Enhancement of peroxisomal enzymes, cytochrome P-452 and DNA synthesis in putative preneoplastic foci of rat liver treated with the peroxisome proliferator nafenopin

The peroxisome proliferator (PP) nafenopin (NAF) enhanced tumordevelopment in rat liver through promotion of a subtype of putativepreneoplastic cell foci, characterized by weak cytoplasmic basophilia(1,2). In order to elucidate the selective growth advantageof these weakly basophilic foci (WBF) we investigated the effectsof NAF on their metabolic phenotype and DNA synthesis. In WBF,as well as in other foci subpopulations and in hepatocellularcarcinomas the occurrence of five NAF-inducible enzymes, i.e.of peroxisomal ß-oxidation (acyl-CoA oxidase, bifunctionalprotein and thiolase), catalase and cytochrome P-452 was studiedby immunohistochemical methods. In untreated livers almost allfoci were stained with the same intensity as the surroundingtissue. When NAF was applied, most of the liver foci showedconsiderably less staining than the non-focal parenchyma inwhich pronounced enzyme induction had occurred. However, thesubpopulation of WBF showed a more heterogeneous pattern ofenzyme expression varying from less to even more than in theadjacent tissue. A similarly broad range of expression of peroxisomalenzymes was found in hepatocellular carcinomas. On average,however, the tumors exhibited less staining and lower activityof peroxisomal ß-oxidation than the surrounding parenchyma.WBF always showed higher rates of DNA synthesis than other focisubtypes and unaltered liver. In     

Fundus-first laparoscopic cholecystectomy

Removal of the gallbladder with commencement of dissection at the fundus is well recognized as a safe technique during difficult open cholecystectomy because it minimizes the risks of damage to the structures in or around Calot's triangle. We report here the routine employment of liver retractors and fundus-first dissection during laparoscopic cholecystectomy (LC) as an alternative to techniques previously described.Retraction of the liver and fundus-first dissection was used in 53 patients who underwent laparoscopic cholecytectomy. There were 16 male and 37 female patients. Seven were operations performed during an acute admission and 20 had moderate or severe adhesions involving the gallbladder. Thirteen patients had a preexisting abdominal incision.The procedure was successful in 52 patients (98%), but in one patient it was converted to open operation because of dense adhesions. Median duration of operation was 90 min (range 35–240 min). There was no mortality and two complications (persistent right upper quadrant pain for 2 weeks after operation and bile leakage from the gallbladder bed).The facility to retract the liver and carry out a fundus-first dissection extends techniques developed for open surgery into the laparoscopic arena. It offers the surgeon the safety and versatility during laparoscopic cholecystectomy that it confers during conventional open surgery.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Nashville, Tennessee, USA, 18–19 April 1994     

The evolution of pathogenic trypanosomes

In the absence of a fossil record, the evolution of protozoa has until recently largely remained a matter for speculation. However, advances in molecular methods and phylogenetic analysis are now allowing interpretation of the "history written in the genes". This review focuses on recent progress in reconstruction of trypanosome phylogeny based on molecular data from ribosomal RNA, the miniexon and protein-coding genes. Sufficient data have now been gathered to demonstrate unequivocally that trypanosomes are monophyletic; the phylogenetic trees derived can serve as a framework to reinterpret the biology, taxonomy and present day distribution of trypanosome species, providing insights into the coevolution of trypanosomes with their vertebrate hosts and vectors. Different methods of dating the divergence of trypanosome lineages give rise to radically different evolutionary scenarios and these are reviewed. In particular, the use of one such biogeographically based approach provides new insights into the coevolution of the pathogens, Trypanosoma brucei and Trypanosoma cruzi, with their human hosts and the history of the diseases with which they are associated.     

