Acute psychosis in two elderly patients.
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Acute Disease↗
Biomedical subjects
K E Anderson
Publications and source records attributed to K E Anderson.
A major protein precursor of zebra mussel (Dreissena polymorpha) byssus: deduced sequence and significance.
The zebra mussel is a nonindigenous invader of North American lakes and rivers and one of the few freshwater bivalve molluscs having a byssus--a sclerotized organ used by the mussel for opportunistic attachment to hard surfaces. We have sequenced a foot-specific cDNA whose composite protein sequence was deduced from a series of overlapping but occasionally nonidentical cDNA fragments. The overall deduced sequence matches tryptic peptides from a major byssal precursor protein--Dreissena polymorpha foot protein 1 (Dpfp1). The calculated mass of Dpfp1 is 49 kDa; but this is known to be extensively hydroxylated and O-glycosylated during maturation. Purified native Dpfp1 analyzed using matrix-assisted laser-desorption ionization mass spectrometry with time-of-flight indicates that the protein occurs as at least two size variants with masses of 48.6 and 54.5 kDa. In all probability, the sequence variants reported in this study are related to the larger mass variant. Dpfp1 has a block copolymer-like structure defined by two consensus motifs that are sharply segregated into domains. The N-terminal side of Dpfp1 has 22 tandem repeats of a heptapeptide consensus (P-[V/E]-Y-P-[T/S/delta]-[K/Q]-X); the C-terminal side has 16 repeats of a tridecapeptide motif (K-P-G-P-Y-D-Y-D-G-P-Y-D-K). Both consensus repeats are unique, with some limited homology to other proteins functioning in tension: marine mussel adhesives, plant extensins, titin, and trematode eggshell precursors.
Amino Acid Sequence↗
Family histories of diabetes mellitus and breast cancer and incidence of postmenopausal breast cancer.
Diabetes-associated endocrine factors may influence the growth of some breast tumors. Therefore, one might expect an association of family history of diabetes mellitus with breast cancer incidence. We analyzed data from a cohort study of 41,837 women ages 55-69 years. During 10 years of follow-up, we identified 1,013 incident cases of breast cancer. There was no consistent association between family history of diabetes mellitus and family history of breast cancer, except among sisters. Women with a family history of diabetes had a higher prevalence of breast cancer risk factors, but family history of diabetes was not associated with risk of postmenopausal breast cancer, regardless of family history of breast cancer status.
Aged↗
A prospective cohort study of intake of calcium, vitamin D, and other micronutrients in relation to incidence of rectal cancer among postmenopausal women.
To investigate whether high intakes of calcium and other micronutrients (carotene, retinol, and vitamins C, D, and E) are related to reduced risks of rectal cancer, we analyzed data from a large cohort study of postmenopausal Iowa women who responded to a mailed survey in 1986. After 9 years of follow-up, 144 incident rectal cancer cases were ascertained among the 34,702 women at risk. Intake levels of micronutrients at baseline were derived from self-reported data on vitamin supplements and dietary intake of 127 foods included in a semiquantitative food frequency questionnaire. After adjustment for total energy intake and other potential confounding factors, a dose-response inverse association was observed between total calcium intake and the risk of rectal cancer: adjusted relative risks (RRs) were 1.00, 0.90, and 0.59 (trend test, P = 0.02) from the lowest to the highest calcium intake tertiles. High intakes of dietary and supplement calcium were both related to a slightly reduced risk of rectal cancer, but neither of the trend tests was statistically significant. Reduced risks of rectal cancer were also observed for high intake of carotene and vitamins A, C, and D, although none of the associations were statistically significant. For vitamin D, the adjusted RRs were 1.00, 0.71, and 0.76 (trend test, P = 0.20) for increasing intake tertiles. Compared with women who consumed low levels of both total calcium and vitamin D, those in the highest intake group of both nutrients were at a 45% reduced risk of rectal cancer (RR, 0.55; 95% confidence interval, 0.32-0.93). This study supports the hypothesis that high intake of calcium and possibly other micronutrients may be beneficial in the prevention of rectal cancer.
Aged↗
The potential of liposomes in oral drug delivery.
