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Biomedical subjects

N Ohashi

Publications and source records attributed to N Ohashi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Delayed treatment of Na+/H+ exchange inhibitor SM-20220 reduces infarct size in both transient and permanent middle cerebral artery occlusion in rats.

SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) is a Na+/H+ exchanger (NHE) inhibitor which has been shown to attenuate cerebral edema in the rat transient focal ischemia model. However, to date, the effect of SM-20220 on cerebral infarction has not been examined. The present experiments were designed to investigate these effects, using both transient and permanent middle cerebral artery (MCA) occlusion models in rats. A dose of 1 mg/kg given intravenously 30 min after the onset of transient MCA occlusion reduced the infarcted area. In the permanent MCA occlusion model, SM-20220 reduced the infarcted area when treatment was delayed for 5, 30 or 60 min after the onset of ischemia. The present results show that NHE has a crucial role in the pathogenesis of ischemic brain damage. This NHE inhibitor may be useful for treating stroke because of its effectiveness with both forms of ischemia and because of its postischemic administration.

Amides↗
PubMed1999

Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts.

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.

Amides↗
PubMed1999

Sodium/hydrogen ion exchange inhibitor ameliorates ischaemia-reperfusion injuries in the rat hind limb.

PURPOSE: This study was designed to investigate the effect of a newly synthesised sodium/hydrogen ion exchange inhibitor, SM-20550, on ischaemia-reperfusion induced injury in a rat hind limb model. METHODS: In order to induce ischaemia of the hind limbs, the abdominal aorta just distal to the renal arteries and the bilateral femoral arteries were clamped. Nineteen rats were divided into three groups. In the sham group (n=5), the vessels were only dissected and a vehicle solution was administered. In the control group (n=7), the vessels were clamped for five hours, and a vehicle solution was administered 10 minutes prior to clamping and continued for five hours after reperfusion. In the SM group (n=7), clamping was maintained for five hours with a bolus injection of SM-20550 and continuous infusion of the solution for five hours after reperfusion. Water content of the left gastrocnemius muscle was calculated. The right gastrocnemius was fixed in 10% formalin. A transverse thin section was stained with antimyoglobin antibody. Stained cells of the right gastrocnemius were counted and the myoglobin staining index was calculated. RESULTS: Water content was significantly (p<0.002) lower in the SM group than in the control group. The myoglobin staining index was significantly (p<0.01) higher in the SM group than in the control group. There was no significant difference between the control and the SM groups in creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH). CONCLUSIONS: Our results indicate that the sodium/hydrogen ion exchange inhibitor, SM-20550, ameliorates oedema formation and ischaemia-reperfusion induced injury of the skeletal muscle.

Amidines↗
PubMed1998

Usefulness of the hydrogen--deuterium exchange method in the study of drug metabolism using liquid chromatography-tandem mass spectrometry.

The usefulness of the hydrogen-deuterium (H-D) exchange method in the study of drug metabolism was investigated. Metabolite samples of denopamine and promethazine prepared in vitro were introduced to a triple stage quadrupole tandem mass spectrometer via a high performance liquid chromatography (HPLC) system using a deuterated mobile phase. Mass spectra by various ionization modes and collisionally induced dissociation (CID) mass spectra were obtained. A metabolite of denopamine was observed to have a shift of 7 mass units by the H-D exchange method, and this shift proved to be a glucuronidated metabolite. Discrimination between N- or S-oxide formation and hydroxylation observed in the metabolism of promethazine was also easily accomplished by this method. In this manner, the structures of the metabolites were elucidated unequivocally by determining the number of labile hydrogen atoms by the use of the H-D exchange method, since various reactions in drug metabolism are accompanied by an increase or a decrease in the number of labile hydrogen atoms. Additional information on the structures was obtained by analysis of the CID spectra of the molecular ion species. Thus, the combination of the H-D exchange method and tandem mass spectrometry was found to be very useful for the study of drug metabolism.

Animals↗
PubMed1998

Immunodominant major outer membrane proteins of Ehrlichia chaffeensis are encoded by a polymorphic multigene family.

