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Biomedical subjects

B Oberg

Publications and source records attributed to B Oberg.

At least 109 records · Page 6Linked to original sources
PubMed1986

Comparison of microbiological contents of compressed air in two Danish hospitals. Effect of oil and water reduction in air-generating units.

In a comparative study microbiological contamination of compressed air for medical use produced in oil-lubricated and oil-free compressors was investigated. Significantly lower levels of bacterial contamination were observed in the air produced by oil-free compressors; but if the air is transported to operating rooms and intensive care units through extensive pipeline systems previously contaminated by oil-lubricated compressors, the bacterial count at peripheral air outlets remains unchanged.

Air Microbiology↗
PubMed1986

PPi analogs as inhibitors of human T-lymphotropic virus type III reverse transcriptase.

Twenty-six PPi analogs were tested for inhibitory effects on human T-lymphotropic virus type III reverse transcriptase. The structural requirements for inhibition and mechanism of action of the most active inhibitors have been investigated. Foscarnet (phosphonoformic acid) was the most potent inhibitor of human T-lymphotropic virus type III reverse transcriptase with 50% inhibition at 0.5 microM. The mechanism was a noncompetitive type of inhibition of a (riboadenylic acid)n . (deoxythymidylic acid)12-18 [(rA)n(dT)12-18]-directed transcription at varied dTTP concentration. At constant substrate (dTTP) concentration and varied amounts of template, (rA)n(dT)12-18, the inhibitory action of foscarnet was of an uncompetitive type. The same pattern of inhibition was seen when the less active inhibitor carbonyldiphosphonate was studied under identical conditions. The structural requirements for inhibition of human T-lymphotropic virus type III reverse transcriptase by PPi analogs were similar to those shown by other reverse transcriptases.

Antiviral Agents↗
PubMed1986

Mode of action, toxicity, pharmacokinetics, and efficacy of some new antiherpesvirus guanosine analogs related to buciclovir.

9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine (3HM-HBG), (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine ([+/-]2HM-HBG), and cis-9-(4-hydroxy-2-butenyl)guanine (2EN-HBG), new acyclic guanosine analogs structurally related to buciclovir (BCV [(R)-9-(3,4-dihydroxybutyl)guanine]), were evaluated in parallel with buciclovir as anti-herpes simplex virus (HSV) agents. In cell cultures, replication of different strains of HSV type 1 (HSV-1) and HSV-2 was inhibited at nontoxic drug concentrations. The concentrations giving 50% inhibition of plaque formation were, however, dependent on virus strain and cell type. In most cell types, the order of activity against HSV-1 strains was 3HM-HBG greater than (+/-)2HM-HBG greater than BCV greater than 2EN-HBG, whereas the drugs showed an approximately equivalent activity against HSV-2 strains in different cells. The cytotoxic effects of the drugs were also cell type dependent, the order of activity being BCV greater than 3HM-HBG = (+/-)2HM-HBG greater than 2EN-HBG. At growth-inhibitory concentrations, the guanosine analogs BCV, 3HM-HBG, and (+/-)2HM-HBG showed clastogenic effects in human lymphocytes, mainly because of the induction of chromatid breaks. When evaluated for their anti-HSV effects in systemic HSV-1 infections in mice, the order of activity was BCV = 3HM-HBG greater than (+/-)2HM-HBG greater than 2EN-HBG, and in mice infected systemically with HSV-2, only BCV and 3HM-HBG showed efficacy. The differences between efficacy in vitro and in vivo could be explained in part by differences in kinetics of the drugs in mouse plasma, as the more efficacious drugs, BCV and 3HM-HBG, showed lower clearances and longer half-lives than the less efficacious ones, (+/-)2HM-HBG and 2EN-HBG. When used topically against a cutaneous HSV-1 infection in guinea pigs, 3HM-HBG showed an effect equivalent to that of BCV, whereas (+/-)2HM-HBG and 2EN-HBG were inactive. Mechanistically, the guanosine analogs were characterized by a high affinity for the viral thymidine kinase and a low affinity fo a cellular thymidine kinase and by their inhibition of viral DNA synthesis in infected cells.

