Biomedical subjects

Takeo Fukuchi

Publications and source records attributed to Takeo Fukuchi.

At least 19 recordsLinked to original sources

PubMed2006

Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma.

PURPOSE: The human trabecular meshwork and ciliary body, which express beta-adrenergic receptors (ADRB1 and ADRB2), control aqueous humor dynamics. We investigated associations of ADRB polymorphisms with open-angle glaucoma (OAG), because ADRB gene polymorphisms alter receptor function. METHODS: We studied 240 Japanese controls and 505 Japanese OAG patients including 211 with primary open-angle glaucoma (POAG), and 294 with normal-tension glaucoma (NTG). Associations of four polymorphisms (Ser49Gly and Arg389Gly in the ADRB1 gene; Arg16Gly and Gln27Glu in the ADRB2 gene) were compared between patients and controls. Age, intraocular pressure (IOP), and visual field defects at diagnosis were examined for associations with polymorphisms. RESULTS: The Arg389Gly polymorphism in the ADRB1 gene showed significantly different allele and genotype frequencies in patients with NTG than in controls (p = 0.004 and 0.006, respectively). Other polymorphisms did not show a significant frequency difference. In POAG patients, carriers of Gly16 in the ADRB2 gene were significantly younger at diagnosis than noncarriers (p<0.001). The IOP at diagnosis was significantly higher in OAG patients carrying 27Glu in the ADRB2 gene than in patients without this allele (p<0.001). Clinical characteristics of OAG patients did not differ significantly in relation to other polymorphisms. CONCLUSIONS: Certain polymorphisms of the ADRB1 and ADRB2 genes influence the pathophysiology of OAG in Japanese patients.

Aged↗

PubMed2006

Paraoxonase 1 gene polymorphisms influence clinical features of open-angle glaucoma.

BACKGROUND: The purpose of this study was to determine whether genetic polymorphisms affecting high-density lipoprotein (HDL)-associated antioxidant enzymes were associated with open-angle glaucoma (OAG). The rationale for this study was that the modification of low-density lipoprotein (LDL) by HDL prevents oxidative modification which can then cause dysfunction of endothelial cells. METHODS: We studied 284 normal Japanese controls and 555 Japanese patients with OAG, including primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). The possible associations of polymorphisms of PON1/L55M, PON1/Q192R, PON2/S311C, and PAF-AH/V279F with OAG were investigated. We compared the genotype distributions and allele frequency in controls and patient groups. The age at diagnosis, intraocular pressure (IOP) at diagnosis, and visual field score at diagnosis were examined for association with polymorphisms. RESULTS: The distributions of genotypes and allele frequency for the four polymorphisms were not significantly different between any patient group and controls. In NTG patients, 55M carriers of the PON1 gene were significantly older at diagnosis than 55M non-carriers (P=0.001). The IOP at diagnosis was significantly higher in glaucoma patients carrying 192R in the PON1 gene than in patients not carrying 192R (P=0.006). No significant differences were seen in clinical characteristics of OAG patients in relation to other polymorphisms. CONCLUSION: PON1 gene polymorphisms may influence the features of Japanese patients with OAG.

Adult↗

PubMed2006

SNPs and interaction analyses of noelin 2, myocilin, and optineurin genes in Japanese patients with open-angle glaucoma.

