Distinct risks, clinical characteristics and outcomes by age at time of HIV diagnosis.

OBJECTIVES: New HIV diagnoses in persons aged > 50 years (hereafter 'older persons') are becoming more common; the clinical features and outcomes of these older individuals are poorly described. METHODS: We conducted a retrospective cohort study of all new adult HIV diagnoses between October 1989 and December 2019 in southern Alberta, Canada. Differences in risk for HIV acquisition and screening, sociodemographic/clinical characteristics, and causes of death were compared between individuals younger and older than 50 years at the time of diagnosis. RESULTS: New HIV diagnoses in persons > 50 years old increased from 7% in 1990 to 18% in 2019. Risk for HIV acquisition and screening reasons differed by age. Heterosexual sex (29%) was the greatest risk factor among older persons, contrasting with male same sex activity in younger persons (51%) (P < 0.001). Illness was the most common indication for testing in older persons (47%), whereas younger persons were more likely to have requested testing (34%) (P < 0.001). Relationship status differed, with 33% of older persons being married to an opposite sex partner versus 12% in younger persons (P < 0.001). Although older persons had a lower mean nadir CD4 count (132 cells/µL) than younger persons (181 cells/µL) (P < 0.001), 80% of deaths between 2010 and 2019 in the older group were attributable to non-AIDS-related causes versus 47% in younger patients. Since 2000, AIDS-related deaths and potential years of life lost have declined for both age groups. CONCLUSION: The increase in new HIV diagnoses in persons aged > 50 years in southern Alberta suggests that older individuals require customized approaches for optimizing HIV diagnosis and treatment.

Wolfram Syndrome: A Case Report and Review of Clinical Manifestations, Genetics Pathophysiology, and Potential Therapies.

BACKGROUND: Classical Wolfram syndrome (WS) is a rare autosomal recessive disorder caused by mutations in WFS1, a gene implicated in endoplasmic reticulum (ER) and mitochondrial function. WS is characterized by insulin-requiring diabetes mellitus and optic atrophy. A constellation of other features contributes to the acronym DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). This review seeks to raise awareness of this rare form of diabetes so that individuals with WS are identified and provided with appropriate care. CASE: We describe a woman without risk factors for gestational or type 2 diabetes who presented with gestational diabetes (GDM) at the age of 39 years during her first and only pregnancy. Although she had optic atrophy since the age of 10 years, WS was not considered as her diagnosis until she presented with GDM. Biallelic mutations in WFS1 were identified, supporting a diagnosis of classical WS. CONCLUSIONS: The distinct natural history, complications, and differences in management reinforce the importance of distinguishing WS from other forms of diabetes. Recent advances in the genetics and pathophysiology of WS have led to promising new therapeutic considerations that may preserve ß-cell function and slow progressive neurological decline. Insight into the pathophysiology of WS may also inform strategies for ß-cell preservation for individuals with type 1 and 2 diabetes.

BL-1023 improves behavior and neuronal survival in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice.

The therapeutic potential of BL-1023, a chemical combination of L-3,4-dihydroxyphenylalanine (L-DOPA) and gamma-aminobutyric acid (GABA), was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Such animals exhibit nigrostriatal degeneration, characteristic of human Parkinson's disease. Drug was administered during and after the development of MPTP-induced nigrostriatal lesions followed by measures of motor function and behavior, surviving nigrostriatal dopaminergic neurons and termini, and striatal dopamine levels. When administered after lesion development, BL-1023 improved motor function of MPTP-mice as measured by rotarod, total floor and vertical plane movements, and stereotypic movements in open field activity tests compared to MPTP-mice without treatment. This also paralleled modest nigral dopaminergic neuronal protection. Such significant improvements in motor function, behaviors, and dopaminergic neuronal numbers were not seen when BL-1023 was administered during MPTP-induced lesion development. The data demonstrate select abilities of BL-1023 to increase dopaminergic neuronal survival and improve motor function in MPTP-mice.

S-adenosyl-L-methionine: transcellular transport and uptake by Caco-2 cells and hepatocytes.

