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Effect of colestimide on the concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dizenzofurans, and polychlorinated biphenyls in blood of Yusho patients

  • Takashi Todaka1Email author,
  • Akinori Honda1,
  • Masami Imaji1,
  • Yoshiko Takao2,
  • Chikage Mitoma3 and
  • Masutaka Furue4
Environmental Health201615:63

https://doi.org/10.1186/s12940-016-0150-z

Received: 17 December 2015

Accepted: 30 May 2016

Published: 4 June 2016

Abstract

Background

Oral colestimide was reported to lower the concentration of PCDDs, PCDFs, and PCB in the blood of humans. A pilot study showed that the arithmetic mean total TEQ concentrations of PCDDs, PCDFs, and PCBs in the blood of subjects after the trial decreased approximately 20 % compared to pre-trial levels, suggesting that colestimide could decrease human dioxin levels. We designed the current clinical trial study based on this information. In this study, we examined whether colestimide could reduce the individual congener concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients.

Methods

Out of the 36 Yusho patients who participated in the clinical trial, 26 patients self-administered colestimide 3 g/day orally for 6 months. The concentrations of PCDDs, PCDFs and PCBs in the blood of 26 Yusho patients before the trial were compared with those after the trial.

Results

The arithmetic mean total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of the 26 Yusho patients before and after the clinical trial were 42–303 (mean: 130, median: 120) and 43–283 (mean: 132, median: 118) pg TEQ/g lipid, respectively. The sums of the concentrations of 58 PCB congeners measured in the blood of Yusho patients before and after the trial were 321–2643 (mean: 957, median: 872) and 286–2007 (mean: 975, median: 806) ng/g lipid, respectively, indicating that the concentrations of PCDDs, PCDFs, and PCBs after the trial were almost the same as those before the trial. Among congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs, most congeners of these compounds did not show a statistically significant decrease after the trial.

Conclusion

Colestimide may not be beneficial in reducing the high blood levels of dioxin-like compounds in Yusho patients.

Keywords

PCDDs PCDFs PCBs Yusho Colestimide Blood concentration

Background

The 1968 Yusho poisoning accident affected over 1800 people in western Japan [1]. Since the Yusho outbreak, the National Study Group for the Therapy of Yusho has carried out medical care and health examinations of patients affected [2]. In 2001, the measurement of PCDDs, PCDFs, and non-ortho PCBs in the blood became possible using small amounts of blood collected from participants during annual medical examinations [35]. We have measured the concentrations of PCDDs, PCDFs, and dioxin-like PCBs in the blood collected from Yusho patients in medical health examinations since 2002 [68]. Moreover, we have conducted a congener-specific analysis of non-dioxin-like PCBs in the blood of these patients since 2004 [9, 10]. Based on these results, we previously reported that Yusho patients continue to have higher concentrations of PCDFs in their blood than unaffected people, and that concentration of PCDFs in the blood is significantly correlated with the intensity of Yusho symptoms [11, 12].

Development of effective therapy to reduce the concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients could improve the health care of these patients. With regard to promoting the excretion of lipophilic contaminants stored in the human body, several studies of dietary supplements such as cholestyramine, mineral oil, hexadecane, and dietary fiber have been reported using laboratory animals [1316]. In addition, another study reported the enhancing effect of non-absorbable lipid substitute olestra on fecal excretion of PCDDs, PCDFs, and PCBs in the human body [17, 18]. Our study group previously conducted a clinical trial to reduce the concentrations of PCDDs, PCDFs, and PCB in the blood of Yusho patients using cholestyramine and rice bran fiber [19, 20]. However, beneficial clinical effects could not be confirmed due to the short trial period.

Colestimide, a 2-methylimidozarol-epichlorohydrin polymer, is widely used to lower serum cholesterol levels in Japan. Recently, oral colestimide was reported to lower the concentration of PCDDs, PCDFs, and PCB in the blood of humans [21, 22]. A pilot study showed that the arithmetic mean total TEQ concentrations of PCDDs, PCDFs, and PCBs in the blood of subjects after the trial decreased approximately 20 % compared to pre-trial levels, suggesting that colestimide could decrease human dioxin levels [21, 22]. We designed the current clinical trial study based on this information. In this study, we examined whether colestimide could reduce the individual congener concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients.