PURPOSE: To evaluate the noelin 2 gene as a disease-causing factor for open-angle glaucoma (OAG) and the interactions between the noelin 2 (OLFM2), optineurin (OPTN), and myocilin (MYOC) genes. METHODS: OLFM2 was analyzed in 770 Japanese subjects including 215 patients with elevated intraocular pressure (IOP), 277 with normal IOP, 38 with juvenile open-angle glaucoma, and 240 control subjects. Two single-nucleotide polymorphisms (SNPs) in OPTN (c.412G-->A and c.603T-->A) and one SNP in MYOC (c.227G-->A) were examined. Single genes were investigated by univariate analysis and the gene-gene interactions by logistic regression analysis. Associations between genotypes and clinical characteristics at the time of diagnosis were examined. RESULTS: In OLFM2, 12 sequence variants were identified in 770 Japanese subjects. Arg144Gln (exon 4) was identified in two (0.3%) of the patients and in none of the control subjects. Combinations of OLFM2/317A and OPTN/412A or OLFM2/1281T and OPTN/412A were associated with patients with elevated IOP (P = 0.018 or P = 0.012, respectively). The combination of OLFM2/317G and OPTN/603A was significantly associated with elevated IOP (P = 0.018). No significant association was detected between SNPs in OLFM2 and in MYOC. Patients with normal IOP and with OLFM2/678A+OPTN/412G or OLFM2/1281C+OPTN/412G had significantly worse visual field scores (P = 0.022 or 0.030, respectively). CONCLUSIONS: The Arg144Gln mutation in OLFM2 is a possible disease-causing mutation in Japanese patients with OAG. Common polymorphisms in OLFM2 and OPTN may interactively contribute to the development of OAG, indicating a polygenic etiology.

Adult↗

PubMed2005

Association between glaucoma and gene polymorphism of endothelin type A receptor.

PURPOSE: Endothelin 1 (ET-1), a potent vasoconstrictor, may affect regulation of intraocular pressure and ocular vessel tone. Thus, ET-1 and its receptors may contribute to development of glaucoma. We investigated whether gene polymorphisms of ET-1 (EDN1) and its receptors ETA (EDNRA) and ETB (EDNRB) were associated with glaucoma phenotypes and clinical features. METHODS: We studied 224 normal Japanese controls and 426 open angle glaucoma (OAG) patients including 176 with primary open angle glaucoma (POAG) and 250 with normal tension glaucoma (NTG). Nine single nucleotide polymorphisms were detected among the participants using the Invader assay; four for EDN1 (T-1370G, +138/ex1 del/ins, G8002A, K198N), four for EDNRA (G-231A, H323H, C+70G, C+1222T), and one for EDNRB (L277L). Genotype distributions were compared between normal controls and OAG. Age at diagnosis, untreated maximum intraocular pressure (IOP), and visual field defects at diagnosis were examined for association with polymorphisms. RESULTS: Of the 9 polymorphisms, genotype distributions showed no significant differences between OAG patients and controls adjusted by age. The GG genotype of EDNRA/C+70G was associated with worse visual field defects in NTG patients (p=0.014; Mann-Whitney U test, and p=0.027; logistic regression analysis). CONCLUSIONS: The polymorphism of EDNRA/C+70G may be related to NTG risk factors.

Aged↗

PubMed2005

Müller Cells as a source of brain-derived neurotrophic factor in the retina: noradrenaline upregulates brain-derived neurotrophic factor levels in cultured rat Müller cells.

Müller cells, the predominant glial cells in the retina, are thought to play important roles in the survival of retinal neurons. Previous studies have demonstrated that Müller cells express brain-derived neurotrophic factor (BDNF), which has a pronounced neurotrophic effect on retinal ganglion cells. In this study, we investigated whether Müller cells express and release BDNF in culture. Reverse transcriptase-PCR, immunocytochemistry and Western blotting revealed that Müller cells produce BDNF mRNA and protein. Using the enzyme-linked immunosorbant assay, BDNF protein levels in Müller cells and their conditioned medium were quantified, demonstrating that Müller cells produce and release high levels of BDNF. Noradrenaline administration caused an upregulation of BDNF mRNA and protein expression by cultured Müller cells. These results suggest that Müller cells may act as an endogenous source of BDNF in the retina. Furthermore, induction of BDNF expression by adrenergic agonists may provide a therapeutic approach to retinal neurodegenerative disorders.

Animals↗

PubMed2005

Genetic polymorphisms in the angiotensin II receptor gene and their association with open-angle glaucoma in a Japanese population.

