Enhanced pancreatic and skin tumorigenesis in cabbage-fed hamsters and mice

Studies were conduded to evaluate the ability of dietary driedcabbage supplements to inhibit pancreatic carcinogenesis inhamsters and skin tumorigenesis in mice. Pancreatic cancer wasinduced by treatment with 40 mg/kg body wt N-nitrosobis-(2oxopropyl)amine(BOP). Cabbage was fed from before carcinogen treatment in lowfat diet and, beginning 1 week after BOP treatment, cabbagewas given in low fat and high fat diets in comparison with therespective non-cabbage containing diets. Dried cabbage was incorporatedat 9 and 11% levels into the low and high fat diets. Feedingcabbage in the high fat diet elevated the yield of BOP-inducedpancreatic ductular cardnoma (1.6 carcinomas/effedive animal)in comparison with that observed in hamsters fed cabbage ina low fat diet or in those given a high fat diet without cabbage, 0.6–0.8 carcinomaa/effedive animal (P 0.05). Furthermore,the incidence of BOP-induced gall bladder adenocadnomm was elevatedin cabbage-fed hamsters irrespedve of dietary fat intake. Effetsof dietary fat and cabbage on food consumption, body weight,and serum T₃ and T₄ values are described. Skin tumorigenesiswas induced in SENCAR mice by 10 nmd 7,12 dlmethylbenz[a]anthracene(DMBA) and promoted beginning 1 week later with twice weeklyapplications of 2 µg 12-O-tetradecanoyl-13-phorbol acetate(TPA). Dried cabbage was incorporated into AIN semi-purifieddiets from before DMBA treatment and throughout TPA treatment.Skin papilloma yield was elevated in DMBA-initiated TPA-promotedmice that were fed diets containing 10% cabbage. Mice fed cabbagedeveloped an average of 8.45 papillomas per mouse following22 weeks of promotion while mice given control diet developed7.25 papillomas per mouse (P < 0.001). Cabbage feeding didnot influence survival, food consumption or body weight of themice. These results suggest the need for further research onthe use of cabbage as a chemopreventive measure.     

Probing peripheral and central cholinergic system responses

OBJECTIVE: The pharmacological response to drugs that act on the cholinergic system of the iris has been used to predict deficits in central cholinergic functioning due to diseases such as Alzheimer's disease, yet correlations between central and peripheral responses have not been properly studied. This study assessed the effect of normal aging on (1) the tropicamide-induced increase in pupil diameter, and (2) the reversal of this effect with pilocarpine. Scopolamine was used as a positive control to detect age-dependent changes in central cholinergic functioning in the elderly. DESIGN: Randomized double-blind controlled trial. PARTICIPANTS: Ten healthy elderly (mean age 70) and 9 young (mean age 33) volunteers. INTERVENTIONS: Pupil diameter was monitored using a computerized infrared pupillometer over 4 hours. The study involved 4 sessions. In 1 session, tropicamide (20 microL, 0.01%) was administered to one eye and placebo to the other. In another session, tropicamide (20 microL, 0.01%) was administered to both eyes, followed 23 minutes later by the application of pilocarpine (20 microL, 0.1%) to one eye and placebo to the other. All eye drops were given in a randomized order. In 2 separate sessions, a single dose of scopolamine (0.5 mg, intravenously) or placebo was administered, and the effects on word recall were measured using the Buschke Selective Reminding Test over 2 hours. OUTCOME MEASURES: Pupil size at time points after administration of tropicamide and pilocarpine; scopolamine-induced impairment in word recall. RESULTS: There was no significant difference between elderly and young volunteers in pupillary response to tropicamide at any time point (p > 0.05). The elderly group had a significantly greater pilocarpine-induced net decrease in pupil size 85, 125, 165 and 215 minutes after administration, compared with the young group (p < 0.05). Compared with the young group, the elderly group had greater scopolamine-induced impairment in word recall 60, 90 and 120 minutes after administration (p < 0.05). CONCLUSION: There is an age-related pupillary response to pilocarpine that is not found with tropicamide. Thus, pilocarpine may be useful to assess variations in central cholinergic function in elderly patients.     

Identifying inadequate response among patients with ankylosing spondylitis and psoriatic arthritis prescribed advanced therapy in a real-world,commercially insured adult population in the USA

Clinical Rheumatology - This study aimed to assess treatment patterns and frequency of inadequate response associated with advanced therapy initiation among patients with ankylosing spondylitis...     

