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Biomedical subjects

I Jansson

Publications and source records attributed to I Jansson.

At least 19 recordsLinked to original sources
PubMed1992

Pulmonary granulocyte accumulation is reduced by nebulized corticosteroid in septic pigs.

Nebulized beclomethasone dipropionate was administered to 14 anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (BDP group). Changes in pulmonary activity from autologous granulocytes labeled with In-111 was detected externally for 12 (n = 8) to 44 h (n = 6). The changes were compared with those in ten pigs (12 h n = 7, 44 h n = 3) subjected to the same insults but given no corticosteroid (placebo group). Serial measurements of blood radioactivity, and cardiac output were performed in animals observed for 12 h. Corticosteroid-treated pigs showed a gradual decline in decay-corrected pulmonary In-111 activity. The placebo group displayed a more varied reaction, but most animals had an increased activity compared to the corticosteroid group. The difference between the groups was significant at 8 h (BDP-group 92% (88-98), placebo-group 107% (97-121), median (lower-upper quartiles), baseline = 100%. P < 0.01, U-test). Blood radioactivity and cardiac output did not differ significantly between the two groups. Nebulized corticosteroid thus diminished pulmonary granulocyte accumulation, which may be of value in the treatment of septic respiratory distress.

Aerosols↗
PubMed1992

Methylprednisolone improves pulmonary function and hemodynamics in experimental gram-positive septicemia.

It has been suggested that the effects of high-dose corticosteroid therapy (HDC) in gram-positive (G+) and gram-negative (G-) septicemia differ. As few data are available on HDC in G+ septicemia, pulmonary and cardiovascular function was studied for 44 hr in five anesthetized pigs subjected to brief infusion of live Staphylococcus aureus (approximately 10(11) cfu) followed by intravenous methylprednisolone (MP, 30 mg/kg) administered as a bolus every 8 hr. Comparisons were made with six septic pigs given no MP but otherwise identically managed. Six control pigs received no bacteria or MP. Infusion of bacteria induced identical transient pulmonary hypertension in both septic groups (52 +/- 7 mm Hg, mean +/- SD), but MPAP remained significantly lower in the pigs with MP (18 +/- 1 mm Hg vs. 30 +/- 9 mm Hg at 8 hr, P less than 0.05). MAP was better maintained in the MP group (107 +/- 9 mm Hg vs. 80 +/- 16 mm Hg at 8 hr, P less than 0.05). Pulmonary function also was less affected in the MP group at 8 hr, with significantly better maintenance of arterial oxygenation (13.5 +/- 1.2 kPa vs. 9.4 +/- 2.2 kPa, P less than 0.05) less venous admixture (11 +/- 6% vs. 34 +/- 23%, P less than 0.05) and superior lung-thorax compliance (29 +/- 5 ml/cm H2O vs. 15 +/- 5 ml/cm H2O, P less than 0.05). Five of five with MP survived, whereas two of six without MP survived (P = 0.045). MP thus attenuated pulmonary and hemodynamic abnormalities induced by S. aureus septicemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis.

BACKGROUND AND METHODS: Hyaluronan is a polysaccharide normally present in low concentrations in the blood, and is rapidly cleared from the blood by the liver. Increased plasma hyaluronan concentrations have been found in patients with sepsis. We studied changes in serum hyaluronan concentrations and their relationship to hemodynamics and survival in a 48-hr porcine model of injury and sepsis. RESULTS: Circulating hyaluronan concentrations increased to high values after induction of experimental sepsis (from mean baseline values of 242 +/- 26 [SEM] to mean maximum concentrations of 964 +/- 255 micrograms/L [p less than .01]) compared with controls (199 +/- 38 to 303 +/- 32 micrograms/L). A weak negative correlation between mean arterial pressure (MAP) and serum hyaluronan values was found (r2 = .47; p less than .01). Nonsurvivors had higher mean serum hyaluronan concentrations than survivors (603 +/- 147 vs. 285 +/- 43 micrograms/L [p less than .05]). CONCLUSIONS: Experimental sepsis is associated with an increase in serum hyaluronan values. The relationship between decreased MAP and increased serum hyaluronan concentrations could point to reduced liver perfusion as a cause. An association between high hyaluronan values and nonsurvival in sepsis is possible.

Analysis of Variance↗
PubMed1991

Nebulized corticosteroid improves pulmonary function and outcome in experimental porcine septicemia.

