Biomedical subjects

A Boman

Publications and source records attributed to A Boman.

At least 19 recordsLinked to original sources

PubMed1992

Shortened cecropin A-melittin hybrids. Significant size reduction retains potent antibiotic activity.

We have earlier reported two 26-residue antibacterial peptides made up from different segments of cecropin A (CA) and melittin (M). We now report a substantial reduction in size at the C-terminal section of the highly active hybrid CA(1-8)M(1-18), leading to a series of 20-, 18- and 15-residue analogs with antibiotic properties similar to the larger molecule. In particular, the 15-residue hybrids CA(1-7)M(2-9), CA(1-7)M(4-11) and CA(1-7)M(5-12) are the shortest cecropin-based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size. Their reduced size and highly alpha-helical structure require an alternative mechanism for their interaction with bacterial membranes.

Amino Acid Sequence↗

PubMed1992

Antibacterial peptides designed as analogs or hybrids of cecropins and melittin.

Eight new analogs of cecropin A, two new analogs of melittin and 30 hybrid peptides containing sequences from cecropins and melittin have been synthesized. The lengths of the peptides have varied from 37 residues (the length of cecropin A) to 18 residues. The peptides have been assayed for lysis of sheep red blood cells and for antibacterial activity against two Gram negative and three Gram positive bacteria. The best analogs of cecropin A maintained the anti-Escherichia coli activity of the parental peptide, and were not lytic for red blood cells. Melittin and its replacement analogs were all lytic for red blood cells, but an analog with transposed segments was not. Several of the hybrid peptides were found to be both non-hemolytic and highly active against all test bacteria. The data were used to define the structural requirements for antibacterial activity.

Amino Acid Sequence↗

PubMed1992

Permeation and destructive effects of disinfectants on protective gloves.

In working situations where there is a possibility of acquiring blood-borne infections, the use of disinfectants is important. It is also important to use protective gloves, both to protect the skin against disinfectants and to protect against infections. Changes in the structure of the glove material may, however, interfere with the protective capability of the gloves. The influence of 4 disinfectants on the material structure and protective effect of 6 different brands of protective gloves was studied. The proposed International Organization for Standardization (ISO) standard method for determining the liquid chemical resistance of air-impermeable materials was used for permeation testing. Pieces of latex and vinyl glove were also exposed to isopropanol and ethanol for 10, 30 and 60 min and then viewed in a scanning electron microscope. Isopropanol permeated through latex and vinyl gloves in less than 10 min. The polyethylene (PE) gloves were of quite variable quality, and the breakthrough time ranged from 4 to greater than 240 min. The latex and vinyl gloves were also permeated by ethanol, but at a much lower rate. The disinfectants Blifacid, based on p-chloro-m-cresol, and Cidex, based on glutaraldehyde, did not permeate any of the gloves tested within 60 min. Isopropanol had a destructive effect on the material, which became opaque, stiff and brittle. This change in structure was verified with the scanning electron microscope. The tested gloves of latex, vinyl and PE, gave acceptable protection from contact with Blifacid and Cidex for at least 60 min. The same gloves do not give any total protection from contact with isopropanol and ethanol.

Disinfectants↗

PubMed1992

Comparative evaluation of permeation testing of protective gloves to solvents: in vitro in permeation cells versus in vivo in guinea pigs.

Most current data on the protective effect of gloves against chemicals are obtained in vitro, using permeation cells. In vivo testing would give additional information on efficiency but is both expensive and time-consuming. It would therefore be valuable to know whether any definitive relationship exists between results obtained in vivo and in vitro. Gloves of natural rubber, butyl rubber and polyvinyl chloride (vinyl) were tested against 3 organic solvents, toluene, 1,1,1-trichloroethane and butanol, in vivo in guinea pigs and in vitro in permeation cells. Breakthrough times, absorption rates and steady state permeation rates were determined and compared on a relative basis. Some of the gloves that had a low degree of resistance to the test solvent in vitro nevertheless showed a rather good reducing capacity on the percutaneous absorption in vivo. However, for 2 gloves where no breakthrough was noted for butanol in vitro, permeation occurred at a degree lower than the minimum detection level. At this low concentration, the solvent was not absorbed through intact skin but through damaged skin. The breakthrough times for the 3 solvents corresponded well for the 2 test systems. The relative absorption rates and relative steady-state permeation rates varied considerably and no definitive relationship between the 2 sets of test results could be seen.