Methods

Sampling

The trial protocol was approved by the institutional ethics committee of Kyusyu University Hospital. Patients who fulfilled the diagnostic criteria for Yusho established by the National Study Group for the Therapy of Yusho were eligible for this study. Patients were recruited at explanatory meetings conducted in Fukuoka and Nagasaki Prefectures. 50 Yusho patients were enrolled in this clinical trial, and 14 patients refused to participate. The remaining 36 patients participated in the trial. Informed consent was obtained for study participation. The patients self-administrated colestimide 3 g/day orally for 6 months. Out of the 36 Yusho patients who participated in the clinical trial, 26 patients completed the trial. The 26 patients ranged in age from 60 to 87 years (mean: 72.9, median: 72.5). Among the 26 patients, there were 13 men (age range 60–87 years; mean: 73.1, median: 74.0) and 13 women (age range 61–81 years; mean: 72.8, median: 72.0). The blood samples examined in this study were collected between April 4, 2008 and July 15, 2009. After collection, the blood samples were stored at 4 °C until analyses.

Materials

Native congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs were purchased from Wellington Laboratories (Guelph, Canada). [13C12]–congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs as internal standards, were also purchased from Wellington Laboratories. An active carbon column was prepared as follows: active carbon was purchased from Nacalai Tesque (Kyoto, Japan), refluxed 3 times with toluene for 1 h, and dried in vacuum, after which 500 mg of the active carbon was mixed with 500 g of anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd., Tokyo, Japan). A silver nitrate/silica gel was purchased from Wako Pure Chemical Industries, Ltd. All reagents and solvents used in this experiment were of the analytic grade of dioxin that is commercially available.

Analysis of PCDDs, PCDFs, and PCBs

The extraction and purification of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs from blood samples were performed using a previously reported method [5, 9]. Concentrations of PCDDs, PCDFs, and dioxin-like PCBs and concentrations of 58 non-dioxin-like PCB congeners were determined by a previously reported method [5, 9].

Quality control

To evaluate the accuracy and reliability of the analysis of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs, our laboratory prepared human blood samples and conducted quality control studies of the analysis of PCDDs, PCDFs, and dioxin-like PCBs in 2007, 2009, 2011, and 2013 and non-dioxin-like PCBs in 2008, 2010, 2012, and 2014. Each quality control study involved the participation of various laboratories that perform measurements for these compounds in human blood in Japan. In each quality control study, our results were compared with those of participating laboratories, and tests confirmed that the average variation among values obtained by each organization performing the analysis was all within 10 %. These results indicated that our laboratory’s analytical methods regarding PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs in human blood provided accurate results.

Data analysis

To estimate the TEQ concentrations, we introduced ND (less than the detection limit) values to half values of the detection limit and calculated based on the TEF values proposed by the WHO [23]. The statistical analysis was conducted using Wilcoxon signed-rank test in the software programs from Statistics Package for Social Sciences (version 22; IBM Armonk, NY, USA). Significant probabilities (p values) were calculated for the respective number of samples analyzed.

Results

The objective of the present study was to evaluate the effectiveness of colestimide on the individual congener concentrations of PCDDs, PCDFs, and PCBs in blood of Yusho patients. Of the 36 Yusho patients who began the trial, 9 patients stopped administrating colestimide due to serious adverse effects, constipation or abdominal distension. Of the 27 remaining patients, we failed to collect a posttreatment blood sample from one patient due to cancellation of hospital visit. The individual congener concentrations of PCDDs, PCDFs and PCBs in the blood of 26 Yusho patients before the trial were compared with those after the trial (Tables 1 and 2).
Table 1

Effect of colestimide on the individual congener concentrations of PCDDs, PCDFs, and dioxin-like PCBs in the blood of Yusho patients

Congeners

Concentration (pg/g lipid)