Factors associated with analgesic and psychotropic medications use by community-dwelling older people with chronic pain

OBJECTIVE: The present study sought to examine use prevalence and factors associated with use of analgesic and psychotropic medications in community-dwelling older people with chronic non-malignant pain. METHOD: The study group comprised 193 community-dwelling older people with daily chronic non-malignant pain who were selected from a random sample of 1,000 older people in Melbourne. RESULTS: The use prevalence for the study group was 63% for analgesics and 39% for psychotropic medications, which is higher than the general older population without chronic pain (p < 0.00001). More women with chronic pain used analgesics, while psycho-social factors such as problems with sleeping and living at home alone were found to be associated with an increased use of psychotropic medications. CONCLUSION: A high proportion of community-dwelling older people with chronic non-malignant pain use analgesic and psychotropic medications. IMPLICATIONS: These findings provide the basis for further investigation into the level and appropriateness of analgesic and psychotropic medication use by older people with chronic pain.     

Methods for assessing the potential of prebiotics and probiotics

Prebiotics and probiotics are microflora management tools designed to improve human health. Both are dietary materials that fortify components of the gut flora seen as 'beneficial'. Gut flora modulation is an important area of the nutritional sciences, however, it is imperative that reliable methodologies be used to determine efficacy. This review will discuss the current techniques used in prebiotic and probiotic research.     

Chocolate craving and hunger state: implications for the acquisition and expression of appetite and food choice

The importance of hunger state for the acquisition and expression of chocolate craving was investigated. Seventeen chocolate cravers and 12 non-cravers were supplied with chocolate and instructed to eat some twice a day for 14 days. Within each group, subjects were allocated to one of two conditions, hungry- or full-trained. Hungry-trained subjects were asked to eat the chocolate exclusively at least 2 h after last eating; full-trained subjects were asked only to eat the chocolate 15-30 min after eating a meal. A diary was kept to encourage and allow assessment of compliance. At the start and end of the 2 weeks, subjects rated their craving for and anticipated intake of chocolate prior to eating it; then, on initial tasting, pleasantness of the taste was rated. All subjects made these ratings on one day when hungry and on another when full, as defined above. For cravers and non-cravers who ate chocolate exclusively when hungry, chocolate craving increased post-training, but, at least for cravers, only when ratings were made while hungry. For full-trained subjects, chocolate craving decreased post-training, but this decrease did not depend on whether subjects were currently hungry or full. A similar pattern of results was found for anticipated intake and pleasantness of taste, except that pleasantness did not increase in hungry-trained subjects. The results are interpreted with reference to learned control of appetite and in particular to recent findings on incentive learning processes. Craving for chocolate or other foods may be an expression of a strong appetite elicited by hunger that has been acquired by repeated experience of eating the craved food when hungry.     

2,4,6-triarylchalcogenopyrylium dyes related in structure to the antitumor agent AA1 as in vitro sensitizers for the photodynamic therapy of cancer.

Cationic chalcogenopyrylium dyes 2-4 were synthesized in six steps from 4-(dimethylamino)phenylethyne (7), have absorption maxima in methanol of 594, 631, and 672 nm, respectively, and generate singlet oxygen with quantum yields [Phi((1)O(2))] of 0.020, 0.064, and 0.037, respectively. Dyes 2-4 are hydrolytically more stable than other chalcogenopyrylium dyes evaluated previously as sensitizers for photodynamic therapy. At 10 microM final concentration, all dyes 2-4 inhibited cytochrome c oxidase during irradiation of tumor mitochondrial suspensions treated with 10 microM dye. The degree of enzyme inhibition was abated in a reduced oxygen environment and in the presence of imidazole, a singlet oxygen trap. Superoxide dismutase, at a final concentration of 30 U, did not alter the photosensitized inhibition of mitochondrial cytochrome c oxidase by dyes 2-4. These data suggest that singlet oxygen may play a major role in the photosensitized inhibition of mitochondrial cytochrome c oxidase. Irradiation of R3230AC rat mammary adenocarcinoma cells in the presence of dyes 2-4 caused a significant loss in cell viability with thiopyrylium dye 2 displaying the greatest phototoxicity. Initial acute toxicity studies in vivo demonstrate that, at 10 mg/kg, none of the three dyes displayed overt toxicity.