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1.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360940

RESUMO

With iron at its core, the tetrapyrrole heme ring is a cardinal prosthetic group made up of many proteins that participate in a wide array of cellular functions and metabolism. Once released, due to its pro-oxidant properties, free heme in sufficient amounts can result in injurious effects to the kidney and other organs. Heme oxygenase-1 (HO-1) has evolved to promptly attend to such injurious potential by facilitating degradation of heme into equimolar amounts of carbon monoxide, iron, and biliverdin. HO-1 induction is a beneficial response to tissue injury in diverse animal models of diseases, including those that affect the kidney. These protective attributes are mainly due to: (i) prompt degradation of heme leading to restraining potential hazardous effects of free heme, and (ii) generation of byproducts that along with induction of ferritin have proven beneficial in a number of pathological conditions. This review will focus on describing clinical aspects of some of the conditions with the unifying end-result of increased heme burden and will discuss the molecular mechanisms that ensue to protect the kidneys.


Assuntos
Heme/metabolismo , Hemoglobinúria/metabolismo , Nefropatias/metabolismo , Rabdomiólise/metabolismo , Animais , Ferritinas/metabolismo , Heme/urina , Heme Oxigenase-1/metabolismo , Hemoglobinúria/patologia , Humanos , Nefropatias/patologia , Rabdomiólise/patologia
2.
ACS Synth Biol ; 10(5): 1132-1142, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33908255

RESUMO

The early detection of blood in urine (hematuria) can play a crucial role in the treatment of serious diseases (e.g., infections, kidney disease, schistosomiasis, and cancer). Therefore, the development of low-cost portable biosensors for blood detection in urine has become necessary. Here, we designed an ultrasensitive whole-cell bacterial biosensor interfaced with an optoelectronic measurement module for heme detection in urine. Heme is a red blood cells (RBCs) component that is liberated from lysed cells. The bacterial biosensor includes Escherichia coli cells carrying a heme-sensitive synthetic promoter integrated with a luciferase reporter (luxCDABE) from Photorhabdus luminescens. To improve the bacterial biosensor performance, we re-engineered the genetic structure of luxCDABE operon by splitting it into two parts (luxCDE and luxAB). The luxCDE genes were regulated by the heme-sensitive promoter, and the luxAB genes were regulated by either constitutive or inducible promoters. We examined the genetic circuit's performance in synthetic urine diluent supplied with heme and in human urine supplied with lysed blood. Finally, we interfaced the bacterial biosensor with a light detection setup based on a commercial optical measurement single-photon avalanche photodiode (SPAD). The whole-cell biosensor was tested in human urine with lysed blood, demonstrating a low-cost, portable, and easy-to-use hematuria detection with an ON-to-OFF ratio of 6.5-fold for blood levels from 5 × 104 to 5 × 105 RBC per mL of human urine.


Assuntos
Técnicas Biossensoriais/métodos , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Hematúria/diagnóstico , Heme/urina , Luciferases Bacterianas/genética , Photorhabdus/enzimologia , Redes Reguladoras de Genes , Genes Bacterianos , Genes Reporter , Heme/genética , Humanos , Medições Luminescentes , Microrganismos Geneticamente Modificados , Óperon , Regiões Promotoras Genéticas
3.
Lab Med ; 47(2): e18-20, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26850032

