The clinical manifestations of hyperostosis frontalis interna: A qualitative systematic review of cases.

Hyperostosis frontalis interna (HFI) is a condition defined as abnormal bone growth on the posterior aspect of the frontal bone. Despite uncertainties regarding its etiology and prognosis, clinicians typically consider HFI a benign pathology. There are no studies organizing all the possible manifestations of the disease. The present study aims to organize all the clinical manifestations of HFI within the current case report/series literature. A blinded PRISMA-guided search of HFI case reports and case series yielded 43 relevant articles and provided 110 patients for analysis. The symptoms presenting alongside HFI were extracted and tabulated. We found high-frequency clinical manifestations of HFI (>20% of patients) to include headaches, obesity, vertigo/dizziness symptoms, cognitive decline, and depression. An additional 15 symptoms were tabulated at frequencies found to be less than 20%. Based on our analysis, we suggest the constellation of high-frequency symptoms can offer a more comprehensive clinical picture of symptomatic HFI which may be valuable to consider for clinicians and future researchers in the field of HFI.

Quality of life of adult patients with hereditary fructose intolerance.

BACKGROUND: Although patients with hereditary fructose intolerance (HFI) generally have a good prognosis on a fructose-restricted diet, relatively little is known about their quality of life. The aim of this study was to investigate the quality of life in adult patients with HFI in comparison to patients with dietary-treated, classical phenylketonuria (PKU). METHODS: Patients with HFI and patients with classical PKU were recruited from the adult metabolic centers in The Netherlands and Belgium and via social media. Patients were asked to fill out the 36-item Short Form Health survey (SF-36) and a modified PKU Quality Of Life (PKU-QoL) questionnaire. RESULTS: Patients with HFI (n = 19) did not report any restrictions in their health-related quality of life, except for vitality and general mental health, which were scored more unfavorable compared to patients with PKU (n = 19) (p < 0.05, adjusted for level of education and country of origin). The results from the modified PKU-QoL demonstrated a statistically significantly greater impact of the disease in the social domain in HFI. A substantial proportion of both HFI and PKU patients (21%) reported a great to severe emotional impact of their disease. Finally, patients with HFI experienced statistically significantly less food temptations, less guilt if dietary restrictions not followed, and less overall difficulty following dietary restrictions. CONCLUSIONS: Although patients with HFI showed to have a generally good quality of life, they scored lower on vitality and general mental health, and reported a greater social impact of the disease. These aspects deserve further study and clinical attention.

Saliency-Based Rotor Spatial Position Displacement Self-Sensing for Self-Bearing Machines.

Self-bearing machines do not contain physical bearings but magnetic bearings. Both rotor rotary and spatial positions displacement are required in these types of machines to control the rotor position while it is levitating. Self-bearing machines often use external sensors for x (horizontal) and y (vertical) spatial position measurement, which will result in additional cost, volume, complexity, and number of parts susceptible to failure. To overcome these issues, this paper proposes a xy-position estimation self-sensing technique based on both main- and cross-inductance variation. The proposed method estimates x and y position based on inductive saliency between two sets of three-phase coils. The proposed idea is applied on a combined winding self-bearing machine which does not require additional suspension force winding. No additional search coil placement for xy-position estimation is required. Therefore, the proposed algorithm can result in a compact size self-bearing machine that does not require external sensors for xy-position measurement and suspension force winding.

Epidemiological aspects of hereditary fructose intolerance: A database study.

Hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism of autosomal recessive inheritance caused by pathogenic variants in the ALDOB gene that lead to aldolase B deficiency in the liver, kidneys, and intestine. Patients manifest symptoms, such as ketotic hypoglycemia, vomiting, nausea, in addition to hepatomegaly and other liver and kidney dysfunctions. The treatment consists of a fructose-restricted diet, which results in a good prognosis. To analyze the distribution of ALDOB variants described in patients and to estimate the prevalence of HFI based on carrier frequency in the gnomAD database, a systematic review was conducted to assess ALDOB gene variants among patients with HFI. The prevalence of HFI was estimated from the carrier frequency of variants described in patients, as well as rare variants predicted as pathogenic by in silico tools. The p.(Ala150Pro) and p.(Ala175Asp) variants are the most frequent and are distributed worldwide. However, these variants have particular distribution patterns in Europe. The analysis of the prevalence of HFI showed that the inclusion of rare alleles predicted as pathogenic is a more informative approach for populations with few patients. The data show that HFI has a wide distribution and an estimated prevalence of ~1:10,000.

n-3 Fatty acids preserve muscle mass and insulin sensitivity in a rat model of energy restriction.

