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Biomedical subjects

S Lundberg

Publications and source records attributed to S Lundberg.

At least 55 records · Page 3Linked to original sources

Organophosphorus anticholinesterases do not mediate analgesia through inhibition of enkephalin degradation.

The effect on enkephalin degradation of the four highly potent organophosphorus anticholinesterases, soman, sarin, tabun and DFP was studied in synaptosomal fractions of rat brain striata. None of the agents effected any of the enkephalin degrading enzymes, the puromycin sensitive aminopeptidase, the p-hydroxymercurybenzoate (p-HMB) sensitive dipeptidyl aminopeptidase or the phosphoramidon sensitive enkephalinase. Furthermore, no peptidase function of acetylcholinesterase was found, when Leu-enkephalin was used as substrate at low concentrations (27 nM). Supporting the in vitro data, no difference was obtained in the striatal levels of Met- and Leu-enkephalin between rats receiving a high single dose of soman and controls. The results show that the analgesic effect of anticholinesterases are more likely due to mechanisms other than inhibition of enkephalin degradation.

Acetylcholinesterase↗

Relative hepatotoxicity of some industrial solvents after intraperitoneal injection or inhalation exposure in rats.

Intraperitoneal LD50 (lethal dose 50% kill) values and minimal liver toxic doses in female Sprague-Dawley rats were determined for the following industrial solvents: toluene, methylene chloride, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloroethylene, ethanol, methyl ethyl ketone, and dioxane. For the following solvents LC50 values and minimal liver toxic air concentrations were also determined: xylene, styrene, chloroform, tetrachloroethylene, and dimethylformamide (DMF). The serum activity of the enzyme sorbitol dehydrogenase (SDH) was used as an indicator of liver damage. Carbon tetrachloride, chloroform, and DMF were hepatotoxic in low doses compared to LD50 values (TD50 (toxic dose 50%) values approximately 30, 90, and 50 mg/kg). Chloroform and DMF were hepatotoxic in comparatively low concentrations after a 4-hr inhalation exposure (TC50 (toxic concentration 50%) values approximately 590 and 740 mg/m3). Even relatively high doses of the other solvents did not raise the SDH activity. Significant direct (metabolite-mediated) hepatotoxicity seems to be an uncommon feature among commonly used industrial solvents.

Animals↗

Partial denervation of the ovaries by transection of the suspensory ligament does not inhibit ovulation in rats treated with pregnant mare serum gonadotropin.

Adrenergic nerves reach the ovary via two routes: along the arteries to the ovary and via the suspensory ligament. Results from earlier investigations suggest that denervation of the nerves along the arteries does not influence the ovulatory process. In the present study we have examined whether denervation by transection of the ovarian suspensory ligament influences the ovulatory process. Partial denervation of the ovary by transection of the ovarian suspensory ligament, sham operation, or only anesthesia were performed on immature 25-day-old rats. To induce ovulation, pregnant mare serum gonadotropin (PMSG) was injected in the morning (0800-0930), when the rats were 26 days old. This PMSG treatment normally induces ovulation around 0200 in the early morning of day 29 with subsequent formation of corpora lutea. Rats were killed 5-8 hr, 3 days, and 5 days after this ovulation time. Ovarian interstitial norepinephrine levels were markedly decreased after transection of the suspensory ligament. Ovulations had occurred in all denervated, as well as sham-operated, and control rats. The various groups did not differ in the number of ovulations per rat. Thus, the adrenergic nerves in the suspensory ligament appear not to be necessary for ovulation. Whether catecholamines themselves play a role in the ovulatory process cannot be elucidated from this experiment, since the norepinephrine content in the ovary was not totally depleted. It seems unlikely that adrenergic nerves reach the corpus luteum via the suspensory ligament, since transection of this structure did not change the luteal content of norepinephrine.

Animals↗

Coevolution of competing species: ecological character displacement.

Character displacement of competing species is studied. A model, originally developed by MacArthur and Levins (Proc. Natl. Acad. Sci. USA 51 (1964), 1207-1210) and further analyzed by Lawlor and Maynard Smith (Amer. Nat. 110 (1976), 70-99), has been reanalyzed. In the present paper, a more formally correct analysis of the MacArthur-Levins model is provided. A standard population genetics approach to sexually reproducing populations is adopted. The same conclusion as proposed by Lawlor and Maynard Smith emerges; competition can lead only to character divergence. In our analysis we either require that allopatrically evolved consumer populations must be able to coexist at an ecologically stable equilibrium (hence, we require mutual invasibility), or consider the feasibility of allopatric equilibria.

