Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anemia is a constant complication of uremia. As it has been suggested that uremic toxins (middle molecules) play an important role in the mechanism of anemia, we studied the activities of three heme-synthesizing enzymes: delta-aminolevulinic acid dehydratase, porphobilinogen deaminase and ferrochelatase. In 26 patients on regular dialysis therapy, all three enzymes had significantly lower values than in normal control subjects. From our results, it can be assumed that the decreased heme biosynthesis in chronic uremic patients might be caused by a lack of erythropoietin or by uremic toxins inhibiting erythropoietin and/or heme-synthesizing enzymes.
 ...
PMID:Heme synthesis in anemia of the uremic state. 75 May 46

Patients with malignant lymphoproliferative diseases, ie, chronic lymphocytic leukemia and lymphoma, were found to have higher porphobilinogen deaminase (PBGD) activity in their peripheral lymphocytes than normal control subjects, patients with other malignant neoplasms, and patients with various infectious diseases. The specificity and sensitivity of the test were 99% and 87%, respectively. The sensitivity of the test was 100% in patients with chronic lymphocytic leukemia and 82% in patients with lymphoma. The diagnostic value of PBGD determinations was shown in a prospective study of a group of patients evaluated because of fever of unknown origin, anemia, or other constitutional symptoms with or without lymphadenopathy or a mediastinal mass. The positive and negative predictive values in these patients were 91% and 100%, respectively. Nearly all patients who were in remission had normal enzyme activity. Lymphocyte PBGD determinations also may be of value in determining when to terminate or reinitiate drug treatment.
 ...
PMID:Increased porphobilinogen deaminase activity in patients with malignant lymphoproliferative diseases. A helpful diagnostic test. 378 1

We have analyzed some parameters of porphyrin metabolism in 60 patients with end-stage renal failure, 20 of them on CAPD and the remaining on HD. In comparison with 56 control subjects, both groups of patients showed the three following findings: low erythrocyte aminolevulinate dehydrase activity, inhibition ability for the activity of this enzyme when their plasma was incubated in vitro with normal erythrocytes, and increased plasma porphyrin levels. Like anemia, these abnormalities were more remarkable in patients on HD who also exhibited increased erythrocyte protoporphyrin levels and compensatory porphobilinogen deaminase activities. Mean weekly porphyrin removal through dialysate was higher in CAPD (90.8 micrograms) than in HD patients (30.4 micrograms). Dialysate and plasma porphyrins were correlated in both circumstances (r = 0.714, P < 0.01 and r = 0.637, P < 0.05, respectively). The less pronounced porphyrin abnormalities found in CAPD patients with respect to HD patients may be due to the more efficient capability of peritoneal dialysis for removing from plasma protein-bound substances, as porphyrins and inhibitors of aminolevulinate dehydrase or other enzymes involved in erythropoiesis. Since no close relationship was found between these abnormalities of porphyrin metabolism and hematocrit values, the anemia of uremia cannot be merely considered as a direct consequence of altered heme biosynthetic pathway.
 ...
PMID:Heme biosynthesis in uremic patients on CAPD or hemodialysis. 812 11

Recombinant human erythropoietin (r-HuEPO) is being successfully used for the treatment of uremic anemia. Several abnormalities of heme biosynthetic pathway have been described in patients with end-stage renal failure. In this condition, the activity of erythrocyte porphobilinogen deaminase has been found to be slightly increased. If this enzyme were to be the key enzyme in erythroid heme regulation, its activity would be increased to an even greater degree during the correction of uremic anemia. To assess this hypothesis, this study followed the variations of this and other parameters of porphyrin metabolism over 12 months of erythropoietin therapy in eight patients with nephrogenic anemia who underwent hemodialysis. By the first month of therapy, an increase of the previously depressed erythrocyte activity of aminolevulinate dehydratase was already evident, in coincidence with a nonsignificant increase of the reticulocyte count. The activity of this enzyme reached its maximal level by Month 3, and did not change up to Month 10. The porphobilinogen deaminase hyperactivity normalized at Month 4. By Month 12, in coincidence with the reduction of erythropoietin doses, the maximal levels of erythrocyte protoporphyrin, and the decrease in aminolevulinate dehydratase activity, the porphobilinogen deaminase values started to increase once again. In conclusion, the administration of r-HuEPO to hemodialyzed patients induced transient normalization of the previously observed porphyrin metabolism abnormalities. However, erythrocyte porphobilinogen deaminase activity did not rise concomitantly with the increase in hematocrit or hemoglobin values, but it did diminish during treatment. Therefore, porphobilinogen deaminase did not behave as a controlling enzyme in heme synthesis during the r-HuEPO-induced correction of uremic anemia.
 ...
PMID:Effects of recombinant human erythropoietin on porphyrin metabolism in uremic patients on hemodialysis. 873 13