In obese subjects, the loss of fat mass during energy restriction is often accompanied by a loss of muscle mass. The hypothesis that n-3 PUFA, which modulate protein homoeostasis via effects on insulin sensitivity, could contribute to maintain muscle mass during energy restriction was tested in rats fed a high-fat diet (4 weeks) rich in 18 : 1 n-9 (oleic acid, OLE-R), 18 : 3 n-3 (α-linolenic acid, ALA-R) or n-3 long-chain (LC-R) fatty acid and then energy restricted (8 weeks). A control group (OLE-ad libitum (AL)) was maintained with AL diet throughout the study. Rats were killed 10 min after an i.v. insulin injection. All energy-restricted rats lost weight and fat mass, but only the OLE-R group showed a significant muscle loss. The Gastrocnemius muscle was enriched with ALA in the ALA-R group and with LC-PUFA in the ALA-R and LC-R groups. The proteolytic ubiquitin-proteasome system was differentially affected by energy restriction, with MAFbx and muscle ring finger-1 mRNA levels being decreased in the LC-R group (-30 and -20 %, respectively). RAC-α serine/threonine-protein kinase and insulin receptor substrate 1 phosphorylation levels increased in the LC-R group (+70 %), together with insulin receptor mRNA (+50 %). The ALA-R group showed the same overall activation pattern as the LC-R group, although to a lesser extent. In conclusion, dietary n-3 PUFA prevent the loss of muscle mass associated with energy restriction, probably by an improvement in the insulin-signalling pathway activation, in relation to enrichment of plasma membranes in n-3 LC-PUFA.

Food insecurity and malnutrition in Chinese elementary school students.

It has been shown that food insecurity is associated with poor diet quality and unfavourable health outcomes. However, little is known about the potential effects of food insecurity on the overall malnutrition status among children. In this study, we investigated the prevalence of food insecurity among 1583 elementary school students, aged 6-14 years, living in Chinese rural areas and examined its association with four malnutrition signs, including rickets sequelae, anaemia, stunting and wasting. Information on food security was collected via questionnaires. Rickets sequelae were assessed by an experienced paediatrician during the interview. Anaemia was determined by the WHO Hb thresholds adjusted by the local altitude. Weight and height were measured during the interview. Stunting and wasting were then evaluated according to WHO child growth standards (2007). We examined the association between food insecurity and the number of malnutrition signs (total number = 4), and the likelihood of having severe malnutrition (presence of 3+ signs), after adjusting for potential confounders, such as age, social-economic status and dietary intakes. During the previous 12 months, the overall prevalence of food insecurity was 6.1% in the entire studied population and 16.3% in participants with severe malnutrition. Participants with food insecurity had a slightly higher number of malnutrition signs (1.14 v. 0.96; P=0.043) relative to those who were food secure, after adjusting for potential confounders. Food insecurity was also associated with increased likelihood of having severe malnutrition (adjusted OR 3.08; 95% CI 1.47, 6.46; P=0.003). In conclusion, food insecurity is significantly associated with malnutrition among Chinese children in this community.

Impact of Zeeman and hyperfine interactions on the magnetic properties of paramagnetic metal ions: II. Super-hyperfine interactions with surrounding nuclei.

