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Biomedical subjects

P Siri

Publications and source records attributed to P Siri.

6 recordsLinked to original sources

Proliferation and death in a binary environment: a stochastic model of cellular ecosystems.

The activation, growth and death of animal cells are accompanied by changes in the chemical composition of the surrounding environment. Cells and their microscopic environment constitute therefore a cellular ecosystem whose time-evolution determines processes of interest for either biology (e.g. animal development) and medicine (e.g. tumor spreading, immune response). In this paper, we consider a general stochastic model of the interplay between cells and environmental cellular niches. Niches may be either favourable or unfavourable in sustaining cell activation, growth and death, the state of the niches depending on the state of the cells. Under the hypothesis of random coupling between the state of the environmental niche and the state of the cell, the rescaled model reduces to a set of four non-linear differential equations. The biological meaning of the model is studied and illustrated by fitting experimental data on the growth of multicellular tumor spheroids. A detailed analysis of the stochastic model, of its deterministic limit, and of normal fluctuations is provided.

Algorithms↗

Post-transcriptional stimulation of the assembly and secretion of triglyceride-rich apolipoprotein B lipoproteins in a mouse with selective deficiency of brown adipose tissue, obesity, and insulin resistance.

A mouse model of insulin resistance and its associated dyslipidemia was generated by crossing mice expressing human apolipoprotein B (apoB) with mice lacking only brown adipose tissue (BATless). On a high fat diet, male apoB/BATless mice became obese, hypercholesterolemic, hypertriglyceridemic, and hyperinsulinemic compared with control apoB mice. Fast performance liquid chromatography revealed increased triglyceride concentrations in intermediate density lipoprotein/low density lipoprotein (LDL) and reduced high density lipoprotein cholesterol concentrations. Inhibition of lipolysis by the drug, tetrahydrolipostatin, demonstrated that very low density lipoprotein-sized particles were initially secreted. Metabolic studies employing Triton WR-1339 and either [(3)H]glycerol or [(3)H]palmitate showed that the hypertriglyceridemia in apoB/BATless mice was due to the increased synthesis and secretion of triglyceride. Furthermore, lipoprotein lipase and hepatic lipase activities were not defective. ApoB was also secreted at increased rates in the apoB/BATless mice. Similar levels of apoB mRNA in apoB and apoB/BATless mice indicated that apoB secretion was regulated post-transcriptionally. LDL receptor mRNA was increased in the apoB/BATless mice, indicating that the observed increase in apoB-lipoprotein secretion was not due to their decreased reuptake. Finally, mRNA levels of the large subunit of microsomal triglyceride transfer protein, a required component for very low density protein assembly, were not different between apoB and apoB/BATless mice. This rodent model should prove useful in exploring mechanisms underlying the regulation of apoB secretion in the context of insulin resistance.

Adipose Tissue, Brown↗

'First steps': using rapid assessment and response methods to develop research, intervention and advocacy capacity for addressing drug use in Rosario City, Argentina.

During the last decade, injecting drug use (IDU) has increased in Rosario City, Argentina, and more than half of all reported HIV cases are thought to be related to the sharing of injection equipment. Despite this, valid and systematic data on the extent and nature of injecting drug use are rare, and only a limited number of HIV prevention interventions currently operate in the city. In response, the Universidad Nacional de Rosario have used the Spanish translation of the Rapid Assessment and Response Guide on Injecting Drug Use (IDU-RAR) developed by the World Health Organization (WHO. The Rapid Assessment and Response Guide on Injecting Drug Use (draft for field testing). Geneva: WHO, 1998) as a first step in producing more detailed research data, identifying urgently needed interventions, and designing a long-term harm reduction strategy for Rosario. This paper describes this process and the outcomes of the assessment where key findings indicate that: 65% of those sampled were HIV positive; 70% shared injecting equipment; the majority were not in contact with drug treatment services; 13% were under the age of 20; and 62% of those injecting drug users with HIV had neither medical care or treatment for their condition.

Journal Article↗

Carbachol-induced bladder mast cell activation: augmentation by estradiol and implications for interstitial cystitis.

OBJECTIVES: Interstitial cystitis (IC) is a painful, sterile bladder disorder that occurs primarily in women, many of whom also experience allergies with symptoms that worsen perimenstrually. Increased numbers of activated bladder mast cells have recently been implicated in the pathophysiology of IC. These mast cells express high-affinity estrogen receptors and are located close to increased bladder nerves, many of which contain the neuropeptide substance P (SP). We therefore investigated whether the neurotransmitter acetylcholine (ACh) and SP could activate bladder mast cells and whether estradiol could influence this effect. METHODS: Bladder pieces from male Sprague-Dawley rats were perfused with carbachol (the stable analogue of ACh), SP, or the mast cell secretagogue compound 48/80 (C48/80) with or without preincubation with beta-estradiol. The effect of carbachol was also investigated after pretreatment with the muscarinic antagonist atropine. Mast cell activation was assessed by release of 3H-serotonin and morphologic evidence of secretion by light and electron microscopy. RESULTS: Carbachol triggered rat bladder mast cell serotonin release in a dose-dependent manner, an effect increased by tissue pretreatment with estradiol and blocked by atropine. The effect of carbachol was accompanied by ultrastructural evidence of mast cell activation and was stronger than that obtained by either C48/ 80 or SP. CONCLUSIONS: Bladder mast cell activation is neurogenically mediated and augmented by estradiol, findings that could possibly explain the painful symptoms of IC and its prevalence in women, as well as the worsening of symptoms perimenstrually.

Acetylcholine↗

Consorting among juvenile Midas cichlids (Cichlasoma citrinellum) in relation to own and to parents' color.

Adults of the Midas cichlid, Cichlasoma citrinellum, are either normal (N) colored or gold (G); they mate assortatively by color, and that choice is influenced by prior experience with their parents. Three groups of N and two groups of G juveniles were reared by parents which were either N or G. After some months of separation from their parents, the juveniles were tested to ascertain whether the color of their parents or of their cohorts affected their affiliative responses; they were given a choice between four G and four N juveniles. There was no demonstrable effect of either their parents' or their own color. All groups spent more time with N than with G and directed more behavior toward N. The subjects differed only in that they attacked more (at a higher rate) at N and spread their fins more (at a higher rate) at G, consistent with findings in earlier studies of the effect of gold color on dominance relationships. Thus mate choice does not result from continuous associations during development.

Animals↗