Search PubMed⌕ Search

Biomedical subjects

K S Kim

Publications and source records attributed to K S Kim.

At least 91 records · Page 5Linked to original sources
PubMed2001

Statistical thermodynamics of membrane bending-mediated protein-protein attractions.

Highly wedge-shaped integral membrane proteins, or membrane-adsorbed proteins can induce long-ranged deformations. The strain in the surrounding bilayer creates relatively long-ranged forces that contribute to interactions with nearby proteins. In contrast, to direct short-ranged interactions such as van der Waal's, hydrophobic, or electrostatic interactions, both local membrane Gaussian curvature and protein ellipticity can induce forces acting at distances of up to a few times their typical radii. These forces can be attractive or repulsive, depending on the proteins' shape, height, contact angle with the bilayer, and a pre-existing local membrane curvature. Although interaction energies are not pairwise additive, for sufficiently low protein density, thermodynamic properties depend only upon pair interactions. Here, we compute pair interaction potentials and entropic contributions to the two-dimensional osmotic pressure of a collection of noncircular proteins. For flat membranes, bending rigidities of approximately 100k(B)T, moderate ellipticities, and large contact angle proteins, we find thermally averaged attractive interactions of order k(B)T. These interactions may play an important role in the intermediate stages of protein aggregation. Numerous biological processes where membrane bending-mediated interactions may be relevant are cited, and possible experiments are discussed.

Lipid Bilayers↗
PubMed2001

Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress.

AIMS: it appears that hypertriglyceridemia (HTG) is a risk factor of atherosclerosis as demonstrated by recent studies. In this study, we analyzed the effects of acute HTG on endothelial function and oxidative stress, which are important mechanisms in the pathogenesis of atherosclerosis. METHODS AND RESULTS: in a high fat meal group (n = 11), serum triglycerides and PMA-activated leukocyte O(2)(-)* production were significantly (P < 0.005) increased from 146 +/- 69 mg/dl and 4.09 +/- 0.93 nmol/10(6) cells/min preprandially to 198 +/- 88 mg/dl and 5.49 +/- 1.19 nmol/10(6) cells/min, respectively, 2 h after eating a high-fat meal. The flow-mediated endothelium-dependent brachial artery dilation (FMD; high-resolution ultrasound) was decreased from 13.7 +/- 3.3% preprandially to 8.2 +/- 3.7%, 2 h after eating a high-fat meal (P < 0.005). However, following a low-fat meal (n = 9), there were no significant changes in triglycerides, leukocyte O(2)(-)* production and FMD. Changes of serum triglycerides were correlated negatively (r = -0.650, P < 0.005) with changes of FMD, but were correlated positively (r = 0.798, P < 0.001) with changes of leukocyte O(2)(-)* production, which - in turn - were correlated negatively (r = -0.784, P < 0.001) with changes of FMD in all study subjects (mean age: 56 years, n = 20). CONCLUSIONS: this study suggests that acute HTG causes endothelial dysfunction via enhanced oxidant stress and this may pave the way for the development of atherosclerosis under chronic conditions.

Acute Disease↗
PubMed2001

Supranormal differential renal function is real but may be pathological: assessment by 99m technetium mercaptoacetyltriglycine renal scan of congenital unilateral hydronephrosis.