The anisotropic Zeeman and strong hyperfine interactions of a Kramers ion can significantly affect its magnetic properties as well as the interactions with the nearby nuclei. The interactions with the local environment are described in the preceding article. In the current work, the change of the spin states of distant nuclei is studied. Analytical expressions describing the depth of the electron spin echo envelope modulation (ESEEM) are obtained for the ions with anisotropic Zeeman and strong hyperfine interactions. Due to the g-tensor anisotropy, the electron Zeeman interaction axis is tilted in respect to the direction of the external magnetic field which makes non-collinear with the Zeeman interaction axes of the ion and the nearby nuclei and significantly modifies the nuclear spin states. Thus, the isotropic hyperfine interaction, and particularly the Fermi contact interaction can directly contribute to the ESEEM. An additional factor, that can significantly modify the ESEEM signal is the mixing of the multiple oscillations arising when several nuclei occur in optimal conditions for the generation of the nuclear coherence. This situation arises when several EPR transitions of the ion covering a wide range of magnetic fields are examined.

Impact of Zeeman and hyperfine interactions on the magnetic properties of paramagnetic metal Ions: I. Local interactions of the electron spin.

The anisotropic Zeeman interaction of an ion, and the strong hyperfine interaction with its own nucleus, can significantly influence its interactions with the local environment. These effects, including the reduction of the effective magnetic moment of the electron spin and the phase memory decay rate, are studied theoretically. Analytical expressions describing the mean magnetic moment of the electron spin are obtained. The results of the theoretical analysis and accompanying numerical computations show that the strong hyperfine interaction of the ion reduces its effective magnetic moment. In particular, a 7% reduction is found for the scandium endofullerene Sc2@C80(CH2Ph) under conditions typical of an X-band EPR experiment.

Impact of Zeeman and hyperfine interactions on the magnetic properties of paramagnetic metal Ions: III. Analysis of the local interactions in a single crystal of 173Yb3+ doped Y5SiO5.

The electron spin echo envelope modulation (ESEEM) technique is a direct method to probe the nuclear spin coherences induced by electron spin transitions. Recently, this approach was used to study an isotopically pure Y2SiO5 crystal doped with 173Yb3+ ions, and the presence of the Fermi contact interaction was proposed to explain the frequency comb detected in the two-pulse ESEEM experiment [Solovarov N. K. et al. JETP Letters 115 (6): 362-67]. Here we simulate the Fourier images of the ESEEM data. The numerical analysis shows that the modulation is mainly due to the nuclear spin coherences induced by the dipole-dipole interactions. However, the correlation between the experimental and simulated data is better when the super-hyperfine interactions of the nearby yttrium nuclei have an additional isotropic contribution. The analysis of the rescaled X-band ESEEM spectra shows that for the EPR transitions at magnetic fields > 100 mT, the main contribution to the modulation comes from the oscillations of the individual nuclei and the effect of interference between coherences originating from several nuclei is not strong. Further experiments to distinguish the sources of the echo modulation are discussed.

Electron and nuclear magnetic properties near ZEFOZ region.

In the vicinity of spin level anti-crossings, electron-nuclear spin systems reveal characteristic features that have been investigated by electron paramagnetic resonance (EPR) methods, including electron spin echo envelope modulation (ESEEM). The spectral properties depend considerably on the difference, ΔB, between the magnetic field and the critical field at which the zero first-order Zeeman shift (ZEFOZ) occurs. To analyze the characteristic features near the ZEFOZ point, analytical expressions for the behavior of EPR spectra and ESEEM traces as a function of ΔB are obtained. It is shown that the influence of hyperfine interactions (HFI) decreases linearly when approaching the ZEFOZ point. The HFI splitting of the EPR lines is essentially independent of ΔB near the ZEFOZ point, while the depth of the ESEEM signal has an approximately quadratic dependence on ΔB with a small cubic asymmetry due to the Zeeman interaction of the nuclear spin.

Endogenous Fructose Production and Metabolism Drive Metabolic Dysregulation and Liver Disease in Mice with Hereditary Fructose Intolerance.

