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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 379 records · Page 21Linked to original sources

Effects of four bisphosphonates on bone resorption, lysosomal enzyme release, protein synthesis and mitotic activities in mouse calvarial bones in vitro.

The effects of 3-amino-1-hydroxy-propylidene-1,1-bisphosphonate (AHPrBP), 1-hydroxyethylidene-1,1-bisphosphonate (HEBP), dichloromethylenebisphosphonate (Cl2MBP) and azacycloheptylidene-2,2-bisphosphonate (AHBP) on bone were examined in organ culture using newborn mice calvaria. AHPrBP, HEBP and Cl2MBP caused a dose-dependent inhibition of PTH-stimulated (10 nmol/l) release of 45Ca from the calvaria, at and above a concentration of 3 mumol/l, whereas AHBP only caused a slight inhibition, at and above 100 mumol/l. AHPrBP inhibited PTH-stimulated release of 3H from bones prelabelled with [3H]-proline. AHPrBP (30 mumol/l) diminished the stimulatory effect of 1 alpha(OH)vitamin D3 (10 nmol/l), prostaglandin E2 (0.1 mumol/l) and renal tumor conditioned media on 45Ca release. AHPrBP and Cl2MBP, at and above 3 mumol/l, decreased PTH-stimulated mobilization of Ca2+ and Pi and in parallel the release of beta-glucuronidase without affecting the release of lactate dehydrogenase. The inhibitory effect of AHPrBP (30 mumol/l) on PTH-induced 45Ca release was irreversible. The inhibition by AHPrBP (30 mumol/l) on spontaneous and PTH-stimulated release of 45Ca can be seen first after 24 h of culture. Similarly the inhibitory effect by HEBP (30 mumol/l) and Cl2MBP (30 mumol/l) was delayed and could be observed after 36 and 24 h of culture, respectively. PTH-stimulated release of Ca2+, Pi, beta-glucuronidase and beta-N-acetylglucosaminidase was reduced by AHPrBP first after 24 h of culture. AHPrBP, HEBP and Cl2MBP, at concentrations which are inhibitory on bone resorption, do not affect protein synthesis and mitotic activities in mouse calvaria. These data show that AHPrBP, HEBP and Cl2MBP inhibit bone resorption in vitro and in parallel decrease lysosomal enzyme release by a mechanism, which is not related to cytotoxicity. In addition, the delayed inhibitory effect on bone resorption and lysosomal enzyme release by all the compounds suggest that bisphosphonates inhibit bone resorption indirectly and not by a direct effect on existing osteoclasts. The delayed inhibition by bisphosphonates on bone resorption may be due to decreased recruitment of new osteoclasts as a consequence of an inhibitory action on mononuclear osteoclast precursor cells.

Animals↗

Recommendation for collection of skin puncture blood from children, with special reference to production of reference values.

Reliable reference values need to be collected under standardized conditions. In order to enable comparison of values observed on patients with reference values, it is also desirable to use the same standardized conditions on patients. The present recommendation was produced as a joint effort of representatives of the clinical chemists and paediatricians of Scandinavia and describes the following details. Preparation of the child before specimen collection (food intake, time of day, physical activity, posture, environment), preparation of skin puncture site (warming, disinfection, ointment), instruments for blood collection (lancet, blood collection vessel), site of puncture (plantar surface of foot, finger, ear lobe), collection of emerging blood and handling and storage of the specimen.

Adolescent↗

Variations in lung volume and compliance during pulmonary surgery.

