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Dietary docosahexaenoic acid levels influence the outcome of arabinosylcytosine chemotherapy in L1210 leukemic mice.

The purpose of this study was to investigate whether dietary supplementation with the n-3 fatty acid docosahexaenoic acid (DHA) in combination with arabinosylcytosine (AraC) chemotherapy could prolong the life expectancy of mice bearing L1210 leukemia. The four control diets included rodent chow, a diet containing 5% of a blended oil mimicking the fatty acid composition of rodent chow, and diets containing 5% or 10% fat with safflower oil as the main oil source. The two DHA-supplemented diets provided 1.5% or 3.5% DHA and 5% or 10% total fat, respectively. After tumor cell inoculation, mice were treated with AraC for 10 days. Mice fed the 5% safflower oil diet (30.1 -/+ 4.1 days), but not those fed the 10% safflower oil diet, survived longer than the chow-fed animals (22.1 -/+ 3.1 days, P = 0.05). The 1.5%-/+ DHA diet (average intake 1.8 g DHA/kg/day) was associated with a longer life span (33.3 -/+ 3.4 days, P < 0.01 vs. chow-fed) and no incidence of death due to drug toxicity. Further increasing DHA intake (4.5 g DHA/kg/day) resulted in shortened survival time (26.5 -/+ 2.0 days), increased circulating tumor cell burden, and lowered red blood cell concentrations. These data suggest that a modest level of dietary DHA or linoleic acid supplementation may improve the antineoplastic efficacy of AraC. However, overconsumption of DHA reverses the beneficial effect of DHA intake on drug sensitivity.

Animals↗

Evaluation of a nematode (Capillaria hepatica Bancroft, 1893) as a control agent for populations of house mice (Mus musculus domesticus Schwartz and Schwartz, 1943).

Sudden, large-scale infestations of house mice (Mus musculus domesticus) occur irregularly in the cereal-growing regions of Australia, resulting in substantial economic losses. Mathematical modelling has been used to evaluate the use of the liver nematode Capillaria hepatica as a potential agent for the biological control of mouse populations. The models suggest that C. hepatica is unlikely to be successful as a single-release control agent: instead, the parasite would need to be released when it becomes apparent that an outbreak is likely. Stage-structured models, including time delays and seasonal mouse demographic parameters, suggest that the parasite may be successful as a control agent, provided it can be introduced into the mouse population at least one year before an outbreak occurs. The optimum time for introduction is in summer or autumn. Some generalisations of this work are discussed. A parasite which affects fecundity alone is unlikely to be a good control agent, because it will destabilize the host population. Macroparasites may be unable to spread sufficiently rapidly to control sudden rises in vertebrate populations.

Animals↗

Parasites associated with pork and pork products.

Three parasites pose a public health risk from the ingestion of raw or undercooked pork, namely: Trichinella spiralis, Taenia solium and Toxoplasma gondii. Inspection procedures, when practised according to prescribed methods, are effective in eliminating the majority of risks from T. spiralis and T. solium. No suitable methods for the post-slaughter detection of T. gondii are available. All three parasites are inactivated by various methods of cooking, freezing and curing; some information is also available on inactivation by irradiation. Good production practices, including a high level of sanitation, rodent and cat control on farms, can prevent opportunities for exposure of pigs to these parasites. Alternatively, meat inspection, proper commercial processing and adherence to guidelines for in-home preparation of meat are effective methods for reduction of risks for human exposure.

Animals↗

Murine typhus: forgotten but not gone.

An occasional patient presents the classical symptoms of a disease that has become uncommon. Typhus is an example of such a disease, since it is now well contained through control of its rodent reservoir. It is readily treated with tetracycline or one of its long-acting analogues, doxycycline or minocycline. Because typhus is infrequently encountered, the physician may not initially include it in his differential diagnosis. Our case serves as a remainder that with the increasingly frequent movement of persons from one geographic area to another, the uncommon rickettsial infection, murine typhus, should continue to be in the differential of a febrile patient. Furthermore, our case underscores the importance of including typhus in the differential of typhoid fever.

