Antipsychotic drug interactions with specific [3H]ketanserin binding sites in membrane fragments derived from human prefrontal cortex and human amygdala

Two regions of the brain potentially significant for psychopathology in schizophrenia are the prefrontal cortex and the amygdala. Antipsychotic compounds bind at serotonin receptors in human prefrontal cortex. We hypothesized that the serotoninergic antagonist [3H]ketanserin would label similar sets of binding sites in these two brain regions. Further, we hypothesized that all antipsychotic compounds would show appreciable affinity for binding sites labeled by [3H]ketanserin in the prefrontal cortex. Our findings indicate some differences in [3H]ketanserin binding between prefrontal cortex and amygdala. We also observed that several antipsychotic compounds had very high affinity for the [3H]ketanserin binding sites in prefrontal cortex.     

Pyridoxine-dependent seizures and cognition in adulthood

A case report of neonatal onset pyridoxine-dependent seizures in a male patient with early diagnosis and treatment is presented. The patient's epilepsy was recognized and treated with pyridoxine (vitamin B6) within 8 hours of birth. Treatment has been nearly continuous since that time. This paper reports the results of a full neuropsychological evaluation at age 37 years and MRI completed at age 31 years. Consistent with other case reports in the literature, there was a significant Performance IQ (PIQ) advantage with decreased Verbal IQ (VIQ) and expressive language skills (Full-Scale IQ 71, VIQ 64, PIQ 85). MRI demonstrated characteristic thinning of the posterior corpus callosum. This report provides an example of early treatment that nonetheless results in a mild mental retardation. The similarity of the structural changes on MRI and the cognitive profile of this patient to those of others reported in the literature suggest that the underlying mechanism for both may be the same.     

Connexin immunoreactivity in glial cells of the rat retina

The rat retina contains two types of macroglial cells, Müller cells, radial glial cells that are the principal macroglial cells of vertebrate retinas, and astrocytes associated with the surface vasculature. In addition to the often-described gap-junctional coupling between astrocytes, coupling also occurs between astrocytes and Müller cells. Immunohistochemistry and confocal microscopy were used to identify connexins in the retinas of pigmented rats. Several antibodies directed against connexin43 stained astrocytes, identified using antibodies directed against glial fibrillary acidic protein (GFAP). In addition, two connexin43 antibodies stained Müller cells, identified with antibodies directed against S100 or glutamine synthetase. Connexin30-immunoreactive puncta were confined to the vitreal surface of the retina and colocalized with GFAP-immunoreactive astrocyte processes. Connexin45 immunoreactivity was associated with both astrocytes and Müller cells. We conclude that retinal glial cells express multiple connexins, and the patterns of immunostaining that we observe in this study are consistent with the expression of connexins30, -43, and possibly -45 by astrocytes and the expression of connexins43 and -45 by Müller cells. As gap-junction channels may be formed by both homotypic and heterotypic hemichannels, and the hemichannels may themselves be homomeric or heteromeric, there exists a multitude of possible gap-junction channels that could underlie the homotypic coupling between retinal astrocytes and the heterotypic coupling between astrocytes and Müller cells.     

Mercapturate metabolism of 4-hydroxy-2-nonenal in rat and human cerebrum

4-Hydroxy-2-nonenal (HNE), a potent toxin formed in the brain from oxidation of polyunsaturated fatty acids, is increased in Alzheimer disease (AD), where it is a proposed effector of amyloid beta peptide-mediated neurotoxicity. Detoxification of HNE via the mercapturic acid pathway (MAP) is the primary means by which other organs, such as liver, limit its toxic effects. Here we examined the distribution and activity of MAP detoxification for HNE in cerebrum. Our results showed that rat cerebral cortex and especially synaptosomes were less well equipped to detoxify HNE via the MAP than liver. Glutathione transferases (GSTs) catalyze the committed step in the MAP; GST-mu and GST-pi, but not OST-alpha, were detected in neurons and astrocytes in cerebrum from AD patients and controls. MAP activity in frontal cortex of AD patients was modestly but significantly increased compared to controls. These data suggest that lipid peroxidation may present a greater toxic burden to cerebrum than to other organs, and that a component of response to injury in late stage AD is a slight increase in MAP activity.     