A 7-year-old boy demonstrating hepatosplenomegaly, mild anaemia, mild mental retardation, yellow-brown teeth and dark red urine had excessively elevated levels of urinary delta-aminolevulinic acid, porphobilinogen and uroporphyrin. Furthermore hepta-, hexa-, penta- and copro(I)porphyrins were highly increased in urine. This pattern of porphyrin precursor and metabolite excretion is characteristic of acute intermittent porphyria. The decreased copro(III)/copro(I+III) ratio, normally not found in acute intermittent porphyria, is discussed. The porphobilinogen deaminase activity in red cells was decreased to 2-4%. Mutation analysis revealed a novel homozygous L81P mutation in exon 6 of the porphobilinogen deaminase gene. The father and mother, shown to be gene carriers of the same mutation, are asymptomatic and have normal urinary porphyrin precursor and metabolite excretion.
 ...
PMID:Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors. 1497 Jul 43

Anemia is a major clinical symptom of a wide variety of pathological conditions a common related to reduced erythropoiesis. Whereas erythropoietin treatment showed an improvement in the patients' condition, it revealed increased risks of thromboembolic and cardiovascular events. Herein we describe stimulation of erythropoiesis by the multifunctional 1-(butyryloxy)ethyl-5-amino-4-oxopentanoate, (AlaAcBu), a 5-aminolevulinic-acid (ALA) derivative, which undergoes metabolic hydrolysis yielding two erythroid differentiation inducers, ALA and butyric acid (BA), each acting through a different mechanism. ALA, the first precursor in the heme biosynthesis, accelerates heme synthesis and BA, a histone deacetylase inhibitor (HDACI) that activates the transcription of globin mRNA. Our results show that the AlaAcBu mutual prodrug is a potent chemical differentiation inducer of K562 human erythroleukemia cells manifested by augmentation of heme and globin synthesis and assembly of hemoglobin. Exposure of K-562 cells to AlaAcBu resulted in an increase in heme synthesis and globin expression. Stimulation of the heme pathway was evident by the over-expression of porphobilinogen deaminase (PBGD) and ferrochelatase. AlaAcBu promoted cellular erythroid differentiation depicted by the expression of the marker glycophorin A and cellular maturation characterized by cytoplasm hemoglobinization, polar arrangement of mitochondria and a developed central vacuolar system preceding nuclear extrusion. The ability of AlaAcBu to promote differentiation along the erythroid lineage and to dramatically induce hemoglobin synthesis presented in this report.
 ...
PMID:A multifunctional 5-aminolevulinic acid derivative induces erythroid differentiation of K562 human erythroleukemic cells. 2270 51

Acute intermittent porphyria is the most common acute porphyria caused by a decrease in hepatic porphobilinogen deaminase activity, resulting in an accumulation of delta-aminolevulinic acid and porphobilinogen. This disease shows nonspecific signs and symptoms that can be confused with other diseases, thereby making the diagnosis difficult. We report a case of acute intermittent porphyria, reviewing clinical and laboratory aspects, highlighting the hematological and biochemical parameters during and after the crisis. A female patient, aged 28 years, suffered two crises, both presenting gastrointestinal disorders. The second presented neuropsychiatric symptoms. The analysis of hematological and biochemical parameters during the second crisis showed anemia, leukocytosis, hyponatremia, mild hypokalemia, uremia and elevated C-reactive protein. The initial treatment included glucose infusion, a diet rich in carbohydrates and interruption of porphyrinogenic drugs. Subsequently, treatment was maintained with oral contraceptive use. According to the observed data, signs and symptoms of gastrointestinal, neurological and psychiatric disorders, associated with laboratory results presented in this paper can be applied to screen acute porphyria, contributing to early diagnosis.
...
PMID:Biochemical and hematological analysis in acute intermittent porphyria (AIP): a case report. 2406