Nebulized beclomethasone dipropionate was administered to six anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (aerosol group). Changes in pulmonary mechanics, gas exchange and hemodynamics during an observation period of 44 h were compared with those in six pigs subjected to the same insults but given no corticosteroid (non-treatment group). Six pigs served as controls, without sepsis or aerosol, but with the same general management (control group). The septic insult induced an acute 3-fold increase in mean pulmonary artery pressure (MPAP) in the aerosol and non-treatment group. MPAP fell to near baseline levels in the aerosol group, but remained significantly higher in the non-treatment group. Mean systemic arterial pressure fell more in the non-treatment than in the aerosol group, reaching its lowest level at 32 h. Pulmonary function was less affected in the aerosol group, with significantly better maintenance of arterial oxygenation, lower venous admixture and superior lung-thorax compliance than in the non-treatment group. Survival was significantly improved in the aerosol group. In this porcine model of septicemia-induced adult respiratory distress syndrome, nebulized corticosteroid thus attenuated the development of respiratory failure.

Administration, Inhalation↗
PubMed1991

Preceding trauma lessens the degree of respiratory dysfunction in septicaemic pigs.

Ten anaesthetised and mechanically ventilated pigs were subjected to musculoskeletal trauma two hours before induction of septicaemia with live Staphylococcus aureus, 10(11) colony forming units (trauma/sepsis group). The effects on haemodynamic and pulmonary function were compared over a period of 44 hours with those on 11 pigs that were identically treated except that they were not subjected to the trauma (sepsis alone group). The induction of sepsis produced similar transient pulmonary hypertension in both groups (mean (SD) in the trauma/sepsis group 48 (5) mmHg compared with 51 (6) mmHg in the sepsis group). In the trauma/sepsis group the decline in lung/thorax compliance was significantly less pronounced at 8 and 20 hours; the arterial oxygen tension was significantly better maintained at 32 and 44 hours; and the haemodynamics were better preserved, with significantly lower mean pulmonary arterial pressures at 20 and 44 hours than in the sepsis group. In conclusion, musculoskeletal trauma preceding septicaemia significantly lessened the degree of ensuing pulmonary dysfunction. This effect could be the results of reduced autoinjury by immunocompetent cells responding subnormally, but these mechanisms require further study.

Animals↗
PubMed1990

Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy.

Seventy-one women who had a proctocolectomy for ulcerative colitis (n = 41) or Crohn's disease (n = 30) were interviewed in the follow-up clinic about gynaecological problems and fertility. All women were examined by an independent gynaecologist and abnormalities of the internal genital tract were registered. Forty-nine per cent (35/71) of the women had a distressing vaginal discharge after proctocolectomy, compared with 9% (6/71) before surgery. At the gynaecological examination 45% (32/71) had a heavy vaginal secretion with- out any signs of an acute vaginal infection. In 68% (30/44) fluid retention in the vagina was associated with a caudally firmly fixed and dilated posterior vaginal fornix. Twelve per cent (8/66) of the women reported dyspareunia before surgery. After surgery, 27% (18/66) complained of this symptom. Fertility was significantly reduced after surgery since only 37% (10/27) of the women who attempted to become pregnant succeeded within 5 years follow-up. The corresponding figure before surgery was 72% (39/54). Those who conceived went through pregnancy and parturition without any incident, 6 of 21 delivered by caesarean incision. In conclusion, conventional proctocolectomy in women will result in distressing vaginal discharge, and dyspareunia in a considerable proportion of the patients. The operation also seems to decrease their chances of becoming pregnant.

Adult↗
PubMed1990

Behavioral effects after intrathecal administration of cholinergic receptor agonists in the rat.

Behavioral effects of nicotine and cytisine, and the cholinesterase inhibitors physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (THA), administered intrathecally (IT) at the lumbar level in the rat have been evaluated. Antinociceptive dose relationships were established using the tail immersion test. Total activity, locomotion and rearing were also measured in computerized test boxes. The nicotinic receptor antagonist, mecamylamine, and the muscarinic receptor antagonist, atropine, were used to study the selectivity of the effects. Physostigmine and THA significantly decreased total activity, locomotion and rearing as compared to control animals. The motor effects of physostigmine were completely antagonized only partly. Mecamylamine had no antagonistic effect. Nicotine did not affect any activity parameter. Cytisin reduced total activity and locomotion 1-6 min after dose. IT physostigmine, 15 micrograms, increased tail immersion latency for 30 min. No significant increase in response latency in this test was observed after the IT administration of nicotine or THA, whereas cytisine elicited a small increase. The IT administration of THA, nicotine and cytisine was also associated with gnawing, vocalization and hyperactivity and in the case of THA, diarrhoea. These effects were blocked by mecamylamine. Physostigmine antinociception as well as the behavioral effects including total activity, locomotion and rearing caused by physostigmine and by THA are most probably due to an action on spinal muscarinic receptors. Nicotinic receptors do not seem to be involved in spinal antinociception. Some aversive behavioral effects caused by the IT administration of nicotinic receptor agonists could, however, be attenuated by the spinal administration of the antagonist mecamylamine, which may indicate the involvement of nicotinic receptors in afferent sensory transmission.

