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Biomedical subjects

T Ikeda

Publications and source records attributed to T Ikeda.

At least 145 records · Page 8Linked to original sources

The mechanism and change in the optic nerve head (ONH) circulation in rabbits after glucose loading.

PURPOSE: To assess the influence of the blood glucose level on ocular capillary circulation, we induced clinically significant hyperglycemia (200--300 mg/dl) in rabbits and investigated the changes in the optic nerve head (ONH) circulation. METHODS: Hyperglycemia was induced by injection of glucose (5.6 mmol/kg) into an auricular vein of healthy albino rabbits and changes in the ONH circulation were measured by the laser speckle method. In order to examine the role of nitric oxide (NO), glucose was administered after intravenous injection of an NO synthetase inhibitor (N(G)-nitro-L-arginine methyl ester, L-NAME, 1 mg/kg), then changes in the ONH circulation were measured. RESULTS: The blood glucose level reached a peak at 30 min after glucose loading and returned to its initial level by 2 hours. ONH circulation showed a 60% increase compared with its initial level at 15 min after glucose loading and subsequently remained almost unchanged throughout the 2-hour observation period. There were no significant changes of the blood pressure, heart rate, or intraocular pressure. The glucose-induced increase of ONH circulation was completely inhibited by pretreatment with L-NAME. CONCLUSIONS: ONH circulation was increased by administration of glucose to healthy rabbits. A high blood glucose level seems to promote ocular capillary circulation and NO as well as insulin appear to have a role in this process.

Animals↗

Interleukin-6 (IL-6) production by cytokine-stimulated human Müller cells.

PURPOSE: To investigate whether or not human Müller cells synthesize interleukin (IL)-6. METHODS: Using RT-PCR, we first confirmed whether cultured human Müller cells express IL-6 mRNA. Then, to determine Müller cell IL-6 production after stimulation, cultured Müller cells were exposed to various concentrations of IL-1beta (0.2 ng/ml, 2 ng/ml, 20 ng/ml) or lipopolysaccharide (LPS) (0.001 microg/ml, 0.1 microg/ml, 10 microg/ml) in 24 hr assays. In addition, to determine Müller cell time-dependent induction of IL-6 production, cultured Müller cells were exposed to IL-1beta (0.02 ng/ml, 2 ng/ml) or LPS (10 microg/ml) for 6, 12, 24, 36 hr. IL-6 production in supernatants was quantified by ELISA: RESULTS: IL-6 mRNA was expressed in cultured human Müller cells, which produced IL-6 after stimulation with either IL-1beta or LPS for 24 hours. IL-1beta was a significantly more potent stimulator of IL-6 production than was LPS. Exposure of cultured human Müller cells to either IL-1beta or LPS stimulated IL-6 production in a time-dependent fashion. CONCLUSIONS: Our findings indicate that human Müller cells can produce IL-6 when stimulated by IL-1beta or LPS. Müller cell IL-6 production may have an important role in various conditions involving ocular inflammation

Cell Division↗

The effect of nipradilol, an alpha-beta blocker, on retinal blood flow in healthy volunteers.

PURPOSE: To study the effects of topically applied nipradilol, an alpha-beta blocker recently developed in Japan as an ocular hypotensive drug, on retinal blood flow (RBF) in healthy volunteers. METHODS: Seven healthy volunteers (mean age, 33 years) underwent measurement of RBF using a newly developed stabilized laser Doppler velocimetry system. In a double-blind trial, retinal arterial blood flow, intraocular pressure (IOP), and blood pressure (BP) were measured before and after the instillation of nipradilol or saline every hour for 5 hours. RESULTS: Retinal arterial blood flow and the diameter of the retinal artery significantly (p< 0.05) increased at 4 hours after instillation in nipradilol-treated eyes. Retinal blood velocity did not change significantly. Nipradilol evoked a significant (p< 0.05) bilateral decrease in IOP. Mean BP decreased significantly (p< 0.05) 3 hours after instillation. Ocular perfusion pressure (OPP), calculated from the mean BP and IOP, did not change significantly during the study. CONCLUSION: Topical nipradilol significantly increased retinal arterial blood flow in healthy volunteers, not through a secondary effect dependent on a change in OPP, but likely through the vasodilatory action of the drug.

Adrenergic alpha-Antagonists↗

Involvement of nitric oxide in the ocular hypotensive action of nipradilol.

PURPOSE: To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a beta-blocker with alpha( 1)-blocking activity. METHODS: Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. RESULTS: Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1 approximately 2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. CONCLUSIONS: Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.