Can foods with added soya-protein or fish-oil reduce risk factors for coronary disease? A factorial randomised controlled trial

BACKGROUND AND AIMS: To develop functional foods which are capable of reducing key risk factors for coronary heart disease in an at risk population. The specific hypothesis tested here was that providing bread, cracker biscuits and snack bars fortified with DHA (long-chain omega 3) and soya-protein would havd a positive impact on cholesterol and blood pressure. METHODS AND RESULTS: A pragmatic, double-blind, factorial placebo-controlled randomised trial recruiting 213 middle-aged men and women with untreated elevated total cholesterol or blood pressure. The factors examined were the effect of giving supplies of bread, cereal bars and cracker biscuits fortified with 2 g fish oils (DHA, 22: 6n-3), or 25 g soya-protein (containing 50 mg of isoflavonoids) for five weeks. Primary and secondary outcomes included total, low-density and high-density cholesterol (HDL-C), and systolic and diastolic blood pressure. Compliance was assessed using biomarkers and food intake histories. DHA enriched foods increased HDL-C by 6.0% (95% CI 2.5%, 9.6%) but had no effect on total or low-density cholesterol or blood pressure. Overall, soya-protein did not influence any of the outcomes assessed. However, in women only, soya-protein increased systolic blood pressure by 5.9% (95% CI 1.73, 9.9%). CONCLUSIONS: Adding DHA (fish-oils) to staple foods might supplement existing methods to help reduce CVD morbidity and mortality. However, these findings highlight the importance of ensuring that functional foods do not present any harms to particular subgroups within a general population, if they are to be made freely available to consumers. This latter point requires further attention by the research community in relation to soya-protein.     

Increase in p53 protein half-life in mouse keratinocytes following UV-B irradiation

Exposure of mammalian cells to UV radiation and other DNA-damagingagents triggers a response known as the UV response. This inductionresponse involves a large number of genes including c-jun, cell-cycleregulatory proteins, specific repair enzymes, and the tumorsuppressor gene p53. Altered expression of these genes followingDNA damage is hypothesized to result in G₁ arrest, thereby allowingcells to repair DNA damage prior to cell division. In the presentstudy, we investigated expression of the p53 gene in mouse keratinocytecell line 308 after exposure to UV-B light at a biologicallyrelevant dose. Irradiation of 308 cells with 40 J/m² UV-B resultedin a 4- to 10-fold induction in the level of p53 protein, peakingat 5 h post-irradiation. Northern blot analysis of RNA fromUV-B Irradiated cells showed no change in the steady-state levelof p53 mRNA following irradiation. However, the half-life ofp53 protein in UV-B irradiated 308 cells was extended     

Dietary energy restriction-induced modulation of protein kinase C ζ isozyme in the hamster pancreas

Dietary restriction in experimental animals enhances life span, delays disease, inhibits immunological perturbations, and ameliorates cancer. Protein kinase C(a) isozymes mediate signals generated by hormones, growth factors, and neurotransmitters for cell proliferation and differentiation. The results of our study showed that a C-terminally directed anti-PKC ζ antibody detected an 81–kDa band in the pancreases of control and energy-restricted hamsters. Syrian golden hamsters were fed energy-restricted diets formulated such that the hamsters received 90%(10% energy restriction(a) ), 80%(20% ER), or 60%(40% ER) of the total energy consumed by control hamsters, with the energy reduced proportionally from fat and carbohydrate. ER decreased PKC ζ isozyme levels by 40–75% in hamsters fed 10, 20, and 40% ER diets for 8 wk. PKC ζ isozyme expression was decreased by 75–80% in hamsters fed ER diets for 15 wk. Although ER caused significant decreases in PKC ζ isozyme levels compared with those of control hamsters at both time points, the relative differences in PKC ζ levels between the dietary ER groups(10, 20, and 40%) were small and not significant. A significant decrease in the body weights of ER animals compared with those of controls was observed at both time points. No differences in tomato lectin and phytohemagglutinin reactivity were observed between control animals and animals fed 10, 20, and 40% ER diets. Furthermore, the cellular expression of PKC ζ in the hamster pancreas did not differ among hamsters fed the various ER diets. These observations may be important for understanding not only the role of dietary ER in pancreatic cancers but also PKC ζ signal transduction mechanisms in normal pancreatic physiology.© 1995 Wiley-Liss, Inc     

Intracellularly recorded responses of neurons of the motor cortex of awake cats to presentations of Pavlovian conditioned and unconditioned stimuli