Several immunodominant major proteins ranging from 23 to 30 kDa were identified in the outer membrane fractions of Ehrlichia chaffeensis and Ehrlichia canis. The N-terminal amino acid sequence of a 28-kDa protein of E. chaffeensis (one of the major proteins) was determined. The gene (p28), almost full length, encoding the 28-kDa protein was cloned by PCR with primers designed based on the N-terminal sequence of the E. chaffeensis 28-kDa protein and the consensus sequence between the C termini of the Cowdria ruminantium MAP-1 and Anaplasma marginale MSP-4 proteins. The p28 gene was overexpressed, and antibody to the recombinant protein was raised in a rabbit. The antibody and serum from a patient infected with E. chaffeensis reacted with the recombinant protein, three proteins (29, 28, and 25 kDa) of E. chaffeensis, and a 30-kDa protein of E. canis. Immunoelectron microscopy with the rabbit antibody revealed that the antigenic epitope of the 28-kDa protein was exposed on the surface of E. chaffeensis. Southern blot analysis with a 32P-labeled p28 gene probe revealed multiple copies of genes homologous to p28 in the E. chaffeensis genome. Six copies of the p28 gene were cloned and sequenced from the genomic DNA by using the same probe. The open reading frames of these gene copies were tandemly arranged with intergenic spaces. They were nonidentical genes and contained a semivariable region and three hypervariable regions in the predicted protein molecules. One of the gene copies encoded a protein with an internal amino acid sequence identical to the chemically determined N-terminal amino acid sequence of a 23-kDa protein of E. chaffeensis. Immunization with the recombinant P28 protein protected mice from infection with E. chaffeensis. These findings suggest that the 30-kDa-range proteins of E. chaffeensis represent a family of antigenically related homologous proteins encoded by a single gene family.

Amino Acid Sequence↗
PubMed1998

Cloning of the heat shock protein 70 (HSP70) gene of Ehrlichia sennetsu and differential expression of HSP70 and HSP60 mRNA after temperature upshift.

Ehrlichia sennetsu is the causative agent of human Sennetsu ehrlichiosis. Heat shock protein 60 (HSP60) and HSP70 (DnaK) are two major bacterial HSPs, and their interaction modulates the stress response. Previously, we cloned and sequenced groE and expressed groEL of E. sennetsu. HSP60 (GroEL) was immunogenic and cross-reactive in Ehrlichia spp. The present study was designed to (i) characterize the HSP70 gene of this organism and (ii) determine whether the expression of these two HSPs is inducible upon exposure to heat stress. A gene encoding an HSP70 homolog was isolated and sequenced from a gene library. The ehrlichial HSP70 gene encoded a 637-amino-acid protein, which had an approximate molecular mass of 68,354 Da and which was homologous to DnaK of Escherichia coli. A DNA sequence resembling -35 and -10 promoter sequences of E. coli dnaK was observed upstream of the ehrlichial HSP70 gene. Alignment of the predicted amino acid sequence with that of E. coli DnaK and Brucella, Salmonella, Borrelia, Chlamydia, and Mycobacterium HSP70s showed 63, 67, 63, 62, 58, and 53% identity, respectively. By reverse transcription-PCR analysis, the mRNA levels of ehrlichial HSP70 and HSP60 were examined after temperature shifts from 28 to 37 degreesC and from 37 to 40 degreesC. HSP70 mRNA induction levels were greater than those of HSP60 mRNA after a 37-to-40 degreesC temperature shift, whereas the reverse was true after a 28-to-37 degreesC temperature shift. Our data suggest that HSP60 and HSP70 may play different roles during transfer from vector temperature to human body temperature and during a febrile condition characteristic of ehrlichial disease. This study also provides a useful model system for examining mRNA expression in obligatory intracellular bacteria.

Amino Acid Sequence↗
PubMed1998

Cloning and expression of the 44-kilodalton major outer membrane protein gene of the human granulocytic ehrlichiosis agent and application of the recombinant protein to serodiagnosis.