RESUMO

BACKGROUND: The ability of health care professionals to provide patient care is potentially compromised when predicated on untested, although longstanding, perspectives. One such example is urinalysis testing, which has been currently simplified to use only urine testing strips for detection of microscopic hematuria. OBJECTIVE: To determine whether urine testing strips are sufficient for identification of clinically significant findings in urinalysis. METHODS: To determine the presence of microscopic hematuria, I examined a collection of urine specimens that had tested heme negative during the 3-month study period. RESULTS: Of the 342 patients from whom urine specimens were examined during this interval, 50 had microscopic hematuria, despite having tested negative for heme via urine testing strip. Also, 30% were not receiving any medication known to produce microscopic hematuria, and 18% had clinically significant pathology. CONCLUSIONS: Diagnosis of significant clinical pathologic manifestations would have been compromised had microscopic examination not been performed on the urine specimens from the cohort individuals. Examination of the novel approach of including microscopic examination of specimens in a specific clinical situation challenges the dominant paradigm of reliance on assaying using urine testing strips only, revealing that the current method is not only unreliable for determining microscopic hematuria but also is less than optimal in general clinical practice. The findings of this study provide evidence of the importance of microscopic evaluation as a routine component of urinalysis.


Assuntos
Hematúria/diagnóstico , Heme/urina , Microscopia , Feminino , Humanos , Masculino , Microscopia/métodos , Pessoa de Meia-Idade , Fitas Reagentes , Estudos Retrospectivos , Urinálise
4.
PLoS Negl Trop Dis ; 7(9): e2431, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24069486

RESUMO

BACKGROUND: Urogenital schistosomiasis remains highly endemic in Africa. Current control is based on drug administration, targeted either to school-age children or to high-risk communities at-large. Urine dipsticks for detection of microhematuria offer an inexpensive means for estimating infection prevalence. However, their diagnostic performance has not been systematically evaluated after community treatment, or in areas with continuing low prevalence. The objective of the present study was to perform meta-analysis of dipstick accuracy for S. haematobium infection in endemic regions, with special attention to performance where infection intensity or prevalence was low. METHODOLOGY/PRINCIPAL FINDINGS: This review was registered at inception with PROSPERO (CRD42012002165). Included studies were identified by computerized search of online databases and hand search of bibliographies and existing study archives. Eligible studies included published or unpublished population surveys irrespective of date, location, or language that compared dipstick diagnosis of S. haematobium infection to standard egg-count parasitology. For 95 included surveys, variation in dipstick sensitivity and specificity were evaluated according to study size, age- and sex-specific participation, region, local prevalence, treatment status, and other factors potentially affecting test performance. Independent of prevalence, accuracy was greater in surveys of school-age children (vs. adults), whereas performance was less good in North Africa, as compared to other regions. By hierarchical ROC analysis, overall dipstick sensitivity and specificity for detection of egg-positive urine were estimated at 81% and 89%, respectively. Sensitivity was lower among treated populations (72%) and in population subgroups having lower intensity infection (65%). When the insensitivity of egg count testing was considered (and diagnosis inferred instead from combined hematuria and egg-count findings), overall dipstick sensitivity/specificity were 82%/97%, with significantly better sensitivity (92%) in high prevalence settings. CONCLUSIONS/SIGNIFICANCE: This analysis suggests that dipsticks will continue to serve as very useful adjuncts for monitoring community prevalence following implementation of population-based control of urogenital schistosomiasis.


Assuntos
Técnicas de Laboratório Clínico/métodos , Hematúria/diagnóstico , Heme/urina , Sistemas Automatizados de Assistência Junto ao Leito , Esquistossomose Urinária/complicações , Infecções Urinárias/complicações , Adolescente , Adulto , África/epidemiologia , Animais , Criança , Pré-Escolar , Feminino , Hematúria/etiologia , Humanos , Lactente , Masculino , Prevalência , Esquistossomose Urinária/epidemiologia , Infecções Urinárias/epidemiologia
5.
Biomed Chromatogr ; 26(8): 1009-23, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22806492

RESUMO

This article discusses the separation, analysis and characterisation of intermediates and oxidative by-products of the haem biosynthetic pathway by liquid chromatography and mass spectrometry. Techniques reviewed include high-performance liquid chromatography, ultra-high-performance liquid chromatography, capillary electrophoresis, ion mobility spectrometry, mass spectrometry and tandem mass spectrometry. The emphasis was on the analysis of biological and clinical samples.