Functional residual capacity (FRC) and breath-by-breath compliance of the ventilatory system (Crs) were measured in 10 mechanically ventilated patients during anaesthesia for lung surgery (pneumonectomy, lobectomy, lung or pleural resections or exploratory thoracotomy). In eight patients not requiring pneumonectomy, FRC of the lower lung decreased by 8 +/- 9% (mean +/- 1 SD) (P less than 0.05) while that of the upper lung increased by 75 +/- 24% (P less than 0.001) when the patient was turned to the lateral position. When the pleura was opened, FRC of the lower lung decreased by a further 10 +/- 10% (P less than 0.01). One-lung ventilation (OLV), however, increased FRC of the lower lung back to the value found in the supine position before surgery. When two-lung ventilation was re-established, FRC of the lower lung was about the same as during corresponding stages before OLV. In the two patients who underwent pneumonectomy, FRC of the remaining lung was about 30% greater after OLV than at corresponding stages before surgery. In the patients not requiring pneumonectomy, Crs decreased from 29 +/- 6 ml/cm H2O to 23 +/- 6 ml/cm H2O (P less than 0.05) on the lower side when the patient was turned on his side. The corresponding figures on the upper side were 24 +/- 8 ml/cm H2O and 30 +/- 5 ml/cm H2O respectively (P less than 0.05). There was no further significant change when the pleura was opened. After surgery when the patient was turned to the supine position, Crs of the lung not operated on was almost the same as before surgery.

Adult↗

Measurement of lung volume by sulfur hexafluoride washout during spontaneous and controlled ventilation: further development of a method.

An open circuit tracer gas washout method for measurement of lung volume in patients during anesthesia and intensive care is described and tested. The method employs a device for dispensing the tracer gas, sulfur hexafluoride (SF6), a fast SF6 analyzer, a pneumotachograph, and a computer. The dispensing device delivers SF6 into the airway in proportion to instantaneous inspiratory flow so that inspiratory SF6 concentration is held constant, usually at about 0.5%, regardless of the inspiratory flow pattern. The amount of SF6 present in the lungs at the end of a washin is calculated during washout from signals representing expired SF6 concentration and expired flow. From this, lung volume is derived. Accurate and reproducible results were obtained in lung model tests during ventilation with air, N2O in O2, and halothane in O2. Functional residual capacity (FRC) was measured both with SF6 washout and nitrogen washout in five mechanically ventilated patients. This gave the regression equation: FRCSF6 = 10 ml + 1.04 x FRCN2, r = 0.99. A similar close agreement was observed for total lung capacity (TLC) and residual volume (RV) measurements in eight healthy, spontaneously breathing subjects: TLCSF6 = 91 ml + 1.01 x TLCN2, r = 0.99; RVSF6 = -32 ml + 0.97 x RVN2, r = 0.95. Comparison with body plethysmography in eight healthy, sitting subjects gave the regression equation: FRCSF6 = 180 ml + 0.96 x FRCbox, r = 0.99. The median (range) for the coefficient of variation at duplicate determinations in 10 anesthetized, paralyzed, and mechanically ventilated adults was 3.0% (0.2-6.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Secretion of pancreatic lipase and colipase from rat pancreas.

Rat pancreatic juice was collected from female, anesthetized Sprague-Dawley rats (200-250 g) during basal secretion and after 45-min intravenous infusion for secretin or secretin with cholecystokinin (CCK). The volume of secretion was measured as well as activity of lipase and colipase. It was shown that the basal secretion of pancreatic juice gave a colipase/lipase (C/L) ratio of about 0.5. Stimulation with secretin or addition of CCK to secretin gave a C/L ratio between 0.4 and 0.6. This was not significantly different from the ratio found in basal secretion. The secretion of lipase and colipase from isolated pancreatic acini was also found to parallel a C/L ratio equal to 0.6 in the basal release and to a ratio between 0.5 and 0.6 after stimulation with CCK, secretin, or carbachol. The total activity ratio of C/L in the pancreas was equal to 0.97. It is concluded that lipase and colipase are secreted in parallel both in vivo and in vitro. The reason for a lower ratio of C/L in the secreted juice compared to the C/L ratio of pancreatic gland is not known.

Animals↗

Allergic dermatitis (sweet itch) of Icelandic horses in Sweden: an epidemiological study.

