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Biomedical subjects

M Chiariello

Publications and source records attributed to M Chiariello.

At least 73 records · Page 4Linked to original sources
PubMed1998

Noninvasive evaluation of left ventricular diastolic function in hypertrophic cardiomyopathy.

Diastolic dysfunction is common in hypertrophic cardiomyopathy (HC). Previous studies suggest that Doppler transmitral flow velocity profiles, and the left atrial (LA) M-mode echogram can be used noninvasively to evaluate left ventricular (LV) diastolic function. However, this has not been proved in HC. In this study we determined the relation of Doppler transmitral flow velocity profiles and the LA M-mode echograms to invasive indexes of LV diastolic function in patients with HC. We studied 25 patients with HC, while off drugs, and calculated LA global and active fractional shortening and the slope of both early and late displacement of the posterior aortic wall during LA emptying by M-mode echocardiography. We calculated peak velocity of early (E) and atrial (A) filling, E to A ratio, and E-wave deceleration time by pulsed Doppler echocardiography, and simultaneous radionuclide angiography, LV pressures, time constant of isovolumic relaxation tau, and the constant of chamber stiffness k by cardiac catheterization. The time constant of isovolumic relaxation tau correlated with the slope of early posterior aortic wall displacement (r = 0.59; p <0.01). LV end-diastolic pressure correlated with global LA fractional shortening (r = -0.75; p <0.001); the constant of chamber stiffness k correlated with active LA fractional shortening (r = -0.53; p <0.02). In a subset of 13 patients, in whom echocardiography and cardiac catheterization were performed simultaneously, similar results were found. LA M-mode recordings provide a more reliable noninvasive assessment of diastolic function in HC than mitral Doppler indexes.

Adolescent↗
PubMed1998

A short burst of oxygen radicals at reflow induces sustained release of oxidized glutathione from postischemic hearts.

Oxygen radical generation induced by postischemic reperfusion can overwhelm endogenous radical scavenging systems, resulting in "oxidative stress." Release of oxidized glutathione (GSSG) upon reflow has been taken as evidence for the occurrence of oxidative stress in postischemic hearts. However, demonstration that GSSG release is due to oxygen radicals and not to other consequences of ischemia/reperfusion is lacking. To address this issue, isolated rabbit hearts underwent 30 min of global ischemia at 37 degrees C. At reflow, control hearts were perfused with standard buffer for 45 min (n = 8); treated hearts received the oxygen radical scavenger superoxide dismutase (hSOD) for 15 min, followed by 30 min of standard perfusion (n = 8). During reperfusion control hearts showed a prominent release of GSSG, which peaked 5 min after reflow. Interestingly, GSSG release was still significantly elevated 45 min into reperfusion, at a time when oxygen radical generation has long ceased. In contrast, in hSOD-treated hearts GSSG release was negligible. Prevention of oxidative stress was also associated with significantly greater recovery of function. Thus, GSSG release occurs in postischemic hearts as a direct consequence of oxygen radical generation, and it may outlast the initial oxidant load.

Animals↗
PubMed1998

Combined evaluation of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the identification of viable myocardium in patients with chronic coronary artery disease.

The purpose of this study was to evaluate whether combined evaluation by discriminant analysis of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the accuracy in identifying viable myocardium in patients with chronic coronary artery disease. Rest-redistribution 201Tl has high sensitivity but low specificity in identifying viable myocardium, while the opposite is true for low-dose dobutamine echocardiography. Forty-six patients underwent low-dose dobutamine echocardiography and rest-redistribution 201Tl tomography on the same day. Rest echocardiography was repeated at least 30 days (mean 40+/-20) after myocardial revascularization. Discriminant analysis was applied to the results of 201Tl tomography and dobutamine echocardiography to classify a/dyskinetic segments as viable or non-viable. In 92 a/dyskinetic segments that were revascularized, rest-redistribution 201Tl tomography yielded an accuracy of 75%, while the accuracy of dobutamine echocardiography was 70% (P<0.05). When discriminant analysis was used, the combined evaluation gave an accuracy of 83% (P<0.05 vs both tests). These findings demonstrate that low-dose dobutamine echocardiography and 201Tl imaging are useful and complementary techniques for identifying viable myocardium in patients with chronic coronary artery disease. Combined evaluation by discriminant analysis significantly improves accuracy, although the cost-effectiveness of such an approach remains to be determined.