Oral liposome drug delivery has been the subject of much cynicism. Results have been quite variable and, for the most part, have not been predicated on specific objectives that would lead to success. Prerequisites are stability in the gastrointestinal environment and binding to specific sites. Transport via paracellular and transcellular routes from normal epithelial tissue or Peyer's patches leads to different outcomes of drug delivery and immunization, respectively. Polymerized, microencapsulated, and polymer-coated liposomes have all increased the potential of oral liposomes. Using targeted liposomes and a greater understanding of their cellular processing will ultimately lead to effective therapies from oral liposomes.
Administration, Oral↗
The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer.
BACKGROUND: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. OBJECTIVE: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. DESIGN: Prospective cohort study. SETTING: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. PARTICIPANTS: Random sample of 41,837 female Iowa residents 55 to 69 years of age. MEASUREMENTS: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index. RESULTS: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10,000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10,000 person-years [CI, 69 to 92 deaths]). CONCLUSIONS: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.
Aged↗
Association of Stein-Leventhal syndrome with the incidence of postmenopausal breast carcinoma in a large prospective study of women in Iowa.
BACKGROUND: The Stein-Leventhal syndrome (SLS), first described in 1935, is characterized by infertility, hyperandrogenization, and obesity. Because this phenotype represents an aggregation of risk factors for postmenopausal breast carcinoma, and because in general, a hormonal imbalance underlies the disorder, the authors examined the association between self-reported SLS and breast carcinoma incidence in a cohort of 34,835 cancer-free women assembled in 1986 and followed through 1992. METHODS: All participants were between the ages of 55 and 69 and held a valid Iowa driver's license. A total of 472 women in the cohort (1.35%) reported a history of SLS at baseline. Incident cases of breast carcinoma were identified annually using the State Health Registry of Iowa. Data were analyzed using Cox proportional hazards regression. RESULTS: During the follow-up period, there were 883 incident breast carcinomas, 14 among women reporting a history of SLS. Women with SLS were more likely than women without SLS to report fertility problems and menstrual irregularities, but there were no significant differences observed regarding body mass index (BMI). Although women with SLS were 1.8 times as likely to report benign breast disease than women without SLS (P < 0.01), they were not more likely to develop breast carcinoma (relative risk [RR] = 1.2; 95% confidence interval [CI] = 0.7-2). Adjustment for age at menarche, age at menopause, parity, oral contraceptive use, BMI, waist-to-hip ratio, and family history of breast carcinoma lowered the RR to 1 (95% CI = 0.6-1.9. CONCLUSIONS: Despite the high risk profiles of some women with SLS, these results do not suggest that the syndrome per se is associated with an increased risk of postmenopausal breast carcinoma.
Aged↗
Ascorbic acid deficiency in porphyria cutanea tarda.
Porphyria cutanea tarda (PCT), the most common form of porphyria, is manifested as skin photosensitivity caused by excess hepatic production of uroporphyrin and heptacarboxylporphyrin. In experimental animal models, ascorbic acid modulates chemically induced uroporphyrin accumulation. The purpose of this study was to determine whether ascorbic acid is decreased in the plasma of patients with PCT. Plasma was obtained after an overnight fast from 21 PCT patients, 16 of whom were infected with hepatitis C virus (HCV), and from a separate group of 9 patients with HCV infection but not PCT. Thirteen PCT patients were studied when they had active disease and 8 after treatment-induced remission. Plasma ascorbic acid was low (<23 micromol/L) in 11 (85%) of the 13 untreated PCT patients and deficient (<11 micromol/L) in 8 (62%). Two patients with normal ascorbic acid levels (45 and 62 micrommol/L) had consumed multivitamins. In 2 patients with deficient ascorbic acid, plasma levels returned to normal after phlebotomy treatment. Of the 8 patients studied during remission, 4 had normal ascorbic acid values and 4 were deficient (5 to 8 micromol/L). Plasma ascorbic acid values were normal for all patients who had HCV but no PCT. These data suggest that plasma ascorbic acid concentrations are commonly low in PCT, but this decrease is unrelated to HCV infection. Ascorbic acid deficiency may be one of the factors that contributes to the pathogenesis of PCT.