A survey of allergic dermatitis (sweet itch) in Sweden contained information on 441 Icelandic horses. Results of a questionnaire indicated that approximately 15 per cent of the country's Icelandic horses suffered from the disease. The prevalence of allergic dermatitis was significantly higher among horses imported from Iceland (26.2 per cent) compared to that of Swedish-born animals (6.7 per cent). In addition, horses born in Iceland were significantly more severely affected than horses born in Sweden. The risk of allergic dermatitis in Sweden appeared to be more than six times higher for horses exported from Iceland to Sweden relative to that of horses originally born in Sweden. The prevalence of disease for horses of seven years or older was 30 per cent for Icelandic-born individuals as compared to 7.3 per cent for horses born in Sweden. Similarly, the risk of allergic dermatitis in Sweden for horses of seven years or older appeared to be nearly 10 times higher for horses imported from Iceland relative to that of horses born in Sweden. Allergic dermatitis usually appeared during the third grazing season for imported horses and during the fourth season for horses born in Sweden. Furthermore, the course of the disease tended to become worse with time. Analysis of the prevalence of allergic dermatitis relative to gender revealed no significant differences. Certain geographical variations in the prevalence of the disease was also found.

Age Factors↗

Inhibiting effect of (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine on varicella-zoster virus replication in cell culture.

The activity and mode of action of the new nucleoside analog (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (2HM-HBG) against varicella-zoster virus (VZV) were determined. In cell culture, replication of different strains of VZV was inhibited to 50% by 0.4 to 0.7 microM 2HM-HBG, while 685 microM was required to inhibit 50% of the DNA synthesis in uninfected human lung fibroblasts. A thymidine kinase-negative VZV strain was not inhibited by 100 microM 2HM-HBG. Inhibition of VZV replication was not reversible after 7 to 14 days of incubation, depending on the multiplicity of VZV. 2HM-HBG was shown to be selectively phosphorylated by purified VZV thymidine kinase, with an inhibition constant of 32.5 microM. The antiviral activity of 2HM-HBG in cell culture was decreased by the addition of deoxythymidine and deoxycytidine but not by other ribo- or deoxyribonucleosides.

Antiviral Agents↗

Acyclic guanosine analogs as inhibitors of human cytomegalovirus.

The acyclic guanosine analogs R- and S-enantiomers of 9-(3,4-dihydroxybutyl)guanine [(R)- and (S)-DHBG], 9-(4-hydroxybutyl)guanine (HBG), and 9-(2-hydroxyethoxymethyl)guanine (ACV) were examined for their effects on human cytomegalovirus (CMV) replication and on CMV DNA synthesis in cell culture as well as for their ability as triphosphates to interact with CMV DNA polymerase. Production of early CMV antigens was not affected. All analogs inhibited CMV DNA synthesis and late viral antigen synthesis. Primary CMV isolates were less susceptible to all tested analogs than was the laboratory strain CMV Ad.169. The triphosphate of ACV was the most potent inhibitor of CMV DNA polymerase, with an observed Ki of 0.0076 microM. The corresponding Ki values of the triphosphates of (R)-DHBG, (S)-DHBG, and HBG were 3.5, 13.0 and 0.23 microM, respectively. All triphosphates of the analogs given above inhibited CMV DNA polymerase in a competitive manner with respect to dGTP. The triphosphates of the analogs also inhibited reactions when the synthetic template poly(dC)oligo(dG)12-18 was used, whereas no inhibition was observed with poly(dA)oligo(dT)12-18. None of the triphosphate analogs supported DNA synthesis in the absence of dGTP, showing that no analog was an alternative substrate to dGTP.

Acyclovir↗

Immune complexes and complement components in Bell's palsy.

The serum levels of circulating immune complexes were studied in 63 patients and the complement system in 36 patients with Bell's palsy. The IgG-C1q and IgG-C3 containing immune complexes were analyzed by an enzyme-linked immunosorbent assay. The levels were found to be significantly elevated in the acute and convalescent stages of the palsy compared with controls. The total complement activity as determined by a CH50 assay and complement component C3 titrations also showed elevated values. The levels of C2 were not altered. The results indicate in Bell's palsy an inflammatory process and an antigen-antibody response which may be triggered by a viral antigen.

Adolescent↗

Neonatal screening for metabolic and endocrine disorders.