A 44-kDa major outer membrane protein of the human granulocytic ehrlichiosis (HGE) agent is an immunodominant antigen in human infection. A gene encoding this protein was cloned and sequenced. Southern blot results revealed the existence of multigenes homologous to the P44 gene in the genome of the HGE agent. The recombinant 44-kDa protein (rP44) was expressed by using expression vector pET30a. The reactivity of the affinity-purified rP44 was evaluated by Western immunoblot analysis and dot blot immunoassay. Western immunoblot analysis showed that mouse anti-rP44 serum reacted with 44- to 42-kDa proteins in six different HGE agent strains tested except strain 2, in which three proteins of 42, 40, and 38 kDa were recognized. Eleven HGE patient serum samples, a horse anti-HGE serum, and a horse anti-Ehrlichia equi serum recognized the rP44 protein. This suggests that rP44 is an HGE-E. equi group-specific antigen. Neither human anti-Ehrlichia chaffeensis serum nor rabbit anti-Borrelia burgdorferi serum reacted with rP44. Sera from two patients coinfected with the HGE agent and B. burgdorferi reacted positively with rP44 and the HGE agent. Sera from 20 HGE patients with indirect fluorescent-antibody (IFA) titers ranging from 1:20 to 1:2,560 gave distinct positive reactions in a dot immunoblot assay. There was a positive correlation between the color densities of the dot reactions and the IFA titers when greater than 50 ng of recombinant antigen per dot was used. The use of the affinity-purified rP44 protein as antigen would provide a more specific, consistent, and simpler serodiagnosis for HGE than the use of whole infected cells or purified HGE agents.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of multigenes encoding the immunodominant 30-kilodalton major outer membrane proteins of Ehrlichia canis and application of the recombinant protein for serodiagnosis.

A 30-kDa major outer membrane protein of Ehrlichia canis, the agent of canine ehrlichiosis, is the major antigen recognized by both naturally and experimentally infected dog sera. The protein cross-reacts with a serum against a recombinant 28-kDa protein (rP28), one of the outer membrane proteins of a gene (omp-1) family of Ehrlichia chaffeensis. Two DNA fragments of E. canis were amplified by PCR with two primer pairs based on the sequences of E. chaffeensis omp-1 genes, cloned, and sequenced. Each fragment contained a partial 30-kDa protein gene of E. canis. Genomic Southern blot analysis with the partial gene probes revealed the presence of multiple copies of these genes in the E. canis genome. Three copies of the entire gene (p30, p30-1, and p30a) were cloned and sequenced from the E. canis genomic DNA. The open reading frames of the two copies (p30 and p30-1) were tandemly arranged with an intergenic space. The three copies were similar but not identical and contained a semivariable region and three hypervariable regions in the protein molecules. The following genes homologous to three E. canis 30-kDa protein genes and the E. chaffeensis omp-1 family were identified in the closely related rickettsiae: wsp from Wolbachia sp. , p44 from the agent of human granulocytic ehrlichiosis, msp-2 and msp-4 from Anaplasma marginale, and map-1 from Cowdria ruminantium. Phylogenetic analysis among the three E. canis 30-kDa proteins and the major surface proteins of the rickettsiae revealed that these proteins are divided into four clusters and the two E. canis 30-kDa proteins are closely related but that the third 30-kDa protein is not. The p30 gene was expressed as a fusion protein, and the antibody to the recombinant protein (rP30) was raised in a mouse. The antibody reacted with rP30 and a 30-kDa protein of purified E. canis. Twenty-nine indirect fluorescent antibody (IFA)-positive dog plasma specimens strongly recognized the rP30 of E. canis. To evaluate whether the rP30 is a suitable antigen for serodiagnosis of canine ehrlichiosis, the immunoreactions between rP30 and the whole purified E. canis antigen were compared in the dot immunoblot assay. Dot reactions of both antigens with IFA-positive dog plasma specimens were clearly distinguishable by the naked eye from those with IFA-negative plasma specimens. By densitometry with a total of 42 IFA-positive and -negative plasma specimens, both antigens produced results similar in sensitivity and specificity. These findings suggest that the rP30 antigen provides a simple, consistent, and rapid serodiagnosis for canine ehrlichiosis. Cloning of multigenes encoding the 30-kDa major outer membrane proteins of E. canis will greatly facilitate understanding pathogenesis and immunologic study of canine ehrlichosis and provide a useful tool for phylogenetic analysis.

Amino Acid Sequence↗
PubMed1998

Hepatitis C virus infection and heart diseases: a multicenter study in Japan.

As a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, a questionnaire was sent out to 19 medical institutions in Japan in order to examine the possible association between hepatitis C virus (HCV) infection and cardiomyopathies. Hepatitis C virus antibody was found in 74 of 697 patients (10.6%) with hypertrophic cardiomyopathy (mean age, 57.7 years) and in 42 of 663 patients (6.3%) with dilated cardiomyopathy (mean age, 56.5 years); these prevalences were significantly higher than that found in volunteer blood donors in Japan (2.4%, 50-59 years of age, each p<0.0001). The prevalence was significantly higher in patients suffering from hypertrophic cardiomyopathy as opposed to those with dilated cardiomyopathy (p<0.01). The presence of HCV antibody was detected in 650 of 11,967 patients (5.4%) patients seeking care in 5 academic hospitals. Various cardiac abnormalities were found among these patients, arrhythmias being the most frequent. These observations suggest that HCV infection is an important cause of a variety of otherwise unexplained heart diseases.