Adrenergic beta-Agonists↗
PubMed1998

Genetic mapping of the mouse Rab7 gene and pseudogene and of the human RAB7 homolog.

Rab proteins are small GTP-ases localized to distinct membrane compartments in eukaryotic cells and regulating specific steps of intracellular vesicular membrane traffic. The Rab7 protein is localized to the late endosomal compartment and controls late steps of endocytosis. We have isolated, by library screening, the 5' region, including the promoter, of the mouse Rab7 gene and a Rab7 pseudogene. We have mapped, by genetic linkage analysis, the mouse Rab7 gene on Chromosome (Chr) 6 and the Rab7-ps1 pseudogene on Chr 9, where the Rab7 gene has been previously reported to map. By radiation hybrid mapping, we have located the human RAB7 gene on Chr 3, in a region homologous to the mouse Chr 6, where the Rab7 gene maps.

Animals↗
PubMed1998

New-onset angina preceding acute myocardial infarction is associated with improved contractile recovery after thrombolysis.

BACKGROUND: Ischaemic preconditioning reduces myocardial infarct size in animal models. Clinical data suggest that episodes of angina immediately before acute myocardial infarction may be associated with smaller infarct size in man. However, it is unclear whether ischaemic episodes preceding acute myocardial infarction also affect contractile recovery in patients. OBJECTIVE: In this study we investigated the recovery of regional myocardial function after thrombolysis in two groups of patients at their first Q-wave acute myocardial infarction; in one group (n = 42) myocardial infarction occurred unheralded, whereas patients of the second group (n = 48) had experienced new-onset angina in the 48 h that preceded infarction. Echocardiographic analysis of myocardial regional function in the infarct area was done at 2, 24 and 72 h after thrombolysis, and at 1 week, and 1 and 3 months follow-up. RESULTS: Peak level of MB-creatine kinase was significantly lower in patients with new-onset angina (96 +/- 47 as compared with 221 +/- 108 IU.l-1, P < 0.01), as was the area under the MB-creatine kinase curve (1321 +/- 876 as compared to 3879 +/- 1555 U.l-1/36 h, P < 0.01). Hypokinetic segments were fewer in patients with pre-infarction angina. Similarly, wall motion score improved significantly earlier in patients who had new-onset angina before acute myocardial infarction. Thus, contractile recovery was more rapid in patients with previous angina than in those in whom infarction occurred unheralded. Complications during the in-hospital outcome and other variables considered during the 4-week follow-up were similar between groups. CONCLUSIONS: Patients who experienced new-onset angina before acute myocardial infarction showed better recovery of regional function after thrombolysis. Our study supports the hypothesis that brief periods of ischaemia immediately before myocardial infarction may precondition the human heart, thus improving contractile recovery.

Angina Pectoris↗
PubMed1998

Pattern of left ventricular filling in hypertrophic cardiomyopathy. Assessment by Doppler echocardiography and radionuclide angiography.

