Uroporphyrin Levels Research Articles

X-linked dominant protoporphyria in a Chinese pedigree reveals a four-based deletion of ALAS2.

BackgroundX-linked dominant protoporphyria (XLDPP) is a rare, hereditary disorder that leads to hepatobiliary and hematologic abnormalities including increased erythrocyte protoporphyrin, cutaneous photosensitivity, and decreased iron stores that is caused by a pathogenic mutation of ALAS2 gene.MethodsThis study aimed to confirm the existence of XLDPP in a Chinese pedigree. We observed and described the dermatoscopic findings of this disorder under dermoscopy, and assessed photo damage in XLDPP patients using the Fotofinder system and very high frequency (VHF) skin ultrasonic system. We performed next generation sequencing and Sanger sequencing to detect and confirm genetic variants in DNA samples from the XLDPP family. Moreover, we monitored the hepatobiliary function as well as hematologic changes in related family members.ResultsAs compared to unaffected control subjects, patients exhibited evidence of severe cutaneous photodamage, causing photoaging, an increase in the size of the gallbladder, increased levels of protoporphyrin in red blood cells, an increase in blood levels of uroporphyrin and hematoporphyrin, and iron deficiency.ConclusionsXLDPP was validated by the identification of a four-base-pair deletion (c.1706_1709delAGTG, p.E569fs) in ALAS2 (NM_000032.4) in the proband which segregated with the disease in an X-linked dominant pattern, with hemizygous males being more severely affected than heterozygous females. We also found a missense variant in GATA Binding Protein 1 (GATA1).

A first report of porphyria cutanea tarda successfully treated with glycyrrhizin.

Porphyria cutanea tarda (PCT) is a condition that affects liver and skin by reduction of hepatic uroporphyrinogen decarboxylase activity. It is characterized by blistering lesions, erosions and crusts on sun-exposed areas. We report a 51-year-old male presenting with recurrent episodes of bullae, erosions, and crust on his neck and dorsum of the hands for 3 months. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase levels, as well as total plasma porphyrin and urinary uroporphyrin levels were elevated. Based on the clinical manifestations, the history and laboratory findings, a diagnosis of PCT was made. The cutaneous and biochemical abnormalities of the patient improved with therapy of glycyrrhizin.

Methotrexate and actinomycin D chemotherapy in a patient with porphyria: a case report

BackgroundDespite their broadly recommended use as chemotherapeutic agents, the porphyrogenicity of methotrexate and actinomycin D have not been confirmed. Accordingly, it is not known whether these agents are safe for use in patients with porphyria.Case presentationIn this report, we present a case of an invasive mole with lung metastasis in a 49-year-old Japanese woman who had previously been diagnosed with acute intermittent porphyria at 27 years of age but had no recent history of acute intermittent porphyria attacks. Her serum human chorionic gonadotropin level was elevated 1 month after hysterectomy, and she was referred to our center for chemotherapy. After she received 100 mg of methotrexate, drug eruptions were observed starting on day 3 and grew progressively worse. Erythema and mucosal erosion spread throughout her body, whereupon she was administered prednisolone. In addition, our patient experienced febrile neutropenia and required granulocyte colony- stimulating factor treatment. No changes in our patient’s urinary coproporphyrin or uroporphyrin levels were detected during this entire episode. Methotrexate was replaced by actinomycin D (0.5 mg/body intravenously on days 1–5 every 2 weeks). After five uneventful cycles of actinomycin D, our patient achieved and maintained a normal serum human chorionic gonadotropin level for 3 years.ConclusionsMethotrexate and actinomycin D did not induce acute porphyric attacks in this patient with acute intermittent porphyria; however, severe adverse effects were noted with methotrexate. Although further investigation is required, our data suggest that these agents are nonporphyrinogenic and can therefore be used to treat patients with comorbid porphyria.

