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At least 1,621 records · Page 90Linked to original sources

PubMed1999

Mesenchymal reprogramming of adult human epithelial differentiation.

The objective of this study was to determine whether neonatal rat seminal vesicle mesenchyme (rSVM) can reprogram epithelial differentiation in a fully differentiated adult human bladder epithelium. For this purpose neonatal rSVM was isolated from newborn (0-day) Sprague-Dawley rats, and normal adult human bladder epithelium (hBLE) was isolated from radical cystoprostatectomy specimens to prepare rSVM+hBLE tissue recombinants in vitro. After overnight culture the tissue recombinants were grafted beneath the renal capsule of male athymic rodent hosts and allowed to grow in vivo for 6 months. As controls, rSVM and hBLE were grafted separately and allowed to grow for the same period. Tissue recombinants and control tissue grafts were harvested, and secretions were collected for biochemical studies. Tissues were fixed both for histologic as well as immunohistochemical staining. Neonatal rSVM induced normal adult human bladder urothelium to form glandular structures resembling prostate. The induced prostatic acini were filled with secretions that expressed human prostate-specific secretory proteins. These findings demonstrate that adult human urothelial cells retain a responsiveness to neonatal prostatic mesenchymal inductors. Change in urothelial histodifferentiation was associated with change in functional activity. The ability of the neonatal rat mesenchymal tissues to induce morphologic as well as biochemical changes in normal adult human urothelium provides a basis for human tissue engineering and organ reconstruction.

Adult↗

PubMed1999

Neuroendocrine responses to an emotional stressor: evidence for involvement of the medial but not the central amygdala.

The amygdala plays a pivotal role in the generation of appropriate responses to emotional stimuli. In the case of emotional stressors, these responses include activation of the hypothalamic-pituitary-adrenal (HPA) axis. This effect is generally held to depend upon the central nucleus of the amygdala, but recent evidence suggests a role for the medial nucleus. In the present study, c-fos expression, amygdala lesion and retrograde tracing experiments were performed on adult rats in order to re-evaluate the role of the central as opposed to the medial amygdala in generating neuroendocrine responses to an emotional stressor. Brief restraint (15 min) was used as a representative emotional stressor and was found to elicit c-fos expression much more strongly in the medial than central nucleus of the amygdala; relatively few Fos-positive cells were seen in other amygdala nuclei. Subsequent experiments showed that ibotenic acid lesions of the medial amygdala, but not the central amygdala, greatly reduced restraint-induced activation of cells of the medial paraventricular nucleus, the site of the tuberoinfundibular corticotropin-releasing factor cells that constitute the apex of the HPA axis. Medial amygdala lesions also reduced the activation of supraoptic and paraventricular nucleus oxytocinergic neurosecretory cells that commonly accompanies stress-induced HPA axis activation in rodents. To assess whether the role of the medial amygdala in the control of neuroendocrine cell responses to emotional stress might involve a direct projection to such cells, retrograde tracing of amygdala projections to the paraventricular nucleus was performed in combination with Fos immunolabelling. This showed that although some medial amygdala cells activated by exposure to an emotional stressor project directly to the paraventricular nucleus, the number is very small. These findings provide the first direct evidence that it is the medial rather than the central amygdala that is critical to hypothalamic neuroendocrine cell responses during an emotional response, and also provide the first evidence that the amygdala governs oxytocin as well as HPA axis responses to an emotional stressor.

Amygdala↗

PubMed2001

Effect of viable or dead Lactobacillus casei organisms administered orally to mice on resistance against Trichinella spiralis infection.

The capacity of viable, dead Lactobacillus casei and supernatant from L. casei culture, administered by oral route, to induce resistance in mice against Trichinella spiralis infection was evaluated. The percentage of adult worm reduction in the intestine five days after T. spiralis infection as compared with the worm burden in the control group fluctuated between between 53.1 and 58% in mice treated with viable L. casei, while reductions in animals treated with dead lactobacilli or supernatant from L. casei culture were of 44 and 32.5% respectively. The percentage of larvae per gram of muscle tissue reductions, as compared with controls, obtained 30 days after infection ranged from 48.4 to 70.7% in rodents which ingested viable L. casei compared with the percentage reductions of 65.9 and 24% obtained respectively in mice treated with dead lactobacilli or with L. casei supernatant. The protective response observed in the present study may be explained on the basis of 1) lactobacilli colonization of the intestine, 2) macrophage processing of dead lactobacilli in local immune tissues and presentation of L. casei antigens to Th1 cells which, in turn, produced IL-2 to activate B cells and other T cells.