Alkaloids↗
PubMed1990

Relationship between phosphorylation and cytochrome P450 destruction.

In our previous report we showed cytochrome b5 to be a competitive inhibitor of cAMP-dependent protein kinase (PKA) for interaction with cytochrome P450 (P450). While P450 was phosphorylated, cytochrome b5 was not. The phosphorylation of P450 resulted in an inhibition of its catalytic activity. In this report we attempt to determine the relationship between phosphorylation of P450 from phenobarbital-induced rat and its destruction. The results indicate there is a considerable alteration of P450 IIB1 when it is put into the phosphorylation medium. This includes destruction, i.e., loss of the hemoprotein nature (Soret peak), as well as denaturation, conversion of a proportion of the P450 to P420. The extent of phosphorylation correlated best with the amount of destroyed hemoprotein, and not with the formation of P420. There did not appear to be phosphorylation-dependent formation of apo-P450. Further, prior conversion of the P450 to P420 using sodium deoxycholate showed the same extent of phosphorylation as before the conversion. Thus, intact P450 is not required for phosphorylation nor is phosphorylation a prerequisite for hemoprotein destruction. P450 CAM (CIA1), which has the PKA substrate recognition sequence internalized, likewise undergoes conversion to P420 but this denaturation does not result in phosphorylation. Destruction of CIA1 with 6 M urea, however, did permit phosphorylation by PKA. P450 IIB1 destruction was greatly diminished by cytochrome b5. This stabilization resulted in a decreased degree of phosphorylation as well as an increase in negative ellipticity in circular dichroism, indicative of an increase in the proportion of alpha-helical content in the P450. Suggestions are made that this structural modification caused by cytochrome b5 stabilizes the P450 against denaturation as well as against destruction and phosphorylation. Further, when the P450 IIB1 was kept stable as P450 in the absence of cytochrome b5 and without loss of hemoprotein during the incubation period, using phosphate-glycerol buffer containing 0.4% Emulgen 911, the phosphorylation of the P450 was greatly diminished, with only minor effects on the protein kinase reaction itself. These results suggest that the protein kinase reaction itself. These results suggest that the protein kinase substrate recognition sequence is not readily accessible to PKA in mammalian P450 IIB1 but requires a destabilization of the protein for phosphorylation to take place.

Animals↗
PubMed1990

Early detection of primary carcinoma of the fallopian tube by endovaginal ultrasound.

About 0.5% of all gynecological malignancies in Sweden are primary fallopian tube carcinomas. Early diagnosis is difficult due to the paucity of symptoms. However, the diagnosis should be entertained in the presence of abnormal vaginal bleeding not explained by gynaecological examination and biopsy of the cervix and endometrium. The possibility of tubal carcinoma should be considered in patients with persistent vaginal discharge and lower abdominal pain without apparent explanation. An early case of fallopian tube carcinoma detected by endovaginal ultrasound is described.

Aged↗
PubMed1989

Phosphorylation of cytochrome P450: regulation by cytochrome b5.

Rabbit liver cytochrome P450 LM2 and several forms of rat liver cytochrome P450 are phosphorylated by cAMP-dependent protein kinase (PKA) and by protein kinase C. Under aqueous assay conditions at neutral pH LM2 is phosphorylated only to a maximum extent of about 20 mol% by PKA. We show that detergents or alkaline pH greatly enhance the extent of phosphorylation of the cytochrome P450 substrates of cAMP-dependent protein kinase. In the presence of 0.05% Emulgen, PBRLM5, which appears to be the best cytochrome P450 substrate for cAMP-dependent protein kinase, incorporates phosphate up to about 84 mol% of enzyme. We reported previously (I. Jansson et al. (1987) Arch. Biochem. Biophys. 259, 441-448) that cytochrome b5 inhibits the phosphorylation of LM2 by cAMP-dependent protein kinase. In this paper, using PBRLM5, we demonstrate, by analysis of initial rates, that the inhibition of phosphorylation by cytochrome b5 is competitive, with a Ki = 0.48 microM. We also show that a number of forms of cytochrome P450 can be phosphorylated by protein kinase C, and that the phosphorylation of these forms by protein kinase C is also inhibited by cytochrome b5. These data suggest that the phosphorylation site(s) of cytochromes P450 may be located within or overlap the cytochrome b5 binding domain of the enzymes.

