Hyperlactatemia and in utero exposure to antiretrovirals: is the control group the clue?

Perinatal antiretroviral (ARV) exposure has been related to hyperlactatemia and lactic acidosis in infants born to HIV-infected mothers. Our objective was to determine the incidence of these conditions during the first year of life in uninfected infants born to HIV-infected mothers and compare the data with infants born to mothers with hepatitis C virus (HCV) infection. We investigated the relationships between hyperlactatemia and neurological and neurodevelopmental disorders by conducting a prospective, comparative cohort study (October 2004 to October 2007) consecutively including children of HIV- and HCV-infected mothers. Liver enzymes, pH, lactic acid, and plasma amino acids were determined at 1.5, 3, 6, and 12 months of life. Pathological hyperlactatemia was defined as lactate >2.1 mmol/liter together with alanine >475 µmol/liter. Seventy-nine patients (39 HIV-exposed patients and 40 unexposed patients) were included. Baseline maternal characteristics in the two groups were similar. Almost 90% of HIV-infected mothers received HAART during gestation, while 10.3% were given AZT monotherapy. Eight newborns received combined therapy and 31 received AZT-based monotherapy. Twelve patients (five exposed and seven nonexposed) had some neurological disorder, and four other patients (one vs. three) showed signs of neurodevelopmental delay, with no significant differences between the groups (p=0.34). Pathological hyperlactatemia was detected in 56.4% (95% CI 39.6-72.2) and 57.5% (95% CI 40.9-73.0) of patients, respectively (p=0.92), and this condition was more frequent in preterm children (p<0.05). ARV use during pregnancy and the neonatal period was not associated with pathological hyperlactatemia. The presence of hyperlactatemia was not associated with neurological or neurodevelopmental disorders. No association was established between the use of ARV agents and the development of hyperlactatemia or neurological disorders in HIV-exposed children during their first year of life.

Glycogen storage disease type III with hypoketosis.

A rare case of glycogen storage disease type III with unusually absent ketone body production during hypoglycemia is presented. A 10-month-old boy presented with asymptomatic hepatomegaly. GOT/GPT 2555/1160 IU/L, CK 302 IU/L, triglycerides 1223 mg/dL, cholesterol 702 mg/dL and uric acid 7.9 mg/dL. After a 9-hour fast, glucose was 27 mg/dL and adequate lipolysis without ketogenesis was observed (total/free carnitine 34.5/20 micromol/L, free fatty acids 1620 micromol/L and beta-hydroxybutyrate 172 micromol/L). Result of MCT (medium-chain triglycerides) load test: basal hydroxybutyrate 29 micromol/L rose to 5748 micromol/L. Treatment with a fat-restricted diet supplemented with formula containing MCT was initiated and the patient presented a satisfactory initial evolution. Three months later, CK were 3000 IU/L. Muscle biopsy was diagnostic of glycogenosis. Enzymatic activity in skin fibroblasts was 0% for amylo-1,6-glucosidase. The diagnosis of glycogenosis type III was established. Echocardiography performed at that time showed non-obstructive ventricular hypertrophy. Until now hypoketosis during hypoglycemia has only been described in glycogenosis type I.

Proteomic analysis in cerebrospinal fluid of patients with atypical nonketotic hyperglycinemia and pulmonary hypertension - A pilot study.

A variant phenotype of nonketotic hyperglycinemia has been described by our group associated with pulmonary hypertension. The aim of this study is to investigate the cerebrospinal fluid proteomes to get an insight into this neurodegenerative process producing leukoencephalopathy with white matter spongiform degeneration. DIGE and MALDI-TOF-TOF analyses were performed to carry out the proteomic study of four patients against three normal controls and one additional control of a classical nonketotic hyperglycinemia. The differential proteomic analysis showed a displacement of some series of spots toward the acidic side. The shifted proteins showed a high degree of carbonylation and increased methionine sulfoxidation was found in cystatin C and in vitamin-D-binding protein. These findings in addition to the increase of serum malondialdehyde concentration provide evidence of an oxidative stress in the patients under study, which is probably systemic rather than mainly confined to the CNS. The similarities of our findings with those found in other neurodegenerative diseases suggest that oxidative damage is commonly involved in these pathologies. DIGE technology improves the 2-D PAGE differential analysis and it is suitable in proteomic studies with a small number of cases.

Reflexiones preliminares sobre una aplicación científico-médica de actualidad: la clonación / Prelminar reflecctions about a present techno medical application: clonatoon / Reflexõe prelimiinares sobre uma aplicaço científico-médica de atualidaade: da clonagem

Este artículo afronta el nuevo reto que la tecnociencia médica ha abierto: la posibilidad de clonación terapéutica o reproductiva. En el presente trabajo se aborda, clara y esquemáticamente, la terminología científico médica, desde los conceptos de reproducción sexual o asexual hasta la endonucleación, pasando por los conceptos de embrión gamético, somático, de cultivo y células madres, para ir realizando un análisis de los conflictos éticos que se abren en cada caso. La última parte del ensayo se centra en el problema ético del embrión y los problemas generados por los embriones sobrantes de los procesos de fertilización in vitro, origen de una importante controversia entre la comunidad científica, que pide que sean utilizados para fines de investigación, diferentes grupos sociales que se oponen a su utilización y la ley que los declara como no utilizables para fines reproductivos cuando su viabilidad no pueda ser garantizada.

This paper reflects about the new medical technoscience challenge opened: the possibility of therapeutic or reproductive clonation. The present paper approximates the medicalscientific terminology clearly and schematically, from the concepts of sexual or asexual reproduction to endonucleation, to the concepts of germinal, somatic or in vitro embryos and stem cells, to carry out an analysis of the ethical conflicts opened in each case. The last part of the essay centers in ethical issues related to the embryo, particularly the problems generated by the surplus embryos of fertilization in vitro, origin of an important controversy between the scientific community, that would like that they be utilized for research, different social groups, that opposed to their use, and the law, that declares them unusabel for reproductive purposes when their viability cannot be guaranteed.

Este artigo confronta o novo desafio que a tecnociência médica abriu: a possibilidade de clonagem terapêutica ou reprodutiva. O presente trabalho aborda de uma forma clara e esquemática, a terminologia científicomédica, a partir dos conceitos de reprodução sexual ou assexual até a endonucleação, passando pelos conceitos de embrião gamético, somático, de cultivos e células tronco, para analisar os conflitos éticos que surgem em cada caso. A última parte do ensaio centrase no problema ético do embrião e nos problemas criados pelos embriões excedentes dos processos de fertilização in vitro, origem de uma importante controvérsia entre a comunidade científica, que pede que sejam utilizados para fines de pesquisa, diferentes grupos sociais que se opõe à sua utilização e a lei que os declara como não utilizáveis para fins reprodutivos, quando sua viabilidade não pode ser garantida.