Administration, Oral↗

PubMed1997

Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis.

Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive to endotoxin liver injury than males. LPS induction of tumor necrosis factor alpha (TNF alpha), the proven affecter of endotoxin liver injury, is no greater in the livers, white adipose tissues, or sera of obese animals than in those of lean controls. Indeed, the lowest serum concentrations of TNF occur in female obese rodents, which exhibit the most endotoxin-induced liver injury. Several cytokines that modulate the biological activity of TNF are regulated abnormally in the livers of obese animals. After exposure to LPS, mRNA of interferon gamma, which sensitizes hepatocytes to TNF toxicity, is overexpressed, and mRNA levels of interleukin 10, a TNF inhibitor, are decreased. The phagocytic activity of liver macrophages and the hepatic expression of a gene encoding a macrophage-specific receptor are also decreased in obesity. This new animal model of obesity-associated liver disease demonstrates that hepatic macrophage dysfunction occurs in obesity and suggests that this might promote steatohepatitis by sensitizing hepatocytes to endotoxin.

Animals↗

PubMed2001

Neonatal mouse model: review of methods and results.

The neonatal mouse model, in various forms, has been used experimentally since 1959 and a large number of chemicals have been tested. The neonatal model is known to be very sensitive for the detection of carcinogens that operate via a genotoxic mode of action. In contrast, it is known not to respond to chemicals that act via epigenetic mechanisms, commonly observed in the two-year carcinogenicity studies. As such, the model has a high sensitivity and specificity in its response. Dose selection for the neonatal model is based on the maximum tolerated or feasible dose. Traditionally, compounds have been tested via the IP route of administration in this model. In some cases, this has limited the amount of material that can be administered because of the low dosing volumes (10 to 20 microL) that can be administered IP. For the ILSI project, the neonatal model was adapted for oral administration, which has the advantages of being the same route for which most pharmaceuticals are administered. In addition, a 10-fold increase in the volume of administration (100 to 200 microL) and the ability to dose drugs in suspension, permits much higher doses to be used as compared to the IP route of administration. The spontaneous tumors in the neonatal model occurred mainly in the liver of male mice and lung of male and female mice with a few tumors observed in the Harderian gland. The positive control, DEN produced a robust, uniform, and reproducible tumor response with the target organs essentially limited to liver and lung. A total of 13 compounds out of the 21 ILSI ACT compounds were evaluated in the neonatal model involving 18 studies with duplicate studies for some compounds. The genotoxic carcinogens including those used as positive controls were clearly positive (cyclophosphamide, diethylnitrosamine, 6-nitrochrysene). The non-genotoxic rodent carcinogens were clearly negative (chlorpromazine, sulfisoxazole, sulfamethoxazole, clofibrate, DEHP, haloperidol, metaproteranol, and phenobarbital). The non-genotoxic human carcinogen (cyclosporin) was clearly negative. The two other human carcinogens phenacetin and DES were negative and interestingly estradiol was negative in one of the two oral studies, but was clearly positive in the other. Considering the mode of action for three of the human carcinogens (DES, cyclosporin and phenacetin), which were negative in this model, the mode of action in humans is likely to be epigenetic. Overall, for the 3 clearly genotoxic chemicals, all were positive. For the 9 clearly non-genotoxic chemicals, all 9 were negative. The two human carcinogens for which genotoxicity may or may not play a role (DES and phenacetin) were negative and estradiol was positive in I of the two oral studies. Overall, the extensive database for compounds tested in the neonatal mouse model would support its use as an alternative model for the assessment of the carcinogenic potential of a chemical. The model responds to chemicals that act via a genotoxic mode of action that represent a greater concern for human cancer risk.

Administration, Oral↗

PubMed1988

The molecular genetics of the incision step in the DNA excision repair process.