Animals↗

PubMed1992

Studies on the allergenicity of Baltic amber.

Baltic amber is a fossil resin deposited 36-7 million years ago and one source may be the extinct tree Pinites (Pinus) succinifer. Palaeobotanical studies of amber have an extensive literature, but the aspect of allergenicity has not been addressed before. The aim of our study was to present the results from sensitization studies with Baltic amber and to discuss these in view of possible cross-reactivity with contact allergens in colophony. It is concluded that allergens found in colophony can also be present in Baltic amber. The main resin acids were identified in an ether-soluble extract of amber. Amber suspended in petrolatum caused positive patch test reactions in patients with contact allergy to colophony. Furthermore, animals sensitized to colophony showed positive reactions to amber, but animals induced with amber did not react when challenged with amber. A use test with an amber necklace in patients with positive test reactions to amber and colophony was negative, which supports the view that amber in personal ornaments is not a clinical problem.

Animals↗

PubMed1991

Percutaneous uptake and kinetics of methyl isobutyl ketone (MIBK) in the guinea-pig.

Continuous intravenous infusion of 0.478 mumol/min methyl isobutyl ketone (MIBK) was performed for 30 min in pentobarbital-anesthetized guinea-pigs. Epicutaneous exposure for 150 min was carried out 2.5 h later after administration of MIBK to a sealed glass ring on the clipped back of the animals. Arterial blood was analyzed for MIBK by gas chromatography. Blood clearance averaged 201 ml.min-1.kg-1 body wt. A maximum percutaneous uptake of 1.1 mumol.min-1.cm-2 was reached 10-45 min after the onset of exposure and decreased to 0.56 mumol.min-1.cm-2 during the latter part of exposure.

Administration, Cutaneous↗

PubMed1991

Animal experiments on the allergenicity of d-limonene--the citrus solvent.

With the increasing use of d-limonene as a substitute for chlorinated hydrocarbons, chlorofluorocarbons (CFC) and other organic solvents, a demand has arisen for more knowledge of the health effects of this substance. The aim of the present study was to investigate the allergenic effect of d-limonene on skin. The sensitizing potential of d-limonene and the influence of air exposure on its allergenicity were studied in guineapigs. d-Limonene of high purity gave no significant allergic reactions, while d-limonene exposed to air for 2 months sensitized the animals. Gas chromatographic analyses indicated that the content of limonene oxide in limonene increased with prolonged air exposure. It is concluded that allergenic compounds are formed from d-limonene upon prolonged air exposure. Products containing d-limonene should therefore be kept in cold storage in closed vessels. Manual handling should be avoided, or gloves worn, in order to reduce the risk of sensitization.

Animals↗

PubMed1991

Percutaneous absorption of 2-butoxyethanol vapour in human subjects.

Four male volunteers were exposed at rest for two periods of two hours, separated by a one hour exposure free interval, to 50 ppm 2-butoxyethanol (BE) vapour generated in an exposure chamber. During the first two hour period the men were exposed by mouth only via a respiratory valve connected by tubes to the exposure chamber. During the second exposure period the men were exposed by skin only while sitting inside the exposure chamber, naked except for shorts, and wearing a respiratory protection mask supplied with compressed air. Capillary blood samples were collected at regular intervals and analysed for BE by a gas chromatographic method. Two experiments separated by at least two weeks were carried out with each volunteer, one at "normal" (23 degrees C, 29% relative humidity) and one at raised (33 degrees C, 71% relative humidity) air temperature and humidity in the chamber. The average concentration in blood and the calculated rate of uptake of BE were about three to four times higher during dermal exposure than during inhalation exposure. These experiments suggest that dermal uptake of BE accounts for about 75% (45-85% in individual experiments) of the total uptake during whole body exposure to BE vapour. Thus it appears that the use of a respiratory protection mask will not protect efficiently against exposure to BE vapours. A tendency towards increased percutaneous absorption rate was seen in the raised temperature and humidity condition.

Adult↗

PubMed1990

All-D amino acid-containing channel-forming antibiotic peptides.

