Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cause of the degeneration of dopamine-containing cells in the zona compacta of the substantia nigra in Parkinson's disease remains unknown. The ability of the selective nigral toxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) (via its metabolite MPP+) to destroy nigral dopamine cells selectively by inhibiting complex I of the mitochondrial energy chain may provide a clue. Indeed, recent studies of post-mortem brain tissue have suggested the presence of an on-going toxic process in the substantia nigra in Parkinson's disease leading to excess lipid peroxidation. This appears also to involve a disruption of mitochondrial function since mitochondrial superoxide dismutase activity is increased and there is impairment of complex I. These changes may in turn relate to a selective increase in the total iron content of substantia nigra coupled to a generalised decrease in brain ferritin content. Piribedil is used in the symptomatic treatment of Parkinson's disease and is particularly effective against tremor. Piribedil (and its metabolites) acts as a dopamine D-2 receptor agonist. However, in our studies in contrast to other dopamine agonists, in vivo piribedil interacts with dopamine receptors in the substantia nigra and nucleus accumbens but not those in the striatum. In patients with Parkinson's disease the beneficial effects of piribedil may be limited by nausea and drowsiness. Indeed, in MPTP-treated primates piribedil reverses motor deficits but marked side-effects occur. However, pre-treatment with the peripheral dopamine receptor antagonist domperidone prevents the unwanted effects and piribedil produces a profound and longer-lasting reversal of all components of the motor syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parkinson's disease: pathological mechanisms and actions of piribedil. 163 7

Eleven patients with beta thalassemia major were entered into the trial of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Their ages ranged from 17 to 26 years (mean +/- SD, 22.3 +/- 2.7). Six were male and five were female. L1 was administered at an initial daily dose of 42.5 to 60 mg/kg as a single dose. After 4 weeks, the dose was increased to 85 to 119 (102 +/- 10.7) mg/kg for 191 to 352 days divided into either two or four doses daily, except for one patient who developed agranulocytosis after 11 weeks and was taken off the trial. Initial serum ferritin values in the remaining 10 patients ranged between 1,000 and 9,580 (5,549 +/- 3,333) micrograms/L and at end of the trial their mean serum ferritin was significantly lower (4,126 +/- 2,278; P less than .05 using the paired t-test). Urinary iron excretion at a daily dose of 85 to 119 mg/kg administered as two divided doses ranged between 0.14 and 0.82 (0.44 +/- 0.26) mg/kg/24 h. In three patients, the four doses per day schedule caused substantially more iron excretion than the same total dose divided into two. During the course of the trial, several possible adverse effects have been encountered. One patient (female, aged 20) developed agranulocytosis 11 weeks after starting treatment and 6 weeks after beginning treatment with a daily dose of 105 mg/kg. This patient's neutrophil count recovered spontaneously 7 weeks after the discontinuation of L1. A decrease in serum zinc levels to subnormal levels was observed in four patients with symptoms of dry skin, with an itchy scaly rash in two that was associated with low serum zinc levels that responded to zinc therapy. Urinary zinc levels ranged from 4.7 to 23.4 (13 +/- 5.5) mumol/24 h and were above 9 mumol/24 h (upper limit of normal) in eight patients. Mild nausea occurred in three patients and transient diarrhea in a fourth. Mild musculoskeletal symptoms occurred in three patients but settled without discontinuation of L1 therapy in two and with temporary discontinuation of L1 in the third. A transient increase in serum aspartate transaminase was also noted in five patients, but serum aspartate transaminase levels subsequently decreased in all of them. No cardiovascular, neurologic, renal, or retinal toxicities were demonstrable. These results confirm that L1 is an effective oral iron chelator. Further clinical trials are needed to determine the incidence and severity of adverse effects.
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PMID:Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major. 846 82

The clinical efficacy and tolerability of gastroprotected ferritin were assessed in children affected by iron deficiency and/or sideropenic anemia. Forty-seven children with iron-deficiency and/or sideropenic anemia were included in the study and were treated with gastroprotected ferritin at a dose of 4-5 mg/kg/day per os for 4 months. Only 33 children correctly completed the entire treatment cycle, achieving a marked improvement of blood parameters (increased Hb, accompanied by higher levels of sideremia and in particular ferritin, with a contemporary decrease in erythrocytic protoporphyrin and transferrinemia) and clinical symptoms, especially pallor, anorexia, debility, somnolence, hyperactivity, disturbed sleep and excessive sweating. Of the remaining 14 children, 9 failed to present for the planned control after the 4 months of therapy, 3 abandoned therapy due to difficulties of assumption and 2 because of intolerance phenomena, such as nausea and diarrhoea. In conclusion, gastroprotected proteoferrin is efficacious and well tolerated in the treatment of iron deficiency in children.
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PMID:[Evaluation of the effectiveness of gastro-protected proteoferrin in the therapy of sideropenic anemia in childhood]. 228 21

