Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats.

Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task.

Prevention of travelers' diarrhea with rifaximin in US travelers to Mexico.

Background: Because bacterial pathogens are the primary cause of travelers' diarrhea (TD), antibiotic prophylaxis is effective in TD prevention. This study assessed the efficacy and safety of the nonsystemic antibiotic rifaximin in preventing TD in US travelers to Mexico.

Methods: Healthy adult students traveling to Mexico received rifaximin 600 mg/d or placebo for 14 days and were followed for 7 days post-treatment.

PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study.

Background: The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality.

Enterotoxigenic Escherichia coli and diffusely adherent E. coli as likely causes of a proportion of pathogen-negative travelers' diarrhea--a PCR-based study.

Background: Enteropathogens cannot be identified in 40% to 50% of subjects with travelers' diarrhea (TD).

Methods: We used polymerase chain reaction (PCR) methods to look for the presence of two bacterial causes of diarrhea in a large group of international travelers after failing to detect a pathogen by conventional tests. DNA was isolated from the diarrheal stool and subjected to PCR from 162 subjects from whom we earlier failed to identify a pathogen in a previous study and included 54 from Antigua, Guatemala, 39 from Guadalajara, Mexico, 29 from Kolkata, India, and 40 from Goa, India.

Glutathione depletion activates mitogen-activated protein kinase (MAPK) pathways that display organ-specific responses and brain protection in mice.

Because mitogen-activated protein kinases (MAPK) are downstream effectors of antioxidant responses, changes in GSH levels in an organism might induce organ-specific responses. To test our hypothesis, mice were treated intraperitoneally with L-buthionine-S-R-sulfoximine (BSO) to inhibit GSH synthesis. A time-related GSH depletion in the liver and kidney correlated with p38(MAPK) phosphorylation and induction of thioredoxin 1 (Tx-1) transcription.

The major Aeromonas veronii outer membrane protein: gene cloning and sequence analysis.

The gene encoding the major outer membrane protein (OMP) from Aeromonas veronii, Omp38, was cloned and characterized. Sequence analysis revealed an open reading frame of 1,047 nucleotides coding for a primary protein of 349 amino acids with a 20-amino-acid signal peptide at the N-terminal and the consensus sequence Ala-X-Ala (Ala-Asn-Ala) as the signal peptidase I recognition site. The mature protein is composed of 329 amino acids with a calculated molecular mass of 36,327 Da.

Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats.

Microinjection of dipyrone (metamizol) into the periaqueductal gray matter (PAG) in rats causes antinociception. This is mediated by endogenous opioidergic circuits located in the PAG itself, in the nucleus raphe magnus and adjacent structures, and in the spinal cord. The clinical relevance of these findings, however, is unclear.

Encoding of noxious stimulus intensity by putative pain modulating neurons in the rostral ventromedial medulla and by simultaneously recorded nociceptive neurons in the spinal dorsal horn of rats.

Neurons in the nucleus raphe magnus and adjacent structures of the rostral ventromedial medulla (RVM) are involved in the control of nociceptive transmission. In the RVM the so-called on-cells are excited, and the so-called off-cells are inhibited, by noxious stimuli applied almost anywhere on the body surface, thus showing that they receive information from spinal and trigeminal nociceptive neurons. In deeply anesthetized rats, recordings were made from RVM neurons that resembled on- and off-cells (herein called putative on- and off-cells) in order to investigate (1) how they encode the intensity of thermal noxious stimuli (46--56 degrees C) applied to a hindpaw, and (2) how their encoding properties relate to those of simultaneously recorded spinal neurons.

Medullary on-cell activity during tail-flick inhibition produced by heterotopic noxious stimulation.

Reflex responses and neuronal excitation elicited by noxious stimuli applied to a given body site can be inhibited by application of noxious stimulation to another, even distant body region. Such heterotopic noxious stimulation (HNS) has been proposed to act via 'diffuse noxious inhibitory controls' (DNIC) which involve supraspinal components. The so-called on-cells of the rostral ventromedial medulla (RVM) in rats are thought to facilitate nociceptive transmission.

Medullary on- and off-cell responses precede both segmental and thalamic responses to tail heating.

Medullary on- and off-cell responses to tail heating were studied in lightly anesthetized rats. In 10 animals the electromyographic (EMG) activation of tail muscles was recorded simultaneously with on- or off-cells. The on-cell burst or the off-cell pause always preceded segmental EMG activation by about 0.