PURPOSE: It is unclear whether supranormal differential renal function of the hydronephrotic kidney is real or artifactual. We investigated the effect of clinical and renographic parameters on differential renal function. MATERIALS AND METHODS: The study included 34 males and 10 females from 1 to 9 months old (median age 2.6 months) with unilateral congenital hydronephrosis. A 99mtechnetium (Tc) mercaptoacetyltriglycine (MAG3) scan was performed, and regions of interest were drawn on the kidneys, and perirenal and lateral backgrounds. Differential renal function was calculated with and without background subtraction at 30-second intervals from 0.5 to 3 minutes after injection of 99mTc-MAG3. The effects of age, sex, obstruction, site and size of the hydronephrotic kidney were analyzed using the generalized estimating equations method. RESULTS: There were 11 right and 33 left hydronephrotic kidneys. An obstructive renographic pattern was present in 33 cases. The trends of differential renal function according to intervals were different between kidneys with and without background subtraction, and differential renal function increased significantly as size increased (p <0.05). Differential renal function of the hydronephrotic kidney with an obstructive renographic pattern increased with time when perirenal or no background subtraction was applied (p <0.05). The effects of age, sex or laterality on differential renal function were not significant. Supranormal function (differential renal function 55% or greater) was present regardless of background subtraction methods and measurement time. CONCLUSIONS: Differential renal function is higher in larger hydronephrotic kidney but function of the kidney with an obstructive pattern is overestimated on later phases of 99mTc-MAG3 renal scan. Supranormal differential renal function is real and may be pathologic since it is prone to occur in larger obstructive hydronephrotic kidneys.

Diuretics↗
PubMed2001

Effect of estrogen on endothelial dysfunction in postmenopausal women with diabetes.

BACKGROUND: Treatment with estrogen causes increased release of nitric oxide and this appears to be an important mechanism involved in the cardioprotective effect of estrogen. Previous studies have clearly shown that estrogen has an acute vasodilatory effect. Recently, abnormality of flow mediated endothelial dilation, which is defined as an endothelial dysfunction, has been proposed as an early manifestation of atherogenesis. However, its effect in type 2 diabetes is unknown. Stimulus-provoked endothelium dependent dilatation, using high-resolution external vascular ultrasound, is a useful method in the measurement of endothelial function. The main advantages of this method are that it is completely non-invasive, accurate and reproducible. This classical method for the measurement of endothelial dysfunction, utilizing non-invasive, high-resolution ultrasonography, has some limitations especially in terms of reproducibility. To improve the accuracy and reproducibility of this method, measurements made for this study involved the use of an additional attachment. This device was an ultrasound probe that was attached to the arm of patient. In addition, this study evaluated not only a change in diameter in terms of flow mediated vasodilation, but also initial and peak response times during this test. The aims of this study are: (1) to evaluate the flow mediated peak vasoreactivity (FMD), the lag time from base line to initiation of vasodilation (IRT) and the peak response of endothelial dependent vasodilation in a control group and in young diabetic patients; and (2) to evaluate the effect of estrogen treatment on flow mediated vasodilation in postmenopausal women with diabetes. METHOD: Measurements were taken for flow mediated vasodilation (endothelial dependent vasodilation: FMD), endothelial independent vasodilation (EID) and lag time from base line to initial reaction of FMD. The aforementioned non-invasive method and attachment were used. Subjects for the experiment were 12 young people with diabetes (six male and six female, mean age 26.3) and 12 age-matched healthy controls (six male and six female, mean age 25.6). In addition, measurements were taken for FMD, EID and lag time in the brachial artery before and after estrogen supplementation (Premarin 0.625 mg for 7 days). Subjects for the experiment were 16 normal postmenopausal women and 18 age-matched postmenopausal women with type 2 diabetes. RESULT: There is no significant difference in BMI (body mass index), mean age, or blood pressure between the control group and the young diabetic group. There were no differences in age, total and LDL cholesterol levels or body mass index between the groups of postmenopausal women (P<0.05). However, the HDL cholesterol level was found to be significantly lower in postmenopausal women with diabetes than in normal postmenopausal women (respectively, a mean+/-SD; 38.95+/-11.96 mg/dl vs. 52.20+/-9.55 mg/dl, P<0.05). The FMD of young diabetic patients is slightly lower than that of age-matched young healthy controls (healthy control: 8.9+/-2.7%, young diabetic patients: 6.3+/-2.1%, P<0.05). There was no difference in endothelial independent vasodilation between the control group and the young diabetic group. The IRT of FMD was significantly shorter in the healthy control group than in the young diabetic group (healthy control: 20.4+/-2.8 s, diabetic group: 29.5+/-5.4 s, P<0.0001). In contrast, the IRT of EID was no different between the two groups. The IRT of FMD showed a significant negative correlation with FMD (r=-0.61, P<0.01) and a significant negative correlation with high-density lipoprotein (HDL) cholesterol (r=-0.68, P<0.0001). The basal endothelium dependent vascular reactivity was significantly decreased in postmenopausal women with diabetes compared with normal postmenopausal women (8.0+/-3.9 vs. 13.7+/-6.2%, P<0.05). Estrogen supplementation increased endothelium dependent vasodilation not only in postmenopausal women with diabetes (from 8.0+/-3.9 to 15.1+/-4.0%, P<0.05) but also in normal postmenopausal women (from 13.7+/-6.2 to 20.1+/-4.7%, P<0.05). In contrast, the responses to sublingual nitroglycerin were comparable between postmenopausal women with diabetes (from 21.1+/-6.0 to 22.1+/-4.1%, P>0.05) and normal postmenopausal women (from 25.8+/-7.8 to 25.2+/-4.5%, P>0.05), both before and after estrogen supplementation. CONCLUSION: These findings indicate that in addition to the percentage change in FMD, lag time from base line to initial response time (IRT) of FMD is a good indicator for evaluation of endothelial dysfunction. Also, this new parameter may be a more sensitive parameter for differentiation between the diseased state and the normal state of the endothelium than percentage changes in FMD. In terms of postmenopausal women, endothelial dysfunction was prominent in women with diabetes and was significantly improved by estrogen but not reversed. These results suggest that other factors in addition to estrogen deficiency play a role in endothelial dysfunction in postmenopausal women with diabetes mellitus.