PURPOSE: The local renin-angiotensin system (RAS) is present in the ciliary body and plays a role in regulating aqueous humor dynamics and thus intraocular pressure (IOP). The purpose of this study was to determine whether gene polymorphisms in the RAS increase the risk of development of glaucoma in the Japanese. METHODS: A case-control study was performed in 698 Japanese subjects: 190 patients with primary open-angle glaucoma (POAG), 268 patients with normal-tension glaucoma (NTG), and 240 normal subjects. Ten polymorphisms in seven genes-AGT/Thr174Met and AGT/Met235Thr; REN/I8-83G-->A; ACE/insertion(I)-deletion(D); CMA/-1930A-->G; AGTR1/-731T-->G, AGTR1/-521C-->T, and AGTR1/1166A-->C; AGTR2/3123C-->A; and CYP11B2/-344T-->C were examined. The age, IOP, and visual field defects, all at diagnosis, were examined to determine whether they were associated with the polymorphisms. The effects of oral angiotensin II receptor blocker (ARB) on IOP were examined in association with the AGTR1 and AGTR2 polymorphisms in 20 normal subjects. RESULTS: Of the 10 polymorphisms, the AGTR2/3123C-->A polymorphisms had a significantly different distribution in female patients with NTG; the frequency of the CA+AA genotypes was significantly higher than in female control subjects (P = 0.0095 for CC versus CA+AA). Although no significant difference was seen in the clinical characteristics of female patients with NTG who carried the AGTR2/3123C-->A genotype, patients with CC in the AGTR2 gene had significantly worse visual field scores if they carried ACE/ID+DD (i.e., D carriers; P = 0.012). ARB significantly lowered IOP in normal subjects, but the male subjects with the AGTR2/3123A genotype had significantly less lowering of IOP than those with the C genotype (P = 0.014). CONCLUSIONS: Angiotensin II receptor gene polymorphisms may be associated with the risk of glaucoma in the Japanese population.

Administration, Oral↗

PubMed2004

Variants in optineurin gene and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma.

PURPOSE: To investigate sequence variations in the optineurin (OPTN) gene and their association with TNF-alpha polymorphisms in Japanese patients with glaucoma. METHODS: The OPTN gene was analyzed in blood samples from 629 Japanese subjects. There were 194 patients with primary open-angle glaucoma (POAG), 217 with normal-tension glaucoma (NTG), and 218 with no eye disease (control subjects). The gene was screened for mutations by denaturing high-performance liquid chromatography. Genotyping of three polymorphisms of -308G-->A, -857C-->T, and -863C-->A in the TNF-alpha promoter region was performed. The associations between the genotypes and age, intraocular pressure (IOP), and visual field defects at the time of diagnosis were examined. RESULTS: A possible glaucoma-causing mutation, His26Asp, was identified in 1 of the 411 Japanese patients with glaucoma. A c.412G-->A (Thr34Thr) polymorphism in the OPTN gene was significantly associated with POAG (genotype frequency, P = 0.011; allele frequency, P = 0.003). The frequency of TNF-alpha/-857T and optineurin/412A carriers was significantly higher (P = 0.006) in patients with POAG than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-857T, the optineurin/412A carriers had significantly worse (P = 0.020) visual field scores than the non-optineurin/412A ones. The frequency of TNF-alpha/-863A and optineurin/603A (or Lys98) carriers was significantly higher in patients with POAG (P = 0.008) or NTG (P = 0.027) than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-863A, the ones with optineurin/603A (or Lys98) had significantly worse (P = 0.026) visual field scores than did those with non-optineurin/603A (or Lys98). CONCLUSIONS: These findings demonstrated that the OPTN gene is associated with POAG rather than NTG in the Japanese. Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-alpha genes that would increase the risk for glaucoma.

Adult↗

PubMed2004

Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells.

Although neurotrophins have been assessed as candidate therapeutic agents for neural complications of diabetes, their involvement in diabetic retinopathy has not been fully characterized. We found that the protein and mRNA levels of brain-derived neurotrophic factor (BDNF) in streptozotocin-induced diabetic rat retinas were reduced to 49% (P < 0.005) and 74% (P < 0.05), respectively, of those of normal control animals. In addition, dopaminergic amacrine cells appeared to be degenerating in the diabetic rat retinas, as revealed by tyrosine hydroxylase (TH) immunoreactivity. Overall TH protein levels in the retina were decreased to one-half that of controls (P < 0.01), reflecting reductions in the density of dopaminergic amacrine cells and the intensity of TH immunoreactivity within them. To confirm the neuropathological implications of BDNF reduction, we administered BDNF protein into the vitreous cavities of diabetic rats. Intraocular administration of BDNF rescued dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of TH expression, demonstrating its therapeutic potential. These findings suggest that the early retinal neuropathy of diabetes involves the reduced expression of BDNF and can be ameliorated by an exogenous supply of this neurotrophin.