S-adenosyl-L-methionine (SAMe) is an endogenous molecule that is known to be protective against hepatotoxic injury. Although oral SAMe appears to be absorbed across the intestinal mucosa, its systemic bioavailability is low. The reason for this is unknown. Using the Caco-2 cell culture model for enterocyte absorption, we determined the mode by which SAMe is transported across this cell monolayer. We also determined the extent it is taken up by both Caco-2 cells and hepatocytes. In Caco-2 cells transport was observed in both apical to basolateral and basolateral to apical directions. The apparent permeability coefficients (Papp) appeared to be concentration independent and were similar in both directions (0.7x10(-6) and 0.6x10(-6) cm s-1, respectively), i.e. identical to that of the paracellular transport marker mannitol (0.9x10(-6) and 0.7x10(-6) cm s-1). This mode of transport was supported by a four-fold increase in the Papp for SAMe transport in Ca++-free buffer. Cellular uptake of SAMe was examined in both Caco-2 cells and cultured rat hepatocytes. Uptake by hepatocytes was not saturable in a concentration range of 0.001-100 microM. Accumulation by both cell types was very low, with a cell:medium ratio at equilibrium of only 0.2-0.5. This low cell accumulation supports the finding of paracellular transport as the only mode of cell membrane transport. Increased hepatocellular protection for SAMe may be accomplished by converting SAMe to a more lipid-soluble prodrug.

The effect of the trichloroethylene metabolites trichloroacetate and dichloroacetate on peroxisome proliferation and DNA synthesis in cultured human hepatocytes.

Dichloroacetate (DCA) and trichloroacetate (TCA) are metabolites of the environmental contaminant trichloroethylene (TCE) that are thought to be responsible for its hepatocarcinogenicity in B6C3F1 mice. TCA and DCA induce peroxisomal proliferation and are mitogenic in rodent liver. The susceptibility of humans to TCA- and DCA-induced hepatocarcinogenesis is unknown. The current studies were aimed at using both primary and long-term human hepatocyte cultures to study the effects of TCA, DCA, and a potent peroxisome, proliferator, WY-14,643, on peroxisomal activity and DNA synthesis in human hepatocytes. Peroxisome proliferation, as assessed by palmitoyl-CoA oxidation activity, was below the limit of detection in all human cell lines tested. However, the human cell lines did display small but significant increases in CYP450 4A1 1 levels following treatment with WY-14,643 (0.1 mmol/L), indicating that the CYP 4A11 gene may be regulated by peroxisome proliferator-activated receptor alpha in humans. Similarly to their effect in rodent hepatocyte cultures, TCA and DCA were not complete mitogens in human hepatocyte cultures. In fact, DNA synthesis tended to be significantly decreased following treatment of the cells with WY-14,643, TCA, or DCA. In contrast to rodent hepatocyte responses, TCA and DCA did not increase palmitoyl-CoA oxidation and caused a decrease in DNA synthesis in human hepatocyte cultures, suggesting that humans may not be susceptible to TCA- and DCA-induced hepatocarcinogenesis.

Expression of PPAR(alpha) in human hepatocytes and activation by trichloroacetate and dichloroacetate.

Dichloroacetate (DCA) and trichloroacetate (TCA) are carcinogenic metabolites of trichloroethylene (TCE), a known hepatocarcinogen in B6C3F1 mice. This hepatocarcinogenesis is believed to result from peroxisome proliferation via PPAR(alpha) and/or stimulation of hepatocyte replication. In this study hPPAR(alpha) levels in six human liver tissues and in a long-term human hepatocyte cell line are compared. PPAR(alpha) levels varied significantly between individual tissues and are generally lower than PPAR(alpha) levels detected in mouse liver. Long-term cultured human hepatocytes display PPAR(alpha) levels only slightly lower than cultured mouse hepatocytes. Transfection studies examining the endogenous hPPAR(alpha) activity revealed little or no receptor activation, even following treatment with high concentrations of peroxisome proliferators. In contrast human hepatocytes transfected with mPPAR(alpha) and mRXR(alpha) display increased expression of PPAR(alpha), and increased PPRE-reporter activity when treated with WY-14,643, TCA, and DCA. This human hepatocyte transfection system is a promising tool for examinin the regulation of genes by PPAR(alpha) from different species.

Galactosamine decreases nitric oxide formation in cultured rat hepatocytes: mechanism of suppression.