Lésions sclérodermiformes dans la porphyrie cutanée tardive : six observations

The clinical features of porphyria cutanea tarda (PCT) are usually distinctive and include blistering on sun-exposed areas, fragile skin, hypertrichosis and hyperpigmentation. Sclerodermatous changes are much less common, and may either reveal PCT or else appear later. We carried out a retrospective study of the files of six female patients presenting such lesions. Six women (age: 45 to 72 years) were referred for sclerodermatous lesions on sun-exposed areas of the upper body. In four patients, these lesions revealed PCT and in the remaining two patients they were indicative of previously treated but relapsing PCT. Four had sclerodermatous skin changes mimicking morphea of the neck and neckline, the top of the back and the face, while one presented more diffuse facial and cervical sclerosis. Associated alopecia was seen in three patients. The last patient presented isolated sclerodermiform alopecia. Associated malar hypertrichosis was seen in five cases and facial hyperpigmentation was noted in three cases. Four exhibited no blisters, cutaneous fragility, milia or photosensitivity. Histological findings were consistent with morphea or scleroderma in all cases. All patients presented abnormal liver tests: cirrhosis was present in four cases (primitive biliary cirrhosis, alcoholic cirrhosis and hepatitis C) and fatty liver in two cases. In four cases, there was excessive alcohol intake. Uroporphyrin levels were above the normal range in all cases. Local corticosteroid therapy associated with phlebotomy and/or low-dose hydroxychloroquine resulted in complete normalisation of porphyrin levels in four patients, with complete resolution of the cutaneous lesions in two patients and partial improvement in the other two. Sclerodermatous changes are uncommon in PCT. They are not always late and secondary to the process of healing of blisters but can in fact constitute the first cutaneous symptom of the disease while revealing the underlying liver disease. Even in the absence of blisters, photosensitivity or cutaneous fragility, a diagnosis of PCT must be suspected in a setting of sclerodermatous changes distributed on the neck and face, or the neckline, or scarring alopecia, if associated with abnormal liver tests. Skin biopsy to confirm the diagnosis of scleroderma may delay the diagnosis, which is in fact based on porphyrin level. Normalization of the latter parameter under treatment allows regression of lesions.

Porphyrin levels in excreta of rabbit as non-destructive biomarkers of diazinon exposure

In the present study the effect of a chronic exposition to the organophosphorous pesticide diazinon on the porphyrin profile in feces of rabbit was evaluated, in order to validate the use of such molecules as non-destructive biomarkers for monitoring exposure of mammals to this environmental xenobiotic. Male and female (12:12) rabbits were exposed to oral single doses of diazinon, feces being sampled at every 10 days, till the end of the experience (30 days). HPLC method was validated from the results obtained, for detection of porphyrins in feces of mammals. Results revealed differences on the porphyrin profile between male and female, the most relevant differences associated to the uroporphyrin levels. In conclusion, porphyrin levels in rabbit's excreta may be used as indicators of exposure to such chemicals, thus providing a useful non-destructive method for monitoring exposure of animals to different environmental pollutants. However, the effect of gender should be taken into account when interpreting results.

Liver Cirrhosis Induced by Porphyria Cutanea Tarda: A Case Report and Review

Porphyria cutanea tarda (PCT) is a metabolic disorder that results in a decrease in uroporphyrinogen decarboxylase activity. It is characterized by photosensitivity, bullae formation, and skin pigmentation. There are four types of PCT: acquired, familial, toxic, and hepatoerythropoietic. Uroporphyrin levels are elevated in the urine of PCT patients. PCT can be differentiated from other porphyrias by its clinical characteristics and the porphyrin levels in the serum, erythrocytes, urine, and feces. This metabolic disorder can lead to liver dysfunction as well as histological changes such as fatty infiltration or hepatic fibrosis. PCT rarely manifests as liver cirrhosis. We report herein a case of PCT-induced liver cirrhosis that progressed to hepatic failure.

Absolute requirement for iron in the development of chemically induced uroporphyria in mice treated with 3-methylcholanthrene and 5-aminolevulinate