p Values

Before the clinical trial

After the clinical trial

Mean

Median

SD

Minimum

Maximum

Mean

Median

SD

Minimum

Maximum

2,3,7,8-TetraCDD

1.8

1.7

0.9

0.5

4.0

2.0

1.8

1.2

0.5

4.7

0.083

1,2,3,7,8-PentaCDD

14

14

4.9

6.6

23

14

12

6.1

6.1

27

0.675

1,2,3,4,7,8-HexaCDD

3.1

3.0

1.7

1.0

7.1

3.3

3.2

1.7

1.0

6.9

0.053

1,2,3,6,7,8-HexaCDD

62

53

36

16

183

63

55

34

15

164

0.258

1,2,3,7,8,9-HexaCDD

5.5

4.5

5.2

2.1

29

5.7

3.9

6.0

1.0

31

0.770

1,2,3,4,6,7,8-HeptaCDD

55

47

25

21

113

52

43

27

20

143

0.137

OctaCDD

699

606

281

323

326

670

543

309

305

1610

0.118

Total PCDD

841

739

315

413

1525

811

688

346

382

1850

0.144

2,3,7,8-TetraCDF

2.8

2.7

1.3

0.5

5.5

2.7

2.6

1.4

0.5

5.8

0.427

1,2,3,7,8-PentaCDF

1.3

1.1

0.9

0.5

3.5

1.5

1.2

1.1

0.5

4.4

0.554

2,3,4,7,8-PentaCDF

241

191

158

48

636

242

205

158

49

613

0.732

1,2,3,4,7,8-HexaCDF

64

51

56

7.8

227

64

52

56

8.1

207

0.990

1,2,3,6,7,8-HexaCDF

26

21

19

6.2

86

26

22

19

5.2

74

0.534

2,3,4,6,7,8-HexaCDF

1.2

1.0

0.7

1.0

3.4

1.2

1.0

0.6

1.0

3.4

1.000

1,2,3,7,8,9-HexaCDF

ND

    

ND

     

1,2,3,4,6,7,8-HeptaCDF

2.2

1.0

1.5

1.0

6.5

2.3

1.0

1.8

1.0

7.8

0.820

1,2,3,4,7,8,9-HeptaCDF

ND

    

ND

     

OctaCDF

ND

    

ND

     

Total PCDF

342

280

229

71

963

344

292

230

71

890

0.732

33'4'4'-TriCB(#77)

6.9

5.0

3.7

5.0

16

8.9

7.5

4.3

5.0

20

0.016

344'5-TriCB(#81)

5.3

5.0

1.4

5.0

12

5.7

5.0

2.4

5.0

15

0.180

33'44'5-PentaCB(#126)

129

100

81

30

391

131

96

85

34

356

0.770

33'44'55'-HexaCB(169)

279

250

144

104

678

293

280

129

114

585

0.101

Total Non-ortho PCBs

420

382

178

183

906

439

406

166

196

789

0.078

233'44'-PentaCB(#105)

4454

3145

3555

1206

13788

4581

3236

3714

5.0

15228

0.501

2344'5-PentaCB(#114)

2800

2365

1688

5.0

7194

2997

2681

1699

5.0

6987

0.118

23'44'5-PentaCB(#118)

21718

16568

17601

5.0

75475

21050

15412

14335

4575

57260

0.990

2'344'5-PentaCB(#123)

304

228

273

5.0

1239

312

214

237

5.0

898

0.581

233'44'5-HexaCB(#156)

50472

32661

46375

13079

195017

51038

30741

43667

9528

180163

0.517

233'44'5'-HexaCB(#157)

13157

8088

13150

3390

53954

12747

7644

11520

2332

46994

0.990

23'44'55'-HexaCB(#167)

4834

4243

3373

5.0

16863

4610

4265

2422

985

10481

0.770

233'44'55'-HeptaCB(#189)

7385

5100

5888

1664

24429

7398

5397

5323

1730

22434

0.829

Total Mono-ortho PCBs

105125

83472

66740

40066

293077

104734

93659

59308

34746

267273

0.829

TEQ from PCDDs

24

24

7.9

11

43

24

24

9.2

11

42

0.809

TEQ from PCDFs

82

63

54

16

223

82

68

54

16

211

0.534

TEQ from PCDDs/PCDFs

106

83

60

27

265

107

87

61

28

249

0.790

TEQ from non-ortho PCBs

21

20

9.8

7.4

54

22

20

9.7

7.8

47

0.485

TEQ from mono-ortho PCBs

3.2

2.5

2.0

1.2

8.8

3.1

2.8

1.8

1.0

8.0

0.829

TEQ from dioxin-like PCBs

24

22

11

9.0

60

25

23

11

9.1

51

0.603

Total TEQ

130

120

65

42

303

132

117

65

43

283

0.869

ND (less than the detection limit) values introduced to half values of the detection limit and calculated the TEQ concentrations

SD standard deviation, CDD chlorinated dibenzo-p-dioxin, CDF chlorinated dibenzofuran

Table 2

Effect of colestimide on the individual congener concentrations of non-dioxin-like PCBs in the blood of Yusho patients