Administration, Topical↗

Vitreous levels of insulin-like growth factor-I in patients with proliferative diabetic retinopathy.

The levels of IGF-I in the vitreous body and the intraocular fluid of patients with proliferative diabetic retinopathy (PDR) were determined using radioimmunoassay (RIA). Eleven vitreous specimens were obtained from the intraocular fluid of eyes of patients with PDR who underwent surgery during the operation. Eleven intraocular fluids from the same patients during reoperations were compared with controls. The expression of IGF-I mRNA in cultured human Muller glial cells was evaluated using reverse transcription-polymerase chain reaction (RT-PCR). The mean IGF-I level in the vitreous samples during initial PDR surgery and reoperation was significantly higher than that found in the vitreous of the control (p < 0.05). The level of IGF-I increased in 6 of the 11 cases. Cultured human Muller cells expressed IGF-I mRNA. The results indicate increased levels of IGF-I both in the initial vitreous and ocular fluid at post-operative re-proliferation. Muller cell is suggested as an origin of local IGF-I production.

Adult↗

Pars plana vitrectomy combined with penetrating keratoplasty.

Pars plana vitrectomy combined with keratoplasty using a temporary keratoprosthesis is a surgical procedure used in patients with vitreoretinal disorders complicated by severe corneal opacification. Temporary keratoprostheses include the Landers type and Eckardt type. Use of the Eckardt temporary keratoprosthesis is superior because of a wider optical diameter and easier visualization of the peripheral fundus. However, one problem with this procedure is that many patients develop postoperative rejection and loss of transparency of the corneal graft. To maintain good transparency of the corneal graft after surgery, vitrectomy must be minimally invasive and postoperative anti-inflammation must be ensured.

Corneal Diseases↗

Isolation and characterization of an N-linked oligosaccharide that is significantly increased in sera from patients with non-small cell lung cancer.

The structures of N-linked oligosaccharides present in human sera from 12 healthy volunteers and from 14 patients with non-small cell lung cancer (NSCLC) were analyzed by our recently developed partially automated systematic method. Thirty different structures of oligosaccharides were deduced, and these accounted for 84.1% of the total N-linked oligosaccharides present in human sera. All of the quantified oligosaccharide levels in healthy human sera were within twice the standard deviation. The amount of a triantennary trigalactosylated structure with one outer arm fucosylation (A3G3Fo) was found to be markedly increased in NSCLC patients in comparison to that in healthy volunteers (p < 0.01). No significant positive correlation with other clinical data was found. Serum A3G3Fo levels can thus be a novel marker for the diagnosis of NSCLC.

Adult↗

Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia.

UNLABELLED: Hypothermia after induction of general anesthesia results largely from core-to-peripheral redistribution of body heat. Both central inhibition of tonic thermoregulatory vasoconstriction in arteriovenous shunts and anesthetic-induced arteriolar and venous dilation contribute to this redistribution. Ketamine, unique among anesthetics, increases peripheral arteriolar resistance; in contrast, propofol causes profound venodilation that other anesthetics do not. We therefore tested the hypothesis that induction of anesthesia with ketamine causes less core hypothermia than induction with propofol. Twenty patients undergoing elective surgery were randomly assigned to anesthetic induction with either 1.5 mg/kg ketamine (n = 10) or 2.5 mg/kg propofol (n = 10). Anesthesia in both groups was subsequently maintained with sevoflurane and 60% nitrous oxide in oxygen. Forearm minus finger, skin-temperature gradients <0 degrees C were considered indicative of significant arteriovenous shunt vasodilation. Ketamine did not cause vasodilation just after induction, whereas propofol rapidly induced vasodilation. Core temperatures in the patients given ketamine remained significantly greater than those in the patients induced with propofol. These data suggest that maintaining vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia. IMPLICATIONS: Core hypothermia during the first hour of anesthesia was less after induction of anesthesia with ketamine than propofol. Maintaining arteriovenous shunt vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia.

Adult↗

Relation between initial blood distribution volume and propofol induction dose requirement.

