. We do here suggest that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA provides opportunities for studies of immunospecific reactions leading to arthritis.

Animals↗
PubMed1989

Persistent impairment of the insulin response to glucose both in vivo and in vitro after streptozotocin exposure: studies with grafted pancreatic islets and islets maintained in culture.

The functional responses of the pancreatic B-cells after cytotoxic damage are still largely unknown. Using in vitro models to clarify this issue, we have recently observed a preferential reduction of glucose-stimulated insulin production and release in mouse pancreatic islets maintained in culture after in vitro exposure to streptozotocin. In order to evaluate the relevance of these findings in vivo, two sets of experiments were performed. First, mouse pancreatic islets were exposed in vitro to 2.2 mmol/l streptozotocin or vehicle alone, cultured for 6 days, and finally grafted under the kidney capsule of normoglycemic nude mice. Two weeks after transplantation there was no difference in the total DNA and insulin content between the two groups of islet grafts, but the insulin concentration, as expressed per microgram DNA, was decreased by 40% in the streptozotocin-treated islets. The insulin release of the grafts, during perfusion of the graft-bearing kidney in situ with 16.7 mmol/l glucose was diminished in the streptozotocin group, whilst perfusion with 16.7 mmol/l glucose plus 5 mmol/l theophylline was able partially to counteract the reduction in insulin release. In the second set of experiments, NMRI mice were injected iv with 160 mg/kg streptozotocin or vehicle alone, and their islets isolated 15 min after the injections. After 6 days in culture, there was no decrease in DNA, glucagon and somatostatin contents, but the insulin content was decreased by 40% in the streptozotocin exposed islets. These islets also showed a 60% decrease in the insulin response to glucose, which was partly counteracted by incubation with 16.7 mmol/l glucose plus 5 mmol/l theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Intraportally transplanted pancreatic islets revascularized from hepatic arterial system.

Isolated pancreatic islets were implanted intraportally into normoglycemic or alloxan-induced diabetic C57BL/6 mice. Each animal was grafted with 200-250 syngeneic islets. Four, 8, 14, or 56 days after the transplantation, 2 to 3 x 10(5) microspheres (10 micron diam) were injected into either the portal vein or the abdominal aorta of anesthetized animals. The presence of microspheres within the islet grafts was determined in stained sections of the livers. In general, the number of microspheres in the liver sections was greater than 10 times higher in mice given microspheres via the portal route. When the microspheres were administered via the arterial system 2 wk after transplantation, approximately 20-30% of the islet sections contained microspheres; only occasional spheres were found in the islets after intraportal administration. This was the case even when as many as 56 days had elapsed. Some but not all mice investigated 4 and 8 days after transplantation had islets that contained microspheres. The intraportally implanted islets in hyperglycemic animals had decreased revascularization compared with normoglycemic mice 2 wk after implantation. The results indicate that intraportally implanted syngeneic pancreatic islets become revascularized mainly from the hepatic artery and that this process starts as early as during the 1st wk postimplantation. Furthermore, hyperglycemia seems to influence this process.

Animals↗
PubMed1989

Influence of hyperglycemia on blood perfusion of autotransplanted pancreatic islets in diabetic rats.

One week after a partial pancreatectomy, which did not affect glucose homeostasis, adult rats were autotransplanted with 500 isolated pancreatic islets beneath the renal capsule. Some rats were rendered diabetic with streptozocin (STZ) before being implanted with the islets, and other rats received no STZ and thus remained normoglycemic. The number of implanted islets was insufficient to revert hyperglycemia, but the STZ-induced diabetic animals were treated with insulin according to one of the following protocols: 1) one daily subcutaneous insulin injection for 28 days after transplantation; 2) insulin injection on days 1-14; 3) insulin injection on days 15-28; or 4) no insulin. Four weeks after transplantation, the blood perfusion of the islet grafts was determined by a microsphere technique. Continuous hyperglycemia after implantation of the islets significantly decreased the volume of the graft and the blood flow per volume compared with normoglycemic animals also receiving islet transplants. Insulin treatment counteracted the decrease in both of these values. This result was achieved regardless of whether the insulin treatment was maintained throughout the 4-wk period or only during the first or second half. The mechanism behind the impaired blood perfusion of the grafts during continuous hyperglycemia is unknown, but it may reflect an effect on the revascularization of the graft or on the intrinsic regulation of the blood perfusion of the graft.

