Impact of the Acetyl Group on Cysteine: A Study of N-Acetyl-Cysteine through Rotational Spectroscopy.

Herein, we report a spectroscopic study of N-acetyl-L-cysteine, an important antioxidant drug, using Fourier-transform microwave techniques and in isolated conditions. Two conformers are observed, where most stable structure adopts a cis disposition, and the second conformer has a lower abundance and adopts a trans disposition. The rotational constants and the barriers to methyl internal rotation are determined for each conformer, allowing a precise conformation identification. The results show that the cis form adopts an identical structure in the crystal, solution, and gas phases. Additionally, the structures are contrasted against those of cysteine.

Astroglial connexin43 contributes to neuronal suffering in a mouse model of Alzheimer's disease.

In Alzheimer's disease (AD), astrocyte properties are modified but their involvement in this pathology is only beginning to be appreciated. The expression of connexins, proteins forming gap junction channels and hemichannels, is increased in astrocytes contacting amyloid plaques in brains of AD patients and APP/PS1 mice. The consequences on their channel functions was investigated in a murine model of familial AD, the APPswe/PS1dE9 mice. Whereas gap junctional communication was not affected, we revealed that hemichannels were activated in astrocytes of acute hippocampal slices containing Aß plaques. Such hemichannel activity was detected in all astrocytes