Cardiomyopathies↗
PubMed1998

[Clinical study of long graft survival in renal transplantation recipients].

BACKGROUND: A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. METHODS: In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. RESULTS: Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). CONCLUSIONS: We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.

Adult↗
PubMed1998

[Immunohistochemical study on pulmonary neuroendocrine cells containing calcitonin gene-related peptide in sudden infant death syndrome].

To examine whether pulmonary neuroendocrine cells (PNEC) is associated with sudden infant death syndrome (SIDS), distribution and function of PNEC were investigated in infants from one to twelve months of age, including 19 cases with SIDS and 18 control cases without congenital heart disease and premature birth. In this study, lung tissue sections were immunostained with antibodies against chromogranin A (CGA) and calcitonin gene-related peptide (CGRP). Although the positivity of CGA in SIDS cases was not significantly different from that in control, the positivity of CGRP in SIDS cases was lower than that in control cases among one to four months old (p < 0.05). Our results suggest that respiratory and/or circulatory regulation of cases with SIDS is disturbed by reduction of CGRP expression, because CGRP is well known to be a vasodilator, a neurotransmitter and a promoter for proliferation of epithelium in airways.

Calcitonin Gene-Related Peptide↗
PubMed1998

[Management of putaminal hemorrhage in patients with chronic renal failure].

The treatments of putaminal hemorrhages (PH) were evaluated in 14 patients (15 hematomas) with chronic renal failure (CRF). We compared the data of our series with the data of co-operative study (1990) on PH. With regard to consciousness level (Neurological Grading, NG) and hematoma volume, significantly more serious cases were observed in PH with CRF than in PH of the co-operative study. In PH with CRF, mortality (40%) was significantly higher than that in PH of the co-operative study. However, the mortality rate was 0%, 0%, 20%, and 100% in NG1, 2, 3, and over 4b. The mortality rate was 0% in non-surgically treated cases with 0 to 30 ml of hematoma volume, and 0% in surgically treated cases with 10 to 50 ml of hematoma volume. These mortality rates were equal to those of the co-operative study with the same NG, and equal to those of the co-operative study with the same hematoma volume. With respect to functional prognosis, "good" (ADL1 and 2) resulted in 67% of non-surgically treated cases with NG1 to 2, and in 33% of surgically treated cases with NG3 to 4a. "Good" resulted in 33% of non-surgically treated cases with 0 to 30 ml of hematoma volume, and in 40% of surgically treated cases with 10 to 50 ml of hematoma volume. These morbidity rates were equal to those of the co-operative study with the same NG, and equal to those of the co-operative study with the same hematoma volume. Therefore, the high mortality in PH with CRF was suspected to be due to the fact that, in our study, there was a higher distribution of serious cases. These findings indicate that protection against enlargement of hematomas in the acute phase may bring about improvement of prognosis in PH with CRF.

Cerebral Hemorrhage↗
PubMed1997

Characterization of Orientia tsutsugamushi isolated in Taiwan by immunofluorescence and restriction fragment length polymorphism analyses.

A total of 10 strains of Orientia tsutsugamushi were isolated from field rodents and chiggers in Taiwan, and characterized by immunofluorescence analysis with monoclonal antibodies and by restriction fragment length polymorphism analysis of the 56-kilodalton (kDa) protein gene. The isolates were divided into two groups consisting of 1 and 9 strains which showed some relation to Gilliam and Karp type strains, respectively. However, all these isolates possessed characteristics distinct not only from those of known prototype strains including Gilliam and Karp but also from all isolates from Japan. These findings suggest the existence of a large number of immunotypic and genotypic variants among the strains of O. tsutsugamushi, and the distribution of distinguishable strains in each area to which this species is endemic.

Animals↗
PubMed1997

Near-Infrared Diode Laser Spectroscopy of the Nitrogen Molecule in Rydberg State: Analysis of the c1Piu - a"1Sigmag+, v = 1-0 Band

A new singlet-singlet absorption band between Rydberg states of the nitrogen molecule was studied by near-infrared diode laser spectroscopy in the 1.3 &mgr;m region. An analysis was made for the band to establish line assignments and determine molecular parameters for both the lower and the upper vibronic states. As a result of the analysis, this band was assigned to the c1Piu-a"1Sigmag+, v = 1-0 band. The anomaly of the Lambda-type doubling structure in the c1Piu (v = 1) state was discussed in connection with the interaction with the b'1Sigmau+ (v = 4) state. The predissociation in the c1Piu (v = 1) state was also discussed relating with the line broadening observed. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Pancreatic carcinoma associated with the Leser-Trélat sign.