Accumulating evidence, including experiments using cytochrome P450 1a2 (Cyp1a2) gene knock-out mice (Cyp1a2(-/-)), indicates that the development of chemically induced porphyria requires the expression of CYP1A2. It has also been demonstrated that iron enhances and expedites the development of experimental uroporphyria, but that iron alone without CYP1A2 expression, as in Cyp1a2(-/-) mice, does not cause uroporphyria. The role of iron in the development of porphyria has not been elucidated. We examined the in vivo effect of iron deficiency on hepatic URO accumulation in experimental porphyria. Mice were fed diets containing low (iron-deficient diet (IDD), 8.5 mg iron/kg) or normal (normal diet (ND), 213.7 mg iron/kg) levels of iron. They were treated with 3-methylcholanthrene (MC), an archetypal inducer of CYP1A, and 5-aminolevulinate (ALA), precursors of porphyrin and heme. We found that uroporphyrin (URO) levels and uroporphyrinogen oxidation (UROX) activity were markedly increased in ND mice treated with MC and ALA, while the levels were not raised in IDD mice with the same treatments. CYP1A2 levels and methoxyresorufin O-demethylase (MROD) activities, the CYP1A2-mediated reaction, were markedly induced in the livers of both ND and IDD mice treated with MC and ALA. UROX activity, supposedly a CYP1A2-dependent activity, was not enhanced in iron-deficient mice in spite of the fact of induction of CYP1A2. We showed that a sufficient level of iron is essential for the development of porphyria and UROX activity.

Hochdosierte Vitamingabe zur Verhinderung einer Porphyria cutanea urämica?

50 Patients with chronic renal failure undergoing hemodialysis with or without porphyria cutanea tarda (PCT)-like skin changes were investigated. The total porphyrin amount in erythrocytes, plasma and dialysate and the distribution of porphyrin metabolites in plasma and dialysate were measured. In plasma, the group of patients with skin changes (referred as PCU = porphyria cutanea uremica) showed significantly increased uroporphyrin levels as compared to the non-symptomatic group. In addition, significant differences concerning the ratio uro-/coproporphyrin in plasma were shown: non-symptomatic patients with 0.87, as opposed to the PCU group with 3.7. Considerable differences between the level of vitamin ingestion were identified between the groups. Patients with PCU took distinctly less vitamins C, E and B than patients without symptoms.

Accelerated development of uroporphyria in mice heterozygous for a deletion at the uroporphyrinogen decarboxylase locus.

Three weeks after a single dose of iron-dextran and Aroclor 1254, mice maintained continuously on delta-aminolevulinic acid supplemented drinking water showed significantly elevated levels of hepatic uroporphyrin and depressed (25% of normal) uroporphyrinogen decarboxylase (URO-D) activity. Depressed URO-D activity was paralleled by the ability of heat denatured cytosol to inhibit rhURO-D activity. Mice heterozygous for a targeted disruption at the URO-D locus (URO-D+/-) exhibited half the URO-D activity of homozygous controls prior to treatment. After treatment, these animals showed URO-D activity and rhURO-D inhibitory activity comparable to similarly treated wild type (URO-D +/+) mice but with significantly greater uroporphyrin accumulation. With only 10 days of treatment, URO-D +/- but not URO-D +/+ mice showed changes similar in magnitude to those seen after 21 days. Prior to treatment, URO-D genotype did not influence overall hepatic P450 concentration in either sex and there was no significant difference between sexes. The treatment regimen significantly elevated P450 in animals of either URO-D genotype and in both sexes, although the induction response at the 10-day point was attenuated in URO-D +/- mice. From differences in the CO absorbance maximum, and by P450 activity analysis, this attenuated induction response resulted from an attenuation of the CYP2B not the CYP1A induction.

Porphyria cutanea tarda in Brazilian patients: association with hemochromatosis C282Y mutation and hepatitis C virus infection.

Porphyria cutanea tarda (PCT) is commonly associated with iron overload and hepatitis C virus (HCV) infection. Association between hemochromatosis C282Y or H63D mutations and PCT has been observed, although not uniformly, and iron overload is also commonly found in chronic HCV hepatitis. The aim of the present study was to investigate the frequency of C282Y and H63D mutations and HCV infection in Brazilian patients with PCT and their relationship with iron overload. Twenty-three patients (19 men) aged 39.6 +/- 11.1 yr were studied. All had dermatological lesions of PCT and high levels of urinary uroporphyrin. HCV infection and iron overload were investigated. DNA samples were analyzed for the presence of HFE mutations. The frequency of C282Y was significantly higher in PCT patients than in 278 healthy individuals (17.4% vs 4%, odds ratio = 5.1, 95% confidence interval 1.5-17.6, p = 0.02), whereas no difference was observed regarding the H63D mutation (30.4% vs 31%, odds ratio = 1, 95% confidence interval 0.4-2.4, p = 1). Biochemical tests in PCT patients showed iron overload with transferrin saturation = 47.3 +/- 20.7% and ferritin = 566.8 +/- 425 ng/ml. Fifteen of 23 (65.2%) patients had HCV infection and alcohol ingestion was observed in 17 of 23 (73.9%). PCT patients exhibited evidence of iron overload, a high frequency of HCV, and an association with C282Y mutation. These data further support the notion that both acquired and inherited factors contribute to the occurrence of PCT, and indicate that screening for C282Y may be justified in PCT patients.