The electrical responses to a conditioned stimulus (click CS) and an unconditioned stimulus (glabella tap US) were studied in single units of the pericruciate cortex of awake cats. There has been no previous direct, in vivo characterization of the intracellular effects in cortical neurons of a CS and US used for associative Pavlovian conditioning. Earlier studies showed that ablation of the pericruciate cortex prevented the development of short latency blink CRs produced by associative pairing of these stimuli. Both the CS and the US produced depolarizing EPSPs and increases in spike discharge in intracellularly recorded units. The magnitude of the EPSPs was greater in response to the tap US than to the click CS, and the degree of unit discharge in response to the tap US was greater than that to the click CS. The onset latencies of the spike responses were distributed in three ranges. For click CS the ranges were 6-15, 20-35 and 40-85 ms. For tap US the ranges were 6-25, 30-45 and 50-85 ms. An additional response was observed in the period 0.5-6.0 ms after tap onset. It was thought to be elicited mechanically by vibration of the electrode tip following tap delivery. Pentobarbital anesthesia abolished the unconditioned motor response to tap, but failed to abolish the neuronal responses in any of the latency ranges, suggesting that the responses were not produced by feedback from the movement. Both the CS and the US are needed for the development of blink conditioning, and are distinguished behaviorally by the US producing an unconditioned motor response whose form resembles that of the conditioned response which develops after the stimuli are paired. Both the click CS and the tap US also produced hyperpolarizing IPSPs. Injection of steady, hyperpolarizing current disclosed two types of IPSPs in response to the tap US. One reversed with hyperpolarization; the other increased in magnitude with hyperpolarization. The magnitude of inhibition, measured by reduced discharge, was greater in response to the click CS than to the tap US. We conclude that the major differences between effects of this CS and US on cells of the motor cortex of cats are that the CS elicits less activity than the US and has a larger inhibiting effect. The US elicits greater depolarization than does the CS, as well as an initial discharge component of greater magnitude and longer duration.     

Who is watching over me?--was the public's perception of the anaesthetist changed by National Anaesthesia Day?

The aim of National Anaesthesia Day on 25 May 2000 was to inform the public about the role and training of anaesthetists. We carried out two surveys of patients attending Derriford Hospital, Plymouth to assess the local impact of National Anaesthesia Day and to assess the public's expectation of the preoperative visit. The first survey was held one month prior to National Anaesthesia Day and was completed by 93 patients. The second survey was held immediately following National Anaesthesia Day and was completed by 70 patients. Thirty five percent of the patients surveyed were unaware that anaesthetists were medically qualified. This result was not altered by National Anaesthesia Day despite a local information campaign. Moreover, knowledge about our role and training was only marginally improved from 1978. The majority of patients expected to see their anaesthetist preoperatively for less than 10 minutes and would not be concerned if they had not been seen one hour before surgery. Style of clothing was unimportant; few preferred a white coat but name badges were desirable. We conclude that the level of ignorance about our profession has not changed since 1978 and the impact of National Anaesthesia Day was not significant. This may be as a result of the anaesthetist's portrayal on television, which is known to be an important source of public information on other areas of medicine. If these statistics are to change in the next 22 years new methods of public education need to be found.     

Comparative studies on the effects of semipurified and commercial diet on longevity and spontaneous and induced lesions in the Syrian golden hamster

Syrian golden hamsters were fed a semipurified or commercial diet from weaning throughout life. Bis(2-oxopropyl)nitrosamine (BOP) was administered at 8 weeks of age (10 mg/kg body wt, sc). Longevity was improved by 26% and 36% increases in the mean life-spans of male and female hamsters, respectively, fed the semipurified diets. Carcinogen treatment did not alter survival. The age-adjusted occurrence rates of pancreatic ductular proliferation, carcinomas, adenomas, and common duct polyps were higher in hamsters fed commercial diet; this indicates an earlier onset of these BOP-induced lesions in hamsters fed this diet. However, their overall incidences were generally similar when the two diet groups were compared. Acinar cell nodules were observed only in hamsters fed semipurified diets and were elevated in BOP-treated females. The onset of pancreatic ductular proliferation and adenomas, bile duct proliferation, parathyroid hyperplasia, and common duct papillary hyperplasia was earlier in females than in male hamsters, especially in groups fed commercial ration. Generalized vascular calcification was observed at an elevated rate and reached a higher overall incidence in hamsters fed commercial ration. The age-adjusted rate of amyloidosis was high in female hamsters and elevated in groups that consumed the commercial ration. In addition, colitis and islet cell hyperplasia occurred more often and earlier in hamsters fed commercial ration, but gallbladder stones occurred most in animals fed semipurified diet. This paper discusses the possible association between these and other observed lesions and survival.