Angiotensin II's role in sodium lactate-induced panic-like responses in rats with repeated urocortin 1 injections into the basolateral amygdala: amygdalar angiotensin receptors and panic.

Rats treated with three daily urocortin 1 (UCN) injections into the basolateral amygdala (BLA; i.e., UCN/BLA-primed rats) develop prolonged anxiety-associated behavior and vulnerability to panic-like physiological responses (i.e., tachycardia, hypertension and tachypnea) following intravenous infusions of 0.5 M sodium lactate (NaLac, an ordinarily mild interoceptive stressor). In these UCN-primed rats, the osmosensitive subfornical organ (SFO) may be a potential site that detects increases in plasma NaLac and mobilizes panic pathways since inhibiting the SFO blocks panic following NaLac in this model. Furthermore, since SFO neurons synthesize angiotensin II (A-II), we hypothesized that the SFO projects to the BLA and releases A-II to mobilizing panic responses in UCN/BLA-primed rats following NaLac infusions. To test this hypothesis, rats received daily bilateral injections of UCN or vehicle into the BLA daily for 3 days. Five to seven days following the intra-BLA injections, we microinjected either the nonspecific A-II type 1 (AT1r) and 2 (AT2r) receptor antagonist saralasin, or the AT2r-selective antagonist PD123319 into the BLA prior to the NaLac challenge. The UCN/BLA-primed rats pre-injected with saralasin, but not PD123319 or vehicle, had reduced NaLac-induced anxiety-associated behavior and panic-associated tachycardia and tachypnea responses. We then confirmed the presence of AT1rs in the BLA using immunohistochemistry which, combined with the previous data, suggest that A-II's panicogenic effects in the BLA is AT1r dependent. Surprisingly, the SFO had almost no neurons that directly innervate the BLA, which suggests an indirect pathway for relaying the NaLac signal. Overall these results are the first to implicate A-II and AT1rs as putative neurotransmitter-receptors in NaLac induced panic-like responses in UCN/BLA-primed rats.

Application of stimulating agents on the immobilized bioluminescence strain Pseudomonas putida mt-2 KG1206, preserved by deep-freezing, for the convenient biomonitoring.

This study was conducted to develop methods for the application of an immobilized bioluminescence strain (KG1206), preserved by deep-freezing (DF), for the monitoring of contaminated environments. The immobilized cells, preserved by DF, required approximately 2 hr for reconstitution of their activity. A large reduction in bioluminescence was observed due to the DF process; 0.07-0.58 times that of the non deep-frozen (NDF) immobilized strain. The decreased bioluminescence activity induced by the DF process was enhanced by the stimulants, sodium lactate (SL) and KNO3. However, regardless of the inducer chemical tested, the immobilized strain modified with KNO3 consistently produced greater bioluminescence than that treated with SL, in the range of 3.0-10.7 (avg. 6.7 +/- 3.69) and 1.2-4.2 (avg. 2.4 +/- 1.47) times that of control, respectively. All KNO3 treatments of contaminated groundwater samples also resulted in an increase in bioluminescence activity, but the rate of stimulation varied for each sample. Also, no strong linear correlation was observed between the bioluminescence and the total concentration of an inducer, which may related to the complex characteristics of the environmental samples. Overall, the results demonstrated the ability of immobilized genetically engineered bacteria, preserved by DF, to measure a specific group of environmental contaminants using a stimulating agent (KNO3), suggesting the potential for its preliminary application in a field-ready bioassay.

Investigations of D-lactate metabolism and the clinical signs of D-lactataemia in calves.

Five clinically healthy calves received an intravenous injection of 25 g sodium D-lactate (223 mmol) in 100 ml sterile water and five control calves were given the same volume of 0.9 per cent sodium chloride. Two clinical examiners who were blinded to the status (test or control) of the calves observed that between eight and 40 minutes after the injections the calves that had received sodium-D-lactate could be distinguished with certainty from the control calves on the basis of their clinical signs, for example, an impaired palpebral reflex, somnolence and a staggering gait. One-compartment and two-compartment analyses of the changes in the plasma concentration of D-lactate, and its renal clearance, indicated that the calves metabolised considerable amounts of D-lactate.

Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucose-degradation products.

Peritoneal dialysis (PD) is a well-established therapy for end-stage renal failure, but its efficiency is limited by recurrent peritonitis. As PD solutions impair local inflammatory responses within the peritoneal cavity, we have analyzed their influence on the in vitro maturation of human monocyte-derived dendritic cells (MDDC). Evaluation of MDDC maturation parameters [expression of adhesion and costimulatory molecules, receptor-mediated endocytosis, allogeneic T cell activation, production of tumor necrosis factor alpha, interleukin (IL)-6 and IL-12 p70, and nuclear factor (NF)-kappaB activation] revealed that currently used PD solutions differentially inhibit the lipopolysaccharide (LPS)-induced maturation of MDDC, an inhibition that correlated with their ability to impair the LPS-stimulated NF-kappaB activation. Evaluation of PD components revealed that sodium lactate and glucose-degradation products impaired the acquisition of maturation parameters and NF-kappaB activation in a dose-dependent manner. Moreover, PD solutions impaired monocyte-MDDC differentiation, inhibiting the acquisition of DC markers such as CD1a and DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (CD209). These findings have important implications for the initiation of immune responses under high lactate conditions, such as those occurring within tumor tissues or after macrophage activation.