Neurotransmitter concentrations and binding at dopamine receptors in rats after maternal exposure to 3,4,3',4'-tetrachlorobiphenyl: the role of reduced thyroid hormone concentrations

Polychlorinated biphenyls (PCBs) are environmental contaminants, which accumulate in the food chain and are transferred to the offspring during prenatal development through the placenta and postnatally via breast milk. It is reported that PCBs exert effects on thyroid hormone levels and brain neurotransmitter levels. Both actions may alter neuronal development. The aim of the present study was to investigate, if PCB-induced effects on concentrations of catecholamines and serotonin can be attributed to PCB-induced reductions in thyroid hormone concentrations. In addition, binding to dopamine D(1) and D(2) receptors was examined. Time-mated Wistar rats were treated prenatally with 1 mg 3,4,3',4'-tetrachlorobiphenyl (PCB 77)/kg bodyweight or the vehicle. A third group serving as the positive control received perinatally 5 mg propylthiouracil (PTU)/l drinking water. There were no overt toxic signs in dams or offspring. Thyroid hormone measurements demonstrated effects in dams and offspring up to postnatal day 40. In particular, total T(4) in serum and in the thyroid were decreased in PCB- and PTU-treated dams and offspring. Only PTU exposed rats exhibited significantly increased concentrations of TSH in the serum and pituitary. Measurement of neurotransmitters revealed changes in the PCB-exposed offspring at PND 40, while PTU-treatment was without effect. Dopamine and DOPAC were increased in the medial prefrontal cortex. In adulthood, there were no PCB-related effects on thyroid hormones and neurotransmitters. Binding studies of dopamine D1 and D2 receptors demonstrated that PCB and PTU had no influence on receptor concentration and affinity. Comparison of PCB 77 exposed offspring to PTU exposed offspring demonstrated differential effects on TSH and neurotransmitter levels, the latter result indicating that not all PCB-induced effects on the nervous system can be ascribed to decreases in thyroid hormone concentrations.     

Finding the underserved: directions for HIV care in the future

The demographic, behavior, and background characteristics of 4,804 participants in 17 national demonstration projects for HIV medical and/or psychosocial support services were coded for an index of "service need" or possible under-representation in the traditional healthcare system. Fifteen items were coded including status as a person of color, lack of private insurance, unemployment/disability, problem drinking, crack cocaine use, heroin use, other illicit drug use, less than 12 years of education, criminal justice system involvement, children requiring care while the patient receives services, sex work, being the sex partner of an injection drug user, unstable housing, primary language not English, and age less than 21 or over 55 years. Most (87.7%) of the program participants had four or more of these factors present. Through CHAID modeling, those groups with the highest levels of service need and vulnerability were identified. These data suggest that these projects, designed to attract and serve individuals potentially underrepresented in the health services system, had in fact achieved that goal. Implications of the changing demographics of the HIV epidemic for the health service delivery system are discussed.     

Ibandronate reduces osteolytic lesions but not tumor burden in a murine model of myeloma bone disease

We determined the effects of the potent bisphosphonate ibandronate in a murine model of human myeloma bone disease. In this model, bone lesions typical of the human disease develop in mice following inoculation of myeloma cells via the tail vein. Treatment with ibandronate (4 micrograms per mouse per day) significantly reduced the occurrence of osteolytic bone lesions in myeloma-bearing mice. However, ibandronate did not prevent the mice from developing hindlimb paralysis and did not produce a detectable effect on survival. There was no significant effect of ibandronate on total myeloma cell burden, as assessed by morphometric measurements of myeloma cells in the bone marrow, liver, and spleen, or by measurement of serum IgG2b levels. These results support clinical findings that bisphosphonates may be useful for the treatment of myeloma-associated bone destruction, but suggest that other therapies are also required to reduce tumor growth.     

Cytochrome P4501A induction in primary cultures of embryonic European starling hepatocytes exposed to TCDD, PeCDF and TCDF

Novel methods that predict the sensitivity of avian embryos to the toxic effects of dioxin-like compounds (DLCs) using either (1) knowledge of the identity of amino acids at key sites within the ligand binding domain of aryl hydrocarbon receptor 1 (AHR1) or (2) a luciferase reporter gene assay that measures AHR1 activation were recently reported. Results from both methods predict that European starling (Sturnus vulgaris) and domestic chicken (Gallus gallus domesticus) embryos have similar sensitivity to the biochemical and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzofuran (TCDF). Chicken embryos are highly sensitive to DLC toxicity, and the prediction that starlings are equally sensitive is surprising given their widespread distribution and large population size. In an attempt to learn more about starling sensitivity to DLCs, we determined concentration-dependent effects of TCDD, PeCDF and TCDF on cytochrome P4501A4 and 1A5 (CYP1A4 and 1A5) mRNA levels in primary cultures of hepatocytes prepared from embryonic European starlings. It has been demonstrated that the sensitivity of avian hepatocytes to CYP1A4/5 induction is well correlated with LD₅₀ values of DLCs for several avian species. The results of the present study indicate that European starling hepatocytes are indeed as sensitive as chicken hepatocytes to CYP1A4/5 induction after exposure to TCDD. However, starling hepatocytes are less sensitive than chicken hepatocytes to CYP1A4/5 induction by PeCDF and TCDF.     