The D enantiomers of three naturally occurring antibiotics--cecropin A, magainin 2 amide, and melittin--were synthesized. In addition, the D enantiomers of two synthetic chimeric cecropin-melittin hybrid peptides were prepared. Each D isomer was shown by circular dichroism to be a mirror image of the corresponding L isomer in several solvent mixtures. In 20% hexafluoro-2-propanol the peptides contained 43-75% alpha-helix. The all-D peptides were resistant to enzymatic degradation. The peptides produced single-channel conductances in planar lipid bilayers, and the D and L enantiomers caused equivalent amounts of electrical conductivity. All of the peptides were potent antibacterial agents against representative Gram-negative and Gram-positive species. The D and L enantiomers of each peptide pair were equally active, within experimental error. Sheep erythrocytes were lysed by both D- and L-melittin but not by either isomer of cecropin A, magainin 2 amide, or the hybrids cecropin A-(1-13)-melittin-(1-13)-NH2 or cecropin A-(1-8)-melittin-(1-18)-NH2. The infectivity of the bloodstream form of the malaria parasite Plasmodium falciparum was also inhibited by the D and L hybrids. It is suggested that the mode of action of these peptides on the membranes of bacteria, erythrocytes, plasmodia, and artificial lipid bilayers may be similar and involves the formation of ion-channel pores spanning the membranes, but without specific interaction with chiral receptors or enzymes.

Amino Acid Sequence↗

PubMed1989

The chemical synthesis of cecropin D and an analog with enhanced antibacterial activity.

Cecropin D was synthesized by solid-phase methods and shown to be homogeneous and of correct composition and molecular weight. It was indistinguishable from natural cecropin D and constitutes a structure proof for this peptide. Several analogs of cecropin D were synthesized and used to draw conclusions about the structural features contributing to antibacterial activity. They included [Lys1]cecropin D, [Gln3, Leu4] cecropin D, and cecropin D-(9-37). It was concluded that a strongly basic NH2-terminal segment is a prerequisite for antibacterial activity. A hybrid analog cecropin A-(1-11) D-(12-37) was designed and predicted to have enhanced potency. It was found to be 5 to 55 times as active as cecropin D against six of the bacteria tested and was slightly more active than cecropin A. However, against Bacillus subtilis Bs11 the analog was 6 times more active than cecropin A.

Amino Acid Sequence↗

PubMed1989

Antibacterial peptides from pig intestine: isolation of a mammalian cecropin.

Pig small intestine was used as starting material for a batchwise isolation of a peptide fraction enriched in antibacterial activities against Escherichia coli (anti-Ec factor) and against Bacillus megaterium (anti-Bm factor). Separation and further purification were by different types of chromatography. Sequence analysis showed the anti-Bm factor to be apparently similar to vasoactive intestinal peptide. The anti-Ec factor was found to have a 31-residue sequence that was cecropin-like. It was named cecropin P1 and its structure was confirmed by solid-phase synthesis. Synthetic cecropin P1 with and without C-terminal amide was assayed on eight different bacteria. Mobility comparison between synthetic and natural cecropin P1 indicates that the natural peptide has a free C-terminal carboxyl group.

Amino Acid Sequence↗

PubMed1989

Design, synthesis and antibacterial activity of cecropin-like model peptides.

In order to investigate structure-activity relationships of cecropins, model peptides that mimic certain structural features of the cecropin molecules were designed and synthesized. The conformational analysis of cecropins and the design of the model peptides were based on Chou-Fasman calculations. The peptides were synthesized by solid-phase methods and purified by reverse-phase liquid-chromatography on C18-silica columns. Their secondary structures were studied by circular dichroism measurements. Antibacterial activities against seven test organisms were determined and compared to the activities of the natural cecropins A and B. These results were discussed on the basis of structural features of the model peptides and on model mechanisms. It was concluded that high antibacterial activity for this class of compounds requires a basic helical amphipathic N-terminal segment that is connected to a hydrophobic helical C-terminal segment by a flexible non-helical hinge region.

Amino Acid Sequence↗

PubMed1989

Percutaneous absorption of 3 organic solvents in the guinea pig (IV). Effect of protective gloves.

The efficacy of 3 protective glove materials against percutaneous absorption of organic solvents was investigated in the guinea pig. All 3 materials gave a reduction in blood concentration of the solvents, particularly in the early phase of exposure. Of the tested materials, butyl rubber showed the best protective effect, followed by PVC and natural rubber. Gloves of polymeric material can be considered as offering sufficient protection against percutaneous absorption of organic solvents only if their selection is based on results obtained in a controlled and adequately performed test.

