1.Protoporphyrin IX Synthesis Induced by 5-aminolevulinic Acid and Its Esters in Normal Mouse Skin.
Hyung Sung KIM ; Eui Young NA ; Sook Jung YUN ; Seong Jin KIM ; Seung Chul LEE ; Young Ho WON ; Hyoung Ryun PARK ; Jee Bum LEE
Korean Journal of Dermatology 2009;47(6):683-689
BACKGROUND: Photodynamic therapy with using 5-aminolevulinic acid (ALA) is a good noninvasive treatment modality that can treat several cutaneous diseases. Yet hydrophilic ALA is not able to easily penetrate the cellular membrane or the lipid layer of the skin. Thus, various ALA alkyl esters been developed. OBJECTIVE: We studied whether novel ALA unsaturated alkyl esters synthesize more protoporhyrin IX (PpIX) than does ALA in mouse skin tissues. METHODS: We applied 5, 10, 15% ALA and ALA esters ointment to the skin of shaved mice, respectively. We harvested the skin tissue, made a preparation and did quantitative analysis according to the fluorescent spectrum for determining the amount of PpIX synthesized in the skin after the elapse of 1 hour and 3 hours, respectively. RESULTS: No matter what the sort or the concentration of the ALA and ALA ester was, the amount of synthesized PpIX increased more after the elapse of 3 hours than that after 1 hour. ALA (hetenyl-, petenyl-, butenyl-, methyl-) esters tended to produce a much greater amount of PpIX than ALA. According to the results of the comparative study with using 5%, 10% and 15% of ALA and ALA esters ointment, the amount of synthesized PpIX was not proportional to the concentration of the ALA and the ALA esters, even though the ALA esters produced more PpIX than the ALA. CONCLUSION: We found that the ALA unsaturated alkyl esters are a good photosensitizer and they are similar to ALA-me, which is an ALA saturated alkyl ester that induces more PpIX, an actual photosensitizer, than ALA can.
Aminolevulinic Acid
;
Animals
;
Esters
;
Membranes
;
Mice
;
Photochemotherapy
;
Protoporphyrins
;
Skin
2.Photodynamic therapy using topically applied 5-aminolevulinic acid for treatment of cervical cancer.
Moon Hee YOUN ; Hyun Chul CHO ; Jin Chul AHN ; Choong Hak PARK ; Jin Wan PARK
Korean Journal of Obstetrics and Gynecology 2010;53(12):1092-1099
OBJECTIVE: The purpose of this study was to investigate the treatment effects of a topical application of 5-aminolevulinic acid (5-ALA) for photodynamic therapy (PDT) to treat cervical cancer. METHODS: We first investigated the effects of 5-ALA cream according to application time. And to find the effective 5-ALA concentration and the distribution times in vivo, 20% 5-ALA cream was topically applied to the tumor of the nude mouse. We then observed the distribution of 5-ALA via fluorescence measurement with using a 532 nm diode laser. 25 nude mice were divided into Control, ALA, Laser, and PDT group. To evaluate the PDT effect at cancer lesion, we applied 20% 5-ALA cream to the tumor by the same method, and the PDT was done by using a 632 nm diode laser at the time of the peak level of fluorescence. We checked the changes of the volume of cancer for 30 days, and then biopsy was done. RESULTS: The effective post-irradiation time after topical ALA application was 9 hours. In the PDT group, 40% (4/10) of the mice showed decreased tumor size. CONCLUSION: The maximum PpIX fluorescence at 9 hours after local applicationof 5-ALA cream was checked. And PDT group did not show any statistical difference than control group in the growth of tumor size than control group. However responding cases (4/10) of PDT group showed the meaningful decrease of tumor size than control group (P<0.05).
Animals
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Biopsy
;
Fluorescence
;
Lasers, Semiconductor
;
Mice
;
Mice, Nude
;
Photochemotherapy
;
Protoporphyrins
;
Triazenes
;
Uterine Cervical Neoplasms
3.5-Aminolevulinic acid esters based photodynamic therapy.