This review describes the evolution of research into the genetic basis of how different organisms use the process of excision repair to recognize and remove lesions from their cellular DNA. One particular aspect of excision repair, DNA incision, and how it is controlled at the genetic level in bacteriophage, bacteria, S. cerevisae, D. melanogaster, rodent cells and humans is examined. In phage T4, DNA is incised by a DNA glycosylase-AP endonuclease that is coded for by the denV gene. In E. coli, the products of three genes, uvrA, uvrB and uvrC, are required to form the UVRABC excinuclease that cleaves DNA and releases a fragment 12-13 nucleotides long containing the site of damage. In S. cerevisiae, genes complementing five mutants of the RAD3 epistasis group, rad1, rad2, rad3, rad4 and rad10 have been cloned and analyzed. Rodent cells sensitive to a variety of mutagenic agents and deficient in excision repair are being used in molecular studies to identify and clone human repair genes (e.g. ERCC1) capable of complementing mammalian repair defects. Most studies of the human system, however, have been done with cells isolated from patients suffering from the repair defective, cancer-prone disorder, xeroderma pigmentosum, and these cells are now beginning to be characterized at the molecular level. Studies such as these that provide a greater understanding of the genetic basis of DNA repair should also offer new insights into other cellular processes, including genetic recombination, differentiation, mutagenesis, carcinogenesis and aging.

Animals↗

PubMed2002

Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol.

Indole-3-carbinol (I-3-C) is among the most widely and popularly known antiestrogens. Due to its putative chemopreventive action, I-3-C is being marketed to the general public in health food establishments. Although it has been demonstrated to prevent cancer in animal bioassays, I-3-C also acts as a promoter in the liver and colon. Because of this potential dual biological activity, it is important to investigate both the inhibitory and promotional activities of I-3-C in multi-organ tumorigenesis animal models. 7,12-Dimethylbenz[a]anthracene, aflatoxin B1 and azoxymethane were used to initiate mammary, liver and colon carcinogenesis, respectively in female Sprague-Dawley rats. The rats were fed continuously on a diet containing I-3-C for 25 weeks after initiation. I-3-C treatment was begun one week after the last carcinogen treatment had been administered. I-3-C treatment resulted in a delay in latency of mammary tumor formation, but did not alter tumor incidence or multiplicity among survivors. In the colon, the protocol produced a 40% decrease in aberrant colon crypt foci. However, in the liver, it strongly-induced GST-P foci in carcinogen-treated (a four-fold increase in volume percent foci) and in the vehicle controls (a 69-fold increase). These data support previous findings in other rodent and fish tumor models that I-3-C both inhibits and promotes carcinogenesis. The results of this study clearly demonstrate that I-3-C is not an appropriate chemoprotective agent for human use, in spite of its effects in the breast and colon in this rat animal model.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Optical imaging and electrophysiology of rat barrel cortex. II. Responses to paired-vibrissa deflections.

A study was undertaken to investigate the response of the rodent somatosensory barrel cortex to paired-whisker stimuli. Cortical responses to controlled whisker deflections were recorded by (i) conventional multi-unit extracellular recording within the cytochrome oxidase rich barrels centers, and (ii) intrinsic signal optical imaging, a technique that measures an optical correlate of neuronal activity thought to be related to the deoxygenation of hemoglobin in activated regions. Stimuli were applied to two whiskers in sequence, at temporal separations ranging from 0 to 60 ms. Over intervals of 10-40 ms, the primary effect of paired-whisker stimulation was suppressive. We suggest that paired-whisker inhibition results from the activation of layer IV fast-spike units within the principle whisker's barrel, by excitatory input arriving from a surround-whisker. Paired-whisker stimulation produces inhibition in intrinsic images, because it results in a net reduction in layer II/III and/or layer IV metabolism. Intra-cortical inhibition may serve to convert the sequence of inputs from the whisker array into a barrel cortex magnitude code that can be read by higher cortical areas.

Animals↗

PubMed1987

Effect of exercise training on resting blood pressure and heart rate in adult and aged rats.

To test the hypothesis that advancing age may have an effect on cardiovascular adaptation (resting blood pressure and heart rate) in response to exercise training, we compared adult (4.5 months at start of training) and aged (21.5 months at start of training) male Fischer 344 rats exercised on a rodent treadmill 5 days/week for 9 weeks. Two additional age-matched control groups were similarly handled and placed on the nonmoving treadmill for the same duration. Chronic exercise did not alter blood pressure in the adult group but lowered resting blood pressure in the aged rats during the midportion of the training period. On the other hand, the adult group demonstrated a significant decrease in the resting heart rate from Weeks 3 through 7 during training, whereas the aged group showed no change in resting heart rate during the entire study. These findings suggest that there may exist an age-related difference in the effect of exercise training on basal cardiovascular homeostasis, which is cardioinhibitory in the adult and vasodepressant in the aged.

Adaptation, Physiological↗

PubMed2004

A lazaroid mitigates postresuscitation myocardial dysfunction.

