Energy shifts and widths of kaonic atoms.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to O Andersen.
Explore the source record for details and available documents.
Conglutinin is a mammalian C-type lectin which agglutinates iC3b-coated erythrocytes. Ingram [13] found that euglobulin from bovine serum may confer partial protection against experimental infections in mice. We now present evidence that the protective activity in euglobulin against infections of BALB/c mice with Salmonella typhimurium is mediated by conglutinin. Conglutinin also demonstrated antibacterial activity against E. coli and S. typhimurium in vitro. The expression of this activity required the presence of heat-labile serum factors and peritoneal exudate or spleen cells, but not antibodies to the bacteria. Antibacterial activity was also demonstrated when the bacteria were pretreated with serum at 37 degrees C before incubation with conglutinin and cells. The activity of conglutinin was not observed when factor I-deficient or EDTA-treated serum was used instead of normal serum. The active peritoneal exudate or spleen cells showed adherence to plastic.
Twenty consecutive patients with spinal arteriovenous malformations (AVMs) were found to have either a progressive, remitting or remitting-progressive course of disease. A characteristic progressive neurological decline was observed in 11 patients with dural fistulas and a similar decline was seen in 5 of the 9 patients with intradural AVMs. In addition to paraparesis and mixed sensory disorder, which ascended to a level of about T10, areas with spared sensation were occasionally found below this level. All cases with this progressive longitudinal myelopathy showed radiological evidence of a dilated medullary venous plexus. All patients were treated by embolization with only a low frequency of complications. Follow-up data verified a significant improvement of motor and sensory function, mainly during the first year after embolization. Cases with progressive neurological decline (dural and intradural AVMs) stopped deteriorating or improved and cases with a history of acute incidents (intradural AVMs) probably run less risk of acute deterioration.
The average annual incidence of definite and probable MS in Gothenburg was re-investigated. For 1950-1954, 1955-1959 and 1960-1964 it was 4.2, 4.2 and 4.3/100,000/year. For the five-year periods between 1974 and 1988 it was 3.0, 2.7 and 2.0/100,000/year. If possible MS was included, the corresponding incidence for 1950-1964 was 5.2, 5.3 and 5.1, and for 1974-1988 it was 3.9, 3.9 and 4.3/100,000/year. Neurological methods and diagnostic criteria were constant throughout the period. The 1950-1964 incidence was based on personally investigated cases, while the 1974-1988 incidence was based partly on review of Gothenburg neurology records. It is concluded that there has been a significant decrease in the incidence of MS in this area. However, the notified decrease may partly be explained by alterations in the case ascertainment procedure. Since the Swedish measles vaccination program started in 1971, the occurrence of measles has been declining and has practically ceased during the 1980s. The time when a possible influence of mass vaccinations against childhood diseases on MS incidence can be monitored is discussed.
Explore the source record for details and available documents.
Herpes simplex virus type 1 was isolated from the cerebrospinal fluid of a patient during the first attack of multiple sclerosis. This is the first virus to be isolated from the central nervous system of a living patient with MS. The virus was identified as herpes simplex virus type 1 by restriction endonuclease analysis and by an enzyme immunoassay using monoclonal antibodies. Antibodies against type 1 but not type 2 were detected in consecutive samples of serum and cerebrospinal fluid. The patient has since entered a progressive phase of multiple sclerosis. The isolated type 1 strain might be of pathogenetic relevance to the development of multiple sclerosis in this patient.
Groups of juvenile brook trout (Salvelinus fontinalis) were acclimated to 12.0-13.0 degrees dechlorified water and a photoperiod of 12 hr light: 12 hr dark. Recombinant human growth hormone (hGH) (10.0 micrograms/g body wt) or insulin-like growth factor 1 (hIGF-1), used in a wide range of dosages (0.001-10.0 micrograms/g body wt), were given weekly as intramuscular injections. The fish receiving hGH were already significantly heavier and longer than the saline-injected control fish after 3 weeks of treatment. In addition, a liver specific growth promoting effect of hGH was found. In contrast, hIGF-1 did not stimulate body growth in any dosage tested. The fish receiving the highest dosages of hIGF-1 were all seriously affected with retarded body growth and high mortality. A possible insulin-like activity of hIGF-1 was verified by measuring the plasma glucose and amino acid levels in brook trout after a single injection of hIGF-1 (2.0 micrograms/g body wt) or bovine insulin (0.01 IU/g body wt). Both hormones caused a reduction in both glucose and amino acid levels to 35% of the control levels 24-72 hr after injection. The results strongly suggest that hIGF-1 does not stimulate growth, but that in high dosages causes profound insulin-like effects in brook trout resulting in hypoglycemia and hypoaminoacidemia.