Acute Disease↗

Methods for control of tick vectors of Lyme borreliosis.

During the IVth International Conference on Lyme Borreliosis in Stockholm, 1990, a workshop on control of Lyme disease vectors briefly reviewed: basic ecological principles for tick control; biocontrol of ticks; chemical control, including the use of repellents and use of permethrin-treated rodent nest material; tick control by habitat modification; and reduction of tick host availability. It was concluded that, although much research work remains, Lyme borreliosis is to a large extent a preventable infection. Avoidance of heavily tick-infested areas, personal protection using proper clothing, and prompt removal of attached ticks remain the most effective protective measures. Many other prophylactic measures are available and could be efficiently integrated into schemes to reduce the abundance of vectors. However, since the ecology of the infection varies greatly between different localities it may be necessary to apply different combinations of control methods in different endemic regions.

Animals↗

Isolation of a complementary DNA encoding the catalytic subunit of protein kinase A and studies on the expression of this sequence in rat hepatomas and regenerating liver.

A complementary DNA (cDNA) clone (B4) encoding the catalytic subunit of a cAMP-dependent protein kinase (PKAc) was isolated from a lambda gt10 rat brain cDNA library, using a synthetic oligonucleotide probe whose sequence was based on the known amino acid sequence of a bovine cardiac PKAc. Sequence analysis of this clone revealed a region of 1002 nucleotides which encodes a protein that is 92% homologous to amino acids 17-350 of the bovine cardiac PKAc protein. This clone lacks coding sequences for amino acids 1-16 of the latter protein. Nevertheless, it provided a useful probe to analyze expression of the related gene in a variety of systems. Northern blot analyses using a 32P-labeled probe prepared from a 0.6-kilobase PstI fragment of clone B4 revealed an abundant 4.6-kilobase band in rat brain RNA and lesser amounts of this 4.6-kilobase RNA in rat heart and liver. A 4.6-kilobase RNA was also detected in RNA samples obtained from mouse fibroblasts. This probe also detected homologous RNA in a variety of nonrodent species. In subsequent experiments, this cDNA was used as a probe to elucidate the role of PKAc in post-surgical hepatic regeneration and diethylnitrosamine-induced hepatomas in the rat. These experiments revealed that, following partial hepatectomy, PKAc mRNA is decreased 3-fold by 12 h, returning to normal by 72 h; hepatomas showed no consistent pattern of change in PKAc mRNA levels as compared to controls. Our results indicate that this cDNA encodes an isoform of PKAc which is distinct from PKAc-alpha isolated by Uhler et al. (Proc. Natl. Acad. Sci. USA, 83: 1300-1304, 1986) but highly homologous to PKAc-beta isolated by Showers and Maurer (J. Biol. Chem., 261: 16288-16291, 1986), that depression of cAMP-dependent protein phosphorylation may be an important mechanism in the regeneration of mature rat liver but is not a consistent alteration in chemically induced hepatoma, and that this cDNA is useful as a probe for the study of the role of PKAc gene expression in growth control, particularly in rodent species.

Amino Acid Sequence↗

Normal patterns of melatonin levels in the pineal gland and body fluids of humans and experimental animals.

The normal 24 hours patterns of melatonin were described in experimental animals and man. The rhythms are generated by neuronal activity originating in the suprachiasmatic nuclei of the hypothalamus; the activity of these nuclei are synchronized by the prevailing light:dark environment as perceived by the retinas. As a consequence of this synchronization, pineal melatonin levels are always high at night and low during the day, irrespective of whether the animal being studied is nocturnally or diurnally active. The rhythmic production of melatonin in the pineal gland is interrupted by the exposure of animals, or man, to light during the normal dark period. Several factors may change the 24 hours pattern of melatonin production. Because daylength changes throughout the year there are seasonal effects on the melatonin rhythm. Also, age is a major factor in determining the ability of the pineal gland to metabolize serotonin to melatonin. In advanced age pineal melatonin production is severely limited in both the human and in experimental animals. A variety of endocrine manipulations have been tested in terms of their impact on the ability of the pineal to produce melatonin. The majority of these have been rather innocuous although hypophysectomy does significantly curtail the synthesis of melatonin. To date, melatonin cycles have been usually described in rodents maintained under controlled environmental conditions in the laboratory; it can only be assumed that these rhythms are similar in animals in their natural habitat.