Adult↗
Photosensitization of experimental hepatocellular carcinoma with protoporphyrin synthesized from administered delta-aminolevulinic acid: studies with cultured cells and implanted tumors.
BACKGROUND/AIMS: Photodynamic therapy using porphyrins or related compounds and laser light is an investigational treatment for neoplasms. The aim of this study was to establish whether this might be applicable for hepatocellular carcinoma using protoporphyrin synthesized in the tissue from administered delta-aminolevulinic acid. METHODS: We measured porphyrin accumulation in normal rat hepatocytes and Morris hepatoma cells in culture, and in subcutaneously implanted hepatomas and other tissues of the rat after administration of delta-aminolevulinic acid, and assessed cell and tissue damage after application of laser light. RESULTS: Porphyrin accumulation after delta-aminolevulinic acid was added to the medium was greater and continued to increase for a longer period of time in hepatoma cells than in hepatocytes (1337+/-42 vs 513+/-31 fluorescence units/cell at 8 h, means+/-SE, p<0.001). After intraperitoneal injection of delta-aminolevulinic acid to rats with subcutaneously growing hepatomas, porphyrin content in tumor and liver was similar at 4 h but was higher in tumor at 6 h. Laser light caused necrosis of normal and malignant liver cells in culture and subcutaneous hepatomas in vivo. CONCLUSIONS: We conclude from these in vitro and in vivo studies that porphyrin accumulation after administration of delta-aminolevulinic acid in this hepatoma is substantial and time dependent, and delivery of laser light locally can cause tumor photosensitization and necrosis.
Aminolevulinic Acid↗
Metabolic activation of aromatic amines by human pancreas.
Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas. Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens. Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [3H]N-hydroxy-ABP) of pancreatic cytosols was high, about twothirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using 32P-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.
Acetyltransferases↗
An interfacial tension model of the interaction of water-soluble polymers with phospholipid composite monolayers.
The axi-symmetric drop-shape analysis-pendant drop technique has been used to measure interfacial tension at the chlorobenzene-water interface in the presence of adsorbed films of dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), DMPC-cholesterol, DPPC-cholesterol, DMPC-cholesterol-dicetyl phosphate (DCP) and DPPC-cholesterol-DCP. A surface-pressure function, pi * = pi lipid-polymer -pi lipid (where pi lipid is the surface pressure of the mono-layer without polymer and pi lipid-polymer is the surface pressure of the lipid mono-layer and adsorbed polymer at equilibrium at the chlorobenzene-water interface) was used to characterize the interaction of eight water-soluble polymers with the lipid films. The equation, delta pi * = pi II*-pi I* (where the subscripts II and I denote the higher and lower lipid composites, respectively) was used to determine the differential effect of cholesterol and DCP on mono-layer characteristics in the presence of 1% w/v polymer. Cholesterol or polymer individually condensed DMPC films and expanded DPPC films. However, composite films of DMPC-cholesterol-DCP and carboxymethylchitin (CM-chitin), poly(acrylic acid) (PAA) or poly(vinyl alcohol) (PVA) were more expanded than DMPC films whereas composite films of DPPC were neither more condensed nor expanded than DPPC films. A polymer impact ratio, P* = pi lipid-polymer/pi lpolymer was calculated and the polymers were ranked in order of their impact on the lipid film. PVA and polysaccharides gave low and high P* values, respectively, corresponding to high and low levels of film interaction, whereas PAA and hydrophobized polysaccharides gave intermediate values, indicating their affinity for and penetration of interfacial films with little disruption of the mono-layer. The results show that measurement of interfacial pressures at the chlorobenzene-water interface might be advantageous for evaluating the action of polymers on biological membranes.
1,2-Dipalmitoylphosphatidylcholine↗
Modulation of baroreflex sensitivity and spectral power of blood pressure by heat stress and aging.
