Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 379 records · Page 21Linked to original sources

PubMed1996

Species difference in the disposition of liposomes among mice, rats, and rabbits: allometric relationship and species dependent hepatic uptake mechanism.

PURPOSE: The species difference in the pharmacokinetics of liposomes was investigated in mice, rats and rabbits. METHODS: Liposomes were intravenously injected at doses of 1, 10 and 100 (nmol/g body weight), and the time courses of liposomes in blood, liver and spleen were measured. Pharmacokinetic parameters were regressed as a function of body weight (BW) and dose of liposomes (D). The uptake mechanism of liposomes was also examined with the isolated perfused liver between rats and mice. RESULTS: Mean residence time increased with the increase of BW and D of liposomes. This increase of mean residence time resulted from the decreased total body clearance, which was principally explained by the species difference in the hepatic uptake clearance (CLh) of liposomes. The parameter CLh was regressed well by a multiple regression as a function of BW and D. In this analysis, an exponent for BW was around 0.5, which clearly indicates that smaller animals have higher uptake clearance per unit BW. Immunohistochemical analysis revealed that there was no significant difference in the density of Kupffer cells among these species. This suggest that the species difference in CLh resulted not from the density of Kupffer cells but from the uptake ability of Kupffer cells among species. In the isolated perfused liver, the hepatic uptake of liposomes was mainly explained by opsonin dependent uptake in rats, while opsonin independent uptake in mice. CONCLUSIONS: These quantitative and qualitative information on the species difference of liposome disposition will provide an useful information for constructing a drug delivery system using liposomes.

Animals↗

PubMed1996

Determination of molecular mobility of lyophilized bovine serum albumin and gamma-globulin by solid-state 1H NMR and relation to aggregation-susceptibility.

PURPOSE: Feasibility of solid-state 1H NMR for determining the mobility of protein molecules in lyophilized cakes was considered. The mobility in cakes with various levels of water content was studied in relation to aggregation-susceptibility. METHODS: Spin-spin relaxation time T2) of protons in lyophilized bovine serum albumin (BSA) and gamma-globulin (BGG) was measured as a function of hydration level by solid state 1H NMR using a 'solidecho' pulse sequence. Moisture-induced aggregation of the lyophilized proteins was also determined by high performance size exclusion chromatography. RESULTS: Lyophilized BSA and BGG became susceptive to aggregation when water content exceeded about 0.2 g/g of protein. T2 of protein protons in the lyophilized cakes started to increase at lower water contents. The increase in aggregation susceptibility observed with increasing water content appears to follow the increase in T2 of protein protons. For lyophilized BGG, both aggregation and T2 of protein protons decreased at water contents above 0.5 g/g protein. CONCLUSIONS: Mobility of protein molecules in lyophilized cakes was successfully determined by solid-state 1H NMR. The aggregation susceptibility of proteins was strongly related to their molecular mobility as indicated by T2.

Chemistry, Pharmaceutical↗

PubMed1996

Effects of sugars and polymers on crystallization of poly(ethylene glycol) in frozen solutions: phase separation between incompatible polymers.

PURPOSE: This study examined the effect of third components (low-molecular-weight saccharides and polymers) on the crystallization of poly(ethylene) glycol (PEG) in frozen solutions, focusing on the relationship between their crystallization-inhibiting ability and molecular compatibility. METHODS: Effects of sugars and polymers on the crystallization of PEG 3000 in frozen solution were monitored by differential scanning calorimetry (DSC). Pulsed-NMR was employed to monitor the molecular mobility of water and solutes in the frozen solutions. Miscibility between PEG and third components in aqueous solution was estimated from the lowering of cloud point of PEG 20,000. Thermal analysis of frozen solutions containing some non-crystallizing solutes was used to examine the possibility of phase separation in frozen solutions. RESULTS: Some sugars and polymers inhibited the crystallization of PEG and formed practically stable amorphous phases among ice crystals. The mobility of solute molecules in the amorphous phase increased above the softening temperature of maximally concentrated solutions (Ts), whereas that of water molecules appeared at a lower temperature. Mono- and disaccharides that are relatively less miscible with PEG in solution inhibit PEG crystallization to a lesser degree. Two Ts regions were observed in frozen solutions containing both polyvinylpyrrolidone (PVP) and dextran, at much lower concentrations than those causing aqueous two-phase separation at ambient temperatures. CONCLUSIONS: Ice crystallization raises the concentration of solutes in the remaining solution, which can lead to phase separation in the amorphous phase. Molecular compatibility between components is an important factor determining their propensity to phase separate and crystallize.

