Tuning surface grafting density of CeO2 nanocrystals with near- and supercritical solvent characteristics.

In this work, the solvent effect on the synthesis of CeO2 nanocrystals synthesized in near- and supercritical alcohols is discussed. The materials prepared displayed a unique morphology of small nanocrystals (<10 nm) aggregated into larger nanospheres (∼100-200 nm). In such syntheses, alcohol molecules directly interact with the nanocrystal surface through alkoxide and carboxylate bondings. The grafting density was quantified from the weight loss measured using thermogravimetric analysis. A direct correlation between the grafting density and the alcohol chain length can be established. It was demonstrated that the shorter the alcohol chain length (i.e. methanol), the higher the surface coverage is. This trend is independent of the synthesis mode (batch or continuous). Additionally, an influence of the grafting density on the resulting nanocrystal size was established. It is suggested that the surface coverage has a high influence on the early stages of the nucleation and growth. Indeed, when high surface coverages are reached, all surface active sites are blocked, limiting the growth step and therefore leading to smaller particles. This effect was noticed with the materials prepared in the continuous mode where shorter reaction time was performed.

Evaluation of out-in skin transparency using a colorimeter and food dye in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a disease of skin barrier dysfunction and outside stimuli can cross the skin barrier. OBJECTIVES: To examine a new method for evaluating the outside to inside skin transparency with a colorimeter and yellow dyes. METHODS: In study 1, a total of 28 volunteer subjects (24 normal and four with atopic dermatitis) participated. After provocation with yellow dye, the skin colour of all the subjects was measured using a colorimeter. The skin transparency index was calculated by the changes of the skin colour to yellow. Other variables of skin function, including transepidermal water loss (TEWL) and stratum corneum hydration, were also measured. In study 2, the skin transparency index was evaluated for a cohort of 38 patients with atopic dermatitis, 27 subjects with dry skin and 29 healthy controls. RESULTS: In study 1, the measurement of skin colour (b*) using tartrazine showed good results. There was a significant relationship between the skin transparency index with tartrazine and the atopic dermatitis score (P = 0.014). No other measurements of skin function, including the TEWL, were correlated. In study 2, the skin transparency index score obtained with tartrazine in the patients with atopic dermatitis was significantly higher than that of the controls and those with dry skin (P < 0.001 and P = 0.022, respectively). However, the TEWL in patients with atopic dermatitis was not significantly higher than that of patients with dry skin and the TEWL in subjects with dry skin was not higher than that of the controls. CONCLUSIONS: This method, which used a colorimeter and food dye, is noninvasive, safe and reliable for the evaluation of out-in skin transparency and can demonstrate the characteristic dysfunction in the skin barrier in patients with atopic dermatitis.

Evaluation of toxicity of green tea catechins with 90-day dietary administration to F344 rats.

Green tea catechins (GTC), polyphenols extracted from the stalks and leaves of Camellia sinensis, are found in the different types of tea beverages and as antioxidant additives to many foods, snacks, fats and fatty oils. As a part of their safety assessment, subchronic toxicity was investigated in male and female F344 rats with dietary administration at concentrations of 0 (control), 0.3%, 1.25% and 5.0% for 90 days. The average daily intakes of GTC in each group were 180, 764 and 3525mg/kg body weight/day, respectively for males, and 189, 820 and 3542mg/kg body weight/day, respectively for females. No mortality or obvious clinical signs were observed throughout the experimental period but body weights were reduced from week 1 to the end of the experiment in 5.0% males. In serum biochemistry, alanine transaminase and alkaline phosphatase in 5.0% males and females and aspartate transaminase in 5.0% females were increased, together with the relative liver weights in both sexes receiving 5.0%. Although decreases were evident for total cholesterol in 0.3-5.0% males and triglycerides in 1.25% and 5.0% males and 5.0% females, these changes were not considered to be adverse. Hematology and histopathological observation revealed no GTC-related toxicological changes. Based on above findings, the no observed adverse effect level (NOAEL) of GTC was estimated to be 1.25% (764mg/kg body weight/day for males and 820mg/kg body weight/day for females).