Adult↗
PubMed2001

Corneal opacity after repeated photorefractive keratectomy.

Corneal opacity developed in an eye that had photorefractive keratectomy (PRK) with a 193 nm excimer laser 5 times over 3 years. Six months after the last PRK, a partial penetrating keratoplasty was performed. The cornea was stained and immunohistochemically evaluated for collagen types. Light microscopy showed thickening of epithelial layers, proliferation of subepithelial fibroblasts, and the absence of Bowman's membrane. Transmission electron microscopy showed irregular collagen lamellae and electron-dense deposits adjacent to keratocytes. The staining was positive for Alcian blue, and immunohistochemistry was positive for type IV and VI collagen. This case suggests that corneal opacity after repeated PRK is the result of deposits of type IV and VI collagen and acidic mucoprotein in the extracellular matrix.

Collagen↗
PubMed2001

His-His-Leu, an angiotensin I converting enzyme inhibitory peptide derived from Korean soybean paste, exerts antihypertensive activity in vivo.

It has been reported that soybean peptide fractions isolated from Korean fermented soybean paste exert angiotensin I converting enzyme (ACE) inhibitory activity in vitro. In this study, further purification and identification of the most active fraction inhibiting ACE activity were performed, and its antihypertensive activity in vivo was confirmed. Subsequently, a novel ACE inhibitory peptide was isolated by preparative HPLC. The amino acid sequence of the isolated peptide was identified as His-His-Leu (HHL) by Edman degradation. The IC(50) value of the HHL for ACE activity was 2.2 microg/mL in vitro. Moreover, the synthetic tripeptide HHL (spHHL) resulted in a significant decrease of ACE activity in the aorta and led to lowered systolic blood pressure (SBP) in spontaneously hypertensive (SH) rats compared to control. Triple injections of spHHL, 5 mg/kg of body weight/injection resulted in a significant decrease of SBP by 61 mmHg (p < 0.01) after the third injection. These results demonstrated that the ACE inhibitory peptide HHL derived from Korean fermented soybean paste exerted antihypertensive activity in vivo.