IUPAC#

Concentration (pg/g lipid)

p Values

Before the clinical trial

After the clinical trial

Mean

Median

SD

Minimum

Maximum

Mean

Median

SD

Minimum

Maximum

TriCB-28

1644

1449

866

324

3809

1837

1866

1226

5

6187

0.025

TriCB-29

20

12

18

5

72

20

5

23

5

99

0.845

TriCB-37

128

5

245

5

847

73

5

165

5

698

0.112

TeteraCB-44

348

248

523

5

2841

415

324

415

107

2261

0.034

TeteraCB-47/48

525

359

437

117

1769

640

471

715

121

3659

0.049

TeteraCB-49

295

179

409

44

1679

344

216

576

5

3070

0.101

TeteraCB-52/69

956

780

836

294

4572

1060

860

745

368

3896

0.052

TeteraCB-56/60

442

306

344

5

1412

489

284

577

104

3010

0.889

TeteraCB-63

116

117

65

5

280

140

118

69

5

360

0.382

TeteraCB-66

2118

1520

1507

586

5853

2181

1536

1691

613

8475

0.551

TeteraCB-70

362

130

807

13

3375

418

143

1308

55

6817

0.280

TeteraCB-71

37

11

56

5

238

126

5

490

5

2524

0.586

TeteraCB-74

14823

12720

9202

3830

41089

14505

11875

9068

2973

35194

0.770

PentaCB-85

247

139

335

5

1592

205

138

218

5

1086

0.657

PentaCB-87

812

797

448

5

1716

747

697

442

5

2059

0.183

PentaCB-92

719

571

482

5

2402

752

669

455

5

2264

0.412

PentaCB-93/95/98

727

637

439

5

1964

1003

746

1165

326

6428

0.258

PentaCB-99

23623

19114

17453

4240

90685

24873

23328

16634

4308

82151

0.182

PentaCB-101

1931

1534

1234

5

5667

2337

1959

1481

600

6915

0.174

PentaCB-107/108

963

785

707

5

3340

961

819

584

5

2435

0.166

PentaCB-110

339

242

325

5

1451

332

298

268

5

1428

0.638

PentaCB-117

1911

1466

1813

435

7951

1722

1306

1642

5

6579

0.280

HexaCB-128

925

685

660

5

3099

949

678

775

5

3899

0.443

HexaCB-130

7065

5603

5780

2080

25122

7238

5886

5578

1913

25258

0.568

HexaCB-132

399

326

252

5

1125

445

397

282

5

1134

0.143

HexaCB-134

25

5

50

5

183

35

5

47

5

168

0.203

HexaCB-135

419

342

318

5

1577

485

330

403

5

1587

0.382

HexaCB-137

10565

7132

9066

2996

41244

10646

7786

8734

2336

39991

0.889

HexaCB-138

96984

89163

52967

25546

240863

97685

84306

53897

23381

244647

0.990

HexaCB-139/149

635

452

619

15

2404

615

292

696

5

2303

0.568

HexaCB-141

328

255

246

5

1044

340

282

287

5

1169

0.716

HexaCB-146

32968

34220

16346

11603

83149

35211

31688

16262

9839

68936

0.086

HexaCB-147

724

567

463

5

1678

768

622

519

5

1806

0.527

HexaCB-151

1329

981

880

428

3402

1349

1008

1098

5

4265

0.258

HexaCB-153

200929

184176

106109

73832

516088

206380

180663

109234

59314

458743

0.501

HexaCB-163/164

48797

47157

25168

17426

113577

49567

47872

22738

15767

88552

0.694

HexaCB-165

ND

    

ND

     