AIMS: The left ventricle in hypertrophic cardiomyopathy is anatomically and functionally non-uniform. This study was undertaken to verify whether a heterogeneity in the pattern of diastolic filling can be detected along the left ventricular inflow tract in hypertrophic cardiomyopathy. METHODS AND RESULTS: Early (E) and late (A) diastolic velocities were recorded by Doppler echocardiography at mitral and at mid-ventricular level in 16 normal volunteers and 30 patients with hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy also underwent radionuclide angiography to assess left ventricular function. E wave decreased significantly in normal volunteers (80 +/- 15 to 60 +/- 14 cm x s(-1); P<0.001), but it increased in hypertrophic cardiomyopathy (76 +/- 22 to 87 +/- 28 cm x s(-1) P=0.04), whereas the A wave decreased similarly in both. By multivariate analysis, systolic asynchrony and the ejection fraction of left ventricular lateral wall were directly related to the pattern of early filling progression (r=0.656, F=9.467; P<0.002). Moreover, systolic asynchrony showed a univariate direct correlation with changes in E velocity (r=0.42; P=0.02). CONCLUSION: Many patients with hypertrophic cardiomyopathy have an acceleration of filling within the left ventricular inflow tract; this phenomenon is directly related to systolic asynchrony and ejection fraction of the left ventricular lateral wall, suggesting increased suction.

Adolescent↗
PubMed1998

Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia.

BACKGROUND: The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl ester to very-low-density lipoprotein (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for the use of anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. OBJECTIVE: To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. METHODS: This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and alpha-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. RESULTS: The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P < 0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P < 0.05). No significant differences in the plasma activity of LCAT were observed among the groups. CONCLUSIONS: Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

Antioxidants↗
PubMed1998

Feasibility and safety of two French electrode catheters in the performance of electrophysiological studies.

UNLABELLED: The aim of this study was to analyze prospectively the feasibility and safety of using 2 Fr versus 6 Fr standard electrode catheters for diagnostic electrophysiological study. METHODS: Two hundred and five consecutive patients were randomized to receive the 6 Fr approach (3 quadripolar, 6 Fr, electrode catheters inserted through the left or right femoral vein and placed in the high right atrium, right ventricular apex, and His bundle area) or the 2 Fr approach (3 quadripolar, 2 Fr, electrode catheters inserted through a single, 7 Fr, triple lumen, guiding catheter and positioned at the same sites as the 6 Fr approach). RESULTS: Introduction time was shorter in the 2 Fr group (133.3 +/- 65 s, range 87-669 s) than in the 6 Fr group (242.8 +/- 91.8 s, range 168-1024 s, P < 0.001). The overall fluoroscopy time was longer in the 2 Fr group (141.2 +/- 40.1 s, range 78-312 s) than in the 6 Fr group (126.4 +/- 39.7 s, range 58-341 s, P = 0.009). However in the last 100 patients there was no more difference between the two groups (137.6 +/- 28.2 s vs 128.4 +/- 23.2 s, P = 0.07). There was no significant difference between 2 Fr and 6 Fr groups in the mean atrial (5.9 +/- 2.2 mV, range 2.2-11.3 mV, vs 6.1 +/- 2.3 mV, range 2.4-12.4 mV, P = 0.57) and ventricular (5.6 +/- 2.1 mV, range 1.9-9.7 mV, vs 5.7 +/- 2.2 mV, range 2.3-10.5 mV, P = 0.66) activation potential amplitudes recorded during sinus rhythm, or in the rate of stable His bundle potential recording (P = 0.3), and catheter dislodgment (P = 0.54). The overall number of complications was significantly higher in the 6 Fr group than in the 2 Fr group (29 vs 5, P = 0.001), as well as the number of entry site related complications (3 vs 12, P = 0.02) and catheter manipulation related complications (2 vs 17, P < 0.001). CONCLUSIONS: The results of this study show that the use of 2 Fr electrode catheters reduces the rates of entry site and catheter manipulation related complications during EPS. Despite their small size, these catheters allow quick and precise positioning of the electrode.

Cardiac Catheterization↗
PubMed1998

Dual chamber pacing in hypertrophic cardiomyopathy: influence of atrioventricular delay on left ventricular outflow tract obstruction.