We have shown that nitric oxide production is dramatically decreased in rat primary hepatocyte cultures exposed to galactosamine. Cotreatment of the cells with uridine, which is known to prevent cytotoxicity, was found to also attenuate NO loss. In the present study, two possible mechanisms for the decreased nitric oxide production were examined. First, we examined the possibility that galactosamine could interfere with the uptake of extracellular arginine by the cultured hepatocytes. Cellular uptake of arginine was determined after addition of 14C-arginine at the time of hepatocyte attachment. Uptake of arginine was rapid in control cultures, and both the rate and level of uptake were unchanged by the addition of a cytotoxic concentration of galactosamine (4 mM). In addition, increased concentrations of arginine in the cell culture medium did not ameliorate the galactosamine-induced decrease in production of nitric oxide. Second, we determined whether the synthesis of inducible nitric oxide synthase in the hepatocyte cultures was inhibited by addition of galactosamine. Hepatocyte levels of inducible nitric oxide synthase were determined immunochemically at various times after the addition of galactosamine (4 mM). In control cultures, inducible nitric oxide synthase was detectable at 7 and 24 hours after attachment. In contrast, no nitric oxide synthase protein was detectable at any time in the galactosamine-treated cultures. Furthermore, addition of galactosamine after inducible nitric oxide synthase had already been synthesized (6.5 h after attachment) did not result in suppression of nitric oxide production in the hepatocyte cultures. The present studies suggest that galactosamine suppresses nitric oxide production in hepatocyte cultures by inhibiting synthesis of inducible nitric oxide synthase, rather than by interference in cellular uptake of arginine.

Galactosamine decreases nitric oxide formation in cultured rat hepatocytes: lack of involvement in cytotoxicity.

Galactosamine hepatotoxicity in vivo has long been associated with rapid and extensive depletion of hepatic uridine nucleotides. Depletion of uridine nucleotides is considered to be causal in the toxicity, as evidenced by the protective effect of uridine administration. However, the exact mechanism of galactosamine-induced hepatic necrosis is still unclear. We have previously shown that the addition of galactosamine to rat primary hepatocyte cultures dramatically decreases production of nitric oxide, as measured in the 24 hour culture medium. The present study investigates whether decreased nitric oxide production contributes to the toxicity of galactosamine in primary hepatocyte cultures. Similar concentration-response curves were observed for the decrease in nitric oxide production and galactosamine cytotoxicity, raising the possibility that there is a similar mechanism for these effects. Suppression of NO synthesis was a direct effect of galactosamine, rather than an indirect effect due to loss of cells from the cultures. Both cytotoxicity and the decrease in nitric oxide production were attenuated by coaddition of 3 mM uridine. However, galactosamine cytotoxicity was not enhanced by prior inhibition of hepatocellular NO synthesis nor was it attenuated by maintenance of culture NO levels with molsidomine or diethylamine NONOate. These data do not support a role for decreased hepatocyte nitric oxide production in galactosamine hepatocyte toxicity.

Dichloroacetic acid induction of peroxisome proliferation in cultured hepatocytes.

Trichloroethylene is a widespread industrial solvent and one of the most common environmental contaminants. Trichloroethylene causes hepatocarcinoma in the B6C3F1 mouse in a dose-dependent manner. Trichloroethylene's hepatocarcinogenicity is thought to be mediated through its metabolites trichloroacetate and dichloroacetate. Although the mechanism of action is not well understood, hepatic tumors are thought to arise as a result of excessive peroxisome-dependent active oxygen production or secondary to enhanced cell replication. The peroxisome proliferative activity of trichloroacetate has been replicated in cultured rodent hepatocytes, while that of dichloroacetate has not been demonstrated. The present experiments were designed to characterize the peroxisome proliferative response to dichloroacetate in hepatocyte cultures from male B6C3F1 mice and male Long Evans rats. The cultured hepatocytes were treated after attachment with 0.1, 0.5, 1.0, 2.0, or 4.0 mM dichloroacetate for 72 hours. Peroxisome proliferation was assessed by measuring palmitoyl-CoA oxidation and by immunoquantitation of peroxisomal bifunctional enzyme. Palmitoyl CoA oxidation increased in a concentration-dependent manner, with maximal induction of 5.5- and 5-fold in mouse and rat hepatocytes, respectively, after treatment with 2.0 mM dichloroacetate. Peroxisomal bifunctional enzyme protein levels also increased in a concentration-dependent manner in both rat and mouse hepatocytes in response to dichloroacetate exposure. These results indicate that the peroxisomal response observed in vivo in response to dichloroacetate administration can be reproduced in primary cultures of rat and mouse hepatocytes treated with dichloroacetate. Further studies using this model system will help elucidate mechanisms of dichloroacetate-induced hepatocarcinogenesis.

