Drosophila divalent metal ion transporter Malvolio is required in dopaminergic neurons for feeding decisions.

Members of the natural resistance-associated macrophage protein (NRAMP) family are evolutionarily conserved metal ion transporters that play an essential role in regulating intracellular divalent cation homeostasis in both prokaryotes and eukaryotes. Malvolio (Mvl), the sole NRAMP family member in insects, plays a role in food choice behaviors in Drosophila and other species. However, the specific physiological and cellular processes that require the action of Mvl for appropriate feeding decisions remain elusive. Here, we show that normal food choice requires Mvl function specifically in the dopaminergic system, and can be rescued by supplementing food with manganese. Collectively, our data indicate that the action of the Mvl transporter affects food choice behavior via the regulation of dopaminergic innervation of the mushroom bodies, a principle brain region associated with decision-making in insects. Our studies suggest that the homeostatic regulation of the intraneuronal levels of divalent cations plays an important role in the development and function of the dopaminergic system and associated behaviors.

Comparative effects of carbapenems on bacterial load and host immune response in a Klebsiella pneumoniae murine pneumonia model.

Doripenem is a carbapenem with potent broad-spectrum activity against Gram-negative pathogens, including antibiotic-resistant Enterobacteriaceae. As the incidence of extended-spectrum ß-lactamase (ESBL)-producing Gram-negative bacilli is increasing, it was of interest to examine the in vivo comparative efficacy of doripenem, imipenem, and meropenem against a Klebsiella pneumoniae isolate expressing the TEM-26 ESBL enzyme. In a murine lethal lower respiratory infection model, doripenem reduced the Klebsiella lung burden by 2 log(10) CFU/g lung tissue over the first 48 h of the infection. Treatment of mice with meropenem or imipenem yielded reductions of approximately 1.5 log(10) CFU/g during this time period. Seven days postinfection, Klebsiella titers in the lungs of treated mice decreased an additional 2 log(10) CFU/g relative to those in the lungs of untreated control animals. Lipopolysaccharide (LPS) endotoxin release assays indicated that 6 h postinfection, meropenem- and imipenem-treated animals had 10-fold more endotoxin in lung homogenates and sera than doripenem-treated mice. Following doripenem treatment, the maximum endotoxin release postinfection (6 h) was 53,000 endotoxin units (EU)/ml, which was 2.7- and 6-fold lower than imipenem or meropenem-treated animals, respectively. While the levels of several proinflammatory cytokines increased in both the lungs and sera following intranasal K. pneumoniae inoculation, doripenem treatment, but not meropenem or imipenem treatment, resulted in significantly increased interleukin 6 levels in lung homogenates relative to those in lung homogenates of untreated controls, which may contribute to enhanced neutrophil killing of bacteria in the lung. Histological examination of tissue sections indicated less overall inflammation and tissue damage in doripenem-treated mice, consistent with improved antibacterial efficacy, reduced LPS endotoxin release, and the observed cytokine induction profile.

Fiebre sin foco en paciente con dolor crónico / Fever without center in patient with chronic pain

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Expression of TCF, TPF/YY1, and the Sp family transcription factors in rabbit endometrium throughout pregnancy.

BACKGROUND: TCF, TPF/YY1, and the Sp family are specific transcription factors that bind sequences found within the uteroglobin (UG) gene promoter region that are necessary for transcription. To date, UG gene expression and regulation in vivo are not fully understood. The purpose of this study was to assess the expression patterns of these factors in the rabbit endometrium throughout pregnancy. METHODS: Endometrial nuclear extracts were obtained from female rabbits on days 0, 3, 5, 7, 15, and 28 after mating. Transcription factor expression was assessed by DNA-protein binding assays using endometrial nuclear proteins and specific oligonucleotides. Band shifts were observed on 4% acrylamide gels and analyzed by densitometry. RESULTS: The expression patterns of the transcription factors analyzed here differed, as TPF/YY1 and Sp3/SpR-2 were expressed constitutively while TCF and Sp1 showed variable expression patterns throughout pregnancy. CONCLUSIONS: Our results suggest that UG gene expression in the intact pregnant rabbit is controlled by two constitutive and two regulated factors, and that the DNA-binding sites are located at the TATA box and the GT1 sites within the gene promoter.