Assuntos
Cromatografia Líquida/métodos , Heme/análise , Espectrometria de Massas/métodos , Porfirias , Animais , Heme/química , Heme/urina , Humanos
6.
East Mediterr Health J ; 16(9): 977-81, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21218726

RESUMO

Avoiding life-threatening complications of rhabdomyolysis depends on early diagnosis and prompt management. The aim of this study was to evaluate the role of urinary dipstick test in the detection of haeme pigment in patients who were at risk of acute renal failure (ARF) due to rhabdomyolysis after suffering injury in the Bam earthquake. Serum creatine phosphokinase (CPK) level was used as the gold standard for prediction of ARF. ARF developed in 8 (10%) of 79 patients studied. We found no significant differences in the sensitivity, specificity and accuracy of dipstick urine and serum CPK tests for identifying patients who were at risk of ARF. However, dipstick urine test is an easy test that can be performed quickly at an earthquake site.


Assuntos
Desastres , Terremotos , Heme/urina , Fitas Reagentes , Rabdomiólise/diagnóstico , Rabdomiólise/urina , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Creatina Quinase/sangue , Estudos Transversais , Desastres/estatística & dados numéricos , Diagnóstico Precoce , Terremotos/estatística & dados numéricos , Humanos , Lactente , Irã (Geográfico)/epidemiologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Rabdomiólise/sangue , Rabdomiólise/epidemiologia , Rabdomiólise/etiologia , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Saúde da População Urbana/estatística & dados numéricos , Ferimentos e Lesões/complicações
7.
Clin Rheumatol ; 25(6): 904-6, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16328090

RESUMO

Idiopathic paroxysmal rhabdomyolysis indicating a classical triad of symptoms consisting of muscle pain, weakness, and discolored urine is known as "Meyer-Betz syndrome". It may result in acute renal failure due to precipitation of the myoglobin casts in the tubuli or to the direct toxic effects of myoglobin to the tubular epithelium. On the other hand, outcome may be uneventful. In this study, we reported the case of a 16-year-old girl who was admitted with red-colored urine after a slight exertion. She had tenderness and weakness in upper parts of her legs and bilateral flank pain. She had a positive urine dipstick test for heme despite absent red cells on microscopic examination. White cell count, liver function tests, serum creatine kinase (CK), lactate dehydrogenase (LDH), and urine myoglobin levels were raised. All metabolic tests were in normal ranges and EMG was normal. A muscle biopsy performed after recurrent exertional rhabdomyolysis attacks demonstrated normal findings and ruled out metabolic disorders. At the time of attacks, hydration along with alkalinization was applied and she did not experience renal failure. She was advised to avoid strenuous physical exertion and had an uneventful outcome for the last 5 months. We reported the clinical course and follow-up of an adolescent girl with Meyer-Betz syndrome.


Assuntos
Perna (Membro) , Debilidade Muscular/etiologia , Doenças Musculares/etiologia , Mioglobinúria/etiologia , Dor/etiologia , Rabdomiólise/complicações , Adolescente , Feminino , Seguimentos , Heme/urina , Humanos , Esforço Físico , Síndrome
8.
J Clin Invest ; 98(9): 2139-45, 1996 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8903334

RESUMO

Considerable attention is directed to a surprising biologic phenomenon wherein tissues exposed to one insult acquire resistance to another. We identify a novel example of acquired resistance to acute renal failure and a mechanism that contributes to such resistance. Nephrotoxic serum, administered to rats 24 h before the induction of glycerol-induced acute renal failure, reduces functional and structural injury that occurs in this model. Since heme oxygenase, the rate-limiting enzyme in heme degradation, protects against heme protein-induced renal injury, we questioned whether induction of heme oxygenase underlies the protection afforded by nephrotoxic serum. Kidney heme oxygenase (HO-1) mRNA was induced 6 h after nephrotoxic serum and renal tubules were identified as the site of expression of heme oxygenase protein. Induction of heme oxygenase was accompanied by increased renal content of ferritin but not by induction of other antioxidant enzymes. Inhibition of heme oxygenase prevented the protection afforded by nephrotoxic serum. Nephrotoxic serum did not protect against ischemic acute renal failure, a model in which heme oxygenase is not induced. Thus, nephrotoxic serum protects against glycerol-induced acute renal failure by inducing heme oxygenase in tubules. This study provides the first demonstration of resistance to tubular injury acquired from glomerular inflammation, uncovers a mechanism for such resistance, and exposes the dialogue that occurs between glomeruli and tubules.