Sujuan ZHANG ; Zhenxi ZHANG ; Dazong JIANG
Journal of Biomedical Engineering 2002;19(2):310-314
As exogenous ALA (5-aminolevulinic acid) esters can induce the production and accumulation of endogenous photosensitizer PpIX (protoporphyrin IX) in tumor tissues more effectively, they have been the most active photosensitizer prodrug in PDT(photodynamic therapy) field. In this article, along with the procedure of ALA esters based PDT, some primary mechanism and experimental results were considered, which include: first, cellular uptake of ALA esters and its conversion into ALA; second, the production and accumulation of endogenous photosensitizer PpIX induced by eNdogenous ALA esters; last, the photosensitization of PpIX.
Aminolevulinic Acid
;
pharmacology
;
Esters
;
pharmacology
;
Photochemotherapy
;
Photosensitizing Agents
;
pharmacology
;
Prodrugs
;
Protoporphyrins
;
pharmacology
4.Effectiveness of zinc protoporphyrin/heme ratio for screening iron deficiency in preschool-aged children.
Nutrition Research and Practice 2011;5(1):40-45
Hemoglobin and zinc protoporphyrin (ZPP) tests are commonly used to screen for iron deficiency, but little research has been done to systematically evaluate the sensitivity and specificity of these two tests. The goal of this study was to evaluate the effectiveness of zinc protoporphyrin/heme (ZPP/H) ratio as a point-of-service screening test for iron deficiency among preschool-aged children by comparing the sensitivity and specificity of hemoglobin, ZPP/H ratio, and serum ferritin (SF). Also completed were assessments for the prevalence of anemia, iron deficiency (ID), and iron deficiency anemia (IDA) with indicators of ferritin models. This study was carried out with 95 children ages 3 to 6 y. Anthropometric measurements were assessed, and blood samples were analyzed for hemoglobin, SF, transferrin saturation (TS), and ZPP. Anemia was common and the prevalences of anemia, ID, and IDA were 14.7%, 12.6%, and 5.2%, respectively. The ZPP/H ratio was strongly and significantly correlated with hemoglobin. And ZPP/H ratio was a more sensitive test for ID than hemoglobin or SF measurement, correctly identifying more than twice as many iron-deficient children (sensitivity of 91.7%, compared to 41.7% for hemoglobin and SF). However, ZPP/H ratio had lower specificity (60.2%, compared to 89.1% for hemoglobin or 96.4% for SF) and resulted in the false identification of more subjects who actually were not iron deficient than did hemoglobin or SF. Low hemoglobin concentration is a late-stage indicator of ID, but ZPP/H ratio can detect ID at early stages and can be performed easily at a relatively low cost. Therefore, ZPP/H ratio can serve as a potential screening test for pre-anemic iron deficiency in community pediatric practices.
Anemia
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Anemia, Iron-Deficiency
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Child
;
Child, Preschool
;
Ferritins
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Hemoglobins
;
Humans
;
Iron
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Mass Screening
;
Prevalence
;
Protoporphyrins
;
Sensitivity and Specificity
;
Transferrin
;
Zinc
5.A Case of Erythropoietic Protoporphyria Screened by RBC Fluorescence Microscopy.
Eun Phil HEO ; Seong Eon KIM ; Won Sup LEE ; Tae Jin YOON ; Tae Heung KIM
Korean Journal of Dermatology 2002;40(1):63-67
Erythropoietic protoporphyria (EPP), caused by decreased activity of the enzyme ferrochelatase, is characterized clinically by burning photosensitivity beginning from childhood, and chemically by excessive amounts of red blood cell protoporphyrins. 1-10% of EPP patients develop potentially fatal protoporphyric hepatic failure. The diagnosis of EPP had been missed in many cases when traditional solvent extraction qualitative screening test was used for blood porphyrins, and use of fluorescence microscopy improved this problem. We report a case of EPP screened by fluorescence microscopy of erythrocytes in a 50-year-old man complaining of photosensitivity. We recommend fluorescence microscopy could be the screening test of choice for the detection of increased red blood cell porphyrins.