1-Butanol↗

PubMed1989

Percutaneous absorption of 3 organic solvents in the guinea pig (I). Effect of physical and chemical injuries to the skin.

The influence of injuries on the percutaneous absorption of 3 organic solvents (butanol, toluene, 1,1,1-trichloroethane) was studied in the guinea pig. Acute (stripping, sandpaper abrasion, needle abrasion, delipidization) and subacute (irritant and allergic contact dermatitis) injuries were induced by physical or chemical treatment of the skin. Absorption of solvents was quantified by blood analysis. Induction of acute injuries markedly altered the absorption pattern of the solvents and correlated to their water solubility. Absorption of toluene and trichloroethane was reduced and that of butanol was increased compared to normal untreated skin. Subacute injuries had a less pronounced effect. Irritant and allergic contact dermatitis reduced the absorption of toluene and trichloroethane, and no effect was seen for butanol. For hydrophobic solvents, it is concluded that in acute injuries strata other than stratum corneum hold the barrier properties.

1-Butanol↗

PubMed1989

Percutaneous absorption of 4 organic solvents in the guinea pig (II). Effect of surfactants.

Percutaneous absorption of 4 organic solvents (1,1,1-trichloroethane, 1,1,2-trichloroethane, toluene and butanol) from various colloidal preparations in a surfactant-water-organic solvent system was studied in vivo in guinea pigs. The preparations examined were binary solutions of organic solvents and surfactants, o/w emulsions and microemulsions. Phase diagram, birefringence microscopy and droplet size distribution analysis were used for characterization of the preparations. It was found that skin absorption of the solvents depends on the type of surfactant, type of preparation and also on phase equilibria in the systems studied. The presence of nonionic surfactants in the solvents and in a microemulsion with butanol caused skin absorption to decrease. A reduced uptake of solvents from o/w emulsions was observed. The absorption of butanol from a microemulsion with anionic surfactant was greater than from the pure solvent.

Animals↗

PubMed1989

Percutaneous absorption of 3 organic solvents in the guinea pig. (III). Effect of barrier creams.

The efficacy of 4 barrier preparations presented as cream or foam against percutaneous absorption of organic solvents was investigated in the guinea pig. An ordinary hand cream was also tested. Slight reduction in blood concentration of the solvents was seen when normal skin treated with barrier creams was exposed. Absorption of butanol through stripped skin treated with barrier creams was higher than absorption through skin not so treated. Barrier creams can be considered to give poor skin protection against the organic solvents investigated.

Animals↗

PubMed1989

Percutaneous absorption of 3 organic solvents in the guinea pig (V). Effect of "accelerants".

The influence of "accelerants" on the percutaneous absorption of 3 organic solvents (butanol, toluene, 1,1,1-trichloroethane) was investigated in the guinea pig. DMSO in binary and ternary mixtures with various concentrations, the result of adding 0.1 M C18 fatty acids, and of pretreatment with DMSO and olive oil, were studied. Addition of DMSO (binary solutions) resulted in increased or decreased absorption of the solvents related to their water solubility. There was reduced absorption of toluene and trichloroethane in binary mixtures with DMSO, while DMSO in binary mixture with butanol gave a marked increase, with concentrations of 50 and 75%. Pretreatment with DMSO resulted in a decrease in the absorption of toluene and a marked increase in the absorption of butanol. The same tendency was seen when skin was pretreated with olive oil under occlusion. The results indicate that the effect of DMSO is related to the water solubility of the penetrant.

Animals↗

PubMed1988

The dorsal cell, one class of primary sensory neuron in the lamprey spinal cord. I. Touch, pressure but no nociception--a physiological study.

The dorsal cells in the lamprey spinal cord are primary sensory neurons. The cells were classified by Martin and Wickelgren in 1971 into 3 different groups, touch, pressure and nociceptive, according to their responses to mechanical stimulation of the skin. While confirming the presence of touch and pressure cells in the present study, we found no evidence for the existence of nociceptive spinal dorsal cells. Further we show that touch and pressure cells have different response latencies to a 40-ms hyperpolarizing current pulse. Measured from the end of the pulse to the initiation of the action potential, touch cells have a response latency shorter than 11 ms, whereas the pressure cells have a response latency longer than 11 ms.

Action Potentials↗