A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death

Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.     

Photodegradable vinyl plastics. III. Comparison of ultraviolet light and sunlight exposure

Polystyrene (PS), polypropylene (PP), and polyethylene (PE) films, blended with additives to enhance photodegradability, were irradiated with UV light and sunlight. In almost every case, photodegradation was greater with outdoor exposure than under laboratory conditions. Explanations for the differences in degradation obtained by the two methods of irradiation are discussed. Based on IR measurements and molecular weight determinations, photo-oxidative changes that occur in PS induced by UV light appear similar to those induced by sunlight. In addition to the additives previously reported, several new classes of photoinitiators were evaluated. These include selected halocarbonyl compounds, haloalkyl sulfur compounds, and halogen compounds containing certain electron-withdrawing groups. The performance of the additives in vinyl polymer blends is discussed.     

Vibrational circular dichroism: an incisive tool for stereochemical applications

Vibrational circular dichroism (VCD) is the extension of circular dichroism (CD) from electronic to vibrational transitions in molecules. In this review, we present the basic concepts of VCD and focus on its growing strength for stereochemical applications. There are three principal areas of application of VCD. These are the determination of optical purity, the determination of absolute configuration and the determination of conformational properties of chiral molecules in solution. Until recently, the application of VCD was restricted to the use of instruments that had been custom assembled in academic research laboratories. This situation has now changed. It is possible to purchase a dedicated Fourier transform infrared (FTIR) VCD spectrometer complete with user friendly software. Combined with rapid advances in the ab initio theoretical prediction of infrared (IR) and VCD spectra, the availability of such technology opens the way for the widespread use of VCD spectroscopy for research and industrial applications.     

Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations

OBJECTIVE: To determine whether cerebrospinal fluid (CSF) methylmalonic acid (MMA) is increased in neurological patients with low serum cobalamin (Cbl, vitamin B12) concentrations as opposed to neurological patients with normal serum Cbl concentrations. MATERIAL AND METHODS: We measured MMA concentrations in serum and CSF of neurological patients with low serum cobalamin concentrations, but without overt cobalamin related manifestations such as anemia or combined disease of the cord, and neurological patients with normal serum cobalamin concentrations (controls). RESULTS: Serum and CSF MMA concentrations were significantly higher in patients than in controls. Serum MMA was elevated in 4 patients of whom 3 had clearly elevated CSF MMA concentrations. CONCLUSION: Strong indications for cobalamin deficiency can be found not only in serum but also in CSF of patients with seemingly asymptomatic low serum cobalamin concentrations.     

The roles of macrophage in immune dysfunction following severe thermal injury

This experimental study in serious scald mice showed that the cytosolic free calcium ion concentration and the capacity of secreting TNF-alpha of macrophage (M phi) were obviously increased while the secretion of IL-1 was significantly decreased, and accompanied with simultaneous apparent rising of serum TNF-alpha in early postburn period. These indicate that M phi have been highly or even over activated after burn. But the ability of antigen presentation of M phi during this period was deeply suppressed rendering the obvious declination of activity and proliferation response of antigen pulsed lymphocytes. It might be concluded that the defective antigen presentation of M phi played a critical role in early immune dysfunction of severe scald mice, and the highly activated or even overactivated M phi by excessive secretion of TNF-alpha were the molecular basis of the alterations of M phi function.     

Acetylcholine activates an alpha-bungarotoxin-sensitive nicotinic current in rat hippocampal interneurons, but not pyramidal cells

The effects of acetylcholine on both pyramidal neurons and interneurons in the area CA1 of the rat hippocampus were examined, using intracellular recording techniques in an in vitro slice preparation. In current-clamp mode, fast local application of acetylcholine (ACh) to the soma of inhibitory interneurons in stratum radiatum resulted in depolarization and rapid firing of action potentials. Under voltage-clamp, ACh produced fast, rapidly desensitizing inward currents that were insensitive to atropine but that were blocked by nanomolar concentrations of the nicotinic alpha7 receptor-selective antagonists alpha-bungarotoxin (alphaBgTx) and methyllycaconitine. Nicotinic receptor antagonists that are not selective for alpha7-containing receptors had little (mecamylamine) or no effect (dihydro-beta-erythroidine) on the ACh-induced currents. Glutamate receptor antagonists had no effect on the ACh-evoked response, indicating that the current was not mediated by presynaptic facilitation of glutamate release. However, the current could be desensitized almost completely by bath superfusion with 100 nM nicotine. In contrast to those actions on interneurons, application of ACh to the soma of CA1 pyramidal cells did not produce a detectable current. Radioligand-binding experiments with [125I]-alphaBgTx demonstrated that stratum radiatum interneurons express alpha7-containing nAChRs, and in situ hybridization revealed significant amounts of alpha7 mRNA. CA1 pyramidal cells did not show specific binding of [125I]-alphaBgTx and only low levels of alpha7 mRNA. These results suggest that, in addition to their proposed presynaptic role in modulating transmitter release, alpha7-containing nAChRs also may play a postsynaptic role in the excitation of hippocampal interneurons. By desensitizing these receptors, nicotine may disrupt this action and indirectly excite pyramidal neurons by reducing GABAergic inhibition.     

Behavioral treatment of Raynaud's disease.

32 20–65 yr olds with idiopathic Raynaud's disease were randomly assigned to receive finger temperature feedback, finger temperature feedback under cold stress, frontalis EMG feedback, or autogenic training. Ss receiving finger temperature feedback demonstrated significant temperature increases, without relaxation, during training and after the removal of feedback. A significant but smaller response was retained 1 yr later, accompanied by a 66.8% reduction in reported attacks. The addition of training under cold stress to temperature feedback significantly improved retention of voluntary vasodilation at follow-up and produced a 92.5% reduction in symptom frequency. These procedures did not change overall levels of tonic peripheral blood flow, recorded over 24 hrs in the natural environment. Following treatment, significantly colder temperatures were needed to produce attacks in these Ss compared to those who had received EMG feedback or autogenic training. These latter techniques produced the expected signs of decreased arousal but were significantly less effective than temperature feedback in increasing finger temperature or decreasing symptom frequency. Cognitive stress management did not significantly affect any procedure. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)