Aging↗

Endrin toxicosis in a cat.

Endrin toxicosis was believed responsible for the sudden death of a cat. Stomach contents contained bird remains, and chemical analysis revealed 233 micrograms of endrin/g. The cat's owner had been using an avicide on the premises just before the cat's death. Endrin is an effective pesticide for control of insects, rodents, and birds. It poses a problem with secondary poisoning in other animals.

Animals↗

Is there a sympathetic regulation of the efficiency of energy utilization?

Brown adipose tissue, a well known effector of regulatory thermogenesis found in mammals, is unique in its ability to steadily increase its heat production several fold for very long periods of time. It constitutes a shunt of energy flow between food intake and heat dissipation, it is activated through its sympathetic nerve supply. There are evidence in the rat, that brown adipose tissue is activated following overfeeding, thus decreasing food efficiency and determining resistance to obesity. Genetically obese (ob/ob) mice fed and kept at 22 degrees C lack the possibility of activating their brown fat energy shunt; they are known to be poorly resistant to cold stress despite their large insulation. This is taken as a further circumstantial evidence of an overlap in thermal and food efficiency regulatory systems in rodents through sympathetically controlled brown fast as a common effector.

Adipose Tissue, Brown↗

DNA fingerprinting for genetic monitoring of inbred laboratory rats and mice.

DNA fingerprinting using a nonisotopically labeled minisatellite probe provided a valuable technique for genetic monitoring/quality control of laboratory rodents. Each of 12 inbred rat strains had a unique fingerprint pattern, and colonies separated for over 20 years had identical or nearly identical patterns. Strain LOU/Iap, which is known to have been genetically contaminated in the past, was clearly different from strain LOU/CN, supporting previous findings of studies using biochemical markers. Inbred strains of mice were also found to differ from each other. The F1 hybrid between C57BL/6 and CBA/Ca could not be distinguished from C57BL/6 by using DNA fingerprints, although they could be distinguished by using biochemical markers. Some congenic strains differed from their inbred partner. A suspected genetic contamination of MRL/Mp-lpr mice could not be detected in a sample of the breeding colony by using biochemical markers; however, DNA fingerprints from the suspect animals clearly demonstrated genetic segregation. DNA fingerprinting will be of particular value in investigating suspected problems as only a small sample of fresh, frozen, or ethanol-preserved tissue is needed. Thus, the actual suspect animals can be studied, rather than samples from a breeding colony from which contaminated animals may already have been eliminated.

Animals↗

EM changes and other toxic effects of firemaster BP-6 (polybrominated biphenyls) in the mouse.

Groups of Swiss ICR mice were fed 1000 ppm polybrominated biphenyls (FireMaster BP-6) in rodent chow for 4, 8, 11, and 14 days. Control groups were fed standard rodent chow without FireMaster BP-6. Animals were killed at the end of each feeding period and the livers examined by electron microscopy. EM changes noted were progressive increase in size of hepatocytes, a decrease in rough endoplasmic reticulum, a marked increase in smooth endoplasmic reticulum, mitochondrial degeneration, increased lysosomes, and a decrease in glycogen. In addition, there was increasing proliferation of microvilli in bile canaliculi with increasing feeding times. A group of mice fed 1000 ppm FireMaster BP-6 in rodent chow for 11 days had livers with a mean of 13.93% of total body weight as compared with 6.49% for the control group (P=0.02). Tissue distribution following ingestion of 100 ppm FireMaster BP-6 for 14 days was studied. Twelve weeks post-feeding, the tissue concentrations of hexabromobiphenyl in order of highest concentration to lowest were as follows: perithymic fat, perirenal fat, adrenal glands, thymus gland, liver and stomach.

