Enrichment of Autotrophic Denitrifiers From Anaerobic Sludge Using Sulfurous Electron Donors.

This study compared the rates and microbial community development in batch bioassays on autotrophic denitrification using elemental sulfur (S0), pyrite (FeS2), thiosulfate (S2O3 2-), and sulfide (S2-) as electron donor. The performance of two inocula was compared: digested sludge (DS) from a wastewater treatment plant of a dairy industry and anaerobic granular sludge (GS) from a UASB reactor treating dairy wastewater. All electron donors supported the development of a microbial community with predominance of autotrophic denitrifiers during the enrichments, except for sulfide. For the first time, pyrite revealed to be a suitable substrate for the growth of autotrophic denitrifiers developing a microbial community with predominance of the genera Thiobacillus, Thioprofundum, and Ignavibacterium. Thiosulfate gave the highest denitrification rates removing 10.94 mM NO3 - day-1 and 8.98 mM NO3 - day-1 by DS and GS, respectively. This was 1.5 and 6 times faster than elemental sulfur and pyrite, respectively. Despite the highest denitrification rates observed in thiosulfate-fed enrichments, an evaluation of the most relevant parameters for a technological application revealed elemental sulfur as the best electron donor for autotrophic denitrification with a total cost of 0.38 € per m3 of wastewater treated.

Intranasal delivery of dexamethasone efficiently controls LPS-induced murine neuroinflammation.

Neuroinflammation is the hallmark of several infectious and neurodegenerative diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive drugs used for controlling neuroinflammation. A delayed diffusion of GCs molecules and the high systemic doses required for brain-specific targeting lead to severe undesirable effects, particularly when lifelong treatment is required. Therefore, there is an urgent need for improving this current therapeutic approach. The intranasal (i.n.) route is being employed increasingly for drug delivery to the brain via the olfactory system. In this study, the i.n. route is compared to the intravenous (i.v.) administration of GCs with respect to their effectiveness in controlling neuroinflammation induced experimentally by systemic lipopolysaccharide (LPS) injection. A statistically significant reduction in interleukin (IL)-6 levels in the central nervous system (CNS) in the percentage of CD45+ /CD11b+ /lymphocyte antigen 6 complex locus G6D [Ly6G+ and in glial fibrillary acidic protein (GFAP) immunostaining was observed in mice from the i.n.-dexamethasone (DX] group compared to control and i.v.-DX-treated animals. DX treatment did not modify the percentage of microglia and perivascular macrophages as determined by ionized calcium binding adaptor molecule 1 (Iba1) immunostaining of the cortex and hippocampus. The increased accumulation of DX in brain microvasculature in DX-i.n.-treated mice compared with controls and DX-IV-treated animals may underlie the higher effectiveness in controlling neuroinflammation. Altogether, these results indicate that IN-DX administration may offer a more efficient alternative than systemic administration to control neuroinflammation in different neuropathologies.

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide.

BACKGROUND: Neuroinflammation (NI) is a key feature in the pathogenesis and progression of infectious and non-infectious neuropathologies, and its amelioration usually improves the patient outcome. Peripheral inflammation may promote NI through microglia and astrocytes activation, an increased expression of inflammatory mediators and vascular permeability that may lead to neurodegeneration. Several anti-inflammatory strategies have been proposed to control peripheral inflammation. Among them, electrical stimulation of the vagus nerve (VNS) recently emerged as an alternative to effectively attenuate peripheral inflammation in a variety of pathological conditions with few side effects. Considering that NI underlies several neurologic pathologies we explored herein the possibility that electrically VNS can also exert anti-inflammatory effects in the brain. METHODS: NI was experimentally induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS) in C57BL/6 male mice; VNS with constant voltage (5 Hz, 0.75 mA, 2 ms) was applied for 30 s, 48 or 72 h after lipopolysaccharide injection. Twenty four hours later, pro-inflammatory cytokines (IL-1ß, IL-6, TNFα) levels were measured by ELISA in brain and spleen extracts and total brain cells were isolated and microglia and macrophage proliferation and activation was assessed by flow cytometry. The level of ionized calcium binding adaptor molecule (Iba-1) and glial fibrillary acidic protein (GFAP) were estimated in whole brain extracts and in histologic slides by Western blot and immunohistochemistry, respectively. RESULTS: VNS significantly reduced the central levels of pro-inflammatory cytokines and the percentage of microglia (CD11b/CD45low) and macrophages (CD11b/CD45high), 24 h after the electrical stimulus in LPS stimulated mice. A significantly reduced level of Iba-1 expression was also observed in whole brain extracts and in the hippocampus, suggesting a reduction in activated microglia. CONCLUSIONS: VNS is a feasible therapeutic tool to attenuate the NI reaction. Considering that NI accompanies different neuropathologies VNS is a relevant alternative to modulate NI, of particular interest for chronic neurological diseases.