Acyclovir↗
PubMed1986

The cordycepin analogue of 2,5A and its threo isomer. Chemical synthesis, conformation and biological activity.

A new synthesis of the cordycepin analogue of 2,5A and its threo isomer is reported along with an assessment of their conformations by circular dichroism spectroscopy. Evidence is also presented showing that these compounds are stable against 2,5A-specific phosphodiesterase and are not able to activate the 2,5A-dependent endoribonuclease, possibly due to a reduced binding to the latter enzyme as compared to that of 2,5A.

Circular Dichroism↗
PubMed1985

Antiherpes effects and pharmacokinetic properties of 9-(4-hydroxybutyl) guanine and the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine.

Three acyclic guanosine analogs with similar structures, the (R) and (S) forms of 9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine, were compared for antiherpes activity in vivo and in vitro. The three guanosine analogs were viral thymidine kinase-dependent inhibitors of virus multiplication. In cell cultures, (S)-9-(3,4-dihydroxybutyl)guanine was the least active of these three drugs against a variety of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) strains. This was also the case for a certain HSV-1 or HSV-2 strain in different cell lines. In cell cultures, (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine had similar antiherpes activities. However, in vivo in cutaneous HSV-1 infections in guinea pigs treated topically and in systemic HSV-2 infections in mice treated orally or intraperitoneally, only (R)-9-(3,4-dihydroxybutyl)guanine had a therapeutic effect. The extremely short half-life in plasma and the high clearance of 9-(4-hydroxybutyl)guanine as compared with those of (R)-9-(3,4-dihydroxybutyl)guanine probably made 9-(4-hydroxybutyl)guanine inefficacious when given intraperitoneally or orally to mice infected with herpesvirus. On the other hand, no kinetic differences between (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine were observed in penetration through guinea pig skin ex vivo, and no preferential metabolism of 9-(4-hydroxybutyl)guanine in skin was noted. We deduced that high thymidine levels in guinea pig skin preferentially antagonize the antiviral effect of 9-(4-hydroxybutyl) guanine in cutaneous HSV-1 infections.

Acyclovir↗
PubMed1985

Activity of the cytomegalovirus genome in the presence of PPi analogs.

PPi analogs and esters of these were studied for their effect on cytomegalovirus (CMV) multiplication. Five aromatic monoesters of phosphonoformate esterified either in the phosphono or the carboxylic group and two diesters were demonstrated to inhibit CMV DNA synthesis and late viral protein synthesis. In a direct assay, the monoesters but not the diesters inhibited CMV DNA polymerase activity. The production of early CMV antigens was not inhibited by any of the compounds. After incubation with either drug for periods up to 7 days, renewed viral production occurred on withdrawal of the compound. All inhibitory esters as well as PPi analogs showed a CMV multiplicity dependence. This was demonstrated both for CMV strain Ad.169 and for all tested CMV isolates. Evidence was found that the esters are hydrolyzed to phosphonoformate and, therefore, may be of importance as useful prodrugs in the specific therapy of CMV infections. The general phenomenon of reversibility to the productive state and the multiplicity dependence of CMV are important factors in any treatment schedule.

Antiviral Agents↗
PubMed1985

Intravenous foscarnet for the treatment of severe cytomegalovirus infection in allograft recipients.

Foscarnet, trisodium phosphonoformate, was administered intravenously to 6 immunosuppressed patients with life-threatening cytomegalovirus infection. Three of the patients were recipients of a kidney and 3 of a bone-marrow transplant. Favourable clinical responses were seen in 5 of the patients, 2 of whom were still in good health 5 and 8 months after the infection had cleared up. No toxic effect of the drug was detected. The results seem to justify further trials, in which foscarnet should be introduced at an earlier stage of the disease.

Adult↗
PubMed1985

Synthesis of adenylyl-(3'----5')-guanosine and some analogues as probes to explore the molecular mechanism of stimulation of influenza virus RNA polymerase.