OBJECTIVE: Lazaroids, a series of 21-aminosteroids, reduce free radical mediated injury after ischemia and reperfusion. We hypothesized that the lazaroid U-74389G would minimize postresuscitation myocardial dysfunction and thereby improve neurologically meaningful survival in a rodent model after resuscitation from 8 mins of ventricular fibrillation. DESIGN: Randomized, controlled laboratory study. SETTING: University-affiliated research institute. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was electrically induced in ten anesthetized Sprague-Dawley rats. The lazaroid agent U-74389G in a dose of 1 mg.kg-1 or its vehicle serving as a placebo was injected into the right atrium after 7 mins of untreated ventricular fibrillation. One minute after injection of the compound, precordial compression was begun together with mechanical ventilation and continued for 6 mins before attempted electrical defibrillation. MEASUREMENTS AND MAIN RESULTS: All animals were successfully resuscitated. Postresuscitation cardiac index, left ventricular end-diastolic pressure, the rate of left ventricular pressure increase measured at a left ventricular pressure of 40 mm Hg, and the maximum rate of left ventricular pressure decline were significantly less impaired in lazaroid-treated animals. This contrasted with control animals, which had significantly greater myocardial impairment, greater neurologic deficit, and lesser duration of survival. CONCLUSIONS: The lazaroid compound U-74389G, administered during cardiac arrest, mitigated postresuscitation myocardial dysfunction and improved survival.

Animals↗

PubMed2005

Zidovudine-induced diaphragmatic contractile dysfunction: impact of an antioxidant diet.

OBJECTIVE: Zidovudine (AZT) is a primary drug therapy used to treat HIV-infected individuals. While AZT inhibits replication of HIV, it also induces a drug-specific myopathy resulting in altered muscle mitochondria, increased oxidative stress and muscle contractile dysfunction. The purpose of this study was to assess the impact of an antioxidant diet (high in vitamins C and E) on AZT-mediated diaphragmatic contractile dysfunction in rodents. METHODOLOGY: Adult, Sprague-Dawley rats were assigned to feeding groups: control (CON, n = 9), AZT-treatment (AZT, n = 8), antioxidant diet only (Anti-Ox, n = 6), and AZT + antioxidant diet (AZT + Anti, n = 9). Two costal diaphragm strips were removed from each animal (under surgical anaesthesia) and evaluated for force-frequency relationship, maximal specific tension, and fatigue resistance using an in vitro preparation. RESULTS: Results indicate significant reductions in normalized force production (20-200 Hz), including maximal specific tension, between AZT animals and all other groups. While AZT reduced diaphragm contractility, the addition of an antioxidant diet eliminated this decrease. CONCLUSION: These data suggest that an increase in oxidative stress mediated by AZT may contribute to AZT-induced muscle contractile dysfunction, and that antioxidant vitamin supplementation may help ameliorate this effect.

Animals↗

PubMed2005

Molecular and neurochemical evidence for the biosynthesis of dehydroepiandrosterone in the adult rat spinal cord.

Various studies have indicated that exogenous dehydroepiandrosterone (DHEA) modulates several mechanisms in the CNS of rodents. As adult rodent glands do not secrete significant amounts of DHEA, its role as endogenous modulator of the CNS remains possible only if DHEA is produced by nerve cells. Therefore, the last decade has been marked by diverse unsuccessful investigations aiming to demonstrate the activity of cytochrome P450c17 (P450c17), the key DHEA-synthesizing enzyme, in adult rodent CNS. Here, we combined molecular, anatomical, cellular and neurochemical approaches to provide the first demonstration of the existence of P450c17 and bioactivity in adult rat spinal cord (SC). Real-time RT-PCR revealed P450c17 gene expression in all SC segments. Western blot analyses allowed identification of a specific P450c17 protein in the SC and immunohistochemical studies localized P450c17 in neurones and glial cells. Pulse-chase experiments combined with HPLC and radioactive steroid detection showed that SC slices converted [3H]pregnenolone into [3H]DHEA, a conversion markedly reduced by ketoconazole, a P450c17 inhibitor. Kinetics studies revealed accumulation of [3H]DHEA newly synthesized by SC slices in the incubation medium as its amount declined slowly. This first cellular mapping of an active P450c17 in adult rodent SC suggests that endogenous DHEA synthesized in spinal neural networks may control various spinally-mediated activities.

Animals↗

PubMed1997

An introduction to the genetics of normal and defective hearing.