Support for bereaved owners of pets

TOPIC: The bond that exists between people and their pets and its impact on physical and mental health. PURPOSE: To review the current literature and explore the clinical implications of bereavement related to pets. SOURCES: A comprehensive review of the bereavement, veterinarian, and agricultural literature related to attitudes and response patterns to pet and animal death. CONCLUSIONS: The death or loss of a beloved pet can be a life-changing event.     

The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk

The extent to which the biodiversity and community composition of ecosystems affect their functions is an issue that grows ever more compelling as human impacts on ecosystems increase. We present evidence that supports a novel function of vertebrate biodiversity, the buffering of human risk of exposure to Lyme-disease-bearing ticks. We tested the Dilution Effect model, which predicts that high species diversity in the community of tick hosts reduces vector infection prevalence by diluting the effects of the most competent disease reservoir, the ubiquitous white-footed mouse (Peromyscus leucopus). As habitats are degraded by fragmentation or other anthropogenic forces, some members of the host community disappear. Thus, species-poor communities tend to have mice, but few other hosts, whereas species-rich communities have mice, plus many other potential hosts. We demonstrate that the most common nonmouse hosts are relatively poor reservoirs for the Lyme spirochete and should reduce the prevalence of the disease by feeding, but rarely infecting, ticks. By accounting for nearly every host species' contribution to the number of larval ticks fed and infected, we show that as new host species are added to a depauperate community, the nymphal infection prevalence, a key risk factor, declines. We identify important "dilution hosts" (e.g., squirrels), characterized by high tick burdens, low reservoir competence, and high population density, as well as "rescue hosts" (e.g., shrews), which are capable of maintaining high disease risk when mouse density is low. Our study suggests that the preservation of vertebrate biodiversity and community composition can reduce the incidence of Lyme disease.     

Acute onset of neutrophilic dermatosis in patients after therapy with a COX-2-specific inhibitor

Case 1 A 31‐year‐old black woman with an 8‐year history of Crohn's disease (CD) presented with multiple, erythematous, tender, leg nodules. She had started to develop these areas approximately 2 weeks earlier. About 1 week prior to the development of these areas, the patient had gone to her primary care physician because of increasing joint pains. She was given rofecoxib, 50 mg/day. A few months earlier, the patient had stopped taking the medication that had been prescribed for CD: sulfasalazine and prednisone. Since stopping sulfasalazine and prednisone, her gastrointestinal symptoms had increased. After starting rofecoxib, the patient did not notice any significant change in her gastrointestinal symptoms, although her arthritic symptoms improved. Earlier on the day of presentation, the patient's gastroenterologist had instructed her to stop rofecoxib, and to re‐start sulfasalazine and prednisone. On physical examination, the patient had multiple erythematous nodules on both legs, predominantly on the lower legs anteriorly and posteriorly ( Fig. 1a ). Some of the nodules showed central pustules and some showed superficial epidermal ulceration ( Fig. 1b ). A biopsy was performed on an indurated lesion that had not yet ulcerated.

Figure 1 Open in figure viewer PowerPoint Multiple, erythematous nodules on the legs of a patient with Crohn's disease (Case 1). Biopsy specimens from some lesions showed subepidermal pustule formation with or without epidermal ulceration     

Adherence to CDC STD guideline recommendations for the treatment of Chlamydia trachomatis infection in two managed care organizations

BACKGROUND: The extent of adherence to the Centers for Disease Control and Prevention (CDC) STD guidelines by clinicians practicing in managed care settings is unknown.GOAL The goal was to assess adherence to the CDC guideline recommendations for the treatment of genital chlamydial infection, by clinicians at two group model managed care organizations. DESIGN: Retrospective cohort study of men and women with laboratory-confirmed chlamydial infection. Patients were members of either the Kaiser Permanente Foundation Health Plan of Colorado or HealthPartners of Minneapolis/St. Paul who had tested positive for cervical or urethral chlamydial infection during the period from January 1, 1998, through June 30, 1999. RESULTS: During the study period, 1,078 patients with positive tests for genital Chlamydia trachomatis were identified. More than 97% of men and nonpregnant women and more than 98% of pregnant women were prescribed treatment, consistent with current CDC guidelines. CONCLUSION: Adherence to CDC-recommended therapy was high for patients with genital chlamydial infections at these two managed care organizations.