HeptaCB-170

69704

60801

39523

16403

194289

69053

62645

37071

9946

142922

0.829

HeptaCB-172

9947

9273

5381

2768

27207

10156

10553

5277

5

20365

0.354

HeptaCB-177

15845

14513

9212

4504

39642

16359

14681

9932

2598

40496

0.424

HeptaCB-178

15885

13134

11788

5

56211

17209

13068

11123

3710

42945

0.012

HeptaCB-179

281

182

296

5

1110

357

202

384

5

1463

0.005

HeptaCB-180

205779

201272

136971

50473

703408

203297

188508

121684

32744

490934

0.970

HeptaCB-181

553

292

671

5

2776

581

296

716

5

2806

0.264

HeptaCB-182/187

76063

60684

61028

14834

270253

81845

61046

63293

14093

238587

0.019

HeptaCB-183

16843

14980

12005

4733

45012

17864

15557

13292

3756

55788

0.182

HeptaCB-191

3078

2922

2008

5

8667

2907

2762

1688

805

7561

0.280

OctaCB-194

31774

32293

22776

5

116675

32519

32465

19427

8258

84219

0.304

OctaCB-195

7832

6835

5594

5

26180

7929

7156

4776

1879

19564

0.381

OctaCB-196/203

17107

15138

11346

5

55263

16821

15312

9331

4346

38617

0.869

OctaCB-198/201

14771

12536

11520

5

56995

14368

11829

8673

4251

34263

0.534

OctaCB-200

659

485

607

5

2350

705

593

609

5

2449

0.083

OctaCB-202

5432

3893

4532

5

22569

5298

3892

3307

1509

12550

0.258

OctaCB-205

977

898

633

5

2795

969

912

456

289

1949

0.770

NonaCB-206

5049

4561

2829

1502

14874

4891

4639

2446

5

10726

0.657

NonaCB-207

922

755

572

5

2501

911

792

522

5

1905

0.326

NonaCB-208

1877

1731

1209

5

6338

1827

1723

953

5

4559

0.778

DecaCB-209

1857

1598

890

893

5115

1900

1946

730

837

4005

0.200

Total TrCBs

1792

1471

999

334

3921

1931

1917

1198

708

6225

0.182

Total TeCBs

20023

17013

11246

6548

50619

20318

16713

11351

5981

43194

0.424

Total PeCBs

31271

26027

19945

7137

102693

32932

31001

19076

7680

93210

0.228

Total HxCBs

402098

373141

196792

152976

892316

411718

358344

198664

131539

769040

0.675

Total HpCBs

413979

401285

265364

105126

1341206

419627

378119

250647

80774

971840

0.620

Total OcCBs

78553

77549

55605

35

281931

78608

77101

44919

21477

186948

0.409

Total NoCBs

7849

6439

4416

2355

23712

7629

7224

3832

15

17159

0.869

Total DeCBs

1857

1598

890

893

5115

1900

1946

730

837

4005

0.200

Total PCBs

957422

871523

520304

320807

2642555

974664

806289

495089

286088

2006817

0.585

ND (less than the detection limit) values introduced to half values of the detection limit and calculated the TEQ concentrations

SD standard deviation, CB chlorinated biphenyl

The arithmetic mean TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of the 26 Yusho patients were 24, 82, 21, and 3.2 pg TEQ/g lipid, respectively, before the trial, and 24, 82, 22, and 3.1 pg TEQ/g lipid, respectively, after the trial. Total TEQ concentration of these dioxin-like compounds equaled 42–303 (mean: 130, median: 120) pg TEQ/g lipid before the trial, and 43–283 (mean: 132, median: 118) pg TEQ/g lipid after the trial, indicating that the concentrations before the trial were almost the same as those after the trial. Regarding the non-dioxin-like PCB concentrations, the sums of the concentrations of 58 PCB congeners in the blood before and after the trial were 321–2643 (mean: 957, median: 872) and 286–2007 (mean: 975, median: 806) ng/g lipid, respectively. The arithmetic mean concentrations of triCBs, tetraCBs, pentaCBs, hexaCBs, heptaCBs, octaCBs, and nonaCBs in the blood of Yusho patients were 1.8, 20, 31, 402, 414, 79, and 7.8 ng/g lipid, respectively, before the trial, and 1.9, 20, 33, 412, 420, 79, and 7.6 ng/g lipid, respectively, after the trial, indicating that concentrations of these PCBs compounds were also almost the same before and after the trial. These results indicated that the concentrations of PCDDs, PCDFs, dioxin-like PCBs and non-dioxin-like PCBs in the blood of Yusho patients were not significantly altered by the intervention with oral colestimide.