Prolactin was isolated from the Atlantic salmon (Salmo salar) pituitary gland by extraction with acid acetone, gel filtration, ion exchange-chromatography, and reversed-phase high-performance liquid chromatography. The yield was 0.6 mg/g wet tissue. The hormone had a molecular weight of 23.5 kDa as determined by SDS-polyacrylamide gel electrophoresis. Isoelectric focusing gave an isoelectric point of 9.2. The N-terminal sequence and the amino acid composition indicated extensive homology between Atlantic and Pacific salmon prolactin. Antiserum against Atlantic salmon prolactin cross-reacted with chum salmon prolactin, but not with human, rat, or sheep prolactin.
Human intoxications with inorganic mercury occur via the oral or pulmonar routes. However, earlier experimental studies of the acute toxicity of inorganic mercury primarily used parenteral administration of soluble inorganic mercury salts. The present study evaluated the effect of dose size on intestinal absorption and relative organ distribution of orally administered mercuric chloride. Experiments were performed with male mice of 2 strains (inbred CBA/Bom and outbred Bom: NMRI). At the highest dose of HgCl2, a delay in fecal elimination of non-absorbed mercury was observed indicating a decreased peristaltic rate. The fractional whole-body retention of mercury at 14 days after dosage was inversely related to the dose size, conceivably due either to saturation of the uptake mechanism or to damage to the kidneys resulting in loss of mercury with the urine at the highest dose levels. The relative organ distribution of mercury after oral exposure was quantitatively different from that reported in the literature after parenteral administration of inorganic mercury. Thus, the relative hepatic deposition was larger than after injection of mercury, presumably due to the first pass effect. A dose dependency in the relative organ distribution of retained mercury was observed, characterized by increasing relative deposition in liver, stomach, intestines, testes, spleen and carcass but decreasing relative renal deposition with increasing dose. The toxicokinetics of inorganic mercury was similar in the 2 mice strains. The present study demonstrates that the toxicokinetics of orally administered inorganic mercury is different from that of parenterally administered inorganic mercury as earlier reported in the literature.
Diethyldithiocarbamate (DDC) efficiently alleviates the acute toxicity of injected cadmium chloride, but enhances the acute toxicity of orally administered cadmium chloride. Further, DDC induces extensive changes in organ distribution of cadmium, and mobilizes aged cadmium depots. The present study investigates effects of DDC on the toxicokinetics of cadmium at lower doses of cadmium than those used in previous studies. During single exposure to subtoxic oral doses of cadmium chloride DDC enhanced intestinal cadmium absorption, both after intraperitoneal and oral administration of DDC. In such acute exposure experiments orally administered DDC only slightly changed the relative organ distribution of absorbed cadmium, while intraperitoneal administration of DDC induced extensive changes in organ preference of absorbed cadmium. The relative hepatic and testicular deposition was reduced, while the relative deposition in heart, spleen, lungs, brain and carcass was increased. Bi-weekly intraperitoneal injections of DDC enhanced the rate of elimination of aged cadmium depots and changed the organ distribution of retained cadmium, compared to the control group. Chronic exposure to DDC in the feed and cadmium chloride in the drinking water did however not result in increased whole-body retention, and the organ distribution in the DDC-exposed group was similar to that in the control group. This result could be due to both increased rate of absorption and increased published extensive changes in the toxicokinetics of cadmium induced by DDC are mainly due to the high cadmium doses employed and the intraperitoneal administration of DDC. At lower doses and more realistic administration routes for cadmium and DDC, the effect of DDC is less. However, still DDC does not seem to have any potential as an antidote for cadmium or for mobilization of cadmium depots in humans.