Calorimetry, Differential Scanning↗

PubMed1996

Effect of destruction force on drug release from multiple unit controlled release dosage forms in humans.

PURPOSE: This study examined the effects of mechanical destructive forces on drug release from controlled release (CR) multiple unit dosage forms in vitro and in vivo and their colonic release, using two CR granules of acetaminophen, AG and BG, which differed in hardness (AG was hard and BG was soft), but which did not depend on agitation speed or pH for their release. METHODS: In vitro release rates were determined using several official methods and the rotating dialysis cell method. Granules were administered to healthy volunteers under fasting and fed conditions. RESULTS: Both granules showed similar release rates under mild destructive conditions in official dissolution tests, but BG showed a faster release rate in the rotating dialysis cell method. In the fasting state, the drug absorption-time profiles of AG and BG were almost equal. In the fed state, the drug release rate of BG increases whereas that of AG is almost equal to the fasted state. The food effect on BG could be caused by an increase in the mechanical stress of the GI tract due to food intake judging from the findings in vitro and in dogs. The colonic release from multiple unit CR products was larger than that from single unit ones. CONCLUSIONS: In vivo release of drug from a multiple unit CR product that is structurally weak is affected by mechanical stresses, which differ among human subjects but are increased by food ingestion. Colonic release from multiple unit CR products is larger than that from single unit products.

Acetaminophen↗

PubMed1996

A single Drosophila melanogaster myosin light chain kinase gene produces multiple isoforms whose activities are differently regulated.

BACKGROUND: Myosin light chain kinase (MLCK) specifically phosphorylates the myosin regulatory light chain in a calcium/calmodulin (Ca2+/CaM)-dependent manner in animal cells. The roles of MLCK are not fully understood, particularly in nonmuscle cells. Therefore, we cloned and characterized a Drosophila MLCK gene as the first step in a genetic analysis of this process. RESULTS: Four transcripts are produced from this gene. These transcripts encode at least three isoforms (isoform-I, -II and -III), which share a kinase domain, a fibronectin type III motif and an immunoglobulin C2 motif. However, regulatory regions differ between isoform-I/II and -III due to the alternative splicing of the exon encoding a CaM-binding domain. As a result, isoform-I and -II are Ca2+/CaM-dependent forms, whereas isoform-III is a Ca2+/CaM-independent form. Northern blotting and in situ hybridization showed that the expressions of these isoforms are distinctly regulated in stage- and tissue-dependent manners. Isoform-I seems to be expressed ubiquitously, while isoform-III is expressed predominantly in muscle tissues. In contrast to these isoforms, isoform-II is specific to late pupa and adult. CONCLUSION: In Drosophila, a single MLCK gene produces multiple isoforms whose regulatory regions and expression patterns are different. These differences suggest various cellular functions of MLCK in Drosophila.

Amino Acid Sequence↗

PubMed1996

Pulmonary toxicity of systemic terbium chloride in mice.

Terbium (Tb) is a rare earth metal that finds use in several emerging technologies. However, little is known about the biological effects of Tb. Thus, in this study the pulmonary toxicity of systemic Tb in mice was investigated. Mice were treated intravenously with a single dose of 20 or 200 mumol Tb/kg, as TbCly and killed at 3, 6, 12, 24, 48, or 72 h later. Administration of Tb at a dose of 200 mumol/kg increased pulmonary weight, lipid peroxidation, and protein content but decreased pulmonary glutathione content. Pulmonary gamma-glutamyl transpeptidase (gamma-GTP) activity was increased after Tb administration at a dose of 200 mumol/kg. Pulmonary alkaline phosphatase (ALP) activity was also increased after Tb administration at a dose of 200 mumol/kg. Investigation of the defense system against oxidative damage in the lung showed that superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all decreased after Tb administration at the higher dose. The concentrations of Tb, Ca, and P in lung was increased by the dose of 200 mumol/kg. These results suggest that pulmonary lipid peroxidation may be an early and sensitive consequence of Tb exposure and that SOD, CAT, and GSH-Px might be considered as potential modulators of Tb-induced lipid peroxidation. The mechanisms involved in Tb-induced pulmonary lipid peroxidation deserve further study.