Animals↗
PubMed1989

Effects of culture conditions on formation and hormone content of fetal porcine isletlike cell clusters.

To establish methods for stimulation of the growth and differentiation of fetal endocrine pancreatic cells, a technique for the in vitro production of fetal porcine isletlike cell clusters (ICCs) was used. By varying the composition of the culture medium with different glucose concentrations and the addition to the culture medium of insulin, growth hormone (GH), amino acids, or nicotinamide, we estimated the formation of ICCs and their hormone content. High glucose content (28.0 mM) stimulated the formation of abundant ICCs that contained decreased amounts of insulin. In contrast, culture at a low (5.6-mM) glucose concentration increased the ICC insulin content but decreased the number of ICCs formed. Addition of seven times the normal amount of amino acids hampered both the formation of ICCs and their insulin content. Neither insulin nor GH supplementation of the medium influenced the ICC insulin content, but GH stimulated an abundant outgrowth of ICCs containing relatively high insulin concentrations. However, ICCs formed under these circumstances contained less than 10% of the insulin content of adult islets, and further work has to be carried out to identify factors responsible for further differentiation of the fetal porcine pancreas.

Animals↗
PubMed1989

Effects of hyperglycemia on function of isolated mouse pancreatic islets transplanted under kidney capsule.

The insulin release from isolated pancreatic islets grafted under the kidney capsule was examined by means of a modified kidney-perfusion technique. The grafts, consisting of 150 C57BL/6 or 250 C57BL/Ks mouse islets, were implanted syngeneically under the left kidney capsule of normoglycemic or alloxan-induced diabetic recipients 4 wk before the perfusion. In both mouse strains, islets grafted to normoglycemic animals showed an immediate distinct peak of insulin release when challenged with high glucose, whereas no response was observed from islets grafted to hyperglycemic mice. In a similar way in C57BL/Ks mice, arginine stimulated insulin release from the islet grafts in normoglycemic but not in hyperglycemic recipients. Insulin treatment of the diabetic recipients, however, partially normalized the insulin response to glucose. Islet grafts were removed in toto and analyzed for contents of insulin, glucagon, somatostatin, and DNA or rates of glucose-stimulated (pro)insulin biosynthesis. In both mouse strains, islets implanted into hyperglycemic animals contained significantly less insulin, and their rates of (pro)insulin biosynthesis were markedly decreased. Insulin treatment only marginally affected these parameters. The glucagon content of the grafted islets was unaffected by the hyperglycemia in both strains of mice, whereas a significant decrease in the somatostatin content was observed in the C57BL/Ks mice. We concluded that grafted islets exposed to prolonged hyperglycemic stress become functionally impaired in mice of both strains. Our perfusion technique of islet-graft-bearing kidneys in combination with biochemical studies on the removed grafts provides a suitable model for studies of the effects of prolonged hyperglycemia on islet beta-cell function.

Animals↗
PubMed1989

Ethical reasoning concerning the feeding of terminally ill cancer patients. Interviews with registered nurses experienced in the care of cancer patients.

In the terminal phase of life, some cancer patients have problems eating. Caregivers then have to decide whether or not to provide the patients with food by artificial means. Taped interviews concerning the treatment of terminally ill, mentally alert, old cancer patients who refuse food were conducted with 20 registered nurses who were regarded as "experienced and good nurses." Not one of these nurses considered using force or violence against the patients. It seemed that the question about whether to feed the patient was not as urgent as the question of whether to accept active euthanasia. The interviewees seemed quite certain about how they would treat the patient in different circumstances, but found it difficult to justify their judgements. Several stressed the importance of their personal experience with dying persons, and thought that one should act according to the Golden Rule.

Adult↗
PubMed1989

Pancreatic and islet blood flow in the regenerating pancreas after a partial pancreatectomy in adult rats.