Ebselen reduces cytochrome c release from mitochondria and subsequent DNA fragmentation after transient focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: The seleno-organic compound ebselen has both antioxidant and anti-inflammatory properties. Although ebselen has been shown to protect the brain against stroke, it is unclear how ebselen provides neuroprotection. In the present study the authors examined whether ebselen inhibits neuronal apoptosis resulting from transient focal cerebral ischemia in mice. The cytochrome c release and DNA fragmentation, both of which are biochemical markers of apoptosis, were compared between vehicle- and ebselen-treated mice. METHODS: Cerebral ischemia was induced by transient middle cerebral artery occlusion for 30 minutes in ICR mice under halothane anesthesia. Ebselen (10 mg/kg) was given orally twice, 30 minutes before ischemia and 12 hours after reperfusion. By Western blot analysis, we examined release of mitochondrial cytochrome c. To evaluate brain damage, the brain sections were treated for terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) and Nissl staining. Prolonged neuroprotective efficacy of ebselen was determined by counting neuronal nuclei (NeuN) immunopositive cells at 21 days after ischemia. RESULTS: - Cytochrome c release was detected in the ischemic hemisphere at 3 to 24 hours after ischemia. Ebselen treatment diminished the cytochrome c release at 12 and 24 hours. In addition, ebselen decreased both DNA fragmentation determined by TUNEL and brain damage volume at 3 days after ischemia. Furthermore, ebselen increased the number of NeuN immunopositive cells at 21 days after ischemia. CONCLUSIONS: These results indicate that ebselen attenuates ischemic neuronal apoptosis by inhibiting cytochrome c release. Ebselen may be a potential compound in stroke therapy.

Association of variants in critical core promoter element of angiotensinogen gene with increased risk of essential hypertension in Japanese.

We examined the association between variants in the core promoter element 1 (AGCE1) of the human angiotensinogen gene (AGT), which acts as a critical regulator of AGT transcription, and the risk for hypertension. One hundred and eighty patients with documented essential hypertension and a family history of hypertension and 194 control subjects without hypertension were selected and frequency matched by age and sex. Genomic DNA from leukocytes was analyzed for genetic variants (position: -20 to -18) in AGCE1. The haplotype in AGCE1 was significantly associated with increased risk of essential hypertension (P<.05). The frequency of subjects with homozygous C allele at position -18(CC/C-18T) was significantly higher in case patients than in control subjects (P<.005), and the evaluated odds ratio for hypertension was 4.2 (95% confidence interval [CI]: 1.4 to 12.8, CC/C-18T versus CT/C-18T). The homozygous threonine allele at codon 235 (TT/M235T) in exon 2 of AGT was also associated with hypertension (P<.02; odds ratio, TT versus other genotypes, 1.8; 95% CI, 1.1 to 2.7). According to haplotype analysis between AGT polymorphisms, we identified linkage disequilibrium between M235T and A-20C and between M235T and C-18T. We conclude that C-18T polymorphism in AGCE1 is a genetic risk factor for essential hypertension in the Japanese and is more tightly and directly associated with hypertension than TT/M235T.

Enhanced predictability of myocardial infarction in Japanese by combined genotype analysis.

To explore the genes responsible for myocardial infarction and restenosis after percutaneous transluminal coronary angioplasty, we performed association studies of the polymorphisms of the angiotensinogen and angiotensin-converting enzyme (ACE) genes. In the first study, normotensive myocardial infarction patients (n = 103) and control subjects (n = 103), who were matched for established risk factors with the myocardial infarction patients, were randomly selected. The angiotensinogen-TT genotype (T indicates threonine instead of methionine at position 235) was more frequent in the myocardial infarction group than in the control group (P < .05). The ACE-DD genotype (D indicates a deletion polymorphism in intron 16) was also more frequent in the myocardial infarction group (P < .0001). The odds ratio estimated by the combined analysis of the angiotensinogen-TT and ACE-DD genotypes (11.2) was markedly increased compared with that estimated separately from the angiotensinogen-TT (1.75) or ACE-DD (4.43) genotype. In the second study, we investigated 91 consecutive patients with acute myocardial infarction who underwent successful direct angioplasty. Combined analysis showed that the angiotensinogen-TT genotype did not enhance the predictability of myocardial infarction from the ACE-DD genotype. In conclusion, the angiotensinogen-TT genotype is a predictor for myocardial infarction, as well as the ACE-DD genotype, and the combined analysis of the angiotensinogen-TT and ACE-DD genotypes further enhanced the predictability of myocardial infarction in Japanese, suggesting its future clinical usefulness.