Porphyria cutanea tarda in Brazilian patients: association with hemochromatosis C282Y mutation and hepatitis C virus infection

OBJECTIVE: Porphyria cutanea tarda (PCT) is commonly associated with iron overload and hepatitis C virus (HCV) infection. Association between hemochromatosis C282Y or H63D mutations and PCT has been observed, although not uniformly, and iron overload is also commonly found in chronic HCV hepatitis. The aim of the present study was to investigate the frequency of C282Y and H63D mutations and HCV infection in Brazilian patients with PCT and their relationship with iron overload. METHODS: Twenty-three patients (19 men) aged 39.6 ± 11.1 yr were studied. All had dermatological lesions of PCT and high levels of urinary uroporphyrin. HCV infection and iron overload were investigated. DNA samples were analyzed for the presence of HFE mutations. RESULTS: The frequency of C282Y was significantly higher in PCT patients than in 278 healthy individuals (17.4% vs 4%, odds ratio = 5.1, 95% confidence interval 1.5–17.6, p = 0.02), whereas no difference was observed regarding the H63D mutation (30.4% vs 31%, odds ratio = 1, 95% confidence interval 0.4–2.4, p = 1). Biochemical tests in PCT patients showed iron overload with transferrin saturation = 47.3 ± 20.7% and ferritin = 566.8 ± 425 ng/ml. Fifteen of 23 (65.2%) patients had HCV infection and alcohol ingestion was observed in 17 of 23 (73.9%). CONCLUSIONS: PCT patients exhibited evidence of iron overload, a high frequency of HCV, and an association with C282Y mutation. These data further support the notion that both acquired and inherited factors contribute to the occurrence of PCT, and indicate that screening for C282Y may be justified in PCT patients.

Clinical application of therapeutic erythrocytapheresis (TEA)

Therapeutic erythrocytapheresis (TEA) has been used in different diseases such as polycythemia vera (PV), secondary erythrocytosis or hemochromatosis as a process of the less cumbersome but more expensive phlebotomy. TEA is preferred in emergency conditions such as thrombocytosis or in conditions such as porphyria cutanea tarda (PCT) or erythropoietic porphyria when plasma exchange (PEX) is often combined with TEA to reduce extracellular levels of uroporphyrin which contribute to plasma hyperviscosity. TEA is often combined with drug therapy that varies from etoposide in PV to EPO and desferoxamine which are used to mobilize and reduce iron stores in hemochromatosis. Benefits from this combination may be more long lasting than expected. Nonetheless for TEA, there is no standard protocol and, clinical experience with this therapy remains highly anecdotal. Therapeutic red cell-exchange (TREX) has been used with much interest over the years, starting with the management of hemolytic disease of the newborn and later used to correct severe anemia in thalassemia patients thereby preventing iron overload. It has also been used for the management of complications of sickle cell disease such as priapism, chest syndrome, stroke, retinal, bone, splenic and hepatic infarction or in preparation for surgery by reducing HbS to less than 30%. Automated apheresis has also favored the use of TREX in conditions such as paroxysmal nocturnal hemoglobinuria and aniline poisioning, arsenic poisioning, Na chlorate intoxicatons and CO intoxications, hemoglobinopathies, autoimmune hemolytic anemia, reactions due to ABO incompatibility, in preparation for ABO incompatible bone marrow transplantation or for preventing anti-D immunization after the transfusion of D + cells to D − recipients. Another field of application has been in the emergency management of intraerythrocytic parasite infections such as malaria and babesiosis. Application of TREX may be wide but its real use remains limited. In our personal experience, in 16 years, only 167 TREX procedures have been carried out in a total of 13,747 therapeutic procedures. This represents only 1.21% of the total.