A long-term clinical trial of acyclovir, 800 mg tid, as a therapeutic agent in multiple sclerosis (MS) is in progress. In three patients paired serum and cerebrospinal fluid (CSF) specimens were sampled after one, four, eight and twelve months of continuous treatment. These samples were collected 1.5 h before or 1.5 h after an oral dose. Acyclovir concentrations were assessed by radioimmunoassay. In the CSF, the acyclovir concentration was relatively stable, with a mean of 0.83 microM, while the serum acyclovir concentration was variable with mean peak and trough concentrations of 4.08 and 2.47 microM, respectively. In two other MS patients the acyclovir concentration time profile in serum and CSF was studied at steady state during the 8 h dose interval. In this study the acyclovir concentration in the CSF was only slightly affected by the fluctuations in serum and the acyclovir CSF/acyclovir serum ratio was apparently not influenced by the blood-brain barrier function. We found no indication of an accumulation of acyclovir in cerebrospinal fluid after one to twelve months of oral treatment.
This study examines the effects of tetraethylthiuram disulfide (TTD; disulfiram, Antabuse) on the toxicokinetics in mice of 109Cd-labelled cadmium chloride, as determined by whole-body and organ gamma-counting. At the highest single dose of orally administered CdCl2, i.e. 70 mumol/kg, orally administered TTD enhanced the inhibitory effect of CdCl2 on intestinal motility and increased the fractional whole-body retention of the dose of cadmium chloride, indicating enhanced intestinal cadmium absorption. Also, TTD induced extensive changes in organ distribution of absorbed cadmium; the relative hepatic and testicular deposition was reduced, while the relative deposition in heart, spleen, lungs, brain and carcass was increased. In a prolonged exposure experiment where CdCl2 was added to the drinking water and TTD to the feed, TTD increased the intestinal absorption of cadmium by more than four-fold as compared to the controls. Further, decreased deposition was seen in the carcass and increased deposition in intestines and liver. In a third experiment, oral doses of TTD given twice weekly had no influence on the rate of excretion of aged cadmium depots, and also the organ distribution was unchanged. Thus, the effect of TTD on cadmium metabolism seems to be exerted only during intestinal absorption and the distribution phase immediately thereafter.
Suppression of absorption by macromolecular chelators have been successful with several metals. In this paper a series of immobilized chelators ranging from DTPA to S-containing soft bases have been synthetized and investigated for ability to suppress intestinal uptake of 109Cd2+ in mice. Dextran-0-ethyl-mercaptan, xanthates derived from polysaccharides and polyvinyl alcohol, dithiocarbamates of polyethylene imine and aminoethyl cellulose, and DTPA immobilized on aminopropyl silica were all ineffective. DTPA immobilized on aminoethyl cellulose even enhanced the intestinal uptake. The macromolecular chelators were without extensive effect on organ distribution of absorbed cadmium, except for dithiocarbamate immobilized on polyethylene imine, which enhanced the deposition of cadmium in several organs including the brain. Although the results are discouraging, they indicate that design and synthesis of immobilized vicinal dithio compounds may represent an avenue for development of non-absorbable chelators with high affinity for cadmium.
Earlier publications have demonstrated that diethyldithiocarbamate (DDC) antagonizes the acute toxicity of injected CdCl2 but enhances the acute toxicity of orally administered CdCl2, most likely due to the high lipophilicity of DDC and the complex formed with the Cd++ ion. This study demonstrates that the hydrophilic dithiocarbamates dihydroxyethyldithiocarbamate (DHE-DTC) and N-methyl-N-glucamyl dithiocarbamate (NMG-DTC) also enhance the intestinal absorption of orally administered CdCl2 in mice, although less efficiently than DDC. After oral as well as intraperitoneal administration 15 min. after a single oral dose of CdCl2 the dithiocarbamates tested enhanced the intestinal cadmium uptake with a relative efficiency, DDC greater than DHE-DTC greater than NMG-DTC, which correlated to the lipophilicity of both the dithiocarbamates and the complexes formed with the Cd++ ion. Intraperitoneal administration of DDC induced extensive changes in the relative organ distribution of absorbed cadmium, compared to the distribution of CdCl2 administered alone. However, the only noticeable effect of administration of DHE-DTC and NMG-DTC was decreased gastrointestinal deposition of cadmium, irrespective of the administration route of the dithiocarbamates. Earlier studies have demonstrated that DDC and various other dithiocarbamates are capable of mobilizing intracellular cadmium deposits, presumably due to some lipophilicity. This study demonstrates that these dithiocarbamates may also enhance the intestinal absorption of cadmium.