Alkaline Phosphatase↗

PubMed1996

Suppression of mouse skin papilloma by canthaxanthin and beta-carotene in vivo: possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid.

Using mouse skin papilloma as a model system, we examined whether the antitumorigenic activity of carotenoids was related to their provitamin A activity. Oral administration of canthaxanthin (CX) or beta-carotene at 200 mg/kg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10-dimethyl-1,2-benzanthracene (p < 0.05), after the accumulation of these carotenoids in the tumors. The levels of a protooncogene, c-myc, were simultaneously suppressed in papillomas in carotenoid-treated mice. Because CX cannot be converted metabolically to retinoids, these results suggested that CX directly inhibited the growth of papillomas. Neither the accumulation of retinoids nor the expression of a retinoic acid-inducible gene, retinoic acid receptor-beta, was found in papillomas of CX- and beta-carotene-treated mice, suggesting that, like CX, beta-carotene might exert the tumor-suppressing effect without being converted to retinoids. Thus a certain antitumorigenic activity of carotenoids appears not necessarily to require their provitamin A activity.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1996

Characterization of monoclonal antibodies reactive with Schistosoma haematobium-soluble egg and infected human urinary antigens.

Six murine monoclonal antibodies (MAbs) [Sh1/71.7 (IgM), Sh2/15.F (IgG1), Sh3/15.28 (IgG1), Sh3/38.2 (IgM), Sh4/14.3 (IgG1), and Sh5/32.30 (IgM)] produced against S. haematobium were extensively characterized. All the MAbs stained the surface membranes of miracidia as determined by the indirect fluorescent antibody test, yet three of them (Sh1/71.7, Sh3/15.28, and Sh3/38.2) also stained internal cytoplasmic antigens. Proteinase-K digestion and periodate oxidation studies showed that these three MAbs bound glycoprotein antigenic determinants, while the rest detected protein epitopes. Only Sh2/15.F, Sh3/15.28, and Sh4/14.3 could bind antigens with the western immunoblot assay. Sh2/15.F bound a 29-kDa antigen and Sh3/15.28 bound three antigen bands (53, 57, and 66 kDa) all in the soluble egg extract of an Egyptian strain of S. haematobium (SEAEgy), while Sh4/14.3 reacted with a 29-kDa antigen present in SEAEgy, as well as in the adult worm antigen extracts of Ghanaian strain(s) of S. haematobium and S. japonicum. Sh4/14.3 also bound a 78-kDa antigen in the S. japonicum worm. Cross-reactivity studies with S. haematobium, S. mansoni, S. japonicum, and Necator americanus revealed that Sh2/15.F and Sh3/15.28 were S. haematobium species-specific. Each of the remaining MAbs detected the three major human schistosomes without cross-reacting with N. americanus egg antigens. Three MAbs, Sh2/15.F, Sh4/14.3 and Sh5/32.30, could detect S. haematobium antigens in infected human urine.

Adult↗

PubMed1996

Limited field evaluation of a rapid monoclonal antibody-based dipstick assay for urinary schistosomiasis.

A rapid, visually read monoclonal antibody (MoAb)-based dipstick assay for specific diagnosis of urinary schistosomiasis was field tested with microscopy and the use of hematuria and proteinuria in a schistosomiasis hematobia endemic area in Southern Ghana. The study group consisted of 229 individuals (114 males and 115 females) aged 1 to 86 years; 145/229 (63.3%) of the subjects submitted stool samples from which no S. mansoni eggs were detected. However, infections with Necator americanus (hookworms) 33.1%, Ascaris lumbricoides 2.8%, Trichuris trichiura (whipworm) 2.8%, and Strongyloides stercoralis 0.7% were detected but did not appear to influence the results of the MoAb-dipstick assay. Urinary schistosomiasis prevalence was estimated as 47.6% by microscopy, 48% by MoAb-dipstick, 39.7% by microhematuria, and 23.6% by proteinuria. The MoAb-dipstick correctly identified 108/109 (99.1%) of microscopically confirmed cases and 118/120 (98.3%) of egg-negative individuals, thereby giving a sensitivity of 99.1% and a specificity of 98.3%. On the other hand, microhematuria and proteinuria were, respectively, 76.1% and 40.4% sensitive, and 94.2% and 92.5% specific when compared to microscopy. Microhematuria and proteinuria had significantly lower sensitivity (P < 0.001) than either microscopy or dipstick.