Influenza virus mRNA synthesis is primed by a capped oligonucleotide which is cleaved off from a cellular mRNA by a viral protein. The dinucleotide A3'p5'G can be used as a primer for the viral RNA polymerase mediated RNA synthesis in a cell-free system. Analogues of A3'p5'G have therefore been synthesized using the phosphotriester approach, and their priming ability for the influenza virus mRNA synthesis has been determined. An absence of the 2'-hydroxyl function in the guanosine residue in the dinucleotide, as in A3'p5'dG, drastically decreased its priming ability. Similarly, an alteration of the 3'----5' phosphate linkage to a 2'----5' phosphodiester linkage affected the priming ability quite severely. However a dinucleotide, with the 2'-hydroxyl function omitted in the adenosine moiety, as in dA3'p5'G, could still stimulate the mRNA synthesis. None of the modified dinucleotides inhibited A3'p5'G or globin mRNA primed influenza mRNA synthesis.

Adenosine Monophosphate↗
PubMed1985

Duration of stretching effect on range of motion in lower extremities.

The duration of the effect of contract-relax stretching on range of motion (ROM) in the lower extremities was measured on eight male volunteers. The stretching procedure was performed as one isometric contraction, followed by relaxation and then a passive extension of the muscle being stretched. The treated muscle groups were the adductors, hamstrings, rectus femoris, iliopsoas, gastrocnemius, and soleus. The total stretching time was 15min. Six ROMs were tested 0, 30, 60, and 90min after the stretching procedure. There was a significant increase in hip abduction (+17% +/- 3), knee flexion (+4% +/- 1), hip flexion (+4% +/- 2), ankle dorsiflexion with knee flexed (+18% +/- 7), and ankle dorsiflexion with knee straight (+16% +/- 5). The increase remained for 90min for all ROMs except for ankle dorsiflexion with the knee straight.

Humans↗
PubMed1984

Muscle strength and flexibility in different positions of soccer players.

One-hundred eighty soccer players were tested for muscle strength in knee extension and knee flexion and for flexibility in the lower extremity. The strength measurements were done with a Cybex II isokinetic device (Lumex, Bay Shore, New York). The range of motion (ROM) was measured according to a method described by Ekstrand et al. (1982). The players were divided into groups according to their player position: goalkeepers, defenders, midfielders, and forwards. The results showed a significantly higher knee extensor torque in goalkeepers and defenders than in forwards (P less than 0.05). The knee flexion/knee extension ratio (H/Q ratio) was significantly higher for forwards compared to goalkeepers (P less than 0.001) and defenders (P less than 0.01). The goalkeepers were significantly more flexible than the other players in hip flexion (P less than 0.001), knee flexion (P less than 0.01), and ankle dorsiflexion (P less than 0.001).

Adolescent↗
PubMed1984

The relative merits and drawbacks of new nucleoside analogues with clinical potential.

A large number of nucleoside analogues have been found to have antiviral activity, mainly against herpesviruses. The involvement of cellular as well as viral enzymes in the mode of action of several nucleoside analogues makes a prediction of clinical efficacy difficult. The possibility and consequences of incorporation into cellular DNA are other important aspects of nucleoside analogues as antiviral drugs. It seems likely that in the next few years enough knowledge about mechanism of action, consequences of incorporation into DNA, efficacy in different test systems and in clinical trials will accumulate to allow an understanding of how to design even better antiviral drugs.

Acyclovir↗
PubMed1984

Two-year follow-up of conservative treatment of knee ligament injuries.