Animals↗
PubMed1989

Macroscopic characterization of ovarian tumors and the relation to the histological diagnosis: criteria to be used for ultrasound evaluation.

Ultrasound is now frequently used for evaluation of pathological findings discovered on gynecological examination and for puncture of ovarian cysts. Although the new, high-frequency vaginal transducers have a very high resolution, only macroscopically visible structures of the tumors can be imaged. For this reason, it seemed important to classify ovarian tumors according to their macroscopic appearance and then relate this to whether the tumor was benign, borderline, or malignant. Such a classification has not been performed before. Medical records from women operated upon due to pelvic tumors over a period of 11 years were scrutinized. There were 1017 women included in the study. Among those tumors characterized as unilocular cysts 0.3% (1/296) was malignant; this tumor had macroscopically visible papillary vegetations on the inside of the cyst wall. This cyst was found in a woman 60 years old. Sixty percent (178/296) of the women who had a unilocular cyst were over the age of 40. Two percent (4/203) of the unilocular solid tumors were classified as malignant. The malignancy rates for multilocular cysts was 8% (20/229), multilocular solid tumors 36% (147/209), and solid tumors 39% (31/80). Papillary vegetation on the cyst wall was the structure that was most frequent in malignant tumors. Neither the thickness of the cyst wall nor the thickness of septa inside the tumor seemed to correlate with malignancy. Among the simple ovarian cysts, 65 had a diameter over 10 cm but none of them was malignant. The one that was malignant had a diameter of approximately 5 cm. In conclusion, unilocular ovarian cyst seems to carry a very slight chance of malignancy even in women over the age of 40. Papillary vegetation on the cyst wall, a structure that can be seen by ultrasound, seems to be a serious sign.

Age Factors↗
PubMed1989

Interactions between noradrenergic and cholinergic mechanisms involved in spinal nociceptive processing.

Antinociceptive effects have been demonstrated after systemic and spinal administration of the adrenoceptor agonist clonidine and cholinomimetic drugs in animals and human. The present investigation was undertaken in rats to study the possible interactions between spinal noradrenergic and cholinergic mechanisms in modulating the reaction to nociceptive stimuli. Using the tail immersion test, an additive antinociceptive effect was found between intrathecal (IT) clonidine (10 micrograms) and physostigmine (15 micrograms, IT). The effect of clonidine was attenuated by atropine (15 micrograms, IT). Physostigmine (15 micrograms, IT) antinociception, which was of short duration was abolished by atropine (15 micrograms, IT) and attenuated by phentolamine (20 micrograms, IT). Neostigmine (5 micrograms, IT) produced a prolonged antinociceptive response. In animals pretreated with 6-hydroxydopamine IT, leading to a selective depletion of spinal cord noradrenaline, physostigmine (15 micrograms, IT) was ineffective in altering the nociceptive test response. Neither clonidine, nor physostigmine produced changes in latency times in the hot plate test (58 degrees C) in the doses employed. In conclusion, a clear-cut interaction exists between spinal noradrenergic and cholinergic systems for antinociception. To explain the interactions, several possible mechanisms may be considered, including cholinomimetic effects produced by clonidine, and the presence of muscarinic receptors in the dorsal horn of the spinal cord.

Adrenergic alpha-Agonists↗
PubMed1989

Characterization of the antinociception induced by intrathecally administered carbachol.

The antinociceptive effect of intrathecally administered carbachol at the L1/L2 level in the rat was evaluated using the tail immersion test. A dose dependent increase in the nociceptive reaction times was evident following intrathecal carbachol in the dose range of 2.5-15 micrograms. At doses of 20 micrograms and above, although still effective in the test, motor impairment was pronounced. The antinociception was antagonized with atropine, and with either pirenzepine (PZ) or AFDX 116, which are selective M1 and M2 muscarinic receptor blocking drugs, respectively. Spinal cholinergic pain modulation was also studied in rats pretreated with DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), which causes a selective depletion of the noradrenergic nerve fibres in the CNS. The increased latency times after spinal carbachol were attenuated in animals depleted of spinal noradrenaline by DSP4. In conclusion, spinal analgesia by carbachol in the rat may therefore be mediated through both M1 and M2 muscarinic receptor stimulation in the spinal cord. It is also concluded that this spinal cholinergic pain modulation is interacting with spinal noradrenergic nerve terminals, but that the mechanism of the interaction remains to be established.

Analgesics↗