Dexamethasone induction of taxol metabolism in the rat.

This study examined the effect of dexamethasone (DEX), 100 mg/kg/day for 3 days, on [3H]taxol metabolism in liver microsomes and hepatocytes of male and female Sprague-Dawley rats. In control rats, two isomeric monohydroxylated metabolites, M1 and M2, were formed. The formation of both metabolites was 2-3 times greater in the male than in the female animals. After DEX treatment, M1 increased 2.6-fold in the male animals and 6.5-fold in the female animals. This was accompanied by similar increases in hepatic cytochrome P4503A protein and testosterone 6 beta-hydroxylation. Three additional metabolites (U1, U2, and U3) were formed in the DEX-treated animals only. Isolation of these metabolites from rat hepatocyte incubates by reversed-phase HPLC permitted structure identification of U2 and U3, using tandem MS. The mass spectrum of U3 was consistent with deacetylation of taxol, whereas the mass spectrum of U2 was consistent with deacetylation of the monohydroxylated taxol metabolite M2. A comparison of HPLC and MS data for U3 with those of standard 10-deacetyltaxol suggested that the site of deacetylation might be the 4-position of the taxane ring. Preliminary observations indicate that the deacetylation is caused by a DEX-inducible cytochrome P450.

Macrophage enhancement of galactosamine hepatotoxicity using a rat hepatocyte culture system.

Prior administration of endotoxin to rats is known to aggravate the hepatotoxicity of galactosamine. It has been proposed that this exacerbation occurs as a result of the release of cytokines and other humoral factors by resident macrophages (Kupffer cells). In order to study this phenomenon we have utilized a co-culture system consisting of rat activated peritoneal macrophages and rat hepatocytes. Peritoneal macrophages were isolated and cultured; LPS was added as a macrophage activator 16 hours later. Rat hepatocytes were isolated and plated in Transwell COL inserts, which were placed in wells with and without activated macrophages. Cytotoxicity was determined 24 hours later by measuring lactate dehydrogenase (LDH) leakage into the culture medium. In the presence of activated macrophages an approximate 3-fold increase in galactosamine-induced hepatocyte toxicity was observed, as compared to the toxicity in hepatocytes cultured alone. Using this co-culture system, we examined the role of leukotriene D4 (LTD4) and nitric oxide (NO) as mediators of this enhancement. Addition of either LTD4 or NO to hepatocytes cultured alone did not exacerbate galactosamine toxicity. Furthermore, addition of the LTD4 receptor antagonist SK & F 104353 (50 microM) or the NO synthase inhibitor N-monomethyl-L-arginine (1.0 mM) to macrophage/hepatocyte co-cultures did not attenuate the enhanced galactosamine hepatocyte toxicity in the co-cultures. Collectively, these data indicate that this co-culture system will be useful in examining the mechanism of macrophage enhancement of chemical-induced hepatoxicity and, further, suggest that LTD4 and NO may not be involved in the exacerbation of galactosamine toxicity to hepatocyte cultures.

Taxol metabolism in rat hepatocytes.

Metabolism of the anticancer drug taxol was investigated in freshly isolated rat hepatocytes. Two main metabolites were separated by reversed-phase HPLC and shown by tandem mass spectrometry to be monohydroxylated metabolites. Kinetic studies revealed apparent Km values of 68 and 61 microM with identical Vmax values for the two metabolites. Verapamil and midazolam, but not phenacetin, showed concentration-dependent inhibition of taxol metabolism with both metabolites being affected equally. The IC50 was about 100 microM for verapamil and 25 microM for midazolam. These observations demonstrate for the first time in vitro metabolism of taxol and suggest that the metabolism may be subject to potentially important interactions with numerous other drugs.

Galactosamine hepatotoxicity: effect of galactosamine on glutathione resynthesis in rat primary hepatocyte cultures.

