Importancia clínica del diagnóstico de la metahemoglobinemia / Clinical importance of the diagnosis of methemoglobinemia

Introducción: La metahemoglobina es una forma de hemoglobina en la que el grupo hemo, usualmente en forma ferrosa, es oxidado a forma férrica, lo que afecta el transporte de oxígeno. El incremento por encima de los valores de referencia se denomina metahemoglobinemia. Objetivo: Actualizar conceptos como prevención, manifestaciones clínicas, diagnóstico de laboratorio y tratamiento de elección de esta enfermedad, con la información disponible de la última década. Métodos: Se realizó una revisión de la literatura en inglés y español, a través del sitio web PubMed, el motor de búsqueda Google académico y Scielo, de artículos publicados en los últimos 10 años. Los términos de búsqueda usados incluyeron metahemoglobinemia, déficit de citocromo b5 reductasa, cianosis y cooximetría. Análisis y síntesis de la información: La metahemoglobinemia se puede clasificar en congénita y adquirida, esta última es la más frecuente. Es importante el diagnóstico de esta enfermedad que aunque es un padecimiento poco común, puede cursar con complicaciones graves e incluso la muerte. Puede ser evitable con diagnóstico temprano y tratamiento oportuno para reducir las complicaciones asociadas a este cuadro. Conclusiones: El diagnóstico y el tratamiento, profiláctico y terapéutico de la metahemoglobinemia en su etapa aguda o de mantenimiento, requieren la adecuada actualización del profesional de la salud(AU)

Introduction: Methemoglobin is a form of hemoglobin in which the heme group, usually in the ferrous form, is oxidized to the ferric form, which affects oxygen transport. The increase above the reference values ​​is called methemoglobinemia. Objective: To update concepts such as prevention, clinical manifestations, laboratory diagnosis and treatment of choice for this disease, with the information available from the last decade. Methods: A review of the literature in English and Spanish was carried out, through the PubMed website, the academic Google search engine and Scielo database, of articles published in the last 10 years. Search terms used included methemoglobinemia, cytochrome b5 reductase deficiency, cyanosis, and co-oximetry. Analysis and synthesis of information: Methemoglobinemia can be classified into congenital and acquired, the latter being the most common. It is important to diagnose this disease, which, although it is a rare condition, can cause serious complications, and even death, which are avoidable with early diagnosis and timely treatment that reduce the complications associated with this condition. Conclusions: The diagnosis and treatment, prophylactic and therapeutic, of methemoglobinemia, in its acute or maintenance stage, require adequate updating of the health professional(AU)

Progress in neonatal methemoglobinemia / 国际儿科学杂志

Neonatal methemoglobinemia is a rare disorder characterized by cyanosis and hypoxemia, which could be caused congenitally by cytochrome b5 reductase enzyme deficiency or hemoglobin M disease, and could be acquired by the exposure to lidocaine, nitrites and other drugs.Blood gas analysis is a simple and accessible way to detect methomoglobin.Methemoglobinemia is related to numerous diseases in neonates, including diarrhea, acidosis, late-onset sepsis.Methylene blue is an effective drug for decreasing MetHb levels.Other therapeutic options, such as vitamin C, N-acetylcysteine and vitamin B2, could also be useful.This article reviews the progress of neonatal methemoglobinemia.

Association between 5α-reductase inhibitors therapy and incidence, cancer-specific mortality, and progression of prostate cancer: Evidence from a meta-analysis / 亚洲男科学杂志(英文版)

5α-reductase inhibitors (5-ARI) are widely employed for the treatment of benign prostatic hyperplasia. It has been noted that 5-ARI exhibit the potential to attenuate the risk of prostate cancer, but consistent agreement has not been achieved. Moreover, the effect of 5-ARI on cancer-specific mortality and progression of prostate cancer remains unclear. Therefore, the goal of the current meta-analysis was to elucidate the impact of 5-ARI on the incidence and progression of prostate cancer. We searched for all studies assessing the effect of 5-ARI on risk of prostate cancer in PubMed, Embase, Medline, and Cochrane Library databases. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were accepted to evaluate the association between 5-ARI and the risk of prostate cancer. Synthetic results implied that subjects who accepted 5-ARI compared with the placebo group experienced a distinctly weakened overall incidence of prostate cancer (RR = 0.74; 95% CI: 0.66-0.82; P 7; RR = 1.19; 95% CI: 0.98-1.43; P = 0.069). The results also showed that 5-ARI treatment did not significantly alter prostate cancer-specific mortality (RR = 1.0; 95% CI: 0.95-1.05; P = 0.916). In addition, it was worth noting that 5-ARI treatment acted in a protective role that presented a dramatic benefit to delay the progression of low-risk tumors (RR = 0.58; 95% CI: 0.43-0.78; P < 0.001).