The recent rapid development of molecular biology techniques applied to the genetics of normal and defective hearing shed a new light on old questions regarding hearing and deafness. Genes are DNA sequences that determine characteristics, normally by specifying the sequence of aminoacids in a protein. The majority of genes is located in the chromosomes (human chromosomes have perhaps 80,000 pairs of genes). In addition there are 37 mithochondrial genes which are inherited only from the mother. One method used to identify candidate genes based on their function or pattern of tissue expression involves the construction of cDNA libraries from the target organ or tissue, in this case from the cochlea. The construction and characterization of cochlear cDNA libraries from humans and other species provide an important resource for rapid identification of cochlear genes involved in normal hearing and hearing disorders. Studies of the molecular genetics of the inner ear are hampered by the relative inaccessibility of the cochlea, by the limited number of cochlear and vestibular cells, and by our inability to maintain many of these cell types in long-term cultures. Several rodent inner-ear cDNA libraries and a human foetal cochlear cDNA library have already been constructed. Human and rodent cochlea-subtracted cDNA libraries are very useful for identifying genes controlling the development and maintenance of hearing. cDNA libraries constructed at different stages of development, and subtracted from each other, could be instrumental in identifying genes important at each stage of cochlear development. In addition, these libraries have the potential of fostering the identification of other proteins unique to the cochlea and will contribute to the identification, characterization, and functional analysis of these cochlea-specific proteins. Another important application of cDNA libraries is in identifying hearing-loss genes. Once the candidate gene for a given type of hearing loss is cloned and decoded, the structure of its protein product can be determined. This will provide insights into the biochemical function of the gene product in normal cochlear tissue, and will show why the genetic mutation results in hearing loss, that is, the recent identification of the myosin VIIa gene in Usher type IB. In addition, through the use of homologous recombination and transgenic technology, in vivo mouse models of inner-ear genetic disorders can be created. To date, 350 different genetic conditions associated with hearing impairment have been described, and during the past five years several of the genes involved in these form have already been mapped and identified.

Animals↗

PubMed1980

Excitability of female rat central gray cells with medullary projections: changes produced by hypothalamic stimulation and estrogen treatment.

1. Effects of estrogen on the excitability of 74 neurons in the central gray of the mesencephalon (CG) antidromically identified from the medulla were investigated extracellularly in female rats under urethan anesthesia. 2. The mean rate of spontaneous discharge of the identified CG cells was higher in estrogen-treated (2.9 Hz) than in untreated ovariectomized rats (0.3 Hz). In the estrogen-treated preparations, 18.5% of the identified cells had discharge rates exceeding 3.0 Hz, while none were found in this range in the untreated animals. 3. Two types of positive-negative biphasic antidromic spike potentials were distinguished. In one ("fast") the initial positive deflection was completed within 500-700 microseconds, while it took longer than 1 ms in the other ("slow" spikes). Slow spikes had a notch in the rising phase of their initial positive deflection, at which antidromic propagation was often blocked. Mean antidromic spike latency for the fast spikes was 6.8 ms, while the value for the slow spikes was 14.7 ms. 4. In slow spikes, the percentage of successful antidromic spike invasions into the somatodendritic complex remained constant for a long time when the response was elicited by repetitive antidromic stimuli at 0.5 Hz. Antidromic propagation into the somatodendritic complex occurred more frequently in the slow spikes recorded from estrogen-treated preparations (94.2%) than in those of ovariectomized untreated animals (55.7%). 5. Electrical stimulation of the preoptic area (POA) reduced the frequency of successful antidromic propagation into the somatodendritic complex. Stimulation of the ventromedial nucleus of the hypothalamus (VMN) increased it. Conversely, electrolytic lesion of the POA facilitated, while VMN lesion reduced antidromic spike invasion. 6. Thus, excitability of some neurons in the CG is facilitated by estrogen. Similar effects of VMN stimulation and POA lesion suggest that the estrogenic effect could be mediated by these structures. The pattern of effects on these CG neurons is that required for their control of lordosis behavior, an estrogen-dependent postural reflex in female rodents. These cells may modulate medullary reticulospinal cells, which in turn govern the reflex.

Animals↗

PubMed2000

Programmed cell death, proliferating cell nuclear antigen and p53 expression in mouse colon mucosa during diet-induced tumorigenesis.