To investigate the effects of hyperthermia and aging on baroreceptor-heart rate reflex sensitivity (BRS), cardiovascular parameters were recorded during a progressive rise in core temperature in conscious mature and senescent Fischer 344 rats. BRS was calculated from spontaneous changes in blood pressure and interbeat interval. Low- (LF, 0.01-0.20 Hz) and mid- (MF, 0.2-0.5 Hz) frequency blood pressure power were also determined. In both age groups, hyperthermia caused an increase in blood pressure, renal resistance, and LF but no changes in renal nerve activity, whereas a tachycardia was only observed in the older rats. Increases in BRS (0.80 +/- 0.14 vs. 1.72 +/- 0.34 ms/mmHg, P < 0.05) and MF (3.10 +/- 0.55 vs. 7.81 +/- 1.89 mmHg2, P < 0.05) and a positive correlation between BRS and MF (r = 0.50, P < 0.01) were observed with heating in mature but not senescent rats. These results indicate that LF, which increased with elevated core temperature, may be modulated by thermal stimuli. The augmented BRS in the mature group may contribute to the hemodynamic adjustments that occur with hyperthermia, whereas the lack of an increase in BRS during heat stress in the senescent group suggests that baroreceptor reflex modulation is impaired with aging. The positive correlation between BRS and MF in mature rats, together with the lack of an increase in renal sympathetic nerve activity, indicates that MF may reflect the modulating influence of the efferent sympathetic portion of the baroreceptor reflex loop on arterial blood pressure rather than merely the activity of the peripheral sympathetic nervous system.
Aging↗
Environmental chemical exposures and disturbances of heme synthesis.
Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria.
Environmental Exposure↗
Clinical pharmacokinetics of naproxen.
Naproxen is a stereochemically pure nonsteroidal anti-inflammatory drug of the 2-arylpropionic acid class. The absorption of naproxen is rapid and complete when given orally. Naproxen binds extensively, in a concentration-dependent manner, to plasma albumin. The area under the plasma concentration-time curve (AUC) of naproxen is linearly proportional to the dose for oral doses up to a total dose of 500 mg. At doses greater than 500 mg there is an increase in the unbound fraction of drug, leading to an increased renal clearance of total naproxen while unbound renal clearance remains unchanged. Substantial concentrations of the drug are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Relationships between the total and unbound plasma concentration, unbound synovial fluid concentration and therapeutic effect have been established. Naproxen is eliminated following biotransformation to glucuroconjugated and sulphate metabolites which are excreted in urine, with only a small amount of the drug being eliminated unchanged. The excretion of the 6-O-desmethylnaproxen metabolite conjugate may be tied to renal function, as accumulation occurs in end-stage renal disease but does not appear to be influenced by age. Hepatic disease and rheumatoid arthritis can also significantly alter the disposition kinetics of naproxen. Although naproxen is excreted into breast milk the amount of drug transferred comprises only a small fraction of the maternal exposure. Significant drug interactions have been demonstrated for probenecid, lithium and methotrexate.
Absorption↗
Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls.
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class. When given orally the absorption of diclofenac is rapid and complete. Diclofenac binds extensively to plasma albumin. The area under the plasma concentration-time curve (AUC) of diclofenac is proportional to the dose for oral doses between 25 to 150 mg. Substantial concentrations of drug are attained in synovial fluid, which is the proposed site of action for NSAIDs. Concentration-effect relationships have been established for total bound, unbound and synovial fluid diclofenac concentrations. Diclofenac is eliminated following biotransformation to glucoroconjugated and sulphate metabolites which are excreted in urine, very little drug is eliminated unchanged. The excretion of conjugates may be related to renal function. Conjugate accumulation occurs in end-stage renal disease; however, no accumulation is apparent upon comparison of young and elderly individuals. Dosage adjustments for the elderly, children or for patients with various disease states (such as hepatic disease or rheumatoid arthritis) may not be required. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), lithium, digoxin, methotrexate, cyclosporin, cholestyramine and colestipol.
Administration, Oral↗
Association of family history of cervical, ovarian, and uterine cancer with histological categories of lung cancer: the Iowa Women's Health Study.