The effect of galactosamine on the resynthesis of glutathione in rat primary hepatocyte cultures was investigated. Cultured rat hepatocytes were treated with galactosamine (4 mM) 1.5 hr prior to concurrent with, or 1.5 hr after cell attachment; total cellular glutathione was then measured over time. Addition of galactosamine at any of these times suppressed methionine-enhanced glutathione resynthesis in the cultures after a lag period of about 120 min. The lag period was not due to slow uptake of galactosamine by the cultured cells, since cellular UTP levels fell to less than 10% of controls within 60 min, a time frame comparable to that observed in vivo. Neither was the lag period a result of interference with cellular uptake of methionine or with conversion of methionine to cysteine, since the phenomenon was observed regardless of whether methionine or cysteine was used to promote glutathione resynthesis. Addition of uridine, which protects against galactosamine hepatotoxicity in vivo by replenishing hepatic UTP levels, did not prevent the suppression of glutathione resynthesis. The data indicate that (a) galactosamine inhibits the time-dependent resynthesis of glutathione in primary hepatocyte cultures, (b) a lag period exists for this response, and (c) this effect is not directly related to depletion of cellular UTP stores.

Differential stability of drug-metabolizing enzyme activities in primary rat hepatocytes, cultured in the absence or presence of dexamethasone.

The effects of primary hepatocyte culture on the rat cytochrome P450-dependent monooxygenase system and several conjugating enzyme activities were examined using a culture system similar to those used for evaluation of chemicals as potential genotoxins. Cytochrome P450 and cytochrome b5 contents progressively decreased throughout the 72-h culture period to less than 25% of initial values, whereas cytochrome P450 reductase rapidly decreased by 50% during attachment, but then remained stable. Cytochrome P450-dependent testosterone hydroxylase activities decreased more rapidly in culture than did cytochrome P450 content reaching less than 50% of attachment levels by 24 h. Cytochrome P450IIIA immunoreactive protein decreased at a similar rate to testosterone-6 beta-hydroxylase. Activated UDP-glucuronyltransferase activities towards 1-naphthol and testosterone declined more slowly over the 72 h than cytochrome P450 and remained at 50-60% of initial values at 72 h. UDP-glucuronyltransferase activity towards digitoxigenin monodigitoxoside (DIG) did not decrease during culture. Glutathione-S-transferase and sulfotransferase activities also declined during the 72 h at rates which appeared to be isozyme-dependent. Addition of 1 microM dexamethasone (DEX) to the culture medium increased UDP-glucuronyltransferase activity towards DIG, cytochrome P450 reductase and testosterone-6 beta-hydroxylase activities up to 2.5-, 2.0- and 7-fold, respectively and induced cytochrome P450IIIA immunoreactive protein(s) in the hepatocytes after 24 and 48 h of culture; DEX was less effective at the 72 h time-point. DEX treatment also significantly accelerated the decreases in glutathione-S-transferase activities and in sulfotransferase activities towards 1-naphthol and estrone. Thus, it appears that primary rat hepatocytes cultured under standard conditions, not only rapidly lose their monooxygenase capabilities, but also some of their capacity for conjugation. Furthermore, the use of DEX in cell culture medium to enhance cell survival does not maintain total drug-metabolizing enzyme capability, but appears to transiently and selectively increase expression of certain isozymes at the expense of others.

Neonatal exposure to Aroclor 1254: effects on adult hepatic testosterone hydroxylase activities.

1. The effects of neonatal exposure to Aroclor 1254 (100 mumol/kg) on the metabolism of testosterone by adult male and female rats were determined by comparing their hepatic microsomal testosterone hydroxylase activities at 60, 90 and 120 days after the initial exposure. 2. The most pronounced effects in male rats were observed 90 days after treatment with Aroclor 1254, whereas in female rats the major changes in testosterone hydroxylase activities were observed after 60 days. 3. Ninety-day-old male rats neonatally treated with Aroclor 1254 exhibited decreased basal testosterone 7 alpha-hydroxylase and increased basal testosterone 16 alpha-, 2 alpha- and 15 beta-hydroxylase activities and androstenedione formation. In addition, the Aroclor 1254-mediated induction of testosterone 7 alpha- and 6 alpha-hydroxylase activities and androstenedione formation was decreased, and that of testosterone 2 beta- and 15 beta-hydroxylase activities was increased. 4. Sixty-day-old female rats exposed neonatally to Aroclor 1254 exhibited increased basal testosterone 16 alpha-, 2 beta-, 6 alpha- and 15 beta-hydroxylase activities and androstenedione formation, and increased Aroclor 1254-induced metabolism of testosterone at all positions except 16 alpha and 2 alpha. 5. Changes in testosterone hydroxylase activities indicative of permanent damage (or imprinting) in androgen metabolism, i.e. altered activities in 120-day-old animals, were observed only in male rats. These activities included basal testosterone 6 beta-, 16 alpha- and 2 alpha-hydroxylase activities and androstenedione formation.