A case of pancreatic carcinoma associated with the Leser-Trélat sign is reported. A 53-yr-old male had complained of mild epigastric discomfort and back pain accompanied by seborrheic keratoses, which had increased in size and number over the previous 6 mo. A tumor was detected in the head of the pancreas and macroscopically curatively resected. His skin lesions diminished after surgery, but progressed again when the tumor recurred. Immunohistology for EGF showed a low level in the pancreatic carcinoma cells but a higher EGF content was recognized in the hyperkeratinized portions of the seborrheic keratoses. Of 130 underlying malignancies described in the 125 reported patients with the Leser-Trélat sign, neoplasms of the gastrointestinal tract were most common, comprising 47.7% of the total. The present case is the third case showing an association between a pancreatic carcinoma and the Leser-Trélat sign, but the first case for which the tumor of the pancreas was diagnosed in an early stage and resected surgically, as a result of the suggestive nature of this sign.

Adenocarcinoma↗
PubMed1997

Effects of aminoguanidine on serum advanced glycation endproducts, urinary albilmin excretion, mesangial expansion, and glomerular basement membrane thickening in Otsuka Long-Evans Tokushima fatty rats.

This study evaluated the effects of treatment with an inhibitor of advanced glycation endproducts, aminoguanidine, on the development of albuminuria, mesangial expansion and glomerular basement membrane (GBM) thickening in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which we found to be an excellent model of non insulin-dependent diabetes mellitus (NIDDM), for its very close similarity to human NIDDM. OLETF rats were randomized into a non-treatment diabetic group (D-group, n = 5) and an aminoguanidine-treated group (AG-group, n = 5). The AG-group was given 100 mg/dl aminoguanidine HCl in free drinking water. Treatment was started at 16 weeks of age. We measured body weight, plasma glucose, total cholesterol, triglycerides and the urinary albumin excretion (UAE) rate before and after treatment at regular intervals. At 56 weeks of age, we measured serum advanced glycation endproducts (AGE), mesangial expansion and glomerular basement membrane. There were no significant differences in pre-treatment body weight, plasma glucose and UAE between the D-group and the AG-group. Likewise, after treatment there were no significant differences in body weight, plasma glucose, total cholesterol, triglycerides and immunoreactive insulin. Significant differences were, however, noted in serum AGE (63.2 +/- 3.5 and 51.8 +/- 3.0 U AGE/ml, P < 0.05), UAE (203.6 +/- 37.7 and 89.8 +/- 18.6 mg/day, P < 0.05), fractional mesangial volume (21.3 +/- 1.7 and 16.7 +/- 0.8%, P < 0.05) and GBM thickness (453 +/- 17 and 366 +/- 50 nm, P < 0.05) between the D-group and the AG-group. Our results suggest that aminoguanidine inhibits the AGE formation and the development of diabetic nephropathy in OLETF rats.

Albuminuria↗
PubMed1997

Specific CYP3A4 inhibitors in grapefruit juice: furocoumarin dimers as components of drug interaction.

Four components were isolated from grapefruit juice that inhibit human CYP3A-mediated drug oxidation. The structures of these compounds were identified as furocoumarin derivatives by absorption spectra, APCI-liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance after their purification by reversed-phase high performance liquid chromatography. They include two new furocoumarins, 4-[[6-hydroxy-7-[[1-[(1-hydroxy-1-methyl)ethyl]-4-methyl-6- (7-oxo-7H-furo[3,2-g][1]benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimeth yl- 2-octenyl] oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-1) and 4-[[6-hydroxy-7-[[4-methyl-I- (1-methylethenyl)-6-(7-oxo-7H-furo[3,2-g][1]benzopyran-4-yl)-4- hexenyl] oxy]-3,7-dimethyl-2-octenyl]oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-4). These furocoumarins are strong candidates for causative agents of grapefruit juice-mediated drug interaction, because of an inhibition potential that is equal to or stronger than the prototypical CYP3A4 inhibitor, ketoconazole, on liver microsomal testosterone 6 beta-hydroxylation.

Beverages↗