Meniscal injuries: detection using MR imaging

Both retrospective and blinded analyses of thin-section, high-resolution magnetic resonance (MR) images of the knee joint, produced using a solenoid surface coil, indicate that MR imaging is an effective technique for evaluating meniscal injuries. Images of 49 patients were evaluated, and the results were correlated with those of subsequent arthroscopy. A grading scale was developed to rate the index of suspicion of a meniscal tear based on the MR images. Overall, approximately 80% of menisci rated grade 4 (definite tear) or 3 (probable tear) were found to have corresponding tears at arthroscopy. In many other patients with a grade 4 or 3 meniscus in whom a corresponding tear was not found arthroscopically, meniscal tears at other sites or other abnormalities were correctly diagnosed using MR. A majority of the false-positive MR images involved the posterior horns of the menisci, the sites of most false-negative arthroscopic diagnoses. The predictive value of a negative MR image was almost 100%. Even in patients with moderate-to-large effusions, the menisci were accurately evaluated. The results imply that MR imaging is useful in the preoperative evaluation of suspected meniscal tears.     

Percutaneous drainage access: a simplified coaxial technique

We describe an access technique that we have used in 150 nephrostomy and biliary drainage procedures and for access to some abscesses and viscera. The system provides safe coaxial access with a 22-gauge removable hub needle, which then acts as a guide wire and is replaced by an 18-gauge cannula. A major advantage is that only one guide wire is used (0.038-inch) for the entire drainage procedure. No significant complications have occurred to date with this method.     

Interventional radiology in the spleen

Despite the widespread use of interventional radiologic techniques, there has been reluctance to apply these to the spleen. Concern for bleeding and difficulty in negotiating around the colon and pleura have limited its use. The authors report their experience with interventional radiology of the spleen in 35 cases, including percutaneous biopsy (n = 5), diagnostic and therapeutic fluid aspiration (n = 14), and catheter drainage of abscesses (n = 9), hematomas (n = 2), intrasplenic pancreatic pseudocysts (n = 2), and necrotic tumor (n = 1). Transsplenic fluid aspiration and biopsy of the pancreas and adrenal gland were performed as well (n = 2). All procedures were performed under computed tomographic or ultrasound guidance. Biopsies were performed with 22- or 20-gauge needles only; no complications were encountered. Diagnoses included primary and secondary malignancies and an infectious process. Drainages were successful in 11 of 14 patients; pleural effusions occurred in two cases, but neither required specific therapy. Interventional radiologic procedures in the spleen are feasible, and the authors discuss methods to promote their safe application.     

Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on long-term potentiation and [3H]MK-801 binding in occipital cortex and hippocampus.

The central nervous system is one of the target organs for polychlorinated biphenyls (PCBs). We measured the effects of maternal exposure of Long-Evans rats to a mixture of PCB congeners reconstituted according to the pattern found in human breast milk (reconstituted mixture, RM) on long-term potentiation (LTP) in two brain regions. Exposure of the dams via food started 50 days prior to mating and was terminated at birth. In the first experiment, adult male and female offspring were exposed maternally to 40 mg/kg of the RM or the commercial mixture Aroclor 1254 (A1254). LTP and paired-pulse inhibition were measured in slices of the visual cortex. In addition, the binding of [3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor-ion channel as well as the [3H]muscimol binding to the GABA-A receptor in membrane preparations from the occipital cortex and hippocampus were determined. LTP as well as [3H]MK-801 binding were significantly reduced in the cortex following PCB exposure, while [3H]MK-801 binding in the hippocampus was not affected. In a succeeding experiment, LTP was determined in cortical and hippocampal slices from rats at postnatal days 10 to 20, following exposure to 0, 5, or 40 mg/kg of the RM. Cortical LTP was significantly affected by the RM while no effects were seen in hippocampal LTP. Taking the two experiments together, PCB exposure significantly reduced LTP, as well as [3H]MK-801 binding, in the cortex and had no effect in the hippocampus. The LTP deficits can only partly be related to the reduction of binding sites to the NMDA receptor; other PCB-induced neurochemical changes have to be assumed.