Principles for the safety evaluation of flavouring substances

This paper reviews efforts by various organizations to develop principles and procedures for the safety evaluation of flavouring substances. Critical factors considered in safety evaluation of these substances include their level of human intake, ease of metabolism to innocuous end-products and the margin of safety between no-observed-effect levels in animal studies and human intakes. These factors form the basis for the principles and criteria laid out in this paper.     

Clinical and microbiological effects of minocycline-loaded microcapsules in adult periodontitis

Clinical and microbiological effects of subgingival delivery of 10% minocycline-loaded (MC), bioabsorbable microcapsules were examined in 15 adult periodontitis patients. Patients received oral hygiene instruction 2 weeks prior to the study. At baseline (day 0) all teeth received supragingival scaling (SC); 2 quadrants received no further treatment and 1 quadrant received subgingival scaling and root planning (SRP). In the fourth quadrant, the tooth with the deepest probing sites (at least 1 site > or = 5 mm) was treated with minocycline microcapsules. The sites were evaluated at baseline and weeks 1, 2, 4, and 6. Clinical indices included bleeding on probing (BOP), probing depths (PD), and attachment loss (AL). Microbiological evaluations included percent morphotypes by phase-contrast microscopy; cultivable anaerobic, aerobic, and black-pigmented Bacteroides (BPB); and percent Porphyromonas gingivalis, Prevotella intermedia, Eikenella corrodens, and Actinomyces viscosus by indirect immunofluorescence. In the SC + MC group, BOP, PD, and AL were significantly reduced from baseline for weeks 1 to 6. BOP in the SC + MC group was significantly reduced compared to the SRP group from weeks 2 to 6. In the SC + MC group the percent of spirochetes and motile rods decreased and the percent of cocci increased after 1 week. The increased cocci and decreased motile rods were statistically greater at weeks 4 and 6 in the SC + MC group compared to the SRP group. This study demonstrates that local subgingival delivery of 10% minocycline-loaded microcapsules as an adjunct to scaling results in reduction in the percent sites bleeding on probing greater than scaling and root planning alone and induces a microbial response more favorable for periodontal health than scaling and root planing.     

Anesthesia information management systems as a cost containment tool

A systematic evaluation of the ability of different bacterial genera to transform 2,4,6-trinitrotoluene (TNT), and grow in its presence, was conducted. Aerobic Gram-negative organisms degraded TNT and evidenced net consumption of reduced metabolites when cultured in molasses medium. Some Gram-negative isolates transformed all the initial TNT to undetectable metabolites, with no adsorption of TNT or metabolites to cells. Growth and TNT transformation capacity of Gram-positive bacteria both exhibited 50% reductions in the presence of approximately 10 microg TNT ml-1. Most non-sporeforming Gram-positive organisms incubated in molasses media amended with 80 microg TNT ml-1 became unculturable, whereas all strains tested remained culturable when incubated in mineral media amended with 98 microg TNT ml-1, indicating that TNT sensitivity is linked to metabolic activity. These results indicate that the microbial ecology of soil may be severely impacted by TNT contamination.     

Molecular events including p53 and k-ras alterations in the in vitro progression of a human colorectal adenoma cell line to an adenocarcinoma

The aim of the current study was to identify genetic abnormalities in human colorectal adenoma and carcinoma derived cell lines, and to determine whether the genetic changes which occur in vitro are relevant to the in vivo situation. Loss of 1p(33-35) region was shown to be the most common chromosome 1 abnormality and loss of heterozygosity (LOH) of the DCC gene and/or adjacent sequences was detected in all adenoma derived cells as well as the carcinoma cell lines. The level of p53 protein was also investigated as increased cellular p53 protein had previously been associated with mutation of the p53 gene. A further aim was to investigate genetic changes in our in vitro model of tumour progression, where the adenoma derived PC/AA cell line has previously been converted in vitro to two distinct tumorigenic phenotypes, producing either an adenocarcinoma or a mucinous carcinoma in athymic nude mice. Progression to the adenocarcinoma phenotype was shown to involve a specific chromosome 1 rearrangement, loss of both normal copies of chromosome 18 (although DCC gene sequences were retained), loss of the remaining wild type allele of k-ras resulting in homozygosity for the k-ras codon 12 mutation and increased cellular p53 protein as detected by SDS-PAGE Western blotting. The increase in p53 protein was shown not to be due to the acquisition of a mutation in the p53 gene. Interestingly, progression of the adenoma derived PC/AA cell line to the mucinous malignant phenotype did not involve any of these molecular rearrangements, suggesting that different genetically distinct pathways are involved in colorectal carcinogenesis. These studies show that the genetic changes in our in vitro model of human colorectal tumour progression are similar to those observed in in vivo studies.     