Effects of chronic low-level oral lead exposure on prepulse inhibition of acoustic startle in the rat.

Previous work has suggested that the behavioral effects of chronic low-level lead exposure on fixed interval (FI) operant behavior result from enhanced dopaminergic neurotransmission in the nucleus accumbens (Cory-Slechta et al., J Pharmacol Exp Ther 286: 794-805, 1998). The present studies were designed to further characterize the effects of chronic low-level oral lead exposure on another behavior that is modulated by dopaminergic neurotransmission in the nucleus accumbens. In these studies acoustic startle and the prepulse inhibition (PPI) of startle were studied in rats following chronic low-level oral lead exposure. Weanling male rats were treated for 5-6 weeks with lead via drinking water (250 ppm lead acetate; controls drank 250 ppm sodium acetate). Acoustic startle reactivity (95, 105, and 115 dB noise bursts) and PPI (prepulses of 1-8 dB over the 70-dB background) of startle were tested following lead exposure. Lead exposure did not affect body weight. Lead exposure also did not significantly affect baseline [i.e., no prepulse inhibition (NO-PPI)] acoustic startle as measured by 1) startle amplitude on the first startle trial (105 dB), 2) the average startle amplitude for the first ten trials (105 dB), or 3) the average startle amplitude for the NO-PPI trials during PPI testing (95, 105, and 115 dB). Lead exposure also did not affect the latency to onset for the startle response. In contrast, for both the 105 dB and 115 dB acoustic startle stimuli, chronic low-level oral lead exposure significantly attenuated the capacity of an acoustic prepulse to reduce the startle response. This effect was present whether the data were presented and analyzed as raw change from baseline or as the percentage of baseline startle. Given the strong link between the modulation of PPI and dopaminergic neurotransmission in the nucleus accumbens, the present data support the hypothesis that chronic low-level oral lead exposure facilitates dopamine neurotransmission in the nucleus accumbens.

[Vitamin D induces proliferation in rat endometrium cultured cells]. / La vitamina D induce la proliferación de células en cultivo del endometrio de rata.

OBJECTIVE: To study the effects of 1,25-dihydroxyvitaminD3 (1,25-(OH)2D3) on proliferation and cell death in the rat uterus. MATERIAL AND METHODS: A rat endometrial cell line (Rentro 1) grown in a Dulbecco Minimal Essential Medium (DMEM) supplemented with 1% charcoal stripped serum was used in all experiments in order to eliminate the steroid hormone. Cell monolayer was incubated in the presence and absence of 1,25-(OH)2D3 or 17 beta-estradiol or vehicle. After stimulation, we evaluated cell proliferation and DNA synthesis by trypan blue counting method and flow cytofluorometry, respectively. Finally, the genomic DNA integrity was evaluated by electrophoresis and the bands visualized with ultraviolet light. RESULTS: The cells in medium containing 1% fetal bovine serum free of steroid hormones stimulated the cell growth 85% more than without serum. Supplement with albumin did not allow cell growth. The cells did not respond to 17 beta-estradiol but the presence of 1,25-(OH)2D3 induced cell proliferation. These results confirm that Rentro 1 cells do not express the estrogen receptor and demonstrate their capacity to respond to 1,25-(OH)2D3. Finally, the integrity of DNA was not affected by 1,25(OH)2D3, suggesting that this hormone is not involved in cell death by apoptosis in our cell line, as seen in other cell lines. CONCLUSIONS: 1) 1,25-dihydroxyvitamin D induced cell proliferation in the endometrial cell line Rentro 1 in a dose-dependent fashion and this effect is independent of the presence of an estrogenic stimulus; 2) the increase in cell number was related to DNA synthesis during the cell cycle; and 3) the presence of the hormone in the culture medium was not able to induce cell death.