Abnormal Uroporphyrin Levels in Chronic Hepatitis C Virus Infection

A strong association between hepatitis C virus (HCV) infection and porphyria cutanea tarda (PCT) has been observed, but the implications of the viral infection in the metabolism of porphyrins in patients without clinical manifestations of PCT are not known. The levels of porphyrin in plasma and uroporphyrin (URO) and coproporphyrin (COPRO) in 24-hour urine were measured in 156 patients with chronic HCV infection showing no clinical evidence of PCT. Levels of URO higher than the upper limit were observed in 35 of 156 patients (22.4%). The range and the mean values +/- standard deviation were 26-1,196 microg/24 hours and 82 +/- 204 microg/24 hours. Increased levels of COPRO and plasma porphyrin were observed in 12 of 156 patients (7.7%) and 2 of 156 patients (1.3%) respectively. There were no differences between patients with increased URO levels and patients with normal URO levels in terms of gender, age, risk factors for HCV infection, alcohol abuse, or hepatitis B viral infection. Transferrin saturation (p = 0.040), gamma glutamyl transpeptidase (p < 0.0001), aspartate aminotransferase (p = 0.006), and alanine aminotransferase (p = 0.040) were significantly higher in patients with abnormal URO than in patients with normal URO. The frequency of cirrhosis was higher, but not significantly different, in patients with increased URO (16.7%) compared with patients with normal URO (3.8%). The authors demonstrated that even without a clinical manifestation of PCT it is possible to detect abnormalities in the metabolism of porphyrins in patients with chronic HCV infection. The implications of these findings deserve additional investigation.

Type of Impaired Porphyrin Metabolism Caused by Hepatitis C Virus Is Not Porphyria Cutanea Tarda but Chronic Hepatic Porphyria

We would like to respond to theArchivesarticles by O'Connor et al¹and Cribier et al.²O'Connor et al reported on the porphyrin abnormalities found in the acquired immunodeficiency syndrome and suggested that the contribution of the hepatitis C virus (HCV) to abnormal porphyrin excretion patterns were characteristic of porphyria cutanea tarda (PCT). In 1994, we analyzed the urinary excretion patterns of porphyrin derivatives in patients with HCV-induced liver disease and HCV carriers using high-performance liquid chromatography.³The levels of urinary porphyrins of 63 HCV-positive patients who had liver diseases (including acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatoma), 37 HCV carriers, and 32 healthy volunteers are summarized in the<b>Table.</b>The levels of uroporphyrin were below the detection limit and a coproporphyrin-predominant excretion pattern was observed in all these groups. Only secondary coproporphyria was observed and no PCT-like excretion pattern was observed. To clarify the

Type of impaired porphyrin metabolism caused by hepatitis C virus is not porphyria cutanea tarda but chronic hepatic porphyria

We would like to respond to theArchivesarticles by O'Connor et al¹and Cribier et al.²O'Connor et al reported on the porphyrin abnormalities found in the acquired immunodeficiency syndrome and suggested that the contribution of the hepatitis C virus (HCV) to abnormal porphyrin excretion patterns were characteristic of porphyria cutanea tarda (PCT). In 1994, we analyzed the urinary excretion patterns of porphyrin derivatives in patients with HCV-induced liver disease and HCV carriers using high-performance liquid chromatography.³The levels of urinary porphyrins of 63 HCV-positive patients who had liver diseases (including acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatoma), 37 HCV carriers, and 32 healthy volunteers are summarized in the<b>Table.</b>The levels of uroporphyrin were below the detection limit and a coproporphyrin-predominant excretion pattern was observed in all these groups. Only secondary coproporphyria was observed and no PCT-like excretion pattern was observed. To clarify the

Toxicity of PCB 77 (3,3′,4,4′-Tetracholorobiphenyl) and PCB 118 (2,3′,4,4′,5-Pentachlorobiphenyl) in the Rat Following Subchronic Dietary Exposure