Excessive intake of sugar, and particularly fructose, is closely associated with the development and progression of metabolic syndrome in humans and animal models. However, genetic disorders in fructose metabolism have very different consequences. While the deficiency of fructokinase, the first enzyme involved in fructose metabolism, is benign and somewhat desirable, missense mutations in the second enzyme, aldolase B, causes a very dramatic and sometimes lethal condition known as hereditary fructose intolerance (HFI). To date, there is no cure for HFI, and treatment is limited to avoiding fructose and sugar. Because of this, for subjects with HFI, glucose is their sole source of carbohydrates in the diet. However, clinical symptoms still occur, suggesting that either low amounts of fructose are still being consumed or, alternatively, fructose is being produced endogenously in the body. Here, we demonstrate that as a consequence of consuming high glycemic foods, the polyol pathway, a metabolic route in which fructose is produced from glucose, is activated, triggering a deleterious mechanism whereby glucose, sorbitol and alcohol induce severe liver disease and growth retardation in aldolase B knockout mice. We show that generically and pharmacologically blocking this pathway significantly improves metabolic dysfunction and thriving and increases the tolerance of aldolase B knockout mice to dietary triggers of endogenous fructose production.

SAGA Complex Subunit Hfi1 Is Important in the Stress Response and Pathogenesis of Cryptococcus neoformans.

The Spt-Ada-Gcn Acetyltransferase (SAGA) complex is a highly conserved co-activator found across eukaryotes. It is composed of a number of modules which can vary between species, but all contain the core module. Hfi1 (known as TADA1 in Homo sapiens) is one of the proteins that forms the core module, and has been shown to play an important role in maintaining complex structural integrity in both brewer's yeast and humans. In this study we successfully identified the gene encoding this protein in the important fungal pathogen, Cryptococcus neoformans, and named it HFI1. The hfi1Δ mutant is highly pleiotropic in vitro, influencing phenotypes, ranging from temperature sensitivity and melanin production to caffeine resistance and titan cell morphogenesis. In the absence of Hfi1, the transcription of several other SAGA genes is impacted, as is the acetylation and deubiquination of several histone residues. Importantly, loss of the gene significantly impacts virulence in a murine inhalation model of cryptococcosis. In summary, we have established that Hfi1 modulates multiple pathways that directly affect virulence and survival in C. neoformans, and provided deeper insight into the importance of the non-enzymatic components of the SAGA complex.

MRI Imaging Appearance of Hyperostosis Frontalis Interna (HFI): A Case Report of Focal Benign Enhancement.

Hyperostosis frontalis interna (HFI) is a common and often incidental finding seen on imaging. There is a significant paucity of radiology literature, particularly regarding the MRI imaging appearance of HFI. We reported two cases of HFI on MRI, which showed focal enhancement. These were stable on long-term follow-up studies and thought to be most consistent with benign enhancement. Further studies are needed to elucidate the underlying pathogenesis; however, it is important to be aware that regions of HFI may demonstrate variable enhancement and are sometimes mistaken for osseous metastatic disease.

Development of tools to facilitate the diagnosis of hereditary fructose intolerance.

Although hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism that classically presents at infancy, the diagnosis is often missed or delayed. In this study, we aimed to develop tools to facilitate the diagnosis of HFI. The intake of fructose-containing food products, that is, fruit, fruit juice and sugar-sweetened beverages, was assessed by a 3-day food diary in adult HFI patients (n = 15) and age, sex, and BMI-matched controls (n = 15). Furthermore, glycosylation of transferrin was examined using high-resolution mass spectrometry and abnormally glycosylated transferrin was expressed as ratio of normal glycosylated transferrin. We found that the sensitivity and specificity of the 3-day food diary for the intake of at least one fructose-containing food product were both 100%. Both mono-glyco:diglyco transferrin and a-glyco+mono-glyco:di-glyco transferrin were greater in HFI patients and had a high-discriminatory power (area under the receiver operating characteristic curve: 0.97 and 0.94, respectively). In this well-characterized cohort of adult HFI patients, the 3-day food questionnaire and the glycosylation pattern of transferrin are valuable tools to facilitate the recognition and diagnosis of HFI in adult patients.