Assuntos
Glomerulonefrite/complicações , Heme Oxigenase (Desciclizante)/biossíntese , Nefropatias/etiologia , Injúria Renal Aguda/fisiopatologia , Animais , Indução Enzimática , Ferritinas/metabolismo , Regulação Enzimológica da Expressão Gênica , Glomerulonefrite/fisiopatologia , Glicerol/toxicidade , Heme/urina , Heme Oxigenase (Desciclizante)/genética , Hemoglobinúria/metabolismo , Imunidade Inata , Nefropatias/enzimologia , Túbulos Renais/metabolismo , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia , Ovinos
9.
Clin Diagn Lab Immunol ; 2(1): 1-9, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7719899

RESUMO

The laboratory plays an important role in the diagnosis, evaluation, and classification of the heterogeneous group of diseases known as the IIM, which are characterized by chronic muscle inflammation. Serial measurements of the levels of muscle-derived enzymes in serum are the traditional laboratory studies used to follow the clinical course of patients with IIM, although other laboratory tests can also be useful in assessing myositis disease activity. Several markers of immune system activation, including cytokines and lymphocyte markers, show promise as possibly more sensitive measures of myositis disease activity. Discovery of a unique group of MSAs over the past decade has provided an immunologic basis for defining relatively homogeneous subsets of patients who share similar clinical features, disease courses, and responses to therapy. Future investigations of novel immunologic activation markers, as well as the cloning and expression of target autoantigens of the MSAs, should allow better diagnostic assays, enhanced prognosis, and a better understanding of the pathogenesis of these disorders.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Proteínas Sanguíneas/análise , Creatina Quinase/sangue , Miosite/diagnóstico , Autoanticorpos/classificação , Doenças Autoimunes/sangue , Doenças Autoimunes/urina , Biopterinas/análogos & derivados , Biopterinas/análise , Contagem de Células Sanguíneas , Sedimentação Sanguínea , Creatina/urina , Citocinas/sangue , Testes Diagnósticos de Rotina , Heme/urina , Humanos , Imunoglobulinas/sangue , Isoenzimas , Proteínas Musculares/sangue , Miosite/sangue , Miosite/etiologia , Miosite/imunologia , Miosite/urina , Neoplasias/complicações , Neopterina , Fator de von Willebrand/análise
10.
Hum Toxicol ; 4(3): 301-9, 1985 May.
Artigo em Inglês | MEDLINE | ID: mdl-4007894

RESUMO

A case of acute lead poisoning due to intravenous injection of lead acetate is reported. The patient developed clinical and biochemical symptoms characteristic for acute hepatic porphyrias. Elevated urinary 5-aminolaevulinic acid and low porphobilinogen correlated to a lead-induced inhibition of 5-amino-laevulinic acid dehydrase with diagnostically indicative reactivation rates by zinc and dithiothreitol. Urinary coproporphyrin excretion was also increased. Additional findings included anaemia and toxic hepatitis. Under the influence of elimination therapy with D-penicillamine pathologic parameters normalized. Except for transient neuralgic pains the patient did not experience any neurologic dysfunctions, thus contrasting the findings in chronic lead intoxication.