Toxicity of PCB 77 (3, 3′,4,4′-Tetrachlorobiphenyl) and PCB 118 (2,3′4,4′,5-Pentachlorobiphenyl) in the Rat Following Subchronic Dietary Exposure. Chu, i., Villeneuve, D. C., Yagminas, A., Lecavalier, P., Hakansson, H., Ahlborg, U. G., Valli, V. E., Kennedy, S. W., Bergman, A., Seegal, R. F. and Feeley, M. (1995). Fundam. Appl. Toxicol. 26, 282-292. The toxicity of 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118) was investigated in rats following subchronic dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats were administered PCB 77 in the diet at 0, 10, 100, 1000, or 10,000 ppb for 13 weeks. PCB 118 was administered to males in the diet at 0, 10, 100, 1000, and 10,000 ppb, while the female groups received 0, 2, 20, 200, or 2000 ppb of the congener for 13 weeks. Growth rate and food consumption were not affected by treatment. No clinical signs of toxicity were observed. Increased spleen weight occurred in male rats fed 1000 or 10,000 ppb PCB 77. Male rats receiving 10,000 ppb PCB 188 had increased liver weight and hepatic ethoxyresorufin O-deethylase (EROD) activity. Increased hepatic EROD activity but not liver weight was observed in female rats given the 2000-ppb PCB 118 diet. Increased EROD activity was also noted in male rats given 10,000 ppb and in female groups receiving 1000 or 10,000 ppb PCB 77. Male rats exposed to 10,000 ppb and in female groups receiving 1000 or 10,000 ppb PCB 77. Male rats exposed to 10,000 ppb PCB 77 had decreased vitamin A in the liver and lung and elevated levels in the kidney. Liver vitamin A of both 1000- and 10,000-ppb PCB 77 female groups was decreased. PCB 118 had no effects on tissue vitamin A at the levels studied. No hematological changes or serum biochemical changes were seen in any of PCB 118- and PCB 77-treated groups, nor were liver uroporphyrin levels altered. A reduction in dopamine and homovanillinic acid in the substantia nigra region of the brain was observed in female rats fed 2000 ppb PCB 118, while 10,000 ppb PCB 77 was associated with an elevation in 3,4-dihydroxyphenylacetic acid in the nucleus accumbens region of male rat brains. Mild to moderate changes were observed in the liver and thyroid of rats given PCB 77 or PCB 118. PCB 118 accumulated in a dose-dependent manner in fat and to a much lesser extent in liver. In contrast, very low levels of PCB 77 residue were found in the tissues examined. Based on the above data it was concluded that the NOAEL of PCB 77 is 100 ppb in diet or 8.7 μg/kg and that of PCB 118 is 200 ppb in diet or 17 μg/kg body wt/day.

Decreased Uroporphyrinogen Decarboxylase Activity in Patients with End-Stage Renal Disease Undergoing Hemodialysis

Raised plasma uroporphyrin levels were found in all the 14 patients with end-stage renal disease studied, 7 of whom were on continuous ambulatory peritoneal dialysis (CAPD) and 7 on hemodialysis (HD). The elevation observed in the HD group was higher than that noted in the CAPD group; 18-fold in the former and 13-fold in the latter. The difference in uroporphyrin plasma levels between the two dialysis populations might be explained, at least partially, by the reduced activity of uroporphyrinogen decarboxylase (UROD), the enzyme which converts uroporphyrinogen to coproporphyrinogen. A decrease of 48% was noted in the HD group, whereas no change was observed in the CAPD group. A significant negative correlation (r = -0.37, p < 0.01) was found between the concentration of uroporphyrin in plasma and the activity of UROD. In view of the data shown, it is suggested that erythrocyte UROD activity should be interpreted with caution in HD patients suspected of having porphyria cutanea tarda.

Subchronic Toxicity of 3,3′,4,4′,5-Pentachlorobiphenyl in the Rat: I. Clinical, Biochemical, Hematological, and Histopathological Changes

