Effect of heat or chemical treatment on leptospiral antigens.

The use of bacterins is one of the primary methods in the control of leptospirosis in domestic animals, especially cattle, swine, and dogs. Bacterins have been made using chemically treated or heat-inactivated organisms. Many of the initial studies indicated that the bacterins gave complete protection, whereas later reports found that some inactivation methods resulted in bacterins that protect against death but not against kidney infection and renal shedding. This raised the possibility that some of the antigens had been altered. To investigate this possibility, we heat or chemically treated Leptospira interrogans serovar icterohaemorrhagiae CF-1, L. interrogans serovar canicola Moulton, L. interrogans serovar grippotyphosa SC4397, L. interrogans serovar hardjo Hardjoprajitno, and L. interrogans serovar pomona MLS. Temperatures used to determine alterations in antigens were 50, 56, 80, 100, and 121 degrees C. The chemicals used were formaldehyde, phenol, and thimerosal. Analysis was done using Laemmli gels and Western blots. We found that heating at 50 or 56 degrees C had the smallest effect on antigens, whereas heating at 80 or 100 degrees C caused the appearance of high-molecular-weight bands on Western blots. Heating at 121 degrees C caused almost all the bands to disappear, in both the stained gel and the Western blot. Both phenol and Formalin treatment altered proteins, whereas thimerosal treatment appeared to have little effect compared with heating at 50 degrees C.     

Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.     

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Protection of photosensitized rats against long ultraviolet radiation by topical application of compounds with structures similar to that of dihydroxyacetone

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.     

Xylose disposition in humans as a function of age

D-xylose disposition was examined in 24 healthy men between 32 and 85 years of age. Xylose was administered as a 5 gm iv infusion and as a 25 gm po solution. Serum xylose concentrations and urinary excretion of intact xylose were determined. There were statistically significant inverse relationships with age for each of the following parameters after intravenous infusion: elimination rate constant (r2 = 0.71); systemic clearance (r2 = 0.66); renal clearance (r2 = 0.66); and nonrenal clearance (r2 = 0.35). Similar inverse relationships were found after oral dosing for the elimination rate constant (r2 = 0.69) and renal clearance (r2 = 0.54). There was no significant age relationship for the apparent volume of distribution or the steady-state volume of distribution. The percentage of the oral and intravenous dose recovered in urine up to 5 hours after dosing was significantly and inversely correlated with age. The implications of the latter finding are discussed with regard to the interpretation of the xylose tolerance test used to assess gastrointestinal absorptive capacity.     

Familial achalasia associated with adrenocortical insufficiency, alacrima, and neurological abnormalities

We report on two brothers with achalasia, adrenocortical insufficiency, alacrima, short stature, microcephaly, ataxia, optic atrophy, and developmental delay. The parents and three sibs are unaffected. Achalasia, adrenocortical insufficiency, and alacrima comprise a recently characterized familial multisystem disorder of unknown cause. Achalasia has also been described in association with microcephaly and mental retardation in one family and ataxia, optic atrophy, and mental retardation in another. The above reports and these sibs may represent variants of a single pleiotropic recessive gene. We suggest that abnormalities of the central nervous system are a manifestation of the achalasia, adrenocortical insufficiency, alacrima syndrome.