Animal Feed↗

Development of a fluorogenic RT-PCR assay (TaqMan) for the detection of Hendra virus.

A rapid and sensitive one-tube RT-PCR assay using a fluorogenic (TaqMan) probe was developed to improve the diagnosis of Hendra virus (HeV) infection. The TaqMan assay was developed to rapidly and specifically identify Hendra virus. The sensitivity of the new TaqMan-based PCR assay compared favourably with conventional RT-PCR. The major advantage of the TaqMan-based assay was the speed of diagnosis with results available within minutes of completing the PCR, and within 4 h of receiving the specimen. This test greatly reduces the chance of false positives through the elimination of second-round PCR and the requirement for agarose gel. Recombinant primer controls consisting of the Hendra virus primer sequence flanking a rodent GADPH probe sequence and recombinant probe controls consisting of the rodent GADPH primer sequence flanking the Hendra virus probe sequence were designed, cloned and transcribed in vitro to generate RNA. This has alleviated the requirement for viral RNA to be used as positive controls, thus reducing the chance of producing a false positive, at the same time eliminating the biosafety risk associated with handling live virus. This assay will provide a rapid diagnosis of future outbreaks of Hendra virus.

Animals↗

Rate controlling steps in fatty acid oxidation by unloaded rodent soleus muscle.

In response to decreased usage skeletal muscle undergoes an adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. Accompanying a shift in fiber type is an increased reliance of carbohydrate metabolism and decreased reliance on fat for energy. These responses have been found with both space flight and ground based models of disuse atrophy including the chronically adapted rodent hind limb suspended (HLS) rat (1, 4-7, 10, 11). In addition, after space flight, the ability of soleus muscle homogenates to oxidize palmitate is decreased. We have previously shown that expression of the mRNA of enzymes involved in beta-oxidation is reduced in the soleus muscle of HLS rats. At the same time mRNA expression of enzymes involved in glycolysis was increased. This study extends these observations to address the question of whether the decrease in beta-oxidation is caused by a reduction in the capacity of the pathway to oxidize fat or the regulation is effected before fatty acids enter the mitochondria, i.e. the reduced capacity of the fatty acid oxidation pathway is because less fat is available for oxidation. The two key steps involved in fatty acid uptake into the cells are lipoprotein lipase and the transport of the free fatty acids produced by lipoprotein lipase into the cell via the carnitine acyltransferase system.

NASA Discipline Regulatory Physiology↗

Immunocytochemical study of tissue distribution and hormonal control of chondroitin-, dermatan- and keratan sulfates from rodent uterus.

The distribution patterns of rat and mouse uterine glycosaminoglycans (GAGs), as well as their modulation by estradiol (E2) and/or progesterone (P), were investigated using monoclonal antibodies (MABs) directed against chondroitin- (CS)/dermatan sulfates (DS), keratan sulfate (KS) and a trophoblast GAG. The localization of GAGs in relation to collagens (I, IV and VI) and fibronectin was also analyzed. We found that uterine GAGs are differentially distributed in the endometrium and myometrium, in a pattern that is species-related. CS-containing proteoglycans (PGs) occur between collagen bundles and fibroblasts, at the periphery of the latter, and in basement membrane zones (BMZs), in a pattern resembling that of collagen VI. BMZs contain preferentially CS-PGs bearing 4-sulfated disaccharides adjacent to the core protein. DS-PGs are mostly associated with collagen bundles. E2 and/or P elicit distinct modifications on the above described pattern, which are also species-related. The simultaneous administration of E2 and P changes the prevalent sulfation of the disaccharides adjacent to the core protein of stromal CS-PGs. In the mouse, an unsulfated intracellular epitope appears following E2 (or E2P) administration, mostly in epithelial cells. In the rat, KS and the trophoblast GAG are E2-dependent and down-regulated by P. The functional significance of the hormone-induced GAG changes, namely the possible role of the E2-dependent KS in implantation, are discussed.

