GABAergic septohippocampal neurons are not necessary for spatial memory.

The medial septum/vertical limb of the diagonal band of Broca (MSDB) provides a major input to the hippocampus and is important for spatial memory. Both cholinergic and GABAergic MSDB neurons project to the hippocampus, and nonselective lesions of the MSDB or transections of the septohippocampal pathway impair spatial memory. However, selective lesions of cholinergic MSDB neurons using 192-IgG saporin (SAP) do not impair or only mildly impair spatial memory. Previously, intraseptal kainic acid was found to reduce levels of glutamic acid decarboxylase, a marker of GABAergic neurons, but not to alter the levels of choline acetyltransferase, a marker of cholinergic neurons. The present study further characterized the effects of kainic acid on GABAergic MSDB neurons and examined the effects of intraseptal kainic acid on spatial memory. Saline, kainic acid, SAP, or the combination of kainic acid and SAP was administered into the MSDB of rats. Spatial memory was assessed in an eight-arm radial maze and a water maze. Kainic acid destroyed GABAergic septohippocampal neurons, but spared cholinergic neurons. SAP eliminated MSDB cholinergic neurons, sparing noncholinergic neurons. Coadministration of kainic acid and SAP destroyed GABAergic and cholinergic MSDB neurons. Acquisition of the radial maze task and performance on this task with 4-h delays were unimpaired by intraseptal kainic acid or SAP, but were impaired by coadministration of kainic acid and SAP. Acquisition of the water maze task was unaffected by intraseptal kainic acid, delayed slightly by SAP, and impaired severely by coadministration of kainic acid and SAP. These results provide evidence that kainic acid at appropriate concentrations effectively destroys GABAergic septohippocampal neurons, while sparing cholinergic MSDB neurons. Furthermore, lesions of the GABAergic septohippocampal neurons do not impair spatial memory. While lesions of cholinergic MSDB neurons may mildly impair spatial memory, the combined lesion of GABAergic and cholinergic septohippocampal neurons resulted in a memory impairment that was greater than that observed after a selective lesion to either population. Thus, damage of GABAergic or cholinergic MSDB neurons, which together comprise the majority of the septohippocampal pathway, cannot totally account for the spatial memory impairment that is observed after nonselective lesions of the MSDB.

Age-related loss of the AMPA receptor subunits GluR2/3 in the human nucleus basalis of Meynert.

Magnocellular cholinergic neurons in the basal forebrain have long been recognized as vulnerable to the pathology of Alzheimer's disease. Despite numerous anatomical, pharmacological, behavioral, and physiological investigations of these neurons the cellular mechanism that underlines their selective vulnerability remains unclear. As part of an ongoing investigation into the molecular mechanism(s) underlying neuronal vulnerability in Alzheimer's disease and normal aging, we employed immunocytochemical techniques and examined the cellular localization of the alpha-amino-3-hydroxy-5-methyl-4-isoaxolepropionate (AMPA) glutamate receptor subunits GluR1 and GluR2/3 in the basal forebrain of eight nondemented elderly human subjects (66-102 years). For each case we observed GluR1-positive magnocellular cells darkly labeled within all main divisions of the basal forebrain (Ch1-Ch4). Double-labeling immunohistochemical techniques confirmed that the overwhelming majority (94%) of these neurons were also positive for the p75NGFr antibody, thus substantiating the cholinergic nature of these neurons. In contrast, GluR2/3 immunolabeling upon magnocellular neurons was relatively faint or nonexistent. The latter observations were most apparent in cases of advanced age and in the posterior part of the nucleus basalis of Meynert (NBM) (i.e., Ch4). In contrast, in adjacent structures (e.g., globus pallidus), a number of robustly labeled GluR2/3-positive cells were observed. In addition to the eight elderly subjects, we examined GluR1 and GluR2/3 immunostaining in the NBM of five younger cases, 5, 33, 36, 47, and 48 years of age. Although practical considerations limited our observations to the Ch4 region, we observed both GluR1 and GluR2/3 labeling upon NBM neurons in this latter region. On average, the distribution of labeled cells and intensity of immunoreaction were comparable between GluR1 and GluR2/3. The presence of GluR2/3- and GluR1-labeled neurons in the Ch4 region of younger cases but primarily GluR1 in cases of advanced age suggests an age-related decrease in GluR2/3. Functionally, the loss of GluR2 from the AMPA receptor complex results in ion channels highly permeable to Ca(2+). These alterations in cation permeability of the AMPA receptor together with the occurrence of a number of other intrinsic and extrinsic events (i.e., decrease Ca(2+)-binding protein) likely contribute to the vulnerability of these neurons in aging and in AD.