Subchronic Toxicity of 3,3′,4,4′,5-Pentachlorobiphenyl in the Rat. I. Clinical, Biochemical, Hematological, and Histopathological Changes. Chu, I., Villeneuve, D.C., Yagminas, A., LeCavalier, P., Poon, R., Feeley, M., Kennedy, S. W., Seegal, R. F., Häkansson, H., Ahlborg, U. G., and Valli, V. E. (1994). Fundam. Appl. Toxicol. 22, 457-468.The systemic toxicity of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) following subchronic dietary exposure was investigated in Sprague-Dawley rats. PCB 126 was administered to rats of both sexes at concentrations of 0.1, 1.0, 10, or 100 ppb in their diet for 13 weeks. Another group of rats received a loading dose of 5 μg PCB/kg body wt at the start of the feeding period followed by exposure to 10 ppb PCB diet for the same period of time as the other groups. Growth suppression and decreased food consumption were observed in the highest dose groups of both sexes. Increased organ/body weight ratios for the liver occurred in the 10 and 100 ppb groups of both sexes. Rats of both sexes exposed to the highest dose of the PCB also exhibited increased relative kidney, spleen, and brain weights. Hematological and most serum biochemical changes were confined to the 100 ppb groups. These included elevated alkaline phosphatase, bilirubin, cholesterol, and aspartate aminotransferase, and decreased serum glucose, hemoglobin, erythrocytes, hematocrit, and platelets. A dose-dependent increase in liver ethoxyresorufin-O-deethylase activity was observed in rats of both sexes starting at 0.1 ppb. A dose-dependent increase in liver uroporphyrin levels was observed in both sexes and significant changes occurred in the female rats at 1.0 ppb and higher dose groups. Decreased liver vitamin A was observed in the 10 ppb group and higher in both sexes. Kidney vitamin A was elevated in the 100 ppb group. No statistically significant changes were noted in concentrations of brain biogenic amines. PCB 126 residues were 10-fold higher in liver than in fat. Treatment-related histopathological changes were observed in the thymus, thyroid, bone marrow, and liver of rats exposed to the 10 ppb diet, but increased frequency of mild changes was observed in most of these tissues at the 1.0 ppb level. Based on the above data, the no adverse effect level was judged to be 0.1 ppb in the diet or 0.01 μg/kg body wt/day.

Association Between Porphyria Cutanea Tarda and Human Immunodeficiency Virus Infection

To the Editor.— We have read with interest the excellent articles by Strauss 1 and Cockerell 2 regarding the endocrine and cutaneous manifestations of acquired immunodeficiency syndrome. In neither of these articles is anything mentioned about porphyria cutanea tarda (PCT), a metabolic illness with prominent cutaneous manifestations associated with infection with human immunodeficiency virus (HIV). We have had the opportunity to treat a patient in whom PCT was diagnosed. Report of a case.— A 44-year-old man, who had occasionally used intravenous drugs and drank 100 g of alcohol per day, sought medical attention because of cutaneous lesions on the forehand, photosensitivity, and increased fragility to trauma, which appeared in the last few months. He also had a discrete elevation of transaminase levels. Twenty-four-hour urine coproporphyrin and uroporphyrin levels were elevated (509 ug/24 h and 1029 μg/24 h, respectively). Porphyria cutanea tarda was diagnosed, and periodical phlebotomies were begun, which effected

Effective control of patients with porphyria cutanea tarda by measuring plasma uroporphyrin

The clinical value of a very rapid spectrofluorometric method for the determination of plasma uroporphyrin levels was studied during follow-up of 122 patients with porphyria cutanea tarda (PCT). Four-hundred and eight measurements were carried out within a 3-year period. In active PCT plasma uroporphyrin varied between 15 and 448 nmol/l (normal 0-1.4). A high correlation was seen between elevated levels of uroporphyrin in the plasma and urine in new cases (r = 0.72, n = 23) and relapses (r = 0.92, n = 37). A parallel course between these variables was noted during the treatment of 31 patients. The correlation was less pronounced (r = 0.42) in remission, i.e. in those cases with urinary uroporphyrin levels lower than 240 nmol/24 h. However, only in nine of 249 measurements taken in remission did plasma uroporphyrin exceed 15 nmol/l. In six of these cases a biochemical relapse had occurred at the next follow-up measurement as judged by an increase of uroporphyrin in the urine. It is suggested that treatment of new cases and relapses should continue until plasma uroporphyrin drops under 10 nmol/l. Values between 15 and 23 nmol/l in individuals already treated raise the suspicion of relapse and should be rechecked in the near future. Retreatment is necessary when the levels exceed 23 nmol/l. The use of the method is recommended as a simple and effective way for monitoring the progress of patients with PCT.