Adolescent↗

PubMed1996

Late-onset hereditary ataxia with global thermoanalgesia and absence of fungiform papillae on the tongue in a Japanese family.

Two Japanese male siblings, aged 68 and 59 years, affected by late-onset progressive ataxia distinguished by extensive sensory and mild autonomic disturbances are described. They had global thermoanalgesia, positive Romberg signs, sensorineural deafness, canal paresis and ageusia. Their autonomic disturbances consisted of absence of overflow tears with usual stimuli, dysphagia, blood pressure and vasomotor instability, diarrhoea/constipation, and urinary frequency. Sensory nerve action potentials were completely absent, whereas motor conduction velocity was slightly reduced only in the lower extremities. Sural nerve biopsy on the younger brother demonstrated a marked loss of myelinated fibres and a reduction in the number of unmyelinated axons. Tongue histology revealed absence of fungiform papillae and taste buds. Autonomic function tests showed widespread but mild sympathetic and parasympathetic failures. Neuro-imaging studies revealed atrophy of the spinal cord, cerebellum, brainstem and corpus callosum, and enlargement of the lateral, third and fourth ventricles. These siblings represent a previously unrecognized variant of late-onset hereditary spinocerebellar degeneration with global thermoanalgesia and absence of fungiform papillae on the tongue.

Biopsy↗

PubMed1996

Synthesis of a squash-type protease inhibitor by gene engineering and effects of replacements of conserved hydrophobic amino acid residues on its inhibitory activity.

Cucurbita maxima trypsin inhibitor I (CMTI-I), a member of the squash-type protease inhibitor family, is composed of 29 amino acids and shows strong inhibition of trypsin by its compact structure. To study the structure-function relationship of this inhibitor using protein engineering methods, we constructed an expression system for CMTI-I as a fused protein with porcine adenylate kinase (ADK). A Met residue was introduced into the junction of ADK and CMTI-I to cleave the fusion protein with CNBr, whereas a Met at position 8 of authentic CMTI-I was replaced by Leu. Escherichia coli JM109 transformed with the constructed plasmid expressed the fused protein as an inclusion body. After cleavage of the expressed protein with CNBr, fully reduced species of CMTI-I were purified by reversed-phase HPLC and then oxidized with air by shaking. For efficient refolding of CMTI-I, we used 50 mM NH4HCO3 (pH 7.8) containing 0.1% PEG 6000 at higher protein concentration. Strong inhibitory activity toward trypsin was detected only in the first of three HPLC peaks. The inhibitor constant of CMTI-I thus obtained, in which Met8 was replaced by Leu, was 1.4 x 10(-10) M. The effect of replacement of Met with Leu at position 8 was shown to be small by comparison of the inhibitor constant of authentic CMTI-III bearing Lys at position 9 (8.9 x 10(-11) M) with that of its mutant bearing Leu at position 8 and Lys at position 9 (1.8 x 10(-10) M). To investigate the role of the well conserved hydrophobic residues of CMTI-I in its interaction with trypsin, CMTI-I mutants in which one or all of the four hydrophobic residues were replaced by Ala were prepared. The inhibitor constants of these mutants indicated that those with single replacements were 5-40 times less effective as trypsin inhibitors and that the quadruple mutant was approximately 450 times less effective, suggesting that the hydrophobic residues in CMTI-I contribute to its tight binding with trypsin. However, each mutant was not converted to a temporary inhibitor.

Chromatography, High Pressure Liquid↗

PubMed1996

Chemotactic responses to an attractant and a repellent by the polar and lateral flagellar systems of Vibrio alginolyticus.