Chronic alcoholics with cirrhosis often develop symptoms of zinc deficiency. Tetraethylthiuram disulfide (TTD) is metabolized to two molecules of diethyldithiocarbamate (DDC). DDC chelates divalent metal ions, including zinc, by forming highly lipophilic neutral bis(dithiocarbamate)-metal complexes. DDC could therefore enhance the intestinal zinc uptake or increase the rate of zinc excretion. Accordingly, treatment of alcoholism with TTD could either aggravate or alleviate zinc deficiency. The present study investigated effects of DDC and TTD on intestinal zinc uptake and on the rate of zinc excretion in mice. When given as very high single oral doses, DDC and TTD increased the intestinal uptake of a single oral dose of zinc. When added to the diet and administered in lower doses, closer to those administered to humans for treatment of alcohol abuse, both compounds were without effect on the rate of excretion of the body's zinc stores. In a long-term experiment, where 65Zn was administered in the drinking water, these doses of TTD and DDC reduced the whole-body retention of 65Zn. No treatment changed the organ distribution of zinc in any of the experiments. In conclusion strong indications emerge from the present study that TTD treatment of alcoholism is more likely to reduce the intestinal zinc absorption than to enhance it as has been suggested by other authors. Thus, the widely used experimental model using single oral exposure to metal and chelator conceivably may give erroneous results, when used to predict effects of prolonged exposures.
Total serum iron, plasma lactoferrin and circulating leukocytes were measured in piglets during the early phase of severe gram-negative septicemia and endotoxemia in 3 experimental settings: intravenous (i.v.) infusion of lipopolysaccharide (LPS) (n = 8), i.v. infusion of live Escherichia coli (n = 7) and intraperitoneal (i.p.) infusion of E. coli (n = 6). Iron dropped significantly during the first 30 min of LPS infusion from a median of 32 microM to 13.4 microM. A similar decrease in serum iron was demonstrated in the 2 other groups with minimum values at 120 min after the start of E. coli infusion. Plasma levels of lactoferrin increased significantly 120 min after the start of LPS infusion (median 6 mg/l) when compared to preinfusion values (0.25 mg/l). After i.v. infusion of E. coli a significant rise of plasma lactoferrin was demonstrated already 30 min after bacterial infusion (to 2.1 mg/l) compared to preseptic values (0.8 mg/l). This increase was accompanied with a significant drop of circulating leukocytes (to 7.3 x 10(9)/l) compared to before the infusion (17 x 10(9)/l) in the pigs given E. coli i.v. After i.p. E. coli infusion no significant change of plasma lactoferrin was observed. The rapid fall of total serum iron seen during endotoxemia and E. coli septicemia may in part be explained by the release of lactoferrin from granulocytes and the clearance of iron-bound lactoferrin in the blood or peritoneal cavity.
Explore the source record for details and available documents.
Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect. Thus, orally administered DDC enhanced cadmium-induced duodenal and ileal tissue damage and inhibition of peristalsis, as indicated by an increased intestinal transit time. At low cadmium doses, the whole-body retention of cadmium was increased by oral DDC administration. Intraperitoneally administered DDC increased cadmium-induced acute mortality and testicular necrosis, and it enhanced cadmium-induced reduction of intestinal motility and increased the whole-body retention of cadmium, indicating increased intestinal cadmium absorption. Also, DDC changed the organ distribution of absorbed cadmium: after i.p. administration of DDC, the relative hepatic deposition was reduced, whereas the relative deposition in other organs, in particular the brain, was increased. This study indicates that medical use of DDC should be avoided in individuals with current exposure to cadmium.