BACKGROUND: Propofol induction dose is variable and depends on many factors, including initial volume of distribution and early disposition. The authors hypothesized that preadministration blood distribution volumes, cardiac output (CO), and hepatic blood flow (HBF) could be examined to establish a propofol induction dose. METHODS: Propofol dose required to reach loss of consciousness, when infused at infusion rate per lean body mass (LBM) of 40 mg x kg(-1) x h(-1), was determined in 75 patients aged 11-85 yr. CO, blood volume (BV), central blood volume (CBV), and HBF were measured with indocyanine green pulse spectrophotometry. Univariate least squares linear regression analysis was used to individually analyze the relation between propofol induction dose and patient characteristics, including LBM, baseline distribution volumes, CO, and HBF. Stepwise multiple linear regression models were used to select important predictors of induction dose. RESULTS: Although there was a significant correlation between the induction dose and each of the eight variables of age, sex, LBM, hemoglobin, CO, BV, CBV, and HBF, only factors of age (partial r = -0.655), LBM (partial r = 0.325), CBV (partial r = 0.540), and HBF (partial r = 0.357) were independently associated with the induction dose (R2 = 0.85) when all variables were included in a multivariate model. CONCLUSIONS: At a constant propofol infusion rate of 40 mg x kg(-1) x h(-1) as a function of LBM in patients with American Society of Anesthesiologists physical status I or II, the induction dose can be determined from four variables: age, LBM, CBV, and HBF.

Adolescent↗

Experimental study using pig eyes for realizing ideal astigmatic keratotomy.

PURPOSE: The effects of varying the incision length and depth were analyzed using pig eyes to acquire information for realizing an ideal method of astigmatic keratotomy (AK). METHODS: Single and paired arcuate incisions were made on pig corneas using a diamond knife. Incisions with varying lengths of 40 degrees, 60 degrees, and 90 degrees were made with the incision depth fixed at 90% of corneal thickness. Next, paired incisions with varying incision depth from 20% to 95% of corneal thickness were made with the incision length fixed at 90 degrees. The changes in corneal shape were analyzed using corneal topography and the degrees of astigmatic change were measured using a surgical keratometer. RESULTS: For short single and paired incisions (40 degrees or 60 degrees in length), narrow areas of flattenings occurred, and steepenings were observed on both sides adjacent to the flattened areas. For long paired incisions of 90 degrees length, wide areas of flattenings and steepenings were observed with an approximately 1:1 coupling ratio, and a positive linear relationship between the incision depth and degree of astigmatic change was observed in the range of incision depth between 40% and 80% of corneal thickness. CONCLUSION: This experimental study suggests that for achieving ideal corneal sphericity after AK, long incisions covering the entire steep areas (paired 90 degrees incisions for regular astigmatism) should be used and the degree of astigmatic correction may be controlled by varying the incision depth.

Animals↗

Possible involvement of endothelin-1 and nitric oxide in the pathogenesis of proliferative diabetic retinopathy.

BACKGROUND: Overproduction of endothelin-1 (ET-1) and nitric oxide (NO) in the retina is demonstrated in experimental diabetic animals. To clarify the possible involvement of ET-1 and NO in the pathogenesis of diabetic retinopathy, the authors examined the vitreous levels of these principal endothelium-derived vasoactive substances in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluid was taken from patients with PDR (ET-1, n = 12; NO, n = 12) and from patients with macular holes as controls (ET-1, n = 10; NO, n = 10) at vitreous surgery. Endothelin-1 and NO metabolites were measured by radioimmunoassay and high-performance liquid chromatography based on the Griess method, respectively. RESULTS: Endothelin-1 levels (mean +/- SE) were 21.5 +/- 1.7 pg/mL in the vitreous of patients with PDR and 16.7 +/- 0.7 pg/mL in the vitreous of patients with macular hole. There was a significant difference between patients with PDR and controls (P = 0.009, Mann-Whitney). Nitrate (NO3) was 49.8 +/- 5.0 micromol/L in patients with PDR and 24.2 +/- 2.8 micromol/L in patients with macula hole; it was also significantly elevated in patients with PDR (P = 0.004, Mann-Whitney), whereas nitrite (NO2) was not detected in this study. CONCLUSION: These results indicate that ET-1 and NO may be related in the pathogenesis of PDR.

Adult↗

Lack of effect of soy isoflavone on thyroid hyperplasia in rats receiving an iodine-deficient diet.