Chemotactic responses in Vibrio alginolyticus, which has lateral and polar flagellar systems in one cell, were investigated. A lateral-flagella-defective (Pof+ Laf-) mutant, which has only a polar flagellum, usually swam forward by the pushing action of its flagellum and occasionally changed direction by backward swimming. When the repellent phenol was added, Pof+ Laf- cells moved frequently forward and backward (tumbling state). The tumbling was derived from the frequent changing between counter-clockwise and clockwise (CW) rotation of the flagellar motor, as was confirmed by the tethered-cell method. Furthermore, we found that the tumbling cells did not adapt to the phenol stimulus. When the attractant serine was added, the phenol-treated cells ceased tumbling and swam smoothly, adapting to the attractant stimulus after several minutes. We isolated chemotaxis-defective (Che-) mutants from the Pof+ Laf- mutant; the tumbling mutants were not isolated. One interesting mutant swam backwards continuously, with its flagellum leading the cell and its flagellar motor rotating CW continuously. A polar-flagella-defective mutant (Pof- Laf+) stopped swimming after phenol addition and then recovered swimming ability within 10 min, indicating that lateral flagella can adapt to the repellent stimulus. This may represent a functional difference between the two flagellar systems in Vibrio cells, and between the chemotaxis systems affecting the two types of flagella.

Adaptation, Physiological↗

PubMed1996

Age-related changes in the olfactory system of dogs.

Age-related changes in the olfactory system were examined in 22 dogs ranging in age from 10 to 19 years old. Atrophic changes with degeneration were observed in the olfactory epithelium of dogs older than 14 years; the changes were prominent in the dogs over the age of 17 years. Immunohistochemistry using an anti-carnosine antibody, which is a marker for the olfactory cells, demonstrated a decrease in the number of olfactory cells. Electron microscopy also showed a decrease in the number of cilia of olfactory cells and microvilli of supporting cells. Atrophic changes with the features of regeneration were rarely observed in the aged animals. Lipofuscin-like granules in the olfactory epithelium became prominent with age. These age-related changes were similar to those reported in the olfactory epithelium of man and rats. Dystrophic neurites were not detected by a modified Bielschowsky stain or by neurofilament, synaptophysin and tau immunohistochemistry in the olfactory mucosa. There was no beta-amyloid- and ubiquitin-immunostaining in the olfactory mucosa. Senile brain changes, including cerebrovascular amyloidosis, age-related astrocytic gliosis and ubiquitin deposits were found in the olfactory bulb, although neurofibrillary tangles and senile plaques were not detected either by a modified Bielschowsky stain or by beta-amyloid immunohistochemistry. These results indicate that dog may be a useful animal model to study the age-related changes in the olfactory system in man.

Age Factors↗

PubMed1996

Molecular analysis of HLA-B in the Malaysian aborigines.

We have examined 56 unrelated individuals from Malaysian aborigines for their DNA polymorphism of the HLA-B gene by sequence specific oligonucleotide probe (SSO) method. Using the SSO hybridization, we found that one specific DNA allele with a B*1513 like pattern of epitope combination (ECB1513) was dominant among the Melayu Asli (Af = 41.9%) and the Senoi (Af = 24%). To determine the nucleotide sequences of ECB1513, a DNA fragment spanning from the beginning of exon 1 to the middle of exon 4 of the HLA-B gene was amplified by polymerase chain reaction (PCR) from two ECB1513 positive individuals, and the PCR products were cloned and sequenced. This sequencing analysis confirmed that ECB1513 was identical to HLA-B*1513 in exon 1, 2, 3, and 4. Amino acid sequence of this major allele, HLA-B*1513, in the aborigines especially around the peptide binding groove (B and F pockets), was compared with that of African B*5301 that had been suggested to confer resistance to malaria infection in Africa. The amino acid residues composing of the F pocket were completely identical in B*1513 and B*5301. These observations suggest that a common environmental factor, the malaria infection, might have independently enhanced the selection of functional change in the polymorphic portion of HLA-B gene in Africa and in South-East Asia.

Adolescent↗

PubMed1996

Treatment of aplastic anemia with antithymocyte globulin, cyclosporin A, methylprednisolone, danazol and recombinant human granulocyte-colony stimulating factor.