A correlating of EKG and pathologic findings in myocardial infarction (Preliminary report)

The autopsy findings of seven cases of myocardial infarction were correlated with their electrocardiograms. Causes for non-correlation with their electrocardiographic and pathologic data are given. (Summary)

Mechanism of the cardiovascular effects of GABAB receptor activation in the nucleus tractus solitarii of the rat.

The effects of baclofen microinjected into the nucleus tractus solitarii (NTS) on blood pressure, heart rate and baroreflex bradycardia were studied in urethane-anesthetized rats. Baclofen caused dose-dependent pressor and tachycardic effects and inhibited the reflex bradycardia elicited by i.v. phenylephrine. The effects of baclofen were inhibited by similarly administered GABAB receptor antagonists, phaclofen and 2-OH-saclofen, or the non-NMDA glutamate receptor antagonist, DNQX, or by pretreatment of rats with intracisternally administered pertussis toxin. DNQX and pertussis toxin, but not the NMDA antagonist, MK-801, also inhibited baroreflex bradycardia. Intra-NTS injections of glutamate caused hypotension and bradycardia, which were potentiated by baclofen, and were not affected by either DNQX or MK-801 or by pretreatment with pertussis toxin. These findings indicate that the cardiovascular effects of stimulation of GABAB receptors in the NTS are due, at least in part, to inhibition of the depressor baroreflex response. Inhibition of the release and/or postsynaptic action of an excitatory amino acid transmitter other than glutamate is the most likely mechanism.

Antihypertensive effect of non-diuretic doses of cicletanine on a stress-induced model in the rat.

Cicletanine was tested at different doses (7.5, 10 and 30 mg/kg, p.o.) on young rats showing high blood pressure readings after social deprivation for 7 consecutive days. At all dose levels, the compound produced a statistically significant decrease in systolic blood pressure of isolated but not group-housed rats. In contrast, the drug did not affect the heart rate in any of the cases. Interestingly, cicletanine was only found to enhance urinary excretion at the highest dose assayed. The putative mechanism of the antihypertensive action of the drug at non-diuretic doses is discussed.

High blood pressure induced by audiovisual stimulation in young rats: effect of antihypertensive agents.

High systolic blood pressure (BP) was induced in young Wistar rats by daily exposure for 30 mins to environmental stimuli consisting of intense (100 dB) sound of 7500 cps and flashing light (0.3 cps). Maximal BP enhancement was obtained after the application of both these stimuli for 3 consecutive days. Such a hypertensive response was detected 24 hrs, but not 1 hr after the trial. High BP backed to normal 72 hrs after discontinuation of the audiovisual stimulation trials. Clinically effective antihypertensive agents (clonidine, prazosin, propranolol, practolol and metoprolol) as well as a new compound under investigation (cicletanine) were proved active in this model. Normotensive nonstressed rats run in parallel did not show any variation in their BP after administration of the same dose of the drugs assayed. This experimental model of hypertension may be a useful tool not only to test new antihypertensive agents but also to study the intriguing question of the role of stress in the development and maintenance of essential hypertension.

Hypotensive effect of naloxone on high blood pressure induced by stress in the rat.

A naloxone-reversible enhancement of systolic blood pressure (BP) was induced in rats by application of three different types of stressor, i.e. intense light and sound, cold and foot-shock. In the case of labile high BP provoked by short-term isolation, the opiate antagonist naloxone (1 mg/Kg, i.p.) was also found to reverse hypertension. Naltrexone (2.5 mg/Kg, i.p.) also diminished high BP readings of briefly isolated rats. Conversely, blockade of the opiate receptor with naloxone did not alter elevated BP in cases of established hypertension (spontaneously hypertensive rats, deoxycorticosterone (DOCA)-salt rats and long-term isolated rats). These data can be taken as an evidence of opioid involvement at the onset of high BP readings induced by stress. However, once hypertension becomes established, the opioid system appears to recover its silent features.