Amacrine Cells↗

PubMed2004

[A case of acute angle-closure glaucoma secondary to annular ciliochoroidal detachment after unsutured cataract surgery].

BACKGROUND: We report a patient with acute angle-closure glaucoma secondary to annular ciliochoroidal detachment after unsutured cataract surgery. CASE: An 82-year-old man was diagnosed with bilateral shallow central anterior chamber depth, flat peripheral anterior chamber, and elevated intraocular pressure. One day previously he had undergone uncomplicated unsutured cataract surgery in the right eye and eight days previously, in the left eye. Ultrasound biomicroscopy revealed annular ciliochoroidal detachment in both eyes. Treatment with intravenous methyl prednisolone deepened the anterior chamber and reduced intraocular pressure. CONCLUSION: Annular ciliochoroidal detachment may lead to anterior rotation of the ciliary body and angle-closure. This clinical entity is indistinguishable from malignant glaucoma when the fundus cannot be visualized.

Acute Disease↗

PubMed2003

BDNF is upregulated by postnatal development and visual experience: quantitative and immunohistochemical analyses of BDNF in the rat retina.

PURPOSE: This study sought to elucidate changes in the levels and distribution of brain-derived neurotrophic factor (BDNF) in the retina throughout aging and depending on visual experience. METHODS: Protein and mRNA levels of BDNF were quantified by enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Levels were assayed in the retinas of rats on postnatal day (P)2, P7, and P14 (approximate time of eye opening) and at 1 month (M), 3M, 8M, and 18M of age. Changes in BDNF expression and localization in the retina were assessed by immunohistochemistry. The effect of monocular deprivation during infancy on retinal BDNF expression was also examined, by ELISA and immunohistochemistry. RESULTS: Both protein and mRNA levels of BDNF in the rat retina increased after P14. Immunohistochemical analyses revealed that the increase in BDNF protein levels occurred in retinal ganglion cells (RGCs) between P14 and 1M. BDNF immunoreactivity in Müller cell processes was observed in the inner nuclear layer at 1M, but not at P14. The levels of BDNF protein in the retinas of visually deprived eyes were lower than those of control eyes, as quantified by ELISA. Immunohistochemistry showed that BDNF immunoreactivity in RGCs was diminished by visual deprivation, whereas Müller cells were unaffected. CONCLUSIONS: These observations indicate that BDNF expression in RGCs is upregulated in an activity-dependent manner, whereas that in Müller cells is regulated only by development.

Aging↗

PubMed2003

[A case of steroid-induced glaucoma after radial keratotomy].

BACKGROUND: We report a patient who was diagnosed as having steroid-induced glaucoma after radial keratotomy(RK) and suffered from severe visual field defect. CASE: A 29-year-old man underwent RK for both eyes. After the operation, he was treated for six months with topical medication including 0.1% and 0.01% betamethasone without measuring intraocular pressure(IOP). When he consulted an ophthalmologist, his IOP was 43 mmHg in the right eye and 51 mmHg in the left eye. At our initial examination, his IOP was 8 mmHg in the right eye and 10 mmHg in the left eye with 750 mg acetazolamide peroral, 0.5% timolol maleate, and latanoprost eyedrops. There were RK 16 incisions on the cornea and we found severe glaucomatous visual field loss. Finally we performed trabeculotomy in both eyes for IOP control with conservative therapy. CONCLUSION: As the keratorefractive surgery becomes popular, we must be careful of problems, such as steroid-induced glaucoma, and the change of refraction following the change of IOP.

Administration, Topical↗

PubMed2002

Establishment of a novel enzyme-linked immunosorbent assay for Thy-1; quantitative assessment of neuronal degeneration.