The impact of the duration of atrioventricular (AV) delay on obstruction in hypertrophic cardiomyopathy was evaluated in 12 patients by cardiac catheterization, and in 8 of them also by Doppler echocardiography. The AV delay was programmed in random order at 125, 100 and 75 ms in the invasive study and at 120, 100 and 80 ms after pacemaker implantation. The arterial pressure did not changed throughout the studies, whereas the gradient decreased significantly by reducing the AV delay value; the greater gradient reduction was obtained, in both studies, with the AV delay set between 75 or 80 and 100 ms. QRS duration increased significantly by reducing the AV delay during both studies. The widest QRS was not associated with the smallest gradient in all patients. Changes in gradients were similar during the invasive and noninvasive protocols.

Adolescent↗
PubMed1998

[Early detection of heart involvement using serial cardiologic controls in the follow-up of patients with AIDS].

New effective therapies have been producing longer survival times for HIV-patients. Thus non-infectious complications of late stage of HIV infection (such as the development of left ventricular dysfunction) have emerged; in fact cardiac involvement has been identified frequently at autopsy and is described in 80% of patients with acquired immunodeficiency syndrome (AIDS) as an evidence of the virus cardiotrophism, while clinical findings of left ventricular dysfunction were only detected in about 15% of the patients. It is possible that the development of heart failure had been underestimated in those years; in fact signs and symptoms of cardiac involvement had been often misinterpreted as the results of non cardiac causes (pulmonary failure or infections) also determining a delay in the beginning of cardiac therapy. The aim of this study was to follow 16 human immunodeficiency-virus positive patients during a 3-year period to evaluate the usefulness of early detection of heart failure in order to start a specific therapy as soon as possible. The follow-up consisted of a clinical and electrocardiographic control every 4 months. Echocardiography was carried out when involvement of the cardiac muscle was suspected. During the follow-up we could reveal an early involvement in 5/16 patients (31.2%) and in 2 of them (40%) early therapy caused clinical and echocardiographic regression of left ventricular dysfunction. The present study demonstrates that periodical clinical and echocardiographic controls are useful in patients with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1998

Identification of viable myocardium in patients with chronic coronary artery disease using rest-redistribution thallium-201 tomography: optimal image analysis.

UNLABELLED: With the widely used 50% threshold, sensitivity is high, but specificity is low in detecting viable myocardium on 201Tl SPECT. In this study, we sought to identify the best threshold for semiquantitative 201Tl analysis. METHODS: Rest-redistribution 201Tl SPECT was performed in 46 patients with chronic coronary artery disease before and after myocardial revascularization. Regional function was evaluated by two-dimensional echocardiography before and after myocardial revascularization using a 3-point scale (1 = normal, 2 = hypokinetic, 3 = a/dyskinetic). Myocardial segments with abnormal systolic function were defined as viable if the systolic function score decreased > or = 1 after myocardial revascularization. A second group of 12 patients with chronic coronary artery disease constituted the validation population. Sensitivity-specificity curves, as well as receiver operating characteristic curves, for rest and redistribution mages were generated by varying the 201Tl uptake threshold. RESULTS: A 65% threshold uptake using resting images was found to be the best for detecting a/dyskinetic segments that improve after myocardial revascularization from those that do not improve. Sensitivity was lower with a 65% threshold (75%) than with a 50% threshold (90%, p < 0.05), but specificity was higher (76% versus 26%, p < 0.05) resulting in better accuracy (76% versus 57%, p < 0.05) and positive predictive value (77% versus 55%), while the negative predictive value was not different (69% versus 75%, p not significant). The area under the receiver operating characteristic curve was significantly (p < 005) larger for rest (0.80 +/- 0.05) as opposed to redistribution (0.72 +/- 0.05) images. Similar results were obtained in a subgroup of patients with low ejection fraction. Significant correlations between the percentage of revascularized viable segments and both the change in ejection fraction and in postrevascularization ejection fraction were found. When these findings were applied in the validation group, a gain in specificity, accuracy and positive predictive value was obtained with the 65% threshold compared with the 50% threshold. CONCLUSION: This study demonstrated that analysis of resting images and use of the 65% 201Tl uptake threshold is preferable for separating viable from not viable dyssynergic myocardial segments in patients with chronic coronary artery disease.