Metabolism of the arylamide herbicide propanil. II. Effects of propanil and its derivatives on hepatic microsomal drug-metabolizing enzymes in the rat.

Propanil (3,4-dichloropropionanilide) is an arylamide herbicide that has been reported to be contaminated with the cytochrome P450 enzyme inducers 3,3',4,4'-tetrachloroazobenzene (TCAB) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB), which are structural analogs of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We determined if treatment of rats with TCAB, TCAOB, propanil, 3,4-dichloroaniline, TCDD, or phenobarbital induced the hepatic microsomal metabolism of propanil and 3,4-dichloroaniline. Acylamidase-catalyzed hydrolysis of propanil to 3,4-dichloroaniline was not induced by any of the pretreatments; however, hydroxylation of propanil at the 2'-position was induced by TCDD, TCAB, TCAOB, propanil, and 3,4-dichloroaniline pretreatments. Ring- and N-hydroxylations of 3,4-dichloroaniline were induced by TCDD, TCAB, TCAOB, and 3,4-dichloroaniline pretreatments. Microsomal 7-ethoxyresorufin-O-deethylase (EROD) and 7-benzoxyresorufin-O-dealkylase (BROD) activities and electrophoretic mobility of microsomal proteins suggested that cytochromes P450c and P450d were induced by TCAB and TCAOB pretreatment. EROD, BROD, and 7-pentoxyresorufin-O-dealkylase activities were slightly increased in microsomes from propanil- and 3,4-dichloroaniline-pretreated rats, which suggests that these compounds may be weak inducers of cytochrome P450 isozymes.

Neonatal modulation of adult rat hepatic microsomal benzo[a]pyrene hydroxylase activities by Aroclor 1254 or phenobarbital.

The constitutive and Aroclor 1254-induced activities of hepatic microsomal benzo[a]pyrene hydroxylases in male and female rats were determined in animals from ages 11 to 120 days. In 11-day-old noninduced male rats, benzo[a]pyrenediones and 9-hydroxybenzo[a]pyrene were the major microsomal metabolites; in 21-day-old males benzo[a]pyrene-diones and benzo[a]pyrene-9,10-dihydrodiol were predominant. In 60- and 120-day-old animals 3-hydroxybenzo[a]pyrene was the major microsomal metabolite. A similar trend was observed for the development of benzo[a]pyrene hydroxylase activities in female rats. With the exception of 4,5-dihydrodiol formation, the highest induction of individual and total benzo[a]pyrene hydroxylase activities by Aroclor 1254 was observed in the 21-day-old immature male rats, in which there was a 330- and 4.5-fold increase in the formation of 3-hydroxybenzo[a]pyrene and quinone metabolites, respectively. The induction of benzo[a]pyrene total metabolite formation by Aroclor 1254 in female rats from 11 to 120 days of age was relatively constant (i.e., 13.3- to 10.1-fold induction); however, the relative induction of the individual benzo[a]pyrene hydroxylases was highly variable. In a second set of experiments, male and female rats were neonatally exposed to phenobarbital (600 mumol/kg) or Aroclor 1254 (100 mumol/kg), and the effects of these xenobiotics on neonatal imprinting of hepatic microsomal benzo[a]pyrene hydroxylase activities were determined in the 120-day-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Iron metabolism in patients undergoing regular dialysis therapy.

Thirteen patients with chronic renal failure maintained on regular renal dialysis were studied. Seven proved to have iron deficiency on the basis of marrow iron studies, reticulocyte iron uptake, and saturation of the serum iron-binding capacity. They absorbed iron when given it by mouth and were able to utilize it for haemoglobin formation. Iron-deficient patients given 600 mg of ferrous sulphate daily for three months showed an increase in haemoglobin, but the failure to replace stores of iron is probably related to their relatively limited ability to absorb iron and the variable but sometimes considerable blood loss occurring with each dialysis.The loss may be occult, and prolonged iron therapy may be required. This is most safely achieved by giving iron by mouth.