The impact of metabolic diseases (inborn errors of metabolism) and endocrine disorders in pediatrics has markedly increased during the last few decades. Critical periods in the development of the central nervous system need special attention in children with these disorders. Early diagnosis and treatment are important in order to prevent mental retardation and serious handicaps in some of these patients. Certain patients with metabolic and endocrine disorders lack early clinical symptoms or have so non-specific signs that permanent neurological handicaps are present when the patients are finally diagnosed. One way to identify these patients is by means of mass screening. A blood sample is then collected from every newborn infant and analyzed for abnormal levels of metabolites or hormones. It is possible to detect at least thirty different disorders in this way. In most European countries screening programmes involve phenylketonuria (PKU) and congenital hypothyroidism. The prognosis for these patients has improved dramatically after the introduction of screening. The Swedish neonatal metabolic screening programme was started in 1965 by screening for PKU. Subsequently, screening for galactosemia and congenital hypothyroidism was added. The result of the screening programme 1965-1985 is as follows: (table; see text) The main benefit of early detection and treatment of children with PKU, congenital hypothyroidism and galactosemia is the prevention of mental retardation and other handicaps. Recently nationwide pilot screening for congenital adrenal hyperplasia (adrenogenital syndrome) was started.

Endocrine System Diseases↗

Effect of phosphatidylcholine and free fatty acids on the activity of pancreatic lipase-colipase.

Mixed micelles of bile salt and phospholipids inhibit the lipase-colipase-catalysed hydrolysis of triacylglycerols. Free fatty acids can reverse this inhibition and reactivate lipase-colipase. This reactivation is either due to the formation of a high-affinity complex between lipase and colipase induced by free fatty acids and/or to a change of the quality of the interface. Lauric acid, oleic acid and linoleic acid are the most potent reactivators, while short-chain free fatty acids have no effect and long-chain, saturated free fatty acids inhibit the lipase-colipase activity further. The physiological relevance of these results is evident as the glyceride emulsion reaching the duodenum already contains free fatty acids due to the activity of lingual lipase in the stomach.

Animals↗

Metabolism and mode of action of (R)-9-(3,4-dihydroxybutyl)guanine in herpes simplex virus-infected vero cells.

The metabolism and mode of action of the anti-herpes compound buciclovir [R)-9-(3,4-dihydroxybutyl)-guanine, BCV) has been studied in herpes simplex virus-infected and uninfected Vero cells. In uninfected cells, a low and constant concentration of intracellular BCV was found, while in herpes simplex virus-infected cells, an increasing concentration of BCV phosphates was found due to metabolic trapping. The major phosphorylation product was BCV triphosphate (BCVTP) which was 92% of the total amount of BCV phosphates. BCV phosphates were accumulated to the same extent in cells infected with either a herpes simplex virus type 1 or a herpes simplex virus type 2 strain while thymidine kinase-deficient mutants of herpes simplex virus type 1 were 10 times less efficient in accumulating BCV phosphates. In uninfected Vero cells, the concentration of the phosphorylated forms of BCV was less than 1% of that found in herpes simplex virus-infected cells. The BCVTP formed in herpes simplex virus-infected cells was highly stable, as 80% of the amount of BCVTP was still present even 17 h after removal of extracellular BCV. BCV was a good substrate for herpes simplex virus type 1- and type 2-induced thymidine kinases but not for the cellular cytosol or mitochondrial thymidine kinases. BCV monophosphate could be phosphorylated by cellular guanylate kinase to BCV diphosphate. BCVTP was a selective and competitive inhibitor to deoxyguanosine triphosphate of the purified herpes simplex virus type 1- and type 2-induced DNA polymerases. BCVTP could neither act as an alternative substrate in the herpes simplex virus type 2 or cellular DNA polymerase reactions, nor could [3H]BCV monophosphate be detected in DNA formed by herpes simplex virus type 2 DNA polymerase, or be detected in nucleic acids extracted from herpes simplex virus type 1-infected cells. These data indicate that BCVTP may inhibit the herpes simplex virus-induced DNA polymerase without being incorporated into DNA.

Acyclovir↗