Assuntos
Intoxicação por Chumbo/fisiopatologia , Adulto , Ditiotreitol/farmacologia , Eletroencefalografia , Heme/urina , Humanos , Injeções Intravenosas , Chumbo/administração & dosagem , Chumbo/sangue , Intoxicação por Chumbo/tratamento farmacológico , Testes de Função Hepática , Masculino , Doenças do Sistema Nervoso/induzido quimicamente , Penicilamina/uso terapêutico , Fatores de Tempo , Zinco/farmacologia
11.
Arch Dermatol ; 116(3): 307-11, 1980 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7369748

RESUMO

In a case of hepatoerythropoietic porphyria (HEP) with unusual features, the patient had onset of photosensitivity in infancy, followed by spontaneous resolution of photosensitivity by the age of 7 years. Seven other cases of HEP have been found in the medical literature; the disease has systemic complications, mainly liver disease and anemia, and is inherited as an autosomal recessive trait. Certain clinical and biochemical features distinguish HEP from erythropoietic porphyria and erythropoietic protoporphyria, the two diseases with which HEP is often confused.


Assuntos
Porfirias/diagnóstico , Dermatopatias/diagnóstico , Adolescente , Adulto , Anemia/complicações , Doenças da Medula Óssea/diagnóstico , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Genes Dominantes , Genes Recessivos , Heme/análise , Heme/urina , Humanos , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Transtornos de Fotossensibilidade/diagnóstico , Porfirias/classificação , Prognóstico
13.
J Clin Pathol ; 25(2): 159-62, 1972 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-5017445

RESUMO

In a study of the urinary excretion of haem precursors in patients with rheumatoid arthritis, iron-deficiency anaemia, and in healthy controls, certain differences were found. In iron-deficiency anaemia the excretion of both porphobilinogen and delta-aminolevulinic acid was increased, whereas in patients with rheumatoid arthritis only the porphobilinogen excretion was increased.A further study on the erythrocyte activity of delta-aminolevulinic acid dehydrase showed a higher activity in the erythrocytes from patients with rheumatoid arthritis compared with healthy controls.


Assuntos
Artrite Reumatoide/metabolismo , Heme/biossíntese , Anemia Hipocrômica/metabolismo , Anemia Hipocrômica/urina , Artrite Reumatoide/urina , Eritrócitos/enzimologia , Heme/urina , Humanos , Hidroliases/sangue , Ácidos Levulínicos/urina , Porfirinas/urina , Pirróis/urina
15.
J Clin Invest ; 49(1): 5-14, 1970 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-4188269

RESUMO

The clearance of plasma protein-bound heme, its sites of removal, and the reutilization of hemeiron were studied by radioisotopic techniques in normal human subjects and in patients with intravascular hemolysis. In normal subjects, injected heme-(59)Fe was bound immediately by albumin and the beta(1)-globulin, hemopexin. Its clearance from the plasma was descr bed by a single exponential equation, and the half-life in plasma was 7-8 hr. Removal was largely by the liver. Iron reutilization began promptly, and half the injected heme-iron was incorporated into circulating red cells within one cell life-span. In patients with intravascular hemolysis, hemopexin was depleted, and injected heme was bound solely to albumin. Plasma clearance was described by a double exponential equation of the form: y = Ae(-k1t) + Be(-k2t). The half-lives of the two components averaged 3.9 and 22.2 hr, respectively. Removal was by the liver in at least some of the patients, and iron reutilization was variable, depending on the state of body iron stores. When hemopex'n was depleted in a normal subject by repeated heme injection, clearance mimicked that observed in the patients.


Assuntos
Doenças Hematológicas/metabolismo , Heme/metabolismo , Hemólise , beta-Globulinas/metabolismo , Eletroforese , Eritrócitos/metabolismo , Heme/análise , Heme/urina , Humanos , Ferro/metabolismo , Isótopos de Ferro , Fígado/metabolismo , Ligação Proteica , Albumina Sérica/metabolismo
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