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Biomedical subjects

L Johanson

Publications and source records attributed to L Johanson.

10 recordsLinked to original sources
PubMed2000

Antiulcer effectiveness of Maytenus aquifolium spray dried extract.

The antiulcer activity of Maytenus aquifolium spray dried extract was studied in rats. Ulcers were induced by means of three experimental models: acidified-ethanol, indomethacin and acute stress. The extract was found to have significant antiulcer activity against all the models studied. These results show that preparation of the extract by means of the spray dried technique does not alter the biological activity of Maytenus aquifolium.

Animals↗
PubMed1999

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions.

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was metabolized by human liver microsomes to 5-hydroxy-, 6-hydroxy-, and N-deisopropyl-fluvastatin. Total metabolite formation was biphasic with apparent Km values of 0.2 to 0.7 and 7.9 to 50 microM and intrinsic metabolic clearance rates of 1.4 to 4 and 0.3 to 1.5 ml/h/mg microsomal protein for the high and low Km components, respectively. Several enzymes, but mainly CYP2C9, catalyzed fluvastatin metabolism. Only CYP2C9 inhibitors such as sulfaphenazole inhibited the formation of both 6-hydroxy- and N-deisopropyl-fluvastatin. 5-Hydroxy-fluvastatin formation was reduced by compounds that are inhibitors of CYP2C9, CYP3A, or CYP2C8. Fluvastatin in turn inhibited CYP2C9-catalyzed tolbutamide and diclofenac hydroxylation with Ki values of 0.3 and 0.5 microM, respectively. For CYP2C8-catalyzed 6alpha-hydroxy-paclitaxel formation the IC50 was 20 microM and for CYP1A2, CYP2C19, and CYP3A catalyzed reactions, no IC50 could be determined up to 100 microM fluvastatin. All three fluvastatin metabolites were also formed by recombinant CYP2C9, whereas CYP1A1, CYP2C8, CYP2D6, and CYP3A4 produced only 5-hydroxy-fluvastatin. Km values were approximately 1, 2.8, and 7.1 microM for CYP2C9, CYP2C8, and CYP3A, respectively. No difference in fluvastatin metabolism was found between the CYP2C9R144 and CYP2C9C144 alleles, suggesting the absence of polymorphic fluvastatin metabolism by these alleles. CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2E1, and CYP3A5 did not produce detectable amounts of any metabolite. This data indicates that several human cytochrome P-450 enzymes metabolize fluvastatin with CYP2C9 contributing 50-80%. Any coadministered drug would therefore only partially reduce the metabolic clearance of fluvastatin; therefore, the likelihood for serious metabolic drug interactions is expected to be minimal.

Biotransformation↗
PubMed1999

Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions.

Biotransformation pathways and the potential for drug-drug interactions of the orally active antifungal terbinafine were characterized using human liver microsomes and recombinant human cytochrome P-450s (CYPs). The terbinafine metabolites represented four major pathways: 1) N-demethylation, 2) deamination, 3) alkyl side chain oxidation, and 4) dihydrodiol formation. Michaelis-Menten kinetics for the pathways revealed mean K(m) values ranging from 4.4 to 27.8 microM, and V(max) values of 9.8 to 82 nmol/h/mg protein. At least seven CYP enzymes are involved in terbinafine metabolism. Recombinant human CYPs predict that CYP2C9, CYP1A2, and CYP3A4 are the most important for total metabolism. N-demethylation is primarily mediated by CYP2C9, CYP2C8, and CYP1A2; dihydrodiol formation by CYP2C9 and CYP1A2; deamination by CYP3A4; and side chain oxidation equally by CYP1A2, CYP2C8, CYP2C9, and CYP2C19. Additionally, characteristic CYP substrates inhibited pathways of terbinafine metabolite formation, confirming the involvement of multiple enzymes. The deamination pathway was mainly inhibited by CYP3A inhibitors, including troleandomycin and azole antifungals. Dihydrodiol formation was inhibited by the CYP1A2 inhibitor furafylline. Terbinafine had little or no effect on the metabolism of many characteristic CYP substrates. Terbinafine, however, is a competitive inhibitor of the CYP2D6 reaction, dextromethorphan O-demethylation (K(i) = 0.03 microM). In summary, terbinafine is metabolized by at least seven CYPs. The potential for terbinafine interaction with other drugs is predicted to be insignificant with the exception that it may inhibit the metabolism of CYP2D6 substrates. Clinical trials are needed to assess the relevance of these findings.