Burns
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Diagnosis
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Erythrocytes
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Ferrochelatase
;
Fluorescence*
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Humans
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Liver Failure
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Mass Screening
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Microscopy, Fluorescence*
;
Middle Aged
;
Porphyrins
;
Protoporphyria, Erythropoietic*
;
Protoporphyrins
6.Assessment of Iron Parameters in Children with Acute Infectious Disease
Ho Yeon HWANG ; Ji Suk KIM ; Jung Hyun LEE ; Yoo Rha HONG ; Jae Sun PARK
Clinical Pediatric Hematology-Oncology 2012;19(2):72-78
BACKGROUND: As some parameters reflecting iron status were known to change with infection or inflammation, we examined the changes of these parameters in children with minor illnesses.METHODS: Hematologic tests were done in 42 young children with acute infection. Iron deficiency anemia (IDA) was defined as having Hb less than age-matched normal range, MCH <27 pg, and either Tfsat (transferrin saturation) <10% or TIBC >360 microg/dL. Iron deficiency (ID) was defined as having Hb equal or more than age matched normal low limit with MCH <27 pg, and either Tfsat <10% or TIBC >360 microg/dL. The others were classified as normal control (NC).RESULTS: The proportion of IDA, ID and NC were 16.6% (7/42), 33.3% (14/42) and 50.0% (21/42), respectively. Comparisons of means of Hb, MCV, MCH, and RDW between groups showed statistical difference in general, while levels of iron, ferritin and hs-CRP showed no statistical difference. Mean blood levels of zinc protoporphyrin (ZnPP) of IDA, ID and NC were 72.21 microg/dL, 57.02 microg/dL, and 45.62 microg/dL, respectively, but the difference was significant only between IDA and NC. ZnPP was inversely correlated with MCV (r=-0.518, P<0.01) and RDW (r=-0.640, P<0.01), but not with hs-CRP or ferritin.CONCLUSION: Combination of RBC indices with newly controlled Tfsat or TIBC can be available for an iron status assessment in children with minor infections. ZnPP levels in blood reflect some aspect of iron status, while ferritin and iron do not reflect it.
Anemia, Iron-Deficiency
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Child
;
Communicable Diseases
;
Erythrocyte Indices
;
Ferritins
;
Hematologic Tests
;
Humans
;
Inflammation
;
Iron
;
Protoporphyrins
;
Reference Values
;
Zinc
7.A Case of Lead Poisoning by Ingesting Herbal Pills Tainted by Lead during the Manufacturing Process.
Young Hoo SHIN ; Jun Seok SON ; Young Wook KIM ; Chang Ho CHAE ; Ja Hyeon KIM ; Chan Woo KIM ; Jun Ho LEE
Korean Journal of Occupational and Environmental Medicine 2010;22(3):271-277
BACKGROUND: This is a case report of lead poisoning after herbal pill ingestion. We report this case here as a reminder that contamination during the manufacturing process is an important issue regarding herbal pills. Case Report: A 37-year-old male was admitted to the hospital with abdominal pain caused by cholecystitis. He was transferred to the Department of Occupational and Environmental Medicine on 26 December 2008, because of anemia. On follow-up examination post cholecystectomy, the patient had increasing blood lead levels. There was no specific finding in his medical history, but he had been taking herbal pills for 3 months to treat dyspepsia. We performed an analysis on the herbal pills, and determined a lead concentration of 1485 mg/kg. When he was admitted to the hospital, the patient had a blood lead level of 84.13 microgram/dL and a zinc protoporphyrin level was 230 microgram/dL. The patient was treated with 250 mg of Penicillamine, 4 times per day. During follow-up 3 weeks later, the patient's blood lead level had been reduced to 36.52 microgram/dL which allowed us to take him off of Penicillamine. By 7 months follow-up, the patient's blood lead concentration had fallen from 36.52 microgram/dL to 20.93 microgram/dL. CONCLUSION: Lead poisoning was confirmed by analyzing blood lead levels and the cause was herbal pills. Upon analysis of the herbal pills, we have discovered that the herbal pills contained an amount of lead acquired during the manufacturing process, based on the high levels of this heavy metal in comparison to other metals. Private herbal pill manufacturing plants need systematic management and oversight.
Abdominal Pain
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Adult
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Anemia
;
Cholecystectomy
;
Cholecystitis
;
Dyspepsia
;
Eating
;
Environmental Medicine
;
Follow-Up Studies
;
Humans
;
Lead Poisoning
;
Male
;
Metals
;
Penicillamine
;
Protoporphyrins
;
Zinc
8.Occupational Health Management in the Lead Industry: The Korean Experience.
