Chronic lithium treatment inhibits pilocarpine-induced mossy fiber sprouting in rat hippocampus.

Lithium remains the gold standard in the treatment of bipolar disorder. Long-term treatment with lithium may lead to specific adaptational changes in gene expression that contribute to a neuroprotective effect. In this study, the pilocarpine model of spontaneous limbic epilepsy was used to induce mossy fiber sprouting (axonal growth of the dentate granule cells that synapse on the pyramidal cells of the CA3 region) to examine the prophylactic neuroprotective effects of lithium in vivo. There were four groups of animals: pilocarpine treated (Pil+/Li-); pilocarpine treated followed by lithium (Pil+/Li+); lithium alone (Pil-/Li+); control (Pil-/Li-). Timm staining was used to obtain density measurements in the stratum oriens and the inner molecular layer of the hippocampus. Mossy fiber density was higher in the pilocarpine-treated animals compared to controls. Chronic lithium following pilocarpine treatment attenuated the density of mossy fibers but lithium alone had no effect. No changes in hilar volume or neuronal number were detected using stereological procedures. The ability of lithium to attenuate activation-induced reorganization in the hippocampus provides evidence for its role as a neuroprotective agent in an in vivo model that may be relevant to its clinical effects in bipolar disorder.     

Elderly cohort study subjects unable to return for follow-up have lower bone mass than those who can return

Longitudinal studies of osteoporosis in older persons may underestimate bone loss because of a lack of follow-up measurements on subjects too frail to return. The authors addressed this possible bias as part of the population-based Framingham Study; in 1996-1997, they used quantitative ultrasound to assess the bone status of elderly subjects regardless of their ability to return to the clinic. Broadband ultrasound attenuation (BUA) and speed of sound of the calcaneus (heel) were measured in 433 subjects at the Framingham, Massachusetts, clinic and in 167 subjects at their homes or nursing homes. All ultrasound parameters were measured with intramachine coefficients of variation of <6.0%. The mean BUA for those subjects evaluated at the clinic was higher than for those measured at home (9.2% higher for men, p = 0.081; 8.6% higher for women, p = 0.034). After adjustment for age and weight, the differences in BUA were no longer significant. Among the elderly subjects participating in this longitudinal cohort study, those who were unable to return for follow-up were older, weighed less, and had a lower BUA than those who did return, suggesting that longitudinal studies of changes in bone mass with aging may underestimate the true population values.     

Local synthesis of IgA in the cerebrospinal fluid of patients with neurological diseases

To date qualitative studies of IgA in the cerebrospinal fluid in neurological disease, particularly multiple sclerosis, have been few and given mixed results. The aim of this study was to identify local synthesis of IgA by detection of clonal IgA bands, in a large cohort of patients with a variety of neurological disorders, using polyacrylamide gel electrophoresis, transfer of protein to nitrocellulose membranes and specific staining. Of 2,097 sequentially analysed patients with suspected neurological disease 54 (2.6%) had locally synthesised IgA; most notably, IgA was present in 39 of 291 (13%) patients with suspected multiple sclerosis. The latter group also had a significant excess of light-chain production, particularly free kappa, when compared to multiple sclerosis patients without local synthesis of IgA. Locally synthesised IgA was also demonstrated in inflammatory, infectious and autoimmune diseases of the central nervous system. This qualitative technique is simple and suitable for routine analysis of cerebrospinal fluid, and further qualitative studies of IgA may be useful in investigating the pathophysiology of certain neurological disorders.     

Structural mass spectrometry: rapid methods for separation and analysis of peptide natural products

A significant challenge in natural product discovery is the initial discrimination of discrete secondary metabolites alongside functionally similar primary metabolic cellular components within complex biological samples. A property that has yet to be fully exploited for natural product identification and characterization is the gas-phase collision cross section, or, more generally, the mobility-mass correlation. Peptide natural products possess many of the properties that distinguish natural products, as they are frequently characterized by a high degree of intramolecular bonding and possess extended and compact conformations among other structural modifications. This report describes a rapid structural mass spectrometry technique based on ion mobility-mass spectrometry for the comparison of peptide natural products to their primary metabolic congeners using mobility-mass correlation. This property is empirically determined using ion mobility-mass spectrometry, applied to the analysis of linear versus modified peptides, and used to discriminate peptide natural products in a crude microbial extract. Complementary computational approaches are utilized to understand the structural basis for the separation of primary metabolism derived linear peptides from secondary metabolite cyclic and modified cyclic species. These findings provide a platform for enhancing the identification of secondary metabolic peptides with distinct mobility-mass ratios within complex biological samples.     

Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation

Retinoblastoma, when it kills by metastasis, almost always does so within 5 years of enucleation. The median time to death was 6.4 months in unilateral cases and 14.2 months in bilateral cases. Multivariate statistical analysis of 361 cases of retinoblastoma indicated that histologic detection of invasion of the tumor into the optic nerve or orbit were the risk factors most highly predictive of death from retinoblastoma. Choroidal invasion was not significantly associated with a fatal outcome. Histologic evidence of a cataract, failure to diagnose retinoblastoma clinically, and bilaterality were also significant risk factors. The authors believe that in at least two of the cases of bilateral retinoblastoma death did not result from metastasis to the brain as was originally diagnosed, but resulted from the development of an independent primary intracranial neuroblastic tumor, a syndrome designated "trilateral retinoblastoma."