Polymorphism of the apolipoprotein E and angiotensin-converting enzyme genes in Japanese subjects with silent myocardial ischemia.

The apolipoprotein epsilon4 allele and homozygous deletion allele (DD) of the angiotensin-converting enzyme gene are reported to be associated with an increase in the incidence of ischemic heart disease. In this study, we examined whether the apolipoprotein epsilon4 genotype and angiotensin-converting enzyme/DD allele are associated with silent myocardial ischemia. We screened 3920 subjects undergoing general checkups who no symptoms of ischemic heart disease. Seventy subjects (2 percent) showed ischemic ST-segment depression during the double two-step exercise test. One hundred and twenty control subjects without ischemic ST-segment depression were recruited from the same population and matched for sex, age, and blood pressure. We performed genotyping of the apolipoprotein E gene (epsilon2, epsilon3, and epsilon4) and angiotensin-converting enzyme gene (I and D) using polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction, respectively. Allele frequently of epsilon4 of the apolipoprotein E gene was higher in the ischemic group (11 percent) than the nonischemic group (5 percent) (chi2 = 5.35, P < .05), but there was no significant association between the allele or the genotype frequency of the angiotensin-converting enzyme gene and the incidence of ischemic ST-segment depression. Furthermore, stepwise multiple regression analysis also revealed that total cholesterol level and epsilon4 genotype were predictors of ischemic change in the exercise tolerance test (chi2 = 12.8, P < .005, R(2) = .051). These results suggest that the apolipoprotein epsilon4 allele is an independent genetic risk factor for silent myocardial ischemia in Japanese subjects.

Chemokine receptor antagonist peptide, viral MIP-II, protects the brain against focal cerebral ischemia in mice.

The authors previously reported that mRNA for macrophage inflammatory protein-1alpha (MIP-1 alpha), a member of the CC chemokines, was expressed in glial cells after focal cerebral ischemia in rats. However, the function of chemokines in the ischemic brain remains unclear. Recently, viral macrophage inflammatory protein-II (vMIP-II), a chemokine analogue encoded by human herpesvirus-8 DNA, has been demonstrated to have antagonistic activity at several chemokine receptors. In the present study, the effects of vMIP-II and MIP-1alpha on ischemic brain injury were examined in mice to elucidate the roles of chemokines endogenously produced in the ischemic brain. Intracerebroventricular injection of vMIP-II (0.01-1 microg) reduced infarct volume in a dose-dependent manner when examined 48 hours after 1-hour middle cerebral artery occlusion followed by reperfusion. However, 1 microg MIP-1alpha increased infarct volume in the cortical region. These results supported the possibility that chemokines endogenously produced in the brain are involved in ischemic injury, and that chemokine receptors are potential targets for therapeutic intervention of stroke.

Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia?

Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor CX3CR1 was investigated in the rat brain. In situ hybridization study revealed that fractalkine mRNA was dominantly expressed in neuronal cells particularly in the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus accumbens. In vitro study using enriched neuronal or glial culture supported the dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1 mRNA was dominantly expressed in glial cells throughout the whole brain. The in vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not astrocytes or neurons. Fractalkine appears to function as a signal molecule from neuron to microglia.

Light microscopic Golgi study of mitral/tufted cells in the accessory olfactory bulb of the adult rat.

Mitral/tufted cells (MTCs) of the accessory olfactory bulb (AOB) of adult rats were investigated light microscopically with the rapid Golgi method. The somata of the MTCs, appearing ovoid or triangular in shape, are distributed throughout the external plexiform layer. The soma size varies from small to large (12-26 microns). Apical dendrites originating from the soma enter the glomerular layer to provide branches that form the glomerular arbors. After making a glomerular arbor, some dendrites develop a second arbor (en passant and terminal arbors, respectively). The MTCs have a very diverse dendritic branching pattern and most have a variable number of glomerular arbors per cell (up to 6); we have tentatively classified the MTCs into simple, intermediate, and complex. Of the glomerular arbors, 80% have a diameter of less than 50 microns. The glomerular arbors have been classified as baskets (small spherical or ovoid) with short loopy processes; balls of yarn (large and nearly spherical) with loosely intermingled thick loops; and bushes (small to large and rather polymorphic) with irregular processes. The MTCs send dendritic arbors to terminate in one or more glomeruli where they are arranged in several different types of endings. Since it is generally believed that the dendrites of mitral and tufted cells of the main olfactory bulb terminate in only one glomerulus, the difference in the termination of the dendrites of the MTCs may represent a morphological characteristic that is relevant to the coding and/or integration of sensory information.