We previously reported that the concentrations of 1,2,3,6,7,8-hexaCDD, 2,3,4,7,8-pentaCDF, 1,2,3,4,7,8-hexaCDF, 1,2,3,6,7,8-hexaCDF, hexaCB-169, hexaCB-156, hexaCB-157, and heptaCB-189 in the blood of Yusho patients were higher than those of the normal controls [8, 9]. These can be considered the characteristic congeners in the blood of Yusho patients. 2,3,4,7,8-PentaCDF is recognized as the most important causative agent for subjective symptoms of Yusho. Blood levels before and after the trial were 48–636 (mean: 241, median: 191) and 49–613 (mean: 242, median: 205) pg TEQ/g lipid, respectively, indicating that the concentration did not significantly decrease with administration of colestimide. This was also the case for the concentrations of other characteristic congeners before and after the trial. Among congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs, most congeners did not show statistically significant differences. According to these results, the therapeutic usefulness of colestimide in reducing the concentrations of PCDDs, PCDFs, and PCBs in blood of Yusho patients could not be confirmed.

Discussion

Over 48 years have passed since the outbreak of Yusho disease. However, some patients are still afflicted with intractable symptoms such as chloracne, general fatigue and neuropathy [12]. There are patients who continue to have much higher concentrations of dioxin-like compounds in their blood than unaffected persons. Moreover, the half-lives of blood concentrations of 2,3,4,7,8-pentaCDF have become long to near infinity in the majority of Yusho patients [24]. To reduce the concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients, our study group previously conducted a clinical trial using cholestyramine and rice bran fiber [19, 20]. Results of that study showed that the amounts of 2,3,4,7,8-pentaCDF in patients’ feces actually increased, although beneficial clinical effects were not apparent, possibly due to a short trial period. A recent study reported that colestimide can decrease the concentrations of PCDDs, PCDFs, and PCBs in blood [21, 22]. Eight male and two female healthy subjects were treated with colestimide (3 g/day) for 6 months. In this report, colestimide was effective for promoting excretion of dioxin-like compounds from the human body. Colestimide is a non-absorbable anion exchange resin and enhances excretion of cholesterol in feces by inhibiting absorption of food-derived cholesterol in the intestinal tract [25]. Based on this result, we designed a clinical trial with colestimide for Yusho patients. However, in the present study, we were unable to confirm a significant decrease in most congeners of PCDDs, PCDFs, and PCBs in the blood of Yusho patients. It is suggested that the PCDDs, PCDFs, and PCBs that have remained in the whole body of patients over the 45 years since the outbreak of Yusho are very difficult to excrete from the body. In the present trial, there may be many limitations such as a small number of participants, duration of administration period and dose of cholestimide. Out of the 36 patients who participated in the trial, 9 patients experienced serious adverse effects (constipation or abdominal distension) by the repeated administration of colestimide. Therefore, we cannot recommend that elderly patients participate in clinical trial studies for such long periods as in the present study.

Conclusion

Although over 48 years have passed since the outbreak of Yusho, many patients still suffer various symptoms such as chloracne, general fatigue and neuropathy. The concentrations of causative dioxin-like compounds in their blood remain at high levels. We examined whether oral administration of colestimide could reduce the concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients. However, the effectiveness of colestimide on the concentrations of these dioxin-like compounds in the blood of Yusho patients could not be confirmed.

Abbreviations

PCDDs, polychlorinated dibenzo-p-dioxins; PCDFs, polychlorinated dibenzofurans; PCBs, polychlorinated biphenyls; WHO, World health oganization; TEQ, toxic equivalent; TEF, toxic equivalency factor

Declarations

Acknowledgements

We would like to sincerely thank the participants to the study and all research staff at Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital.

Funding

This research was supported by a Grant-in-Aid for scientific research from the Ministry of Health, Labour and Welfare, Japan.

Availability of data and materials

We do not wish to share the data included in this manuscript. Patients who fulfilled the diagnostic criteria for Yusho established by the National Study Group for the Therapy of Yusho were eligible for this study. Therefore, we want to protect the patients’ identities and personal information.

Authors’ contributions

TT developed the analytical method, and drafted the initial manuscript. AK, MI and YT examined the data quality for analyses. CM and MF interpreted the results. MF coordinated the project. All authors approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Patients were recruited at explanatory meetings conducted in Fukuoka and Nagasaki Prefectures. 50 Yusho patients were enrolled in this clinical trial, and 36 patients participated in the trial. Informed consent was obtained for study participation. We also confirmed their consent for publication of this manuscript.

Ethics approval and consent to participate

The study project was approved by the institutional ethics committee of Kyushu University Hospital (reference 18034).

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Kitakyushu Life Science Center, Public Interest Incorporated Foundation
(2)
Fukuoka Institute of Health and Environmental Sciences
(3)
Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital
(4)
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University

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Copyright

© The Author(s). 2016

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