Sixteen patients with old knee ligament injuries and symptoms of instability or pain were treated with a 3-month thigh muscle strength training program. Nine patients had a tear of the anterior and six patients a tear of the posterior cruciate ligament. One patient had a tear of both cruciates. Knee function was determined with a knee scoring scale, and thigh muscle strength with a Cybex-II dynamometer before training, after 1 and 3 months of training, and at a late follow-up after 2 years. Ten patients who increased their quadriceps strength by more than 15 per cent increased their score over 30 per cent. Three patients who showed a minor increase in strength did not increase their score significantly. Three patients did not increase their strength at all. All of these admitted a reluctance to train. Four patients, all with anterior cruciate ligament tears, were operated on after the 3-month training period. All four patients increased their strength. Two of them increased their functional score also, but they strove for a very high activity level and were therefore operated on. The other two patients had no symptomatic relief and were therefore also operated on. Improvements in muscle strength and knee function were unchanged at the 2-year follow up. Before planning a knee ligament reconstruction, a period of strength training is recommended.

Adult↗
PubMed1983

Antiherpetic activity and mechanism of action of 9-(4-hydroxybutyl)guanine.

9-(4-Hydroxybutyl)guanine was synthesized and tested for antiherpes activity. In cell cultures, different strains of herpes simplex virus type 1 (HSV-1) and type 2(HSV-2) were inhibited by 50% at 2-14 microM of 9-(4-hydroxybutyl)guanine, while a HSV-1 mutant lacking thymidine kinase (HSV-1 TK-) was resistant. Linear competitive inhibition of purified HSV-1-induced thymidine kinase (TK) with thymidine as a variable substrate was observed for 9-(4-hydroxybutyl)guanine with an apparent Ki value of 2.06 microM while the corresponding Ki value for the cellular TK was greater than 250 microM. By using high performance liquid chromatography, the formation of 9-(4-hydroxybutyl)guanine monophosphate by HSV-1 TK was measured and the rate of product formation was found to be about 10% of that found by using thymidine as a substrate. A selective inhibition of HSV-1 DNA synthesis by 9-(4-hydroxybutyl)guanine was observed in infected Vero cells. 9-(4-Hydroxybutyl)guanine had a low cellular toxicity. A weak therapeutic effect on herpes keratitis in rabbits was observed whereas cutaneous HSV-1 infection in guinea pigs and systemic HSV-2 infection in mice were not affected by this compound.

Acyclovir↗
PubMed1983

Effect of aphidicolin on DNA synthesis in HSV-1 infected and uninfected Vero cells.

The effect of aphidicolin on DNA synthesis in herpes simplex virus type 1 (HSV-1) infected and uninfected Vero cells was determined by isodensity banding of [32P]-labelled DNA. A 50% inhibition of HSV-1 DNA synthesis was observed at 0.07 microM aphidicolin while 2.1 and 1.3 microM were required to inhibit the cellular DNA synthesis to 50% in infected and uninfected Vero cells, respectively. When the viral DNA synthesis was totally inhibited by 10 microM aphidicolin, the cellular DNA synthesis was inhibited to about 90% in both infected and uninfected cells. Aphidicolin inhibited the cellular DNA synthesis in HSV-1 infected and uninfected Vero cells remaining in the presence of 250 microM foscarnet to the same extent as the DNA synthesis in the absence of foscarnet.

Animals↗
PubMed1983

Synthesis and antiviral activity of distamycin A analogues: substitutions on the different pyrrole nitrogens and in the amidine function.

Several new analogues of the antiviral antibiotic distamycin A were synthesized and assayed for their effects on influenza and herpes simplex virus. The new compounds 5b-j (R1-3 = H, CH3, and C2H5, R4,5 = H and CH3) were obtained via stepwise prepared formylated trimeric benzyl 4-aminopyrrole-2-carboxylates 3a-h, which after catalytic hydrogenolysis were coupled as N-succinimidyl esters directly with the proper beta-aminopropionamidine, unsubstituted or substituted with one or two methyl groups in the amidine function. Most of the new analogues did not exhibit significant effects on the viruses studied, but three compounds (5f-h) displayed activity on herpes virus as demonstrated in plaque formation and virus yield assays. Elevated cytotoxicity was simultaneously observed for 5g and 5h. For compound 5f, a partial separation of antiherpes activity and cytotoxicity was accomplished. The differences in antiherpes activity did not correspond to the differences in the inhibition of herpes virus DNA polymerase.

Animals↗