A family history of cervical, ovarian, or uterine cancer has been shown to be associated with increased lung cancer risk among postmenopausal women. The present report examines the hypotheses that a family history of cervical cancer is positively associated with histological subtypes of lung cancer most strongly associated with smoking and that a family history of ovarian or uterine cancer are positively associated with risk of adenocarcinoma of the lung. Data are from the Iowa Women's Health Study, a prospective cohort study of 34,480 women ages 55-69 in 1986. Personal smoking histories, use of alcohol, and family history of selected cancers in first- and second-degree relatives were collected at baseline. Follow-up for cancer occurrence was achieved through the State Health Registry of Iowa. After baseline exclusions, a total of 343 incident lung cancers were identified in the cohort at risk through 1994. Women with a family history of cervical cancer in a first-degree relative had a multivariate-adjusted relative risk of lung cancer of 1.6 [95% confidence interval (CI): 0.98-2.6] compared to women without a family history. The risk was particularly high for malignancies most strongly associated with smoking (squamous, small cell, and large cell tumors; relative risk, 2.0; 95% CI, 1.1-3.7). Consistent with our hypotheses, a family history of ovarian cancer was associated with an approximately 2-fold increased risk (multivariate adjusted) of adenocarcinoma of the lung; the association with malignancies more strongly associated with smoking was inverse (relative risk, 0.6; 95% CI, 0.2-2.4). A family history of uterine cancer was not associated with adenocarcinoma, but there was a positive association observed for the most strongly smoking-associated histological types. These results suggest that a family history of cervical cancer is a modest independent risk factor for lung cancers most strongly associated with smoking, and a family history of ovarian cancer is a risk factor for adenocarcinoma of the lung.
Adenocarcinoma↗
Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women's Health Study.
To assess the relationship of smoking and coffee, tea, and alcohol intake to the risk of cancer of the exocrine pancreas, analyses were performed using data from a prospective cohort study of 33,976 postmenopausal Iowa women who responded to a mailed questionnaire in 1986 and were followed through 1994 for cancer incidence and total mortality. At baseline, information on cigarette smoking, consumption of tea, coffee, and alcoholic beverages, and other dietary and lifestyle factors was obtained. Age-adjusted relative risks of pancreatic cancer (n = 66 cases) showed a dose-response association with smoking. Those with fewer than 20 pack-years and those with 20 or more pack-years of smoking exposure were 1.14 (95% confidence interval, 0.53-2.45) and 1.92 (95% confidence interval, 1.12-2.30) times more likely, respectively, to develop pancreatic cancer than were nonsmokers. Current smokers were twice as likely as were nonsmokers to develop pancreatic cancer. Relative risks of pancreatic cancer increased with the amount of alcohol consumed (Ptrend = 0.11) after adjustment for age, smoking status, and pack-years of smoking. Relative risks of pancreatic cancer according to alcoholic beverage intake were as strong among never-smokers as they were in the total cohort. After the data were adjusted for age, smoking status, and pack-years of smoking, there was a statistically significant 2-fold (95% confidence interval, 1.08-4.30) elevated risk of pancreatic cancer for those who drank > 17.5 cups of coffee per week, compared to those who consumed < 7 cups/week; among never-smokers, the relative risks across coffee intake categories were still positive but were attenuated somewhat (P trend = 0.17). Tea intake was not related to cancer incidence. In summary, these findings provide evidence of an association of both alcoholic beverage and coffee consumption with pancreatic cancer incidence that is independent of age and cigarette smoking.
Age Factors↗
Effects of chloroquine in hematoporphyrin-treated animals.
Porphyrins and related compounds are useful in photodynamic therapy but can cause cutaneous photosensitivity. We determined whether chloroquine, which is effective in treating porphyria cutanea tarda, would mobilize an administered porphyrin from tissues and enhance its excretion. Hematoporphyrin with and without chloroquine was administered to chick embryos, mice, and rats. Tissue and plasma porphyrin levels were markedly increased after hematoporphyrin dosing. Porphyrin concentrations in liver, spleen, and kidney were not significantly affected by chloroquine. Total urinary and fecal porphyrin excretion in rats treated with hematoporphyrin (50 mg/kg, i.p.) was not influenced by chloroquine treatment (100 mg/kg, s.c.). Excretion of heptacarboxylporphyrin, normally a minor fraction of urinary porphyrins, was significantly increased in chloroquine-treated rats. These results suggest that chloroquine is unlikely to be useful after photodynamic therapy for mobilizing exogenous porphyrins from tissues such as liver, spleen, and kidney. Increased urinary excretion of heptacarboxylporphyrin may contribute to the beneficial effect of chloroquine in porphyria cutanea tarda.
Animals↗