A Case Report of Hyperostosis Frontalis Interna.

A routine dissection of an 89-year-old female cadaver who had died of cardiopulmonary arrest revealed a unique case of hyperostosis frontalis interna (HFI). Multiple layers of spongy bone growth deep to the internal table were coupled with asymmetrical nodular growths. Slight superior sagittal sinus growth was also noted, which is atypical of this condition. Additionally, this cadaver represents one of the rarer and more severe forms of HFI, class C. A clear consensus on whether HFI presents a clinical risk has not been reached. We hope that this report on a unique manifestation of HFI will help clinicians in evaluating patients with this condition.

The Impact of Obesity on Cardiovascular Fitness in Young Individuals.

Background Young individuals are often at a higher risk for cardiovascular disease and obesity due to lifestyle changes like less physical activity and a sedentary lifestyle. Objective The aim of this study is to determine cardiovascular fitness in young individuals and to study the effects of obesity on their cardiovascular fitness. Material and methods In this study, 100 young individuals, out of which 50 were individuals with obesity and 50 were controls, including males and females, of the age group 18-25 years were included. Cardiovascular fitness was assessed in them using body mass index (BMI) and waist-to-hip ratio (WHR). Parameters like SBP (systolic blood pressure), DBP (diastolic blood pressure), PR (pulse rate), and HFI (Harvard fitness index) were measured. Results There was no difference found in the PR of the group with obesity compared to the control group (79.020/min ± 8.651 versus 79.42/min ± 6.737; p value = 0.797). However, a significant increase was observed in both SBP and DBP amongst the group with obesity compared to the control group (SBP = 122.72 mmHg ± 12.287 versus 110.92 mmHg ± 11.803; p-value < 0.001, DBP = 81.96 mmHg ± 7.913 versus 73.24 mmHg ± 11.06; p-value < 0.001). There was a significant reduction in HFI in the group with obesity than in the control group (57.44% ± 9.322 versus 80.34% ± 12.594; p-value < 0.001). When we compared males with obesity and females with obesity, we observed a non-significant difference in PR between males with obesity and females with obesity (77.12/min ± 6.02 versus 80.92/min ± 10.44; p-value = 0.122). However, we found a significant increase in SBP in males with obesity compared to females with obesity (127.76 mmHg ± 10.93 versus 117.68 mmHg ± 11.66; p-value < 0.01). A significant decrease in DBP in males with obesity (78.80 mmHg ± 7.55 versus 85.12 mmHg ± 7.07; < 0.01) than in females with obesity was also observed. Along with a non-significant increase in HFI value in males with obesity compared to females with obesity (58.96% ± 8.14 versus 55.92% ± 10.31; p-value = 0.253). Conclusion Results suggest that both male and female young individuals with obesity are at higher risk for developing cardiovascular comorbidities in the future. So, we need to focus on encouraging activities that promote physical fitness.

Evaluation of overall gait quality in Perthes disease. Are global gait indices of value for a local musculoskeletal disorder?

BACKGROUND: Until now follow-up- and outcome evaluations in Perthes disease are analysing predominantly subjective results and clinical/radiological parameters. To enlarge the assessment by quantitative, functional aspects a summary measure for overall gait quality would be helpful. Therefore, the objective of this study is to evaluate whether commonly used global gait indices are sensitive to detect gait deviations during the early stages of the Perthes disease. METHODS: 3D gait data of 70 patients scheduled for containment improving surgery with the diagnosis of Perthes were included. A group of 31 healthy children served as a control group. Based on 4 gait cycles of each subject the Gait Deviation Index, the Gillette Gait Index, the Hip Flexor Index and the Gait Deviation Index-Kinetic were calculated for the involved and non-involved side. The gait indices were compared (1) between patients and controls, (2) among patients sub-grouped by ROM/radiological classifications and (3) between the two limbs. FINDINGS: All applied gait indices besides the Gait Deviation Index-Kinetic of the patient-group are significantly different from the controls. The subgroup-analysis resulted only in significant differences between the radiological groups Herring B and C for the Gillette Gait Index. Comparing involved and non-involved side showed no significant differences. INTERPRETATION: The evaluated gait indices are sensitive to identify a pathologic gait pattern in Perthes disease, so they can be used as a functional outcome parameter evaluating treatment concepts. Nevertheless, these are not applicable to identify the pathologic side indicating that a local hip problem leads to global gait deviations.