Can HCV affect the efficacy of anti-HIV treatment?

To evaluate the impact of new antiretroviral combinations (HAART: Highly Active Anti Retroviral Therapy) on HCV replication and liver enzyme levels, we analysed the changes in HCV viremia and aminotransferase levels in HIV and HCV co-infected patients. Moreover, to evaluate the influence of HCV infection on the efficacy of HAART, we compared the virological, immunological and biochemical response to antiretroviral combinations in anti-HIV positive subjects with or without HCV infection. We enrolled eight consecutive outpatients with HIV-HCV coinfection and with indications for HAART (Group A). For each patient in group A, we selected an anti-HIV negative patient with indications for HAART, pair-matched for age, sex, risk factor for HIV infection, presumed duration of infection, number of CD4 cells, HIV viremia and treatment schedule (Group B). A statistically significant increase in CD4 in both groups was found at 1st, 3rd and 6th month of antiretroviral therapy. A decrease in HIV-RNA in both groups was observed at 1st and 6th month of treatment. The percentage of patients with undetectable HIV-RNA at the 1st month was higher in Group B than in Group A (8/8 vs. 3/8, p = 0.025). Basal HCV-RNA viremia was very high in each case and no variations during treatment were observed. During therapy the aminotransferase levels slightly decreased in Group A and consistently increased in Group B. In Group A the differences were not significant to the statistical analysis; in Group B the aminotransferase levels at 3rd and 6th month were significantly higher than those observed at the baseline.

Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: role of cholinergic medial septal neurons in spatial working memory.

Rats were administered 192-IgG saporin (SAP) or vehicle into the medial septum-vertical limb of the diagonal band (MS-vDB). Starting 1 week later, the effects of intraseptal scopolamine, oxotremorine, and muscimol were tested in a T-maze alternation task. Choice accuracy in the absence of infusions did not differ between control and SAP-treated rats. Intraseptal scopolamine or muscimol impaired the choice accuracy of SAP-treated but not control rats. Oxotremorine impaired accuracy similarly in control and SAP-treated rats. The enhanced effects of scopolamine and muscimol produced by SAP are consistent with the hypothesis that cholinergic MS-vDB neurons are used in spatial working memory. The finding that SAP alone did not alter choice accuracy provides further evidence that cholinergic MS-vDB neurons are not necessary for spatial working memory. Thus, cholinergic MS-vDB neurons are involved in but not necessary for spatial working memory.

Sonographic diagnosis of bowel obstruction presenting with fluid-filled loops of bowel.

When intestinal obstruction presents with fluid-filled bowel loops instead of air-distended loops, subtle elongated masses representing these bowel loops may be missed on plain abdominal radiographs. In these cases, ultrasound will show sausage-shaped, cystic structures, with uneven margins representing mucosal folds, distributed throughout the abdomen and sometimes accompanied by peristalsis. These features differentiate fluid-filled bowel loops from other cystic structures in the abdomen and help make a diagnosis of bowel obstruction.

Chronic ectopic pregnancy.

A chronic ectopic pregnancy is a form of tubal pregnancy in which there is gradual disintegration of the tubal wall with slow and/or repeated episodes of hemorrhaging leading to the formation of a pelvic mass. A review of 22 pathologically proven cases of this entity revealed the pelvic mass to be a hematocele, or a sealed-off inflammatory mass composed of blood clots, organized hematomas, and surrounding adhesions. Sonographically, the abnormality is manifested by an extrauterine, complex mass in the adnexa(e) and cul-de-sac. The mass may obliterate uterine margins and be confused for pelvic inflammatory disease, endometriosis, or uterine leiomyomas. With an increased awareness of this entity and its mildly symptomatic and protracted clinical course, a preoperative diagnosis should be possible.

Tc-99m MDP and indium-111 chloride scintigraphy in skeletal tuberculosis.

A case of diffuse osseous tuberculosis with changes on skeletal Tc-99m methylene diphosphonate (MDP) and indium-111 chloride scintigraphy is presented. Only two other cases of bone scan findings in osseous tuberculosis (TB) were reported in the literature and both show patterns similar to diffuse metastatic disease. In addition, the demonstration of corresponding areas of decreased tracer activity on indium-111 bone marrow scintigraphy is a finding that has not been previously reported for skeletal tuberculosis.