Analysis of Variance↗

Delayed dimethylformamide biotransformation after high exposures in rats.

Rats were exposed to two dimethylformamide (DMF) air concentrations (2250 and 565 ppm for 4 h). Concentrations of DMF and the biotransformation product monomethylformamide (MMF) were measured in blood and some tissues at different times after the end of exposure. MMF concentrations 0 and 3 h after the end of the high exposure were generally lower than MMF concentrations at the same time after the low exposure. The results suggest that DMF biotransformation to MMF is delayed after the high exposure. As the hepatotoxic effect of DMF has been correlated with MMF, this could contribute to the previously observed slower appearance of hepatotoxicity after a high compared to a low DMF dose.

Adrenal Glands↗

Morphine concentrations in serum, brain and cerebrospinal fluid in the rat after intravenous administration of a single dose.

Morphine has been determined in serum, cerebrospinal fluid (c.s.f.) and in five brain regions in the rat after a single intravenous dose, using high performance liquid chromatography with an electrochemical detector. In pure solution 50 pg morphine and 200 pg naloxone could be detected. Maximal concentrations of morphine were observed in serum and in most brain regions 5 min after administration of morphine. There was a rapid decline in morphine concentrations during the first 30 min, in serum and in all brian regions studied. The morphine concentration in the c.s.f. was constant for the first 30 min, but 30 min later there was a dramatic increase, suggesting that elimination through the c.s.f. could be an important way of eliminating morphine in the central nervous system.

Animals↗

Cerebral blood flow and cerebral metabolism in children following cardiac surgery with deep hypothermia and circulatory arrest. Clinical course and follow-up of psychomotor development.

Between November 1975 and June 1977, 49 children underwent repair of complicated cardiac defects with the aid of deep hypothermia. Circulatory arrest was used in 28 cases. Nine children died (18%) due to early postoperative heart failure. A decisive cause of death in terms of important cardiovascular defects, which were either unknown or not correctable at the time of repair, was found in 6 patients. Children with complicated forms of congenital heart disease requiring an extensive repair were overrepresented among those who died. Hence, there was an excess in the duration of bypass among nonsurvivors (p less than 0.01) whereas the patient's age at operation, the use of circulatory arrest and the duration of aortic occlusion had no bearing on operative mortality. Cerebral blood flow (CBF) and cerebral metabolism were studied in 9 survivors. A negative correlation (r = -0.67) was found between the duration of circulatory arrest and CBF measured directly after surgery. CBF was reduced to values below 0.2 ml . g-1 . min-1 in 3 children with long periods of circulatory arrest. The cerebral uptake of oxygen and glucose was normal both before and after surgery. Two separate interviews with the parents were performed, the first one 3-22 months and the second one about 3 years after surgery. No serious neurological symptoms or psychomotor disturbances were reported. However, in 3 children operated with circulatory arrest, difficulties in performing more delicate motor activities were noted by the parents. The findings indicate that circulatory arrest should be used with caution and total arrest periods exceeding 60 min avoided.

3-Hydroxybutyric Acid↗

Peritoneal dialysis in infants and children after open heart surgery.

Over a period of 5 years, 1975-1979, 418 infants and children were operated on for congenital cardiac malformations using cardiopulmonary bypass. Fifteen patients (4 with transposition, 4 with Fallot's tetralogy, 1 with pulmonary atresia and 6 with complex composite malformations) developed acute renal failure with anuria, which did not respond to volume load, afterload reduction, low dose dopamine, diuretics and controlled ventilation. Continuous peritoneal dialysis was started within a few hours of anuria. During dialysis the patients remained sedated, intubated and on controlled normocapnic ventilation. No complications occurred caused by the dialysis per se. Ten patients recovered and had normal serum creatinine when discharged from hospital (mean duration of dialysis: 6 days). Complex cardiac malformations were overrepresented in the 5 patients who died early in the postoperative period due to myocardial failure (mean duration of dialysis: 3 days).