Safety and Health at Work 2011;2(2):87-96
In 1967, the problem of occupational lead exposure came to public attention in Korea. Since then, regular progress has been made in lowering workplace lead exposures, instituting new workplace controls, and implementing health examinations of exposed workers. Past serious lead poisoning episodes made it possible to introduce biological monitoring programs on a voluntary basis in high-lead-exposure facilities in Korea. Industry-specific occupational health services for lead workers in Korea during the last 22 years can be categorized into three phases. During the first phase (1988-1993), efforts were directed at increasing awareness among workers about the hazards of lead exposure, biological monitoring of blood zinc protoporphyrin began, and a respiratory protection program was introduced. During the second phase (1994-1997), a computerized health management system for lead workers was developed, blood-lead measurement was added to biologic monitoring, and engineering controls were introduced in the workplace to lower air-lead levels to comply with air-lead regulations. Finally, during the third phase (1998-present), a new biomarker, bone-lead measurement by X-ray fluorescence, was introduced. Bone-lead measurement proved to be useful for assessing body burden and to demonstrate past lead exposure in retired workers. Occupational health service practice for lead workers, including the industry-specific group occupational health system, has brought considerable success in the prevention of lead poisoning and in reducing the lead burden in Korean lead workers during the last several decades. The successful achievement of prevention of lead poisoning in Korea was a result of the combined efforts of lead workers, employers, relevant government agencies, and academic institutes.
Academies and Institutes
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Achievement
;
Body Burden
;
Environmental Monitoring
;
Fluorescence
;
Government Agencies
;
Korea
;
Lead Poisoning
;
Occupational Health
;
Occupational Health Services
;
Porphyrins
;
Protoporphyrins
;
Social Control, Formal
;
Zinc
9.Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic beta-Cell Injury.
Eun Mi LEE ; Young Eun LEE ; Esder LEE ; Gyeong Ryul RYU ; Seung Hyun KO ; Sung Dae MOON ; Ki Ho SONG ; Yu Bae AHN
Diabetes & Metabolism Journal 2011;35(5):469-479
BACKGROUND: Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic beta-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic beta-cells from high glucose-induced apoptosis. METHODS: Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations. RESULTS: CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP. CONCLUSION: Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.
Apoptosis
;
Caspase 3
;
Cell Survival
;
Diabetes Mellitus
;
Flow Cytometry
;
Glucose
;
Heme
;
Heme Oxygenase-1
;
Insulin
;
Protoporphyrins
;
Reactive Oxygen Species
;
RNA, Messenger
;
Up-Regulation
10.Involvement of endogenous carbon monoxide in regulation of respiratory rhythm in vitro.
Wen-Xing YANG ; Qi-Lan ZHANG ; Hai-Yan HU ; Jin LIU ; Yong-Bo LI ; Hua ZHOU ; Yu ZHENG
Acta Physiologica Sinica 2007;59(3):325-330
The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on respiratory rhythm. The experiments were carried out on the medullary slices of newborn Sprague-Dawley rats. The rhythmic discharge frequency (DF) of hypoglossal rootlets was taken as an index of rhythmic respiratory activity. The slices of medulla oblongata were superfused with ZnPP-9 (inhibitor of heme oxygenase), CO and hemin (substrate of heme oxygenase), respectively, to observe their effects on respiratory rhythm. The preparations were divided into 5 groups: control group of artificial cerebrospinal fluid (ACSF), group of ZnPP-9, group of exogenous CO, group of hemin and group of ZnPP-9 + hemin. The results obtained were as follows. In ZnPP-9 group, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05); while in exogenous CO group, it was decreased (P<0.05). In the groups of hemin and ZnPP-9 + hemin, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05). It is suggested that endogenous CO may play an important role in the regulation of respiratory rhythm.
Animals
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Animals, Newborn
;
Carbon Monoxide
;
physiology
;
Female
;
Hemin
;
pharmacology
;
Hypoglossal Nerve
;
drug effects
;
physiology
;
Male
;
Protoporphyrins
;
pharmacology
;
Rats
;
Rats, Sprague-Dawley
;
Respiration