The differentiation of bacterial from aseptic meningitis in postoperative neurosurgical patients has traditionally been based on the clinical setting, a recent history of steroid administration, and cerebrospinal fluid (CSF) studies, including the total and differential leukocyte counts, Gram stain, glucose, and total protein. Recent reports questioning both the validity of a relative CSF lymphocytosis in excluding bacterial meningitis and the usefulness of standard CSF testing prompted the authors to reevaluate these standard criteria. The type of operation, the presence of a foreign body, use of steroids, postoperative day on which symptoms developed, altered mental status, neck stiffness, headache, and nausea were not helpful in the differential diagnosis. High fever, new neurological deficits, an active CSF leak, and elevated leukocyte counts in the CSF and peripheral blood favored a bacterial etiology. The CSF glucose level and the differential leukocyte count were less helpful. No criterion or combination of criteria was sensitive and specific enough to reliably differentiate aseptic from bacterial meningitis in the majority of patients. The possibility of improving diagnostic accuracy with newer tests, such as CSF lactate, ferritin, total amino acids, C-reactive protein, and amyloid-A, should be assessed.
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PMID:Differentiation of aseptic and bacterial meningitis in postoperative neurosurgical patients. 318 29

Thirty-six women with menorrhagia were treated with mefenamic acid during all menstrual periods for more than 1 year. These women had experienced objective and subjective benefit--menstrual blood loss was reduced and other menstrual symptoms improved during a preliminary 4-cycle double-blind placebo-controlled trial with mefenamic acid (placebo cycles: 65.6 +/- 5.3 ml; mefenamic acid cycles: 45.3 +/- 5.1 ml, mean +/- SEM). This reduction in menstrual blood loss was maintained at 6 to 9 months (49.2 +/- 9.9 ml) and at 12 to 15 months (42.8 +/- 4.8 ml) after the trial. These reductions were significant at the 6- to 9-month (paired t test = 2.18; P less than .05) and the 12- to 15-month interval (paired t test =- 4.40; P less than .001). Significant sustained reductions in blood loss were seen in the women with menorrhagia due to ovulatory dysfunctional bleeding and in those who had undergone tubal sterilization. Significant reductions were also seen in dysmenorrhea, headache, nausea, diarrhea, depression, number of sanitary towels used, and number of mefenamic acid capsules taken. A significant increase in serum ferritin was found between admission and completion of the follow-up trial in 11 women (P less than .01).
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PMID:Long-term treatment of menorrhagia with mefenamic acid. 633 54

This report updates the combined experience of four centres involved in the long-term treatment of transfusional iron overload in 84 patients with the oral iron chelator deferiprone (L1) over 167 patient-years. The source of L1 was variable, including two university research laboratories and three pharmaceutical firms. Compliance was rated as excellent in 48%, intermediate in 36%, and poor in 16% of patients. On a mean L1 dose of 73-81 mg/kg/d, urinary iron excretion was stable, at around 0.5 mg/kg/d, with no indication of a diminishing response with time. Serum ferritin showed a very steady decrease with time from an initial mean +/- 1 SD of 4207 +/- 3118 to 1779 +/- 1154 micrograms/l after 48 months (P < 0.001). 17 patients abandoned L1 therapy. Major complications of L1 requiring permanent discontinuation of treatment included agranulocytosis (three), severe nausea (four), arthritis (two) and persistent liver dysfunction (one). The remaining patients abandoned treatment because of low compliance (three) and conditions unrelated to L1 toxicity (four). Lesser complications permitting continued L1 treatment included transient mild neutropenia (four), zinc deficiency (12), transient increase in liver enzymes (37), moderate nausea (three) and arthropathy (17). There was no treatment-related mortality. Although the complications associated with L1 treatment are significant and require close monitoring, they do not preclude effective long-term therapy in the vast majority of patients. Further well-controlled prospective studies of L1 are required in order to enable proper judgement of its suitability for general long-term clinical use.
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PMID:Results of long-term deferiprone (L1) therapy: a report by the International Study Group on Oral Iron Chelators. 757 38

To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.
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PMID:Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. 806 39