We have reported a dramatic synergism between soy intake and iodine deficiency regarding induction of thyroid hyperplasia in rats. Because isoflavones are active constituents of soybeans, in the present study, their possible contribution was examined. Female F344 rats were divided into 8 groups, exposed to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS) alone, 20% DS + ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced by SI, but was increased by the ID and DS diets with a further significant increment in the DS + ID group (P < 0.01). Compared to the control value, serum T(4) was significantly (P < 0.01) increased by 20% DS alone and decreased in all groups given the ID treatment (P < 0.001). Serum thyroid stimulating hormone (TSH) level was increased by ID, and further enhanced by DS (P < 0.01) but not SI. Histopathologically, diffuse hypertrophy and / or hyperplasia of thyroid follicles were observed in the ID-treated groups, the severity being enhanced by DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were elevated in the ID diet groups and again enhanced by DS, but not SI. These results thus suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency.

Animals↗

Synergistic effects of high-dose soybean intake with iodine deficiency, but not sulfadimethoxine or phenobarbital, on rat thyroid proliferation.

The specificity and dose dependence of the synergistic effects of soybean intake with iodine deficiency on the induction of thyroid proliferation were investigated in female F344 rats. In the first experiment, rats were divided into 6 groups, each consisting of 5 animals, and fed a basal diet containing 20% gluten, an iodine-deficient basal diet alone or an iodine-deficient diet containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding synergistically induced thyroid hyperplasias with iodine deficiency only at the 25% dose. In the second experiment, rats were also divided into 6 groups, each consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05% phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM treatments significantly (P < 0.05 - 0.01) increased the thyroid weights, but this increase rate was less prominent in the SDM + soybean group than in the SDM alone group. The PB treatment was also associated with a tendency for increase in thyroid weight, but again this was smaller in the PB + soybean group than in the PB alone group. Although the SDM or PB treatments reduced the serum triiodothyronine and thyroxine levels and consequently increased the serum thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or rather attenuated these changes. Our results clearly indicate that soybean feeding does not synergistically enhance the effects of SDM or PB on the rat thyroid. Thus it can be concluded that soybean intake specifically interacts with iodine deficiency in induction of thyroid proliferative lesions in rats, only at high doses.

Animals↗

Predicting the recurrence of ventricular tachyarrhythmias from T-wave alternans assessed on antiarrhythmic pharmacotherapy: a prospective study in patients with dilated cardiomyopathy.

BACKGROUND: Microvolt T-wave alternans (TWA) has been proposed as a useful index to identify patients at risk of ventricular tachyarrhythmias. Recent studies have demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide, decrease the prevalence of TWA. In this study, we tested whether TWA in patients on antiarrhythmic pharmacotherapy significantly predicts the recurrence of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. METHODS: To evaluate the ability to predict the recurrence of ventricular tachyarrhythmias, determinate TWA and left ventricular ejection fraction (LVEF) were prospectively assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17 patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study endpoint was the first recurrence of sustained VT or VF on treatment during the follow-up period. RESULTS: TWA was positive on antiarrhythmic pharmacotherapy in 30 patients (61%). During a follow-up of 13 +/- 11 months, the sustained VT or VF recurred in 21 of the 41 patients (51%) with available follow-up data. The sensitivity of TWA and LVEF for predicting recurrence of ventricular tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan-Meier event-free analysis revealed that TWA was a significant risk stratifier (P = 0.02), whereas LVEF was not. CONCLUSIONS: This prospective study suggests that TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs for ventricular tachyarrhythmias.

Adult↗

Overexpression of interferon gamma-inducible protein 10 in the liver of patients with type I autoimmune hepatitis identified by suppression subtractive hybridization.

OBJECTIVE: To clarify gene expression profiles in the liver may elucidate the pathogenesis of type I autoimmune hepatitis (AIH). Using suppression subtractive hybridization (SSH), we identified genes overexpressed in the liver of AIH. METHODS: A small liver biopsy sample from a patient with definite AIH was available to be analyzed in our system. By mixing cDNA synthesized from this sample as a 'tester' and cDNA from a normal liver as a 'driver,' we subtracted cDNA to enrich genes overexpressed in AIH. After polymerase chain reaction (PCR) amplification and subcloning, we identified subtracted genes by sequencing 50 randomly selected clones. RESULTS: Only one cDNA fragment, which is identical to interferon inducible protein 10 (IP-10), was overexpressed by > 10 times in the liver of AIH, as compared with control. We confirmed IP-10 overexpression in all eight patients with AIH by reverse transcription PCR. Immunohistochemical analysis demonstrated increased IP-10 expression in hepatocytes in the liver of AIH. Reverse transcription PCR analysis of 63 liver biopsy samples with various liver diseases revealed that IP-10 expression was significantly higher in AIH (p = 0.025) and chronic hepatitis C (p = 0.0043) than in other liver diseases. Interestingly, the amount of IP-10 mRNA expression was correlated with serum ALT values in AIH (p = 0.0006), but not in chronic hepatitis C (p = 0.43). CONCLUSION: These results indicate the IP-10 expression in the liver might be used as a preferential marker of AIH, and that IP-10 has some pathophysiological roles in the liver damage of AIH.