Antifungal Agents↗
PubMed1994

The second intron of the K-ras gene contains regulatory elements associated with mouse lung tumor susceptibility.

We have previously demonstrated the preferential activation of the K-ras gene from the susceptible A/J parent in lung tumors from F1 mouse hybrids. In the present study, the mechanism of this observation is further investigated. Higher levels of expression of A/J K-ras allele were detected in lung adenomas (30 of 30) from the C3A mouse. In addition, three K-ras alleles, designated as susceptible (Ks), intermediate (Ki), or resistant (Kr), were identified by sequence analysis of the second intron of the K-ras gene from 32 strains of mice. These K-ras alleles are associated with differences in mouse lung tumor susceptibility. All Kr alleles have a tandem 37-bp direct repeat (nt 282-355) in the second intron of the K-ras gene. Ks and Ki alleles have only one copy of the 37-bp sequence (nt 282-318). Ks strains have three base variations at nt 288, 296, and 494, and Ki strains have two base variations at nt 288 and 494 in the second intron of the K-ras gene. Differential protein-binding patterns were observed in gel-mobility-shift experiments between the duplicated 37-bp sequence of the Kr allele and the single 37-bp sequence of the Ks and Ki alleles. DNase I footprinting assay revealed protein binding sites in the second intron of the K-ras gene that correspond to the tandem repeat sequences. Our data suggest that higher expression of the A/J allele relative to C3H allele may be responsible for the allele-specific activation of the K-ras gene in lung tumors from F1 hybrid mice.

Adenoma↗
PubMed1989

[Oral rehydration immediately after appendectomy].

An experimental study of 20 patients with appendicitis was carried out in order to know if after the appendectomy they tolerate the hidratation with rehidratant salts by mouth in place of endovenous hydratation. The oral hydratation was indicated in all the cases immediately after the operation and only was one failure (5%). In the 95% the oral hydratation was tolerated, 45% without gastric symptoms, 35% with mild gastric symptoms and in 15% with moderate gastric symptoms. The association of gentamycin-metronidazol administered by intramuscular and oral way respectively was used in 100% of the patients. In 80% as profilaxis and in 20% as treatment. Two cases had complication as sepsis of the wound one of the profilactic group (5.9%) and another of the treatment group. In conclusion the oral hydratation with rehydrating salts were tolerated for the patients immediately after the appendectomy.

Administration, Oral↗
PubMed1982

Neonatal rupture of the bladder secondary to posterior urethral valves.

Rupture of the neonatal urinary bladder during pregnancy or delivery is an extremely rare event, in some patients secondary to posterior urethral valves. In a recent case early diagnosis facilitated prompt surgical repair. A temporary bladder fistula secured survival and micturition cystourethrography establishment of the valves, which were successfully resected at two weeks of age.

Humans↗
PubMed1980

Childhood intussusception: hydrostatic reducibility and incidence of leading points in different age groups.

A series consisting of 658 radiologically diagnosed intussusceptions is analysed. Hydrostatic reduction was successful in 85.2% of cases, the incidence of failure amounting to 14.8%. Analysis demonstrated a marked difference in reduction rate in different age groups. The lowest rate of success was recorded in children over 5 years of age, the group with the highest incidence of leading points. The next lowest rate of success was in those below age 1 year where the frequency of failure was more than 50% higher than in the ages between 1 and 5 years. However, the rate of leading points was approximately the same in both the latter groups and close to the average in entire series. There is no reason to refrain from barium enema reduction in any age group although special care should be exercised in the neonate. With a reasonable experience of method, the risk of overlooking a surgically significant lesion is negligible.

Age Factors↗
PubMed1980

Occurrence of reflux in children with ureteral jets.

The urograms of 186 boys and 145 girls were scrutinized in order to reveal the incidence of ureteral jets demonstable during intravenous pyelography (IVP). In this series a unilateral jet was observed in 26 cases and a bilateral jet in 6 cases. Ureteral jets were almost three times as common in patients with normal urograms compared with those revealing urinary abnormalities. The incidence of a positive jet sign, usually unilateral, varies with the employed technique of examination, but the highest incidence in routine IVP seems to be about 30%. Although infrequent, significant ipsilateral vesico-ureteral reflux (VUR) may occur. This fact together with the reported low rate of bilateral jets restricts the value or Unilateral jets being used as an indicator of absence of gross VUR. The need for micturition cysto-urethography (MCU) at the uro-radiological work-up remains unchallenged.

Adolescent↗