A prospective, controlled, double-blind, double-dummy, multicenter clinical trial was made to assess the efficacy and tolerability of iron-protein-succinylate (ITF 282) in comparison with a well known iron preparation in the treatment of iron deficiency or iron deficient anemia. One thousand and ninety-five patients affected with iron deficiency or overt iron deficient anemia were randomized to receive either two ITF 282 tablets/day (60 mg iron each) or a commercially available ferrous sulphate controlled release tablet (one tablet containing 105 mg iron/day). Five hundred and forty-nine patients received ITF 282; 546 patients were treated with ferrous sulphate. Both treatments lasted 60 days. The treatment outcome was checked by evaluating special hematology, symptomatology, safety hematology and hematochemistry. After two months of treatment, the normalization of the main hematologic parameters in both groups was detected. Although in the first month the reference treatment appears to provide somewhat faster results, at the end of the observation, the values of hematocrit, hemoglobin and ferritin were greater in the ITF 282 group, indicating a more progressive and steady therapeutic effect. The overall clinical rating was significantly in favor of ITF 282, with 78.9% of favorable results vs 67.6%. By dividing the patient population according to pathological conditions (iron deficiency or overt anemia), or according to the etiopathogenesis of the iron deficiency (increased requirement, or increased loss in adults and in the elderly), separate analyses on the treatment outcome were made (and have been included). The general tolerability, although favorable with both treatments, was significantly more favorable with ITF 282. With this medication, 63 patients (11.5%) complained of 69 adverse reactions (25 heartburn, 19 constipation, 25 abdominal pain) vs 141 events reported by 127 patients (26.3%) with the reference medication (33 heartburn, 31 epigastric pain, 23 constipation, 32 abdominal pain, 8 skin rash, 14 nausea). These observations confirm that, although the most modern preparations of ferrous sulphate exhibit a relatively low frequency of adverse events of limited clinical concern, it is nevertheless possible to decrease both the prevalence and the duration of such events without prejudice for the clinical efficacy, with the use of more "physiological" preparations in which the iron is reversibly bound to a protein carrier, thus effectively removing one of the main obstacles to the correct compliance with treatments that must be administered for prolonged periods of time.
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PMID:Iron protein succinylate in the treatment of iron deficiency: controlled, double-blind, multicenter clinical trial on over 1,000 patients. 846 8

The levonorgestrel (LNg) IUD releases 20 mcg LNg/day and protects against pregnancy for 5 years (Pearl index = 0.1/100 women years of use). Its mode of action is reduced amount of cervical mucus and suppression of the endometrium. A multicenter study in Denmark, Finland, Hungary, and Sweden comparing the LNg IUD and the Nova T IUD found the 5-year continuation rate of the LNg IUD to be 46.9% (44.5% for Nova T). The leading reasons for LNg IUD removal at 5 years were planning pregnancy (15.2%), bleeding (13.7%), and hormonal reasons (11.9%). Bleeding disturbances occurred significantly less often in the LNg IUD users than in the Nova T users (13.7% vs. 20.7%; p = .002). Since LNg has a strong effect on endometrium suppression, LNg IUD users were more likely to quit using the IUD due to amenorrhea than Nova T users (6% vs. 0; p = .0001). The cumulative gross expulsion rate after 5 years was 5.8. Termination for genital infections was more likely in Nova T users than LNg IUD users, especially when the infections were pelvic inflammatory disease (2.2% vs. 0.8%; p .01) and endometritis (4% vs. 1.5%; p .01). Hormonal side effects were acne, hirsutism, weight changes, mood changes, breast tenderness, nausea, and headache. Women in the LNg IUD group experienced return to fertility at a higher rate than those in the Nova T group (79.1% at 12 months and 86.6% at 24 months vs. 71.2% and 79.7%, respectively), but the differences were not significant. Progestin-releasing IUDs can be used to treat menorrhagia, thereby making them an alternative to hysterectomy or endometrial resection. The LNg IUD reduced menstrual blood loss by 86% at 3 months and by 97% at 12 months in women with menorrhagia, resulting in an increase in hemoglobin and serum ferritin. This IUD also effectively opposes the proliferative effect of estrogen on the endometrium in women on hormonal replacement therapy.
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PMID:Hormonal intrauterine devices. 848 51

We performed an open, nonrandomized, multicenter phase-II trial to evaluate the efficacy and toxicity of 1 year of treatment with the oral iron chelator deferiprone in 38 mainly nonthalassemic patients with transfusional iron overload. Initial serum ferritin varied between 996 and 11.644 micrograms/l. Patients were treated with 3-6 g of deferiprone daily. Mean urinary iron excretion (UIE) in 36 evaluable patients was 21.0 mg/24 h and was significantly higher in the patients with thalassemia than in those with myelodysplasia. Negative iron balance was achieved in 20 patients (56%). The median duration of treatment was 10 months; due to side effects and other causes only 20 patients completed 1 year of treatment. Mean serum ferritin levels decreased from 3563 micrograms/l at the start of the trial to 2767 micrograms/l at 6 months (26 patients, p < 0.004) and to 2186 micrograms/l at 12 months (20 patients, p < 0.005). Serum ferritin levels normalized in two patients who were no longer transfusion dependent. Deferiprone was clearly not effective in three patients (two with myelofibrosis, one with myelodysplasia). One patient with myelodysplasia developed agranulocytosis after 12 months of treatment; this was rapidly reversible after stopping deferiprone. Three patients had a mild and transient decrease in white blood cell count. Other side effects leading to withdrawal from the trial consisted mainly of nausea (3 patients), arthralgia (2), and skin rash (1). No clinical signs of zinc deficiency were seen, although zinc excretion was increased in three patients. No changes were seen in liver enzymes, creatinine, antinuclear factor, T-cell subsets, cardiac function, visual acuity, and audiogram. Although our results confirm deferiprone as an effective iron chelator in patients with thalassemia and in some patients with other forms of iron overload, there is still some concern about the safety of this drug, which therefore, at this time, should be used exclusively in well-controlled clinical trials.
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PMID:Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. 895 43


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