Amino Acid Sequence↗
PubMed2001

Antimicrobial resistance of Shigella sonnei in Korea during the last two decades.

Eighty-eight strains of Shigella sonnei isolated in Korea during the period 1980 to 1999 were tested for susceptibility to 13 antimicrobial agents. S. sonnei isolates demonstrated high frequencies of resistance to sulfamethoxazole (97.7%), tetracycline (96.6%), and trimethoprim (95.5%). S. sonnei isolates from the 1990s were more resistant to nalidixic acid than isolates from the 1980s (100 vs 7.7%), while isolates from the 1990s were more susceptible to chloramphenicol than isolates from the 1980s (0 vs 100%). Ampicillin-resistant S. sonnei isolates produced the TEM-1 beta-lactamase with a pI of 5.4. The TEM-1 gene was located on conjugally transferable plasmids in the majority of isolates. S. sonnei isolates were all susceptible to cefotaxime, cefoxitin, ceftazidime, ciprofloxacin, and norfloxacin. These results indicate that cephalosporins and quinolones may be alternative antibiotics for the treatment of S. sonnei infections in Korea.

Anti-Bacterial Agents↗
PubMed2001

Apoptotic cell death induced by Acinetobacter baumannii in epithelial cells through caspase-3 activation.

Epithelial cell death induced by Acinetobacter baumannii infection was investigated using in vitro assays. Eight hours after live A. baumannii infection, HeLa cells exhibited detachment from the dish, rounding morphologies, high proportions of trypan blue-positive cells and extensive DNA breakdown with faint apoptotic banding, which is indicative of cells undergoing apoptosis. The enzymatic activity of caspase-3 was increased in cells as early as 2 h after infection. In addition, apoptosis of HeLa cells was induced by treatment with bacterial culture filtrates but not with formalin-killed bacteria. These results indicate that A. baumannii infection triggers apoptosis in HeLa cells through caspase-3 activation.

Acinetobacter↗
PubMed2001

Effect of head rotation on lateral cephalometric radiographs.

The purpose of this study was to identify the potential projection errors of lateral cephalometric radiographs due to head rotation in the vertical Z-axis. For this investigation, 17 human dry skull samples with permanent dentition were collected from the Department of Anatomy in the College of Medicine, Chosun University. They had no gross asymmetry and were well preserved. Each dry skull was rotated from 0 degrees to +/- 15 degrees at 1 degrees intervals. A vertical axis, the Z-axis, was used as a rotational axis to have 527 lateral cephalometric radiographs exposed. The findings were that: (1) angular measurements have fewer projection errors than linear measurements; (2) the greater the number of landmarks on the midsagittal plane that are included in angular measurements, the fewer the projection errors occurring; (3) horizontal linear measurements decrease gradually in length as the rotational angle toward the film increases, whereas a small increase and then decrease of the length occurs as the rotational angle toward the focal spot increases; (4) horizontal linear measurements have more projection errors than vertical linear measurements according to head rotation; and (5) projection errors of vertical linear measurements increase as the distance from the rotational axis increases. In summary, angular measurements of lateral cephalometric radiographs are more useful than linear measurements in minimizing the projection errors associated with head rotation on a vertical axis.

Cephalometry↗
PubMed2001

p21(WAF1) is associated with CDK2 and CDK4 protein during HL-60 cell differentiation by TPA treatment.

TPA-treated HL-60 cells are mainly arrested in G1 by p21(WAF1) accumulation. We investigate the downstream changes following such accumulation. Increased p21(WAF1) is associated with CDK2 and CDK4. pRb is dephosphorylated in the presence of p21-CDK2/4 complexes, and the Rb-E2F1 complex increases after TPA treatment, whereas the Rb-HDAC1 complex decreases slightly. Our results suggest that increased p21(WAF1) is associated with CDK2/4, and that these complexes induce pRb dephosphorylation. In turn, hypophosphorylated pRb are mainly complexed with E2F1, but HDAC1 appears not to be a key component in this process.