Performance of impregnated bronze bearings at low speeds

The performance of bronze bearings impregnated with graphite and MoS₂ was studied and the effects of speed, pressure and running time are discussed in detail. A performance chart is provided to aid the selection of bearings for practical use.     

The lymph nodes of the porta hepatis

The area under the liver was dissected in 27 human autopsy specimens to search for lymph nodes in the fissures. Nodes were present in all instances. They were in the transverse fissure, posterior to the portal vein, posterior to pars transversus of the left portal vein and associated with the left hepatic artery. The size varied from 2 millimeters to 2 centimeters. Each node was histologically confirmed. Nodes were infrequent and small on the right. Nodes were not found between the portal vein, hepatic artery and bile ducts in the fissures. Nodes were found outside the fissures in the fascia between the bile duct and hepatic artery. Occlusion of the portal vein and hepatic artery could be expected before occlusion of the bile duct. Node enlargement in the transverse fissure is anticipated as a rare cause of jaundice.     

Chronic effects of smokeless tobacco extract on rat liver histopathology and production of HSP-90

Tobacco consumption is a worldwide problem. The recent increase in the consumption of the smokeless tobacco products (snuff and chewing tobacco) has stimulated interest into the carcinogenic effects of these forms of tobacco. The use of smokeless tobacco products has increased in popularity as the use of cigarettes has become less socially acceptable. For most individuals the use of tobacco is a chronic process. Therefore, the effects of an aqueous extract of smokeless tobacco (STE) in rats following low-dose exposure were examined. Female Sprague-Dawley rats were treated orally with 25 mg STE/kg every other day for 90 days. In order to obtain information regarding the cytotoxicity of STE, the ultrastructural changes occurring in livers of rats following administration of STE were examined under light and electron microscopy. Electron microscopy revealed that in the perisinusoidal spaces an accumulation of indistinct filamentous material occurred following 60 days of treatment, occupying most of the sinusoids. Moreover, the lipids were in a state of disintegration. Significant increases in 90 kDa protein expression were also observed due to chronic treatment with STE. Western blot analysis using a polyclonal mouse antibody against heat shock/stress protein 90 (HSP90) confirmed that the overexpressed proteins were heat shock/stress proteins (HSPs). The HSPs are believed to serve as adaptive or survival functions involving a rapid but transient reprogramming of cellular metabolic activity to protect cells from oxidative damage.     

Crosslinked polymer from N-vinylcarbazole and formalin

A crosslinked polymer has been synthesized from the reaction of N-vinylcarbazole and formalin in toluene in the presence of dry HCl gas. The copolycondensate is insoluble in all common solvents for poly-N-vinylcarbazole, and exhibits higher thermal stability than the unmodified poly-N-vinylcarbazole. However, this polymer is less thermally stable than the corresponding furfural modified poly-N-vinylcarbazole. A mechanism for the overall reaction has been suggested and the factors affecting the synthesis have been discussed.     

Management of mania in the elderly: an update

Twenty-eight genetic loci have been physically mapped to specific large restriction fragments of the Streptococcus mutans GS-5 chromosome by hybridization with probes of cloned genes or, for transposon-generated amino acid auxotrophs, with probes for Tn916. In addition, restriction fragments generated by one low-frequency-cleavage enzyme were used as probes to identify overlapping fragments generated by other restriction enzymes. The approach allowed construction of a low resolution physical map of the S. mutans GS-5 genome using restriction enzymes ApaI (5'-GGGCC/C), SmaI (5'-CCC/GGG), and NotI (5'-GC/GGCCGC).