Case-Control Studies↗
PubMed1998

Mechanisms of restenosis after angioplasty and approach to therapy (Review).

Angioplasty is a principal treatment for occlusive vascular disease but 30-50% of patients show a restenosis of the vessel. There is no clinical effective therapy for this disease. It has been demonstrated, in animal models, that various drugs such as NO-donor, plasminogen inhibitor tranexamic acid and MMP (matrix metalloproteinases) reduce the rate of restenosis. Other therapeutic approaches are cytotoxic therapy, and strategies to inhibit cell cycle progression. Systemic administration of conventional pharmacologic agents inhibit cell cycle kinases and vascular lesion formation in animal models. As cell cycle progression is accompanied by fluctuations in the concentration of adenosine 3',5-monophospate (cAMP) and in the activity of the cAMP dependent protein kinase (PKA), local administration of cAMP and phospodiesterase-inhibitor drugs (aminophylline or amrinone) markedly inhibit neointima formation. The successful use of local radiation therapy to inhibit neointima formation after vascular injury may reflect a similar combination of cell-cycle arrest and vascular cell apoptosis. The most effective therapy for occlusive vascular disease will likely combine intravascular stenting with an antiproliferative therapy.

Journal Article↗
PubMed1998

[The heterogeneity of myocardial sympathetic innervation in normal subjects: an assessment by iodine-123 metaiodobenzylguanidine scintigraphy].

123I-radiolabeled metaiodobenzylguanidine (123I-MIBG) cardiac imaging has been used to evaluate the distribution of sympathetic nervous system (SNS) in the heart. Different heart diseases have shown impaired cardiac SNS distribution as reflected by MIBG activity. The aim of this study was to assess the cardiac distribution of SNS in normal subjects, using MIBG imaging. Ten normal subjects (1 male and 9 females, mean age 46 +/- 9 years) with no cardiac abnormalities underwent myocardial 123I-MIBG scintigraphy, Tc-99m methoxyisobutylisonitrile (MIBI) cardiac perfusion imaging and equilibrium radionuclide angiography (RNA). Regional myocardial MIBG and MIBI activities were quantitatively evaluated using a region of interest analysis. For this purpose, the left ventricle was divided into 6 myocardial regions as anterior, apical, inferior, septum, lateral and posterolateral. In particular, myocardial MIBG and MIBI activities were measured as myocardium to mediastinum ratio. Regional left ventricular function was assessed by RNA. Myocardial MIBG uptake was homogeneous in anterior (2.2 +/- 0.5), inferior (2.5 +/- 0.7), septal (2.4 +/- 0.4), lateral (2.3 +/- 0.4), and posterolateral (2.3 +/- 0.4) regions. Conversely, MIBG uptake was significantly lower in the apical region (1.9 +/- 0.3) compared to all other left ventricular segments (p < 0.05). Regional myocardial perfusion, as measured by MIBI uptake, was homogeneous in all regions. No regional left ventricular wall motion abnormalities were observed by RNA. In conclusion, our data suggest that a decreased MIBG uptake may be observed in the left ventricular apical region of normal subjects reflecting reduced sympathetic innervation of the apex. This finding is not related to myocardial perfusion or wall motion abnormalities. The knowledge of cardiac sympathetic innervation in normal subjects may be helpful to assess SNS abnormalities in heart disease.

3-Iodobenzylguanidine↗
PubMed1997

Occurrence of the same peroxidative compounds in low density lipoprotein and in atherosclerotic lesions from a homozygous familial hypercholesterolemic patient: a case report.