Insulin-Regulated Aminopeptidase Inhibition Ameliorates Metabolism in Obese Zucker Rats.

The aim of our study was to determine the influence of inhibition of insulin-regulated aminopeptidase/oxytocinase (IRAP) on glucose tolerance and metabolism of skeletal muscle and visceral adipose tissue in obese Zucker rats. Obese Zucker rats administered with IRAP inhibitor-HFI-419 at a dose of 29 µg/100 g BW/day by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hour intraperitoneal glucose tolerance test (ipGTT) was performed in fasting rats. Plasma oxytocin levels were measured by enzyme immunoassay after plasma extraction. In the musculus quadriceps and epididymal adipose tissue, the expression of factors affecting tissue oxidative status and metabolism was determined by real-time qPCR and/or Western blot analysys. The plasma and tissue enzymatic activities were determined by colorimetric or fluorometric method. Circulated oxytocin levels in obese animals strongly tended to increase after HFI-419 administration. This was accompanied by significantly improved glucose utilization during ipGTT and decreased area under the curve (AUC) for glucose. In skeletal muscle IRAP inhibitor treatment up-regulated enzymes of antioxidant defense system - superoxide dismutase 1 and 2 and improved insulin signal transduction pathway. HFI-419 increased skeletal muscle aminopeptidase A expression and activity and normalized its plasma levels in obese animals. In epididymal adipose tissue, gene expression of markers of inflammation and adipocyte hypertrophy was down-regulated in obese rats after HFI-419 treatment. Our results demonstrate that IRAP inhibition improves whole-body glucose tolerance in insulin-resistant Zucker fatty rats and that this metabolic effect of HFI-419 involves ameliorated redox balance in skeletal muscle.

Kidney and vascular function in adult patients with hereditary fructose intolerance.

Objective: Previous studies have shown that patients with hereditary fructose intolerance (HFI) are characterized by a greater intrahepatic triglyceride content, despite a fructose-restricted diet. The present study aimed to examine the long-term consequences of HFI on other aldolase-B-expressing organs, i.e. the kidney and vascular endothelium. Methods: Fifteen adult HFI patients were compared to healthy control individuals matched for age, sex and body mass index. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) and endothelial function by peripheral arterial tonometry, skin laser doppler flowmetry and the endothelial function biomarkers soluble E-selectin [sE-selectin] and von Willebrand factor. Serum creatinine and cystatin C were measured to estimate the glomerular filtration rate (eGFR). Urinary glucose and amino acid excretion and the ratio of tubular maximum reabsorption of phosphate to GFR (TmP/GFR) were determined as measures of proximal tubular function. Results: Median systolic blood pressure was significantly higher in HFI patients (127 versus 122 mmHg, p = .045). Pulse pressure and cf-PWV did not differ between the groups (p = .37 and p = .49, respectively). Of all endothelial function markers, only sE-selectin was significantly higher in HFI patients (p = .004). eGFR was significantly higher in HFI patients than healthy controls (119 versus 104 ml/min/1.73m2, p = .001, respectively). All measurements of proximal tubular function did not differ significantly between the groups. Conclusions: Adult HFI patients treated with a fructose-restricted diet are characterized by a higher sE-selectin level and slightly higher systolic blood pressure, which in time could contribute to a greater cardiovascular risk. The exact cause and, hence, clinical consequences of the higher eGFR in HFI patients, deserves further study.

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model.

Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n=15) and incubated with 3mM Hcy to induce vascular dysfunction in vitro for 1h. HFI419 was added 5min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5±8.9% relaxation vs 79.2±37% constriction, p<0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9±4.6% relaxation vs 11.1±5.2%, constriction, p<0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm.