Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture.

The effect of the neurotoxic nitric oxide derivative, the peroxynitrite anion (ONOO-), on the activity of the mitochondrial respiratory chain complexes in cultured neurones and astrocytes was studied. A single exposure of the neurones to ONOO- (initial concentrations of 0.01-2.

Neonatal carnitine palmitoyltransferase-2 deficiency: a case presenting with myopathy.

Mitochondria were isolated from liver, heart and skeletal muscle of a 34-day-old female infant who died from a myopathic illness. Muscle biopsy showed lipid accumulation and no obvious pathology in any other organ. Enzymatic analysis of skeletal muscle extracts revealed normal activities of the markers pyruvate dehydrogenase and citrate synthase.

Effect of oxygen concentration on in vitro fertilization and embryo culture in the human and the mouse.

Objective: To compare the effect of culturing oocytes, zygotes and embryos under low (5%) versus ambient (20%) oxygen conditions on human IVF results and on mouse blastocyst formation.

Design: A prospective, randomized study of 257 consecutive IVF treatment cycles in 186 couples undergoing oocyte retrieval for various reasons of infertility. Gametes and resulting embryos after IVF were alternately allocated to fertilization and culture either under a gas phase of 5% CO2/90% N2/5% O2, or 5% CO2/95% air (20% O2).

Tetrahydrobiopterin deficiency and brain nitric oxide synthase in the hph1 mouse.

Tetrahydrobiopterin (BH4) is the cofactor for the aromatic amino acid monoxygenase group of enzymes and for all known isoforms of nitric oxide synthase (NOS). Inborn errors of BH4 metabolism lead to hyperphenylalaninaemia and impaired catecholamine and serotonin turnover. The effects of BH4 deficiency on brain nitric oxide (NO) metabolism are not known.

Trolox protects mitochondrial complex IV from nitric oxide-mediated damage in astrocytes.

The efficacy of cystine, ascorbate and trolox, a vitamin E analogue, at protecting against nitric oxide-mediated mitochondrial complex IV damage has been investigated in cultured astrocytes. Of these compounds, only trolox afforded protection. It is suggested that lipid peroxidation is responsible for nitric oxide-mediated mitochondrial damage and that inhibitors of this process may be of therapeutic benefit in conditions where excessive nitric oxide production is implicated.

Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid.

A case of dilated cardiomyopathy in a young boy secondary to type II 3-methylglutaconic aciduria is described. A metabolic cause for his dilated cardiomyopathy was suspected because of the development on the electrocardiogram of an unusual "camel's hump" shape of the T waves, and of progressive thickening with increasing echogenicity of the left ventricular wall. He initially improved on digoxin treatment, but did not maintain the response with conventional dietary treatment for this condition.

Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes.

The Ca(2+)-independent form of nitric oxide synthase was induced in rat neonatal astrocytes in primary culture by incubation with lipopolysaccharide (1 microgram/ml) plus interferon-gamma (100 U/ml), and the activities of the mitochondrial respiratory chain components were assessed. Incubation for 18 h produced 25% inhibition of cytochrome c oxidase activity. NADH-ubiquinone-1 reductase (complex I) and succinate-cytochrome c reductase (complex II-III) activities were not affected.

Chlamydia trachomatis antibody testing is more accurate than hysterosalpingography in predicting tubal factor infertility.

Objective: To compare the likelihood of abnormal Chlamydia trachomatis antibody test results with that of abnormal hysterosalpingography (HSG) test results in patients with tubal factor infertility.

Design: Anti-C. trachomatis immunoglobulin G antibodies were determined prospectively in 211 consecutive infertility patients by means of an indirect fluorescent antibody technique.

Isolated capillary proliferation in Leigh's syndrome.

An infant with hypotonia and recurrent apneic spells died with a diagnosis of pyruvate dehydrogenase deficiency and showed typical pathological changes of Leigh's syndrome at postmortem. Despite the prominence of symptoms suggesting dysfunction of brainstem respiratory centers during life, lesions were not found in the upper medulla. However, quantitative morphometric analysis demonstrated abnormal capillary hyperplasia in the region including and between the nucleus ambiguus and nucleus tractus solitarius.

Hypoglycaemia in the neonate: how and when is it important?

Cerebral metabolism is known to be highly dependent upon glucose utilisation. In the neonate, severe hypoglycaemia is now recognized to be associated with subsequent adverse neurodevelopment and in extremis glial and neuronal cell death. However, the level at which hypoglycaemia becomes clinically important is not well understood.