Oxidative modification of low density lipoprotein (LDL) and its byproducts may play a fundamental role in atherosclerosis. We report an in vitro analysis of LDL peroxidative compounds in an homozygous familial hypercholesterolemic (HFH) patient who subsequently died. During the autopsy, we analyzed lipids extracted directly from different atherosclerotic plaques, and we also provided an immunocytochemical analysis using the specific monoclonal antibody MDA2 (directed against malondialdeyde-lysine epitopes of oxidized LDL). The results showed that the same species of peroxidative compounds were present both in LDL in vitro and in lipids extracted directly from atherosclerotic lesions. Moreover, the immunocytochemistry analysis revealed a positive staining of atherosclerotic plaques, confirming the presence of LDL oxidation-specific epitopes. Although observation of a single case is necessarily limited, our findings are consistent with the hypothesis that oxidative modification of LDL is involved in human atherogenesis.

Adult↗
PubMed1997

Role of the small GTPase Rab7 in the late endocytic pathway.

Rab7 is a small GTPase localized to the late endosomal compartment. Its function was investigated by overexpressing dominant negative or constitutively active mutants in BHK-21 cells. The effects of such overexpression on the internalization and/or degradation of different endocytic markers and on the morphology of the late endosomal compartment were analyzed. We observed a marked inhibition of the degradation of 125I-low density lipoproteins in cells transfected with the Rab7 dominant negative mutants while the rate of internalization was not affected. Moreover in these cells there was an accumulation of many small vesicles scattered throughout the cytoplasm. In contrast, overexpression of the activating mutants led to the appearance of atypically large endocytic structures and caused a dramatic change in the distribution of the cation-independent mannose 6-phosphate receptor. Our data indicate that the Rab7 protein in mammalian cells is present on a late endosomal compartment much larger than the compartment labeled by the cation-independent mannose 6-phosphate receptor. Rab7 also appears to play a fundamental role in controlling late endocytic membrane traffic.

Animals↗
PubMed1997

Role of oxidative metabolism on endothelium-dependent vascular relaxation of isolated vessels.

The obligatory role of endothelium in mediating vasodilator response to numerous humoral agents has been definitely accepted. However, the chemical identity of endothelium-derived relaxing factor(s) (EDRF) and the mechanisms underlying its synthesis and release remain unclear. Much evidence suggests a compartmentalization of ATP into cells, such that ATP derived from glycolysis or from oxidative metabolism is used for different cellular functions. To investigate which energy source (i.e. oxidative v glycolytic metabolism) is preferentially used for the biosynthesis and/or release of EDRF, rings of rabbit thoracic aorta were studied in organ chambers. After preconstriction with PGF2 alpha, inhibition of glycolysis with either iodoacetate (300 microM) (n = 6) or 2-deoxyglucose (20 mM) (n = 6) did not affect concentration-response curve to the endothelium-dependent agent acetylcholine. In contrast, inhibition of oxidative metabolism with either 1 mM amytal or 5 microM rotenone markedly impaired relaxation to acetylcholine. In fact, maximal relaxation was 75 +/- 5% in control rings (n = 6), and 42 +/- 7% (P < 0.01) in amytal-treated rings (n = 6), whereas rotenone converted acetylcholine relaxation into constriction (n = 6; P < 0.001). The effect of amytal on endothelium-dependent relaxation was reversible, suggesting that endothelial cells were not damaged by the inhibitor. Amytal also markedly reduced endothelium-mediated relaxation to ADP (37 +/- 6%; P < 0.05; n = 5), as well as to the calcium ionophore A23187. Neither mitochondrial inhibitor affected relaxation to nitroglycerin, an endothelium-independent agent. Finally, amytal did not affect relaxation to S-nitrosocysteine (a recently proposed EDRF) (n = 5), suggesting that the effects on acetylcholine and ADP responses were not due to non-specific interferences with EDRF once released from endothelial cells. In conclusion, our data demonstrate that the active process of biosynthesis and/or release of EDRF requires energy derived mainly from mitochondrial oxidative metabolism.

Acetylcholine↗