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 x 10(9)/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17-53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.

Adolescent↗

PubMed1996

Intravesical ureterocele presenting bladder outlet obstruction in an adult male.

Large ureteroceles in adult males causing bladder outlet obstruction are rare. We report a case of a large intravesical orthotopic ureterocele in an adult male presenting as acute urinary retention. Incisional transurethral endoscopy was successful with decompression of ureteral end obstruction, enabling smooth urination immediately and no occurrence of vesicoureteral reflux.

Adult↗

PubMed1996

Investigation into the 5-hydroxytryptamine-induced atropine-resistant neurogenic contraction of guinea-pig proximal colon.

1. The aim of this study was to characterize the receptors mediating the atropine-resistant neurogenic contraction to 5-hydroxytryptamine (5-HT) in the longitudinal muscle of the guinea-pig proximal colon and to determine the type of tachykinin receptors involved in the contractile response to 5-HT by the use of selective antagonists. 2. In the presence of atropine (0.3 microM), guanethidine (5 microM), hexamethonium (100 microM), ketanserin (0.1 microM) and indomethacin (3 microM), 5-HT (0.01-3 microM) produced concentration-dependent neurogenic contractions of colonic strips and at 0.3 microM produced a maximal effect (pEC50 = 7.39 +/- 0.09, n = 18). The 5-HT4 receptor stimulant, 5-methoxytryptamine (5-MeOT, 0.03-10 microM) also produced neurogenic contractions with similar maximum effect to those of 5-HT (pEC50 = 6.89 +/- 0.16). 3. The 5-HT4 receptor antagonist, DAU 6285 (3 microM) shifted the concentration-response curves to both 5-HT and 5-MeOT to the right without significant depression of the maximum, but the 5-HT1/5-HT2 receptor antagonist, metitepine (0.1 microM) and the 5-HT3 receptor antagonist, ondansetron (0.3 microM) had no effect on the control curves to 5-HT and 5-MeOT. 4. The selective NK1 receptor antagonist, FK 888 (1 microM) markedly attenuated the contractions to 5-HT and 5-MeOT. In contrast, the selective NK2 receptor antagonist, SR 48968 (10 nM) and the selective NK3 receptor antagonist, SR 142801 (10 nM) had no effect on the contractions to 5-HT and 5-MeOT. 5. These results indicate that the 5-HT-induced atropine-resistant neurogenic contraction of guinea-pig proximal colon is due to activation of 5-HT4 receptors, presumably located on excitatory motor neurones, innervating the longitudinal muscle. The contraction evoked by activation of the 5-HT4 receptors is mediated primarily via NK1 receptors but not NK2 or NK3, suggesting that the 5-HT4 receptor-mediated contraction is evoked indirectly via tachykinin release from tachykinin-releasing excitatory neurones.

5-Methoxytryptamine↗

PubMed1996

Preservation of endothelium-dependent relaxation in cholesterol-fed and streptozotocin-induced diabetic mice by the chronic administration of cholestyramine.

1. Experiments were designed to investigate the effects of the low density lipoprotein (LDL)-lowering drugs cholestyramine on serum LDL levels and endothelium-dependent relaxation to acetylcholine (ACh) in cholesterol-fed or streptozotocin (STZ)-induced diabetic mice. 2. In aortic rings from control mice, ACh or A23187 caused concentration-dependent relaxation. The relaxations caused by ACh or A23187 were significantly attenuated in aortic rings from cholesterol-fed and STZ-diabetic mice. The attenuated vasodilatation in both cholesterol-fed and diabetic mice was returned to normal by chronic administration of cholestyramine. The endothelium-independent relaxations of aortic rings induced by sodium nitroprusside (SNP) were not significantly different between control, cholesterol-fed and STZ-induced diabetic mice. 3. The increased LDL levels in cholesterol-fed and diabetic mice were returned to normal by the chronic administration of cholestyramine. Chronic administration of cholestyramine had no effects on serum glucose levels. 4. These results suggest that attenuated endothelium-dependent vasodilatations in both cholesterol-fed and STZ-diabetic mice are improved by the chronic administration of cholestyramine, and these effects are, at least in part, due to lowering serum LDL levels.

Acetylcholine↗