In the central nervous system (CNS), Thy-1 is expressed predominantly on neurons and serves as a specific marker for neurons. In the present study, we established a two-site enzyme-linked immunosorbent assay (ELISA) that detects trace amounts of Thy-1 protein. Recombinant Thy-1 protein expressed in Escherichia coli was purified and used as a standard. Of the regions of the nervous system examined, the highest Thy-1 concentration was found in the striatum followed by the hippocampus, neocortex, cerebellum, spinal cord, retina and optic nerve. We found that injection of a neurotoxin, N-methyl-D-aspartate, into the vitreous cavity reduced the Thy-1 level in the retina. Thy-1 ELISA will be useful for quantitative assessment of neurodegeneration in the CNS.

Animals↗

PubMed2002

Corneal endothelial damage after trabeculectomy with mitomycin C in two patients with glaucoma with cornea guttata.

PURPOSE: To report two patients with glaucoma who exhibited severe damage to the corneal endothelium after a trabeculectomy with mitomycin C (MMC). METHODS: This study includes clinical histories and specular microscopic pictures of the cases. RESULTS: Both patients were middle-aged women, underwent trabeculectomy with MMC, had moderate to severe cornea guttata preoperatively, and developed a shallow to flat anterior chamber, classified as grade 2 according to Spaeth early in the postoperative period. Stromal opacity caused by corneal edema associated with severe Descemet's membrane folds appeared within 2 to 5 days in both cases. The density of the corneal endothelium was decreased on specular microscopic examination. The severe corneal endothelial damage seen after the trabeculectomy with MMC was likely owing to a combination of the preexisting cornea guttata, the flat anterior chamber, and possibly the administration of MMC. CONCLUSION: Severe endothelial damage after trabeculectomy with MMC may occur in patients with glaucoma and associated cornea guttata. The use of tight sutures on the scleral flap or a modified operative method, nonpenetrating trabeculectomy, may be effective in preventing a shallow to flat anterior chamber postoperatively.

Adult↗

PubMed2002

[Changes in filtering bleb with laser treatment after non-penetrating trabeculectomy].

PURPOSE: Ultrasound biomicroscopy(UBM) was performed on filtering blebs with laser treatment including laser gonioplasty(GP), laser iridotomy(LI), and YAG laser trabeculopuncture(YLT) after non-penetrating trabeculectomy(NPT). The filtering blebs were grouped into four types, L, H, E and F, and the spaces under the scleral flap were classified into three. La, S, and N. CASES: In case 1, an F type, an S bleb was not changed despite laser treatment 9 months after NPT. In case 2, YLT was performed twice to release the incarcerated iris. The filtering bleb was changed to the L type, an La bleb. In case 3, an F type, an S bleb was turned into an H type after GP, LI, and YLT. In case 4, GP effectively released peripheral anterior synechia formation and the filtering bleb was kept as an L type, La. CONCLUSION: Appropriate laser treatment may be effective in turning a flattened and localized bleb into a good filtering bleb.

Anterior Eye Segment↗

PubMedDate not supplied

Quantitative analyses of mRNA and protein levels of neurotrophin-3 in the rat retina during postnatal development and aging.

PURPOSE: In this study, we sought to elucidate changes in the levels of neurotrophin-3 (NT-3) in the rat retina throughout postnatal development and aging. METHODS: We demonstrated NT-3 localization in the retina by immunohistochemistry. Protein and mRNA levels of NT-3 were quantified by enzyme-linked immunosorbant assay and semiquantitative reverse transcriptase-polymerase chain reaction, respectively. NT-3 protein levels were assayed in the various regions of the central nervous system. Age-associated changes in protein and mRNA levels of NT-3 in the retinas were assessed. RESULTS: NT-3-immunoreactivity localized in the ganglion cell layer, inner nuclear layer, and outer nuclear layer. NT-3 content in the retina was relatively high in the examined regions of the central nervous system. Retinal NT-3 protein levels decreased after eye opening, whereas mRNA levels were constant. Both mRNA and protein levels of NT-3 in the retinas of aged animals remained constant. CONCLUSIONS: Our observations suggest that NT-3 regulation in the retina is independent of increasing visual stimuli after eye opening. Stable expression of NT-3 in the adult retina suggests a possible role in the maintenance of the retinal environment throughout later life.