Alanine Transaminase↗

A numerical analysis of phonation using a two-dimensional flexible channel model of the vocal folds.

A two-dimensional flexible channel model of the vocal folds coupled with an unsteady one-dimensional flow model is presented for an analysis of the mechanism of phonation. The vocal fold is approximated by springs and dampers distributed in the main flow direction that are enveloped with an elastic cover. In order to approximate three-dimensional collision of the vocal folds using the two-dimensional model, threshold values for the glottal width are introduced. The numerical results show that the collision plays an important role in speech sound, especially for higher resonant frequency components, because it causes the source sound to include high-frequency components.

Computer Simulation↗

Sequences in the NS5A protein of hepatitis C virus and the serum alanine aminotransferase response to interferon therapy in Japanese patients.

BACKGROUND AND AIMS: Chronic hepatitis C is a slowly progressive disease and eventually causes hepatocellular carcinoma in many patients. Although interferon (IFN) therapy has been used for viral eradication, its success rate is only about 30%. In patients in whom it has failed (non-responders), there are several patterns of serum alanine aminotransferase (ALT) values, and detection of serum HCV-RNA during and after IFN therapy and improved long term prognosis were reported in patients whose serum ALT values were normalised by IFN therapy even if HCV viraemia persisted. The present study sought to clarify the virological characteristics contributing to these differences. METHODS: Complete or partial length dominant sequences of hepatitis C virus genotype 1b (HCV-1b) were determined by direct sequencing. Firstly, the complete sequences of HCV-1b genomes were determined in six non-responders; three showed normalisation of serum ALT values during IFN-alpha therapy and the other three did not. Subsequently, the amino acid residues that were different in the two groups were further analysed retrospectively in another 82 patients. RESULTS: Comparison of the sequences suggested an association between amino acids 2154-2172 of HCV-1b and serum ALT normalisation. A retrospective analysis of 82 patients revealed that the number of amino acid substitutions in this region was the only statistically significant variable associated with ALT normalisation (odds ratio 31.0; 95% confidence interval 5.0-286) in multivariate analyses. CONCLUSIONS: A HCV genomic region that correlates with the ALT response to IFN therapy appears to be present in virologically IFN ineffective patients.

Adult↗

Urinary prostaglandin D synthase (beta-trace) excretion increases in the early stage of diabetes mellitus.

OBJECTIVE: Circulating levels of lipocalin-type prostaglandin D synthase (L-PGDS)/beta-trace reportedly increase in renal failure as well as in cardiovascular injuries. We investigated the alterations of L-PGDS in urine and plasma in the early stage of type-2 diabetic patients. METHOD: Thirty-six type-2 diabetic patients and 29 normal subjects were studied. Overnight spot urine and plasma samples were obtained in the morning. L-PGDS was measured by ELISA method using anti-L-PGDS antibody. Variables indicating renal function were determined. RESULTS: Plasma L-PGDS concentration was slightly higher in the patients with diabetes mellitus than in the control subjects, whereas the urinary L-PGDS excretion almost doubled in the diabetic patients as compared with that in the control subjects. Plasma L-PGDS was determined by plasma creatinine (Cr) concentration while urinary L-PGDS excretion was correlated solely with urinary protein excretion. There was no relationship between plasma L-PGDS concentration and urinary L-PGDS excretion. The averaged plasma concentration of L-PGDS in the diabetics with a normal Cr level in plasma, corresponding to that in the controls, was determined by the plasma Cr concentration. On the other hand, the urinary L-PGDS excretion was determined by the amount of proteinuria and greater in the diabetics with a normal Cr level in plasma than in the controls even when the patients exhibited urinary protein excretion equal to that in the control subjects. CONCLUSIONS: Urinary L-PGDS excretion increased in the early stage of kidney injury in patients with type-2 diabetes mellitus. The urinary excretion was correlated independently with urinary protein excretion even when there was no difference in urinary protein or albumin excretions, thereby suggesting that urinary L-PGDS excretion is possibly a more sensitive indicator of renal injuries than proteinuria. Urinary L-PGDS may thus predict the progression of renal injuries in diabetic patients.

Analysis of Variance↗