Acute Kidney Injury↗

Some observations on dimethylformamide hepatotoxicity.

Dimethylformamide (DMF) and its biotransformation products monomethylformamide (MMF) and formamide (F) were administered intraperitoneally to rats. Serum levels of sorbitol dehydrogenase (SDH) were studied at 3 h intervals from 9 h to 30 h after administration. Liver histology at 12, 21 and 30 h proved elevated SDH levels to be an indication of liver necrosis. DMF 479 mg/kg produced elevated enzyme levels at 27 h and 30 h while half the dose, 240 mg/kg, produced elevated levels from 15 h onwards. MMF 387 mg/kg produced elevated SDH levels at all times studied. F did not give elevated levels at any time. DMF (479 mg/kg) and MMF (387 mg/kg) administered simultaneously produced elevated SDH levels from 24 h onwards. These findings suggest that DMF hepatotoxicity is mediated by a degradation product of MMF and that DMF delays the hepatotoxic effect induced by MMF.

Animals↗

Plasma colloid osmotic pressure during open-heart surgery using non-colloid or colloid priming solution in the extracorporeal circuit.

Two different priming solutions for the heart-lung machine were compared in 14 patients during aortic valve replacement. Colloid osmotic pressure (COP), and albumin in plasma, blood erythrocyte volume fraction (B-EVF) and arterial oxygen tension (PaO2) (FIO2 = 1.0) were followed before, during and after perfusion. The two priming solutions were 2,000 ml Ringerdex (7 patients) or 1,800 ml Ringerdex + 200 ml 20% albumin (7 patients). COP and B-EVF were normal before bypass. After 10 min on bypass, when about 1,000 ml of crystalloid cardioplegic solution had been given, COP was reduced by about 50% and B-EVF fell to 23%, indicating a small loss of water from the circulation when compared with in vitro dilution curves. COP was slightly lower in the non-colloid group (p less than 0.02). Both COP and B-EVF remained unchanged during perfusion, despite transfusion from the heart-lung machine of a mixture of blood and crystalloid solution with a calculated very low COP (6 mmHg) and B-EVF (15%). After perfusion the restitution of COP and B-EVF was rapid and parallel. Both returned to normal levels after 2 hours. There was a good correlation between COP and albumin measured in the same plasma samples (r = 0.83, p less than 0.001). At one hour after bypass PaO2 (FIO2 = 1.0) tended to decrease in the non-colloid group, compared with preperfusion level. 40 g of albumin was a too small amount of colloid to diminish substantially the reduction of COP during perfusion. The unchanged levels of COP and B-EVF during perfusion, despite further dilution as well as the parallel normalization after perfusion, can only be explained by loss of water from the circulation.

Adult↗

Pulmonary oxygenation, central haemodynamics and glomerular filtration following cardiopulmonary bypass with colloid or non-colloid priming solution.

Plasma colloid osmotic pressure (COP), blood erythrocyte volume fraction (B-EVF), arterial oxygen tension at an inspired oxygen concentration of 30% (PaO2 (FIO2 0.3)), cardiac index, stroke volume, arterial mean pressure, left atrial mean pressure, pulmonary av-difference of oxygen (Ca-v O2) and creatinine clearance were studied in 16 patients during isolated aortic valve replacement. The patients were divided into two groups with different priming solutions in the oxygenator. In the non-colloid group 2,000 ml of Ringerdex was used, while the colloid group had 1,600 ml of Ringerdex and 400 ml of albumin 20% (80 g). COP differed significantly between the groups (p less than 0.01) during and for 1 hour after bypass. The greatest reductions were 56% and 30%, respectively. Haemodilution (los B-EVF) was of longer duration in the colloid group. No differences between the groups were found with respect to pulmonary oxygenation, myocardial behaviour or glomerular filtration rate. Cardiopulmonary bypass produced no changes in cardiac index, stroke volume, arterial mean pressure, left atrial mean pressure, Ca-v O2 or creatinine clearance in either of the groups. PaO2 (FIO2 0.3) remained unchanged in the non-colloid group and showed a small but significant reduction (p less than 0.01) in the colloid group. No positive effects of a colloid prime were demonstrated.

Adult↗