CDC2-CDC28 Kinases↗
PubMed2001

Heterogeneity of IgE epitopes of vinyl sulphone reactive dye: human serum albumin that react with IgE.

BACKGROUND: Vinyl sulphone reactive dye (vRD), which consists of vinyl sulphone reactive groups and a chromogen, can elicit IgE-mediated occupational asthma (OA) by haptenation. Human serum albumin (HSA) is known as the most reliable carrier protein for the vRD, the IgE epitopes of vRD-HSA are not well characterized. In this study we evaluated the epitope of vRD-HAS-specific IgE. METHODS: Two vRD (Remazole Black-GR and Remazole Orange-3R), Procion Red-MX-5B, which has a dichlorotriazine reactive group, and vinyl sulphone (VS), were haptenated to HSA, respectively. vRD-HSA was denatured by heat or mercaptoethanol treatment and the allergenicities of denatured and non-denatured vRD-HSA were compared by ELISA and IgE immunoblotting using the sera of six vRD-OA patients. vRD-HSA-specific, Procion Red-MX-5B (pRD)-HSA-specific and VS-HAS-specific IgE were also measured with ELISA and the cross-reactivity between them was evaluated with ELISA inhibition. RESULTS: Denaturation of vRD-HSA by heat affected its allergenicity markedly in five of six sera of RD-OA. When vRD was conjugated to the pre-heated HSA, its allergenicity also disappeared or was markedly attenuated compared with the vRD-HSA in five of six sera. Mercaptoethanol treatment markedly affected the allergenicity of the RD-HSA in all six RD-OA sera. Immunoblotting from non-denatured PAGE showed strong IgE affinity to vRD-HSA but immunoblotting from denatured SDS PAGE did not show IgE affinity. Among six RD-OA patients, five and four patients had pRD-HSA-specific and VS-HSA-specific IgE, respectively. However, the vRD-HSA-specific IgE was neither inhibited by pRD-HSA nor VS-HSA CONCLUSION: We considered that the conformational structure of HSA would be critical for the IgE epitopes during the haptenation process and both of the chromogen and reactive groups of the vRD would contribute to the formation of IgE epitope. Our results also confirmed the heterogeneity of IgE epitopes in the RD-HSA complex.

Adult↗
PubMed2001

An open pilot trial of olanzapine for delirium in the Korean population.

This study was performed to assess the efficacy and safety of olanzapine for the treatment of delirium in a Korean population. An open trial of olanzapine was conducted in Korean patients with delirium caused by multiple medicosurgical conditions. All subjects were evaluated by Delirium Rating Scale (DRS), which is known to be one of the most sensitive scales for delirium. In addition, other data for profiles of side-effects were collected and analyzed. Twenty patients were treated by olanzapine with doses of 5.9 +/- 1.5 mg/day. The initial dose was 4.6 +/- 0.9 mg/day and maximal dose of olanzapine was 8.8 +/- 2.2 mg/day. The average duration of treatment was 6.6 +/- 1.7 days and the day of maximal response was 3.8 +/- 1.7 treated days. The scores of DRS were significantly improved from 20.0 +/- 3.6 at the time of pretreatment to 9.3 +/- 4.6 at the post-treatment. All subjects showed no definite serious side-effects including anticholinergic and extrapyramidal symptoms. Olanzapine treatment for patients with delirium was effective and safe. This newer drug may be a useful alternative agent to classical antipsychotics in the treatment of delirium.

Adult↗
PubMed2001

Polymorphism of CTLA-4 gene for major depression in the Korean population.