Modulation of embryonic Na(+)-K(+)-ATPase activity and mouse preimplantation development in vitro in media containing high concentrations of potassium.

The effect of various potassium concentrations (ranging from 1.4 mM to 30 mM K+) in modified Tyrode's medium on the culture of mouse zygotes obtained after in vitro fertilization to the blastocyst stage was examined. A clear dose-dependent negative effect of increasing K+ concentrations on the preimplantation embryonic development in vitro was found.

Five different histological subtypes of germ cell malignancies in an XY female.

A case of a 19-year-old female with 46 XY gonadal dysgenesis and five different histological subtypes of germ cell malignancies is described. Both adnexa were removed, preserving the uterus. Pathology revealed gonadoblastoma with dysgerminoma differentiation present in both gonads and in the left gonad mature teratoma, embryonal carcinoma, and endodermal sinus tumor were identified as well.

Molecular genetic characterization of an X-linked form of Leigh's syndrome.

We report a patient with necrotizing encephalomyelopathy (Leigh's syndrome) associated with a deficiency of pyruvate dehydrogenase complex activity. The underlying mutation is an A to C transversion in the pyruvate dehydrogenase complex E1 alpha subunit gene. As the E1 alpha subunit is encoded on the X chromosome, this observation confirms that some patients with Leigh's syndrome may potentially exhibit X-linked inheritance.

Oral phosphate supplements reverse skeletal muscle abnormalities in a case of chronic fatigue with idiopathic renal hypophosphatemia.

A 57-yr-old man presented with a long history of undiagnosed fatigue but no evidence of bone disease. He was noted to have hypophosphatemia due to an idiopathic phosphaturia. Marked abnormalities of exercising skeletal muscle detected by phosphorus magnetic resonance spectroscopy and by plasma metabolite measurements were consistent with mitochondrial dysfunction.

Families of mtDNA re-arrangements can be detected in patients with mtDNA deletions: duplications may be a transient intermediate form.

In three patients with mitochondrial DNA duplications, there are two additional re-arranged molecules derived from mitochondrial DNA. Two forms of closed circular deletions of mitochondrial DNA have been characterised in all three patients, one being a monomer, and the other a dimer. The junction fragments appear to be the same in the deletion and the duplication, suggesting that both re-arrangements arose from the same initial recombination event, followed by homologous recombination.

Development of enzymes of energy metabolism in the neonatal mammalian brain.

The metabolic capability for the complete oxidation of glucose, i.e. aerobic glycolysis, is highly developed in the brains of neurologically mature (precocial) species at birth, whereas this activity is severely limited in the brains of neurologically immature (non-precocial) species such as the rat and human.

Glutaric aciduria type 1 an atypical presentation together with some observations upon treatment and the possible cause of cerebral damage.

This report describes an infant diagnosed aged twenty-five months as having glutaric aciduria Type 1 (GA 1). Initial presentation was with isolated macrocephaly at four months of age. Severe hypertonia, and dystonia, within 24 hours of minor head injury occurred at nineteen months of age.

Immunohistochemical analysis of estrogen and progesterone receptors in fallopian tubes during ectopic pregnancy.

Objective: To study decidualization, estrogen receptor (ER), and progesterone receptor (PR) expression in fallopian tubes containing an ectopic pregnancy (EP).

Design: Assessment of decidual reaction by light microscopy, staining of ER and PR in epithelium and stroma by immunohistochemical methods.

Setting: Academic hospital.

Effect of the number of inseminated spermatozoa on subsequent human and mouse embryonic development in vitro.

It has been shown, in both human and mouse in-vitro fertilization (IVF), that an excess number of spermatozoa in the insemination medium leads to reduced fertilization rates. In this study, we evaluated human embryonic development after dividing the oocytes of each of 62 IVF attempts into two groups on the basis of insemination with two widely used concentrations (50,000 and 100,000 spermatozoa/ml). The embryonic growth was retarded in the group inseminated with 100,000 spermatozoa/ml: significantly fewer fast developing embryos (4-cell and 5- to 8-cell stages) were found (53.

Lack of effect of peritoneal endometriosis on fertility in the rabbit model.

Study Objective: To study the isolated influence of peritoneal endometrial implants on fertility in an adhesion-free rabbit model.

Study Design: Thirty-two rabbits with endometrium implants were used; 31 rabbits with fat implants served as controls. In these rabbits parameters of early embryonic development were investigated.