Animals↗

Immunological control of chronic Trypanosoma brucei gambiense in outbred rodents.

Recent human isolates of Trypanosoma brucei gambiense generally fail to become or remain patent in laboratory rodents. The purpose of this study was to determine if this was due to acquired immunity and if so which immunosuppressive method was the most efficient in raising parasitemia levels. Prior to infection, rats and mice were immunosuppressed by treatments with cobra venom factor, anti-lymphocyte sera, hydrocortisone acetate, cyclophosphamide; by splenectomy; or by lethal X-irradiation. While no parasites were detected in the blood of most of the untreated rodents for 30 days postinfection, all immunosuppressive procedures resulted in patent parasitemias in at least fifty percent of the treated animals. The most effective method, lethal X-irradiation, consistently caused fulminating infections typical of acute African trypanosomiasis. Cyclophosphamide had the same effect as X-irradiation in rats but was less effective in mice. Splenectomy allowed fulminating first peak parasitemias in two-thirds of the rodents while cobra venom factor and anti-lymphocyte sera in general allowed only low first peaks of parasitemia that were resolved within 10 days of infection. Hydrocortisone acetate allowed low grade and sporadically patent infections throughout the 30-day study. To determine if in untreated rodents, the parasites were eliminated or maintained in a subpatent state, rodents infected for 30-45 days were immunosuppressed with cyclophosphamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ontogeny of ingestive behavior.

Review of the ontogeny of the controls of independent ingestion reveals that some of the direct and indirect controls of meal size identified in adult rats function in the first three postnatal weeks. The controls appear sequentially and some of them change their potency after they emerge. Indirect controls exerted by metabolism and adiposity do not emerge until the fourth postnatal week or later in the postweaning period. Recent experiments in rats with monogenic obesities involving the leptin and cholecystokinin receptors have demonstrated the usefulness of independent ingestion in the detection of the earliest expression of hyperphagia. Although much remains to be learned about the normal controls of independent ingestion, it is clear that it provides relevant information about the development of normal and abnormal controls of meal size in rodents that is useful for translational research into the controls of meal size in normal and obese children.

Animals↗

Delta opioid discrimination learning in the rat: assessment with the selective delta agonist SNC80.

The majority of reports assessing opioid drug discrimination learning (DDL) have concentrated on characterizing the stimulus properties of compounds selective for mu and kappa opioid receptors. Assessments of delta opioid DDL have been limited and, to date, these assessments have been restricted to the monkey and pigeon. No assessment of delta stimulus control has been examined in rodents. To that end, the present experiment examined discriminative control by the selective delta agonist SNC80 in rats and its generalization to and antagonism by compounds relatively selective to the delta and mu receptor subtypes using the conditioned taste aversion baseline of DDL. Animals injected with 5.6 mg/kg of SNC80 prior to a saccharin-LiCl pairing and with the SNC80 vehicle prior to saccharin alone acquired the discrimination within seven conditioning cycles. The discriminative effects of SNC80 were maximal at 20 min, partial at 120 min, and lost at 240 min. The discrimination was dose dependent in that as the dose of SNC80 increased, the amount of saccharin consumed decreased. In subsequent generalization tests, the delta agonist SNC162 produced SNC80-appropriate responding at a dose of 18 mg/kg. Conversely, the mu agonist morphine produced vehicle-appropriate responding at all doses tested. These selective generalization patterns with SNC162 and morphine suggest that the discriminative effects of SNC80 are mediated at the delta, but not the mu, receptor, a conclusion supported by the fact that SNC80's discriminative control was completely blocked by the delta-selective antagonist NTI, but not by the mu-selective antagonist naltrexone. The present findings indicate that not only do rats readily discriminate both mu- and kappa-selective agonists from their respective vehicles, but they also discriminate compounds that are selective for the delta receptor subtype, thus extending the class of compounds that can serve such discriminative functions for the rat.

Animals↗