This study was carried out to verify the relationship between major depression and cytotoxic T lymphocyte antigen-4 (CTLA-4), which is related to immunological function such as T-cell regulation. Among the Korean patients diagnosed with major depression according to DSM-IV, 77 patients without neurological illness, hormonal disorder, or comorbid mental illness were selected. The stored data on 149 normal Koreans from the Catholic Hemopoietic Stem Cell Bank of Korea, were used as a control group. The data of the Korean control group were compared with those of the studies of different ethnic groups. DNA was extracted from whole blood using proteinase K and the exon 1 region of CTLA-4 gene was amplified by polymerase chain reaction. Gene typing was performed using single strand conformation polymorphism. The results were assessed. There were significant differences in frequencies of CTLA-4 allele (chi2 = 56.472, d.f. = 1, P = 0.001) and genotype (chi2 = 46.132, d.f. = 2, P = 0.001) between the Korean population and the Caucasian population. However, we could not find any differences between the Korean and the Japanese population. There were no significant differences in genotype frequencies of CTLA-4*G/G, CTLA-4*G/A, and CTLA-4*A/A between the patients with major depression and the control group in the Korean population (48.1% vs. 46.3%, 41.6% vs 39.6%, 10.3% vs. 14.1%, respectively). There were no significant differences in allelic frequencies of CTLA-4*G and CTLA-4*A between the patients with major depression and the control group in the Korean population (68.8% vs. 66.1%, 31.2% vs. 33.9%, respectively). Although the present study produced negative results for the association of exon 1 polymorphism of CTLA-4 gene with major depression in the Korean population, further systematic research, including diverse clinical variables, would be necessary.

Abatacept↗
PubMed2001

Regulation of the tyrosine hydroxylase and dopamine beta-hydroxylase genes by the transcription factor AP-2.

The retinoic acid-inducible and developmentally regulated transcription factor AP-2 plays an important role during development. In adult mammals, AP-2 is expressed in both neural and non-neural tissues. However, the function of AP-2 in different neuronal phenotypes is poorly understood. In this study, transcriptional regulation of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) genes by AP-2 was investigated. AP-2 binding sites were identified in the upstream regions of both genes. Electrophoretic mobility shift assays (EMSA) and DNase I footprinting analyses indicate that the AP-2 interaction with these motifs is more prominent in catecholaminergic SK-N-BE(2)C and CATH.a than in non-catecholaminergic HeLa and HepG2 cell lines. Exogenous expression of AP-2 robustly transactivated TH and DBH promoter activities in non-catecholaminergic cell lines. While AP-2 regulates the DBH promoter activity via a single site, transactivation of the TH promoter by AP-2 appears to require multiple sites. In support of this, mutation of multiple AP-2 binding sites but not that of single site diminished the basal promoter activity of the TH gene in cell lines that express TH and abolished transactivation by exogenous AP-2 expression in cell lines that do not express TH. In contrast, mutation of a single AP-2 binding site of the DBH gene completely abolished transactivation by AP-2. Double-label immunohistochemistry showed that AP-2 is coexpressed with TH in noradrenergic and adrenergic neurons in both the central and peripheral nervous systems of adult rodents. Numerous non-catecholaminergic cell groups within the spinal cord, medulla, cerebellum, and pons also express AP-2. The concentration of AP-2 in dorsomedial locations along the neuraxis suggests a regionally specific role for this transcription factor in the regulation of neuronal function. Based on these findings we propose that AP-2 may coregulate TH and DBH gene expression and thus participate in expression/maintenance of neurotransmitter phenotypes in (nor)adrenergic neurons and neuroendocrine cells.

Animals↗
PubMed2001

Structural and functional characterization of the 5' upstream promoter of the human Phox2a gene: possible direct transactivation by transcription factor Phox2b.