Aging↗

PubMedDate not supplied

Mitochondrial DNA mutations with Leber's hereditary optic neuropathy in Japanese patients with open-angle glaucoma.

PURPOSE: Abnormal optic disc excavations are found in patients with Leber's hereditary optic neuropathy (LHON). The purpose of this study was to determine whether heteroplasmy for the major three LHON mutations or for the rare LHON mutations are risk factors for open-angle glaucoma. METHODS: Blood samples from 835 Japanese subjects were screened with the Invader assay for ten LHON-associated mutations: three major mutations (G3460A, G11778A, T14484C) and seven rare mutations (T9101C, G9804A, C14482A, C14482G, G14459A, T14498C, and A14510G). Of the 835 subjects, 241 were patients with primary open-angle glaucoma (POAG), 310 were patients with normal-tension glaucoma (NTG), and 284 were healthy controls. RESULTS: Five POAG patients and three NTG patients had one of five mutations, C9099A, T9101G, T9101C, G9804A, or G11778A, but none of these patients had LHON. The C9099A (Ile191Met) and T9101G (Ile192Ser) mutations were novel and identified within the probes by lack of signal in the assay. Two patients with the G11778A mutation showed heteroplasmy, with 15% mutant mtDNA in the male patient and 80% in the female patient. The remaining LHON-associated mutations were not detected in any of the subjects. A case-control study did not show a significant difference (P = 0.099): eight potentially disease-associated variants in 551 patients versus zero variants in the 284 controls. CONCLUSIONS: Rare LHON-associated mitochondrial DNA mutations were found in Japanese patients with open-angle glaucoma (OAG). However, whether mitochondrial DNA mutations are risk factors for OAG is still open to question.

Aged↗

PubMedDate not supplied

Comparison of fornix- and limbus-based conjunctival flaps in mitomycin C trabeculectomy with laser suture lysis in Japanese glaucoma patients.

PURPOSE: To analyze the results of mitomycin C (MMC) trabeculectomy and laser suture lysis using either fornix-based (FB) or limbus-based (LB) conjunctival flaps. METHODS: Eighty-two Japanese glaucoma patients were treated by MMC trabeculectomy, with 38 eyes receiving an FB conjunctival flap and 44 eyes receiving an LB conjunctival flap. Postoperative intraocular pressure (IOP), the probability of success, and complications were compared between the FB and LB groups. RESULTS: The IOP of the FB group decreased from 21.6+/-7.90 mmHg to 9.75+/-3.23 mmHg at 12 months postoperation, and the IOP of the LB group decreased from 21.3+/-6.77 mmHg to 9.30+/-3.16 mmHg. The postoperative IOPs were similar in the two groups at all postoperative time points. A life-table analysis (Kaplan-Meier method) showed that the survival rate was similar in the two groups but tended to be lower in the early postoperative period in the FB group. Complications were similar also, with the exception of increased leakage in the FB group. CONCLUSIONS: MMC trabeculectomy results were similar between FB and LB conjunctival flaps, in agreement with previous reports. However, increased care may be warranted when an FB flap is used in MMC trabeculectomy.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

The outcome of mitomycin C trabeculectomy and laser suture lysis depends on postoperative management.

PURPOSE: To verify that postoperative management affects the outcome of mitomycin C (MMC) trabeculectomy and suture lysis. METHODS: A total of 108 eyes in 108 Japanese patients were treated with MMC trabeculectomy. They were divided into two groups based on when the operation was performed: group A, 57 eyes in 1998, and group B, 51 eyes in 2001. The results, including postoperative intraocular pressure (IOP), complications, and postoperative management, were compared between groups. In addition, they were evaluated by a Kaplan-Meier life-table analysis. RESULTS: Postoperative IOP was lower and the probability of success by life-table analysis was higher in group B than in group A. Postoperative management, including laser suture lysis and subconjunctival injection of 5-fluorouracil, was started significantly earlier in group B than in group A patients. Although more postoperative complications occurred in group B, none were severe and all were adequately managed. CONCLUSIONS: Starting postoperative management earlier, particularly laser suture lysis, may be necessary to achieve lower and longer IOP control in MMC trabeculectomy.

Antibiotics, Antineoplastic↗