High concentration of glucose induces the expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells.

Atherosclerosis is known to be accelerated in patients with diabetes mellitus. We have examined the effect of glucose on the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human umbilical vein endothelial cells (HUVEC) and the adhesion of cells of monocyte-like cell line, THP-1, to HUVEC. HUVEC exposed to a high glucose concentration (16.7 mM) showed a 1.4-fold increase in the adhesion of THP-1 cells and a 1.3-fold increase in cell surface expression of ICAM-1 after 6 h exposure compared with those cultured in medium with a low glucose concentration (5.6 mM). ICAM-1 expression began to increase after 3 h exposure, was maximal at 6 h and gradually decreased afterwards. At 16.7 mM, raffinose stimulation produced a significantly lower expression of ICAM-1 on HUVEC than glucose, furthermore it caused a significantly lower expression than low glucose stimulation (5.6 mM). We conclude that a high concentration of glucose can induce ICAM-1 in endothelial cells and that this effect may play an important role in atherogenesis in patients with diabetes mellitus.

High levels of serum lipoprotein(a) in patients with ischemic heart disease with normal coronary angiogram and thromboangiitis obliterans.

To determine whether lipoprotein(a) (Lp(a)) contributes to the acceleration of cardiovascular diseases without atherosclerotic lesion, we have measured serum Lp(a) level in male subjects aged 40-69 years with thromboangiitis obliterans (n = 40) and ischemic heart disease (IHD) with normal coronary angiogram (n = 35) in addition to subjects with arteriosclerosis obliterans (n = 123) and IHD with atherosclerotic coronary lesion (n = 203). Cases who had no IHD, arteriosclerosis obliterans or thromboangiitis obliterans were selected as a control group (n = 316). Subjects without any diseases or abnormal findings in physical examination and laboratory data were selected from the control group as the healthy control group (n = 156). The Lp(a) levels of arteriosclerosis obliterans and IHD with atherosclerotic coronary lesion were significantly higher (17.0 mg/dl and 13.1 mg/dl; median) than those of control and healthy control groups (9.9 mg/dl and 9.4 mg/dl, respectively) (P < 0.01), in agreement with previous reports. Furthermore, the Lp(a) level of IHD with normal coronary angiogram group was significantly higher (18.9 mg/dl) than those of the control and healthy control groups (P < 0.05). The Lp(a) level of thromboangiitis obliterans group was also much higher (21.3 mg/dl) than that of the healthy control group (P < 0.05). The current study suggests that Lp(a) is one of the independent risk factors for the development of atherosclerotic diseases such as arteriosclerosis obliterans and IHD with atherosclerotic coronary lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Linkage analysis of endothelial nitric oxide synthase gene with human blood pressure.

OBJECTIVE: Endothelial nitric oxide exerts important effects on the regulation of vascular tone and structure. Variants of the endothelial nitric oxide synthase gene (eNOS) have been associated with hypertension and myocardial infarction, although some reports have shown negative linkage with hypertension. To examine whether the region encoding the eNOS gene is linked with physiological blood pressure variation, we undertook a linkage analysis of this region in the general population. DESIGN: In healthy volunteer families, we used two independent quantitative linkage analyses to examine the relationship between genotypes and phenotypes, with both parametric and non-parametric and single-locus and multi-point methods. METHODS: We selected 260 families comprising mother and father (aged 40-70 years) and two natural offspring (aged 18-30 years) from the Victorian Family Heart Study. After standardized measurement of clinical data and extraction of DNA, all family members were genotyped at five microsatellite loci including the CA repeat in the eNOS gene by a PCR method. The quantitative linkage analyses were conducted according to two different analysis programs, the Genetic Analysis System (GAS) and the MAPMAKER/SIBS. RESULTS: With both linkage analyses, we found no linkage between any of the loci on chromosome 7q35-36 and the phenotypes systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, pulse rate, weight, height and body mass index. CONCLUSION: Based on these results, we conclude that in this population the eNOS gene is not linked to the physiological variation of blood pressure and other related phenotypes.

Type 2 interleukin-1 receptor mRNA is induced by kainic acid in the rat brain.

The in situ hybridization technique was used to examine the expression of type 2 interleukin-1 receptor (IL-1R2) mRNA in the rat brain following the systemic injection of kainic acid at a convulsive dose. The expression of IL-1R2 mRNA was not detected in any brain regions of the saline-injected control rats. 8 h after the systemic injection of kainic acid, weak expression of IL-1R2 mRNA was observed in the dentate gyrus and basolateral amygdaloid nucleus. At 12 and 24 h after the injection of kainic acid, IL-1R2 mRNA was markedly induced in various brain regions including the CA1 and CA3 fields of the hippocampus, dentate gyrus, basolateral amygdaloid nucleus, piniform cortex, claustrum, tenia tecta, arcuate hypothalamic nucleus, dorsomedial hypothalamic nucleus, suprachiasmatic nucleus, tuberal magnocellular nucleus and supramammillary nucleus. In these regions, the signals of IL-1R2 mRNA were observed on likely neuronal cells. Around the mediodorsal thalamic nucleus and the paraventricular thalamic nucleus, dispersed intense signals were observed on the non-neuronal cells. In addition, the expression of the mRNA on the venules was observed at 12 h. The strength of signals significantly decreased by 48 h after the injection. These findings revealed the spatiotemporal induction of IL-1R2 mRNA in the rat brain following the systemic administration of kainic acid, which has shown to cause neuronal degeneration, suggesting the pathological roles of IL-1R2 in the brain.

Localization of calcitonin receptor mRNA in the mouse brain: coexistence with serotonin transporter mRNA.

To elucidate the sites of and mechanisms of analgesic effect of centrally injected calcitonin, we examined expression of calcitonin receptor mRNA in the mouse brain by in situ hybridization techniques. Calcitonin receptor mRNA was expressed in various brain regions, including the preoptic area, dorsomedial hypothalamic nucleus, lateral hypothalamic area, periaqueductal gray, dorsal raphe nucleus, locus coeruleus, lateral parabrachial nucleus, gigantocellular reticular nucleus alpha part, lateral paragigantocellular nucleus, raphe magnus nucleus and solitary tract nucleus, which are known to play important roles in pain modulation. In addition, a double in situ hybridization technique demonstrated the intense expression of calcitonin receptor mRNA on serotonergic neurons in some raphe nuclei and the lateral paragigantocellular nucleus, suggesting the involvement of central serotonergic pathways in analgesic effect of calcitonin.

Human taste cells express the G protein alpha-gustducin and neuron-specific enolase.

Expression of the alpha-subunit of the taste-specific G protein alpha-gustducin and the glycolytic enzyme neuron-specific enolase (NSE) was investigated immunohistochemically in human circumvallate and foliate taste papillae. Immunofluorescence for alpha-gustducin was observed in taste cells of both types of papillae and exhibited two patterns of immunofluorescence, plasmalemmal and cytosolic. The plasmalemmal pattern showed intense immunofluorescence localized to the apical region, and was exhibited by most immunoreactive taste cells. In contrast, the cytosolic pattern, observed in one or two immunoreactive cells in a taste bud per section, showed immunofluorescence distributed throughout the cytoplasm. A subpopulation of alpha-gustducin-immunoreactive taste receptor cells, most of which exhibited the cytosolic pattern, also expressed NSE. Optical sectioning, using confocal laser scanning microscopy, demonstrated the highest level of expression of alpha-gustducin in the apical microvillar region of the taste cells in close apposition to the taste pore. These studies indicate conservation of epitopes of alpha-gustducin in humans and rats, and suggest that this G protein is associated with taste transduction in both rats and humans. The patterns of expression of alpha-gustducin, and coexpression with NSE, may correlate with specialized subtypes or developmental stages of taste receptor cells.

Beta2-adrenoceptors on the glial cells mediate the induction of interleukin-1beta mRNA in the rat brain.

Interleukin-1beta mRNA was induced by i.c.v. injection of the beta-adrenoceptor agonist isoproterenol. Lower doses of procaterol, a beta2-adrenoceptor agonist showed stronger induction of the mRNA than isoproterenol. These inductions were primarily observed in the glial cells. On the other hand, the beta1-adrenoceptor agonist dobutamine induced expression of this mRNA only in the meninges. These results suggest the existence of a system for regulation of interleukin-1beta gene expression via beta2-adrenoceptors in the brain parenchyma.

Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction. The Ohasama study.

The polymorphism of the angiotensin-converting enzyme gene is considered to be associated with increased risk for stroke, but there is a diversity in the results obtained. The genetic involvement of the renin-angiotensin system in stroke also remains unclear. To predict the genetic risk of lacunar infarction, we conducted an association study in an Ohasama population, which is the cohort in a rural region of northern Japan. A total of 134 subjects without major neurological, cardiovascular, or metabolic disorders were recruited. Using brain magnetic resonance imaging, the number of lacunae in each of four brain regions were calculated, and periventricular hyperintensity was classified into five grades. We used the following four candidate gene polymorphisms: angiotensin converting enzyme (ACE)/Insertion(I)-Deletion(D), angiotensinogen (AGT)/M235T, angiotensin II type 1 receptor (AT1)/ A1166C, type 2 receptor (AT2)/C3123A, to examine the association between polymorphisms and the severity of lacunar infarction. AGT/M235T was significantly associated with the number of lacunae in the brain stem, the basal ganglia (P < .05), and whole brain (P < .005) regions. The AT1 polymorphism was also significantly associated with the number of lacunae in the basal ganglia and whole brain regions (P < .05), and with periventricular hyperintensity grade (P < .005) in the younger population. However, ACE and AT2 polymorphisms failed to show an association with either the number of lacunae or the PVH grade. We concluded that AGT and AT1 polymorphisms are independent genetic risk factors for lacunar infarction.

Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure.

The activity of a sodium-proton exchanger is enhanced in the patients with essential hypertension and regulated via G-protein, which is a signal transducer between receptors and intracellular effectors. A recent study has revealed that a novel variant (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimetric G proteins (GNB3) is a genetic factor predisposing to hypertension in Caucasians. We examined the association between GNB3/ C825T and blood pressure, lipids, electrolytes, and other parameters in a Japanese population. Subjects (n = 352) were selected from the Ohasama Study, the population of which is regarded as from a rural community in Japan. To obtain precise clinical measurements, 24-h ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI), and carotid ultrasonography (CUS) were conducted in this population. In addition, we recruited 762 subjects from outpatients at the Osaka University Medical School to carry out the association study between hypertension and GNB3. The GNB3 genotype distribution did not differ significantly between normotensives and hypertensives in either of the two studies. The T825 allele of GNB3 was not associated with the presence of hypertension, blood pressure level, the number of brain lacunae or carotid wall thickness. However, the serum potassium and total cholesterol levels were significantly higher in subjects with the T allele (P < .005). The T825 allele of GNB3 is associated with increased serum potassium and total cholesterol levels but not with blood pressure in a Japanese population.

Insulin resistance is related to silent cerebral infarction in patients with essential hypertension.

Recently, hyperinsulinemia or insulin resistance has been suggested to be a risk factor for cardiovascular diseases. We evaluated the role of insulin resistance in the occurrence of silent cerebral infarction in 28 patients with essential hypertension (40 to 75 years, 157 +/- 4/89 +/- 2 mm Hg). Patients with diabetes mellitus or obesity (BMI > or = 30) were excluded. Insulin resistance was evaluated by means of constant glucose infusion rate (M value) during euglycemic-hyperinsulinemic glucose clamp test. Infarction was defined as a focal area with prolonged T1 and T2 relaxation times that was > 5 mm in diameter on brain magnetic resonance imaging. The severity of periventricular hyperlucency was evaluated by the distribution of the high intensity area. The number of silent infarctions significantly correlated only with the M value (F = 7.58, R2 = 0.23, P = .01) in multiple regression analysis using all variables: age, blood pressure, smoking history, lipid profile, levels of plasma glucose and insulin on fasting, and total amounts during 75-g OGTT. However, the severity of periventricular hyperlucency did not show a correlation with any factors. The occurrence of cerebral infarction was significantly correlated with thickening of the intima-media complex (IMC) of the common carotid artery on B-mode ultrasonography (F = 8.43, R2 = 0.25, P < .01). In conclusion, insulin resistance and thickening of IMC show a close relationship with the occurrence of silent cerebral infarction. Therefore, it may be important to improve insulin resistance for prevention of cerebral infarction in essential hypertensives.