A 60% partial pancreatectomy or a sham operation was performed in adult, male Sprague-Dawley rats. Measurements of pancreatic blood flow (PBF) and islet blood flow (IBF) were achieved by a microsphere technique either before surgery or 1, 2, 4, 8, or 16 weeks after the operation. An intraperitoneal glucose tolerance test (2 gm glucose/kg body weight) was made 2 days before the blood flow measurements. There were no aberrations in glucose homeostasis at any time point after the partial pancreatectomy. The sham-operated animals had both PBF and IBF values similar to those of nonoperated animals at all time points. The rats that underwent partial pancreatectomy, however, showed significantly increased PBF values 2 and 4 weeks after surgery but values similar to those of the sham-operated rats 1, 8, and 16 weeks after surgery. The IBF values of the animals that underwent pancreatectomy were significantly increased from week 2 onward when expressed per gram of pancreas and from week 4 onward when expressed as a fraction of PBF. Compared with the sham-operated animals, the total blood perfusion of the islet organ was increased in the rats that underwent partial pancreatectomy despite a reduction in total pancreatic mass. It is concluded that a partial pancreatectomy induces both a transient increase in PBF and a more long-lasting increase in IBF. It is conceivable that these observations reflect the regeneration of exocrine and endocrine cells and an increased functional load on these tissues.

Animals↗
PubMed1988

The volume and area of the capillaries in the endocrine and exocrine pancreas of the rat.

The capillary volumes in the endocrine and exocrine parenchyma of the pancreas were compared with a point-sampling technique. The islets were found to have a capillary volume of approximately 3.5%, while the value for the exocrine pancreas was significantly (P less than 0.001) lower at 2%. When the capillary wall area was measured, however, both types of parenchyma had a similar value of approximately 20 mm2/mm3 tissue. The reason for the discrepancy between these parameters is probably the lack of lymphatic capillaries, with their relatively small lumen in the islets.

Alkaline Phosphatase↗
PubMed1988

The influence of cyclosporin A on the vascular permeability of the pancreatic islets and on diabetes induced by multiple low doses of streptozotocin in the mouse.

The aim of the present study was to investigate the influence of cyclosporin A on the course of multiple low dose streptozotocin induced diabetes in mice, an animal model for human type I diabetes mellitus. C57BL/Ks mice were treated on five consecutive days with intraperitoneal injections of streptozotocin or citiric acid buffer. Thirty min before the injections the animals were given cyclosporin A (10 or 50 mg/kg body weight) or saline. Cyclosporin A did not protect against the hypoglycaemia and at the higher dose it potentiated the diabetogenic effect. Furthermore, cyclosporin A did not affect the development of insulitis when the pancreatic glands were examined by light microscopy. Using a technique for monitoring vascular permeability in vivo with the aid of the pigment Monastral Blue B, it was found that the development of diabetes was accompanied by an increased vascular leakage. Control animals treated with cyclosporin A also showed an increased islet staining with Monastral Blue B. The data indicate that cyclosporin A potentiates diabetes induced by low doses of streptozotocin. This can be attributed to a direct toxic effect of cyclosporin A on the pancreatic B-cells and may also be due to an increased vascular leakage induced by cyclosporin A. The latter would allow an increased migration of inflammatory cells into the islets and the consequent release of B-cytotoxic substances.

Animals↗
PubMed1988

Estrogen-induced suppression of collagen arthritis. III. Adult thymectomy does not affect the course of arthritis or the estrogen-mediated suppression of T-cell immunity.

Type II collagen-induced arthritis is dependent on the activation of T-helper cells and is modulated by female sex hormones. It is shown that treatment of castrated female DBA/1 mice with beta-estradiol decreases the incidence (32% vs 88%) as well as the severity of the disease. The estrogen-induced suppression of both the development of collagen arthritis and T-cell immunity were not dependent on the thymus. Thus, estrogen treatment of thymectomized and castrated female mice suppressed the incidence (21% versus 100% in controls) and severity of arthritis. Similarly, estrogen treatment of thymectomized and castrated female mice suppressed both antigen-specific delayed-type hypersensitivity and T-cell proliferative responses. These data suggest that the estrogen-mediated suppression of arthritis and T-cell immunity is not dependent on the presence of an intact thymus.

Animals↗