Effects of di-(2-ethylhexyl) phthalate and five of its metabolites on rat testis in vivo and in in vitro

In an attempt to establish which compound or compounds are responsible for the testicular damage observed after administration of di-(2-ethylhexyl) phthalate (DEHP) in rats, the effects of the parent compound and five of its major metabolites (mono-(2-ethylhexyl) phthalate (MEHP), 2-ethylhexanol (2-EH), mono-(5-carboxy-2-ethylpentyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-(2-ethyl-5-hydroxyhexyl) phthalate) were investigated in vivo and in vitro. The concentrations of MEHP and the three MEHP-derived metabolites in plasma were determined after single and multiple oral doses of DEHP. The plasma concentrations and areas under the plasma concentration-time curves (AUC's) of each of the MEHP-derived metabolites were considerably lower than those of MEHP both after single and after repeated administration of 2.7 mmol of DEHP/kg body weight. The mean elimination half-life of MEHP was significantly shorter in animals given repetitive doses than in those given a single dose, but there was no statistically significant difference between the mean AUC values. No testicular damage was observed in young rats given oral doses of 2.7 mmol of DEHP or 2-EH/kg body weight daily for five days. In animals which received corresponding doses of MEHP the number of degenerated spermatocytes and spermatids was increased, whereas no such effects were found in animals given the MEHP-derived metabolites. MEHP was also the only compound that enhanced germ cell detachment from mixed primary cultures of Sertoli and germ cells.     

Pigmentary type of orthochromatic leukodystrophy (OLD): a new case with ultrastructural and biochemical study

A 34-year-old woman with no family history of orthochromatic leukodystrophy (OLD) developed progressive intellectual deterioration, a frontal syndrome and spastic tetraparesis. She died four years after the onset of the clinical illness. Neuropathological studies included light and electron microscopy of cerebral and nerve biopsies, and a complete postmortem examination. Light microscopy demonstrated OLD with pigmented macrophages and glial cells. Electron microscopy showed electron-dense, membrane-bound intracytoplasmic lamellar inclusions with curved or straight parallel arrangement, or fingerprint pattern, in white matter macrophages, astrocytes and oligodendrocytes. Cortical cells contained lipofuscin which was normal in type and amount. This suggests that the material in white matter glial cells and macrophages is ceroid pigment, however, the distribution is not that seen in ceroid-lipofuscinosis. Similar inclusions have been found in oligodendrocytes in other forms of OLD. Biochemical study did not show evidence of demyelination. Galactolipids were normal. Polyunsaturated fatty acids were decreased. The most striking feature was an increase in plasmalogens.     

Percutaneous drainage of a tuberculous liver abscess

The authors describe the management by percutaneous drainage of a rare solitary tuberculous liver abscess in a 37-year-old woman. Open surgical drainage of such abscesses can be avoided using percutaneous drainage combined with transcatheter infusions of antituberculous agents. For the safe and successful use of this method three criteria must be met: the abscess should be unilocular, there must be a safe access route and a previously sterile compartment must not be contaminated. In addition a small (22 or 23 gauge) needle should be used for the initial puncture.     

Increased sensitivity of virus-infected cells to inhibitors of protein synthesis does not correlate with changes in plasma membrane permeability

Semliki Forest virus-infected BHK cells or herpes simplex virus-infected Vero cells were incubated with the protein synthesis inhibitors hygromycin B and gougerotin. Infected cells take up no more [3H]hygromycin or [3H]gougerotin than do mock-infected cells, at a time p.i. at which either compound is more inhibitory to protein synthesis in infected, than in mock-infected cells. The concentrations of hygromycin and gougerotin required to inhibit protein synthesis in intact cells (irrespective of whether they are infected or not) are several orders of magnitude higher than those required in either permeabilized cells or in cell-free systems. Infected cells take up 86Rb+ at the same rate as mock-infected cells, their intracellular content of K+ is the same, and the activity of the Na+ pump is the same. It is concluded that the increased efficacy of hygromycin and gougerotin in virus-infected cells is a consequence of altered intracellular compartmentation and that increases in permeability of the plasma membrane, if any, are so small as to be undetectable by direct methods.     

25-Hydroxyvitamin D3 metabolism in a human leukemia cell line

Summary 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D₃ (25(OH)D₃) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD₃ to 1,25(OH)₂D₃ by HL-60, we exposed HL-60 cells to 25OHD₃ and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)₂D₃. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD₃ (19-Nor-25OHD₃). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD₃ also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)₂D₃ and similar to that of 25OHD₃. In agreement with the effect upon cell maturation, 19-Nor-25OHD₃ displaces³H-1,25(OH)₂D₃ from its HL-60 receptor with an efficiency comparable to 25OHD₃. Hence, HL-60 cells convert 25OHD₃ to 19-Nor-25OHD₃, and 19-Nor-25OHD₃ induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD₃.     

Cerebral lymphoma and HIV encephalitis in a case of paediatric AIDS,with Pre-Existing multicystic eneephalomalacia

A case of intracerebral malignant B cell lymphoma associated with encephalitis typical of Human Immunodeficiency Virus (HIV) infection is described in a 4 year old child, with post-transfusion Acquired Immune Deficiency Syndrome (AIDS) and severe pre-existing cystic encephalomalacia. This report further documents B cell lymphoma as the commonest cause of an intracerebral mass, and an important cause of death in paediatric AIDS. That more than one pathological process may be responsible for neurological symptoms in paediatric AIDS is also emphasised.     

Early Intervention for Trauma: Current Status and Future Directions

Although psychological debriefing (PD) represents the most common form of early intervention for recently traumatized people, there is little evidence supporting its continued use with individuals who experience severe trauma. This review identifies the core issues in early intervention that need to be addressed in resolving the debate over PD. It critiques the available evidence for PD and the early provision of cognitive-behavioral therapy (CBT). Based on available evidence, we propose that psychological first aid is an appropriate initial intervention, but that it does not serve a therapeutic or preventive function. When feasible, initial screening is required so that preventive interventions can be used for those individuals who may have difficulty recovering on their own. Evidence-based CBT approaches are indicated for people who are at risk of developing posttraumatic psychopathology. Guidelines for managing acutely traumatized people are suggested and standards are proposed to direct future research that may advance our understanding of the role of early intervention in facilitating adaptation to trauma.