Western-style diets (WDs) trigger and sustain the early phases of tumorigenesis in mouse colon, and when continued throughout the life span lead to the development of dysplastic crypts. In order to evaluate the roles both of cell proliferation and programmed cell death (PCD) in WD-induced tumorigenesis, immunohistochemical detection of proliferating nuclear antigen (PCNA), in situ end labeling (TUNEL) of DNA breaks, and p53 protein were carried out in mouse colonic mucosa during prolonged feeding of two WDs. PCNA Labeling Index of colonic crypts was significantly higher in WD-treated animals than in controls only at the beginning of the nutritional study, the gap rapidly bridged by increased cell proliferation spontaneously occurring in the colonic mucosa during aging. A transient early homeostatic activation of PCD at the base of the crypt also was observed in WD groups. No changes in PCD were seen in the upper third of the crypt or in surface epithelium throughout the study, indicating that PCD in that colonic crypt segment produces a constant flux of cell loss, uninfluenced by homeostatic fluctuations. A major finding was an irreversible, progressive, age-related decline of PCD at the crypt base in both control and treated animals that occurred during the second half of the rodents' life span. p53 protein was not immunohistochemically detected, suggesting that neither overexpression of wild-type nor mutated forms of the protein are involved in the above mentioned changes.

Animals↗

PubMed1994

Localization of the CAMKG gene encoding gamma isoforms of multifunctional calcium/calmodulin-dependent protein kinase (CaM kinase) to human chromosome 10 band q22 and mouse chromosome 14.

Multifunctional calcium/calmodulin-dependent protein kinase (CaM kinase) is an enzyme mediating calcium-dependent signal transduction pathways. CaM kinase exists in a variety of isoforms, each with a distinct tissue-specific expression pattern, that enables the kinase to regulate multiple functions in mammalian systems. Here we report the chromosomal localization of the previously cloned human gamma-CaM kinase gene (CAMKG). By using a mapping panel of human x Chinese hamster somatic cell hybrid lines and fluorescence in situ hybridization, we have assigned human CAMKG to chromosome 10q22. We have partially cloned the murine gamma-CaM kinase gene and mapped it Camkg to mouse chromosome 14 by analyzing a panel of mouse x rodent somatic cell hybrid lines. A recessive gene, asa, implicated in the control of autoimmune response, is located within the predicted region for Camkg.

Animals↗

PubMedDate not supplied

Aspirin and neoplasia of the digestive tract: is there a chemopreventive effect?

There has been much recent interest in the hypothesis that aspirin and other non-steroidal anti-inflammatory agents (NSAIDs) protect against gastrointestinal, particularly colorectal, carcinoma. Three lines of evidence support this hypothesis: First, NSAIDs inhibit the growth of colorecal neoplasms in laboratory rodents. Epidemiological studies in humans also suggest a protective effect. Three case control and two cohort studies have examined the relation between aspirin use and large bowel neoplasia, and four of these five studies found a risk reduction for either incidence or mortality of about 50% in regular users of aspirin. Finally, two small intervention studies in patients with familial polyposis showed a short-term reduction in polyp formation in patients treated with NSAIDs. In contrast, a large randomized trial of aspirin in human subjects detected no reduction in incidence of colorectal carcinoma in those assigned to aspirin compared to placebo. Colorectal cancer is common and an effective primary prevention strategy could lead to significant public health benefits. Further research into the potential of aspirin to achieve this is keenly awaited. It is, however, premature to recommend it specifically for this purpose on the basis of current evidence, given the known adverse effects of aspirin and related compounds, especially on the gastrointestinal tract.

Adenomatous Polyposis Coli↗

PubMed1994

In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

The present study evaluated the involvement of glucose transport and phosphorylation in glucose-stimulated insulin release from pancreatic islets. Using quantitative histochemical techniques, we investigated basal islet glucose content, islet glucose uptake in situ during acute extreme experimental hyperglycemia, and islet glucokinase activity in several animal models of diabetes and obesity. The basal islet glucose content in anaesthetized diabetic or obese rodents was either the same or higher than that in their relevant controls. The rate of glucose uptake of islet tissue in these animals after an i.v. glucose injection was different. The db+/db+ mouse and the obese Zucker rat exhibited significantly reduced islet glucose uptake rates. RIP-cHras transgenic mice, BHE/cdb rats and partially pancreatectomized rats showed normal islet glucose uptake rates. The activity of islet glucokinase was increased to a different degree related to the blood glucose level. All five animal models of diabetes or obesity exhibited either a delay or a reduction of insulin release in response to supra maximal glucose stimulation. Our results indicate that the impairment of glucose-induced insulin release in diabetes is not consistently associated with a reduction of islet glucose uptake nor a change of glucokinase activity.

Animals↗