The specification of neurotransmitter identity is a critical step in neural development. Recent progresses have indicated that the closely related homeodomain factors Phox2a and 2b are essential for development of noradrenergic (NA) neuron differentiation, and may directly determine the neurotransmitter identity. With a long-term goal of understanding the regulatory cascade of NA phenotype determination, we isolated and characterized a hPhox2a genomic clone encompassing approximately 7.5 kb of the 5' upstream promoter region, the entire exon-intron structure, and approximately 4 kb of the 3' flanking region. Using mRNAs isolated from the Phox2a-expressing human cell line, both primer extension and 5'-rapid amplification of cDNA ends analyses identified a single transcription start site that resides 172 nucleotides upstream of the start codon. The transcription start site was preceded by a TATA-like sequence motif and transcripts from this site contained an additional G residue at the 5' position, supporting the authenticity of this site as the transcriptional start site of hPhox2a. We assembled hPhox2a-luciferase reporter constructs containing different lengths of the 5' upstream sequences. Transient transfection assays of these reporter constructs in both hPhox2a-positive and -negative cell lines show that 1.3-kb or longer upstream sequences of the hPhox2a gene may confer NA cell-specific reporter gene expression. Furthermore, cotransfection assays in the Phox2a-negative HeLa cell line show that forced expression of Phox2b, but not that of Phox2a or MASH1, significantly transactivates the transcriptional activity of hPhox2a. This study will provide a frame to further delineate the regulatory cascade of NA neuron differentiation.

Amino Acid Sequence↗
PubMed2001

Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes.

The inhibition of aflatoxin B1 (AFB1) metabolism by a water extract of the root of Scutellaria baicalensis and its flavonoids was examined in liver microsomes. AFB1 is known to be metabolized to aflatoxin M1 (AFM1), aflatoxin Q1 (AFQ1), and AFB1-8,9-epoxide (AFBO). The water extract potently inhibited the production of AFM1 by cytochrome P450 (CYP)1A1/2 and slightly reduced AFBO formation by CYP1A1/2, CYP2B1, CYP2C11 and CYP3A1/2 in TCDD-treated rat liver microsomes. IC50 values for AFM1 and AFBO formation were 6.8 and 122.4 microg/ml, respectively. Wogonin showed the highest inhibitory activity towards AFM1 formation among the flavonoids isolated from the extract. On the other hand, the extract had no effects on the formation of AFBO and AFQ1 in human liver microsomes, and on the activities of CYP2B1, CYP2C11 and CYP3A1/2 which were detected by hydroxylation patterns of testosterone. These results demonstrated that the extract of the root of Scutellaria baicalensis has a specific inhibitory effect on CYP1A1/2 among CYP enzymes involved in AFB1 metabolism by rat and human microsomes.

Aflatoxin B1↗
PubMed2001

Potential role of human brain microvascular endothelial cells in the pathogenesis of brain abscess: inhibition of Staphylococcus aureus by activation of indoleamine 2,3-dioxygenase.

Cerebral abscess is a rare complication of staphylococcal septicemia in infants associated with high mortality and morbidity. In the pathogenesis of abscess formation, S. aureus, one major causative agent, interacts with endothelial cells of the brain vessels before reaching the central nervous system. This study examined the growth of S. aureus in human brain microvascular endothelial cells (HBMEC) cultures stimulated with cytokines. IFN-gamma inhibited S. aureus replication by the induction of indoleamine 2,3-dioxygenase (IDO) in HBMEC. This activation of IDO in HBMEC could be shown by RT-PCR and by detection of kynurenine in culture supernatants of activated cells. Resupplementation of L-tryptophan abrogated the inhibitory effect of IFN-gamma on the growth of staphylococci, hence confirming the activation of indoleamine 2,3-dioxygenase as being responsible for the induced bacteriostasis. Addition of TNF-alpha enhanced the IFN-gamma mediated antibacterial effects, whereas TNF-alpha alone had no influence on staphylococcal growth. Stimulation of HBMEC with IFN-gamma failed to activate inducible nitric oxide synthase (iNOS) and subsequent production of nitric oxide (NO). Thus, intra- and extracellular depletion of L-tryptophan seems to be an important process in the defense against staphylococcal brain abscesses by means of creating an unfavorable microenvironment.

Brain Abscess↗