Identification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency / 亚洲男科学杂志(英文版)

In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis.

Congenital methemoglobinemia

@#This report a case of a ten-year-old female with progressive cyanosis and dyspnea on exertion. Clinical and laboratory work up ruled out a cardiac and pulmonary pathology warranting further investigation for possible hemoglobinopathies. Enzyme assay showed deficiency in cytochrome b5 reductase seen in patients with congenital methemoglobinemia. Ascorbic acid at 200mg daily afforded gradual improvement in cyanosis.

Molecular construction of NADH-cytochrome b5 reductase inhibition by flavonoids and chemical basis of difference in inhibition potential: Molecular dynamics simulation study.

NADH-cytochrome b5 reductase, a flavoprotein, plays a central role in many diverse metabolic reactions. NADH-cytochrome b5 reductase has been shown to be responsible for the generation of free radicals from heterocyclic amines. Flavonoids compounds share remarkable similarity in structure but showed differences in their cytochrome b5 reductase inhibition pattern. Our molecular dynamics simulation studies revealed that the difference in substitution at C3 position of ring C may lead to difference in interaction with enzyme. Absence of hydroxyl group substitution at C3 in luteolin facilitates the strong cation-π interaction between Lys185 and ring A, and C and π-π between Phe92 and ring A, and C along with h-bonding between Lys185 and oxo group. Ring B of luteolin showed strong π-π interaction with FAD. These interactions were found absent in quercetin and taxifolin. These results suggest that absence of hydroxyl group substitution at C3 increases the potency of flavonoid inhibitors for cytochrome b5 reductase.

Steroid 5?-reductase and 5?-reductase type 2 deficiency / 基础医学与临床

Two types of steroid 5?-reductase isozymes were found in human and rats.5?-reductase type 2 deficiency in male lead to male pseudohermaphroditism and other related phenotypes.The content of this review includes:① The progress in the fields of 5?-reductase research;②Biochemical characteristics and physiological effects of 5?-reductase.③ Gene structure and mutation in 5?-reductase genes,clinical and chemical features of 5?-reductase type 2 deficiency syndrome.④Inhibitory agents of 5?-reductase and their mechanism and clinical use.The investigation in 5?-reductase help to illuminate physiological effect and sexual differentiation of androgen.The development of new inhibitory agents for 5?-reductase creats new strategy for diseases caused by imbalance of androgen action.Their mechanism and long effects of clinical use need further investigation and observation.

UV-spectrophotometric screening of 5?-reductase inhibitors for benign prostatic hyperplasia treatment / 中国病理生理杂志

0.05).Concentration of ethanol above 1.6 % could obviously suppress enzymatic activity(P0.05).CONCLUSION: A handy and fast screening method for type Ⅱ5?-reductase inhibitors has been set up using UV-spectrophotometry.It may be used to screening drugs for BPH treatment.

5a-REDUCTASE ACTIVITY IN STROMA AND EPITHELIUM OF NORMAL AND HYPERPLASTIC HUMAN PROSTATES / 中华内分泌代谢杂志

To study the influence of 5?-reductase on the pathogenesis of human benign prostatic hyperplasia (BPH), the activity of this enzyme was measured in mechanically separated stroma and epithelium from 7 normal and 16 hyperplastic prostates. Samples were incubated in the presence of tritium labelled testosterone. The yield of DHT was used to estimate the enzyme activity. The results showed that the specific activity of the enzyme (pmol DHT / mg protein/30 rain) was91.4?18,1 and 28.6?7.4 in stroma (S) and epithelium (E) of BPH, 44.7?8.9 and 23.9?6.8 in S and E of normal prostates respectively. It indicated that the enzyme is predominantly localized in the stroma and is elevated ia BPH, the primary abnormality of BPH is in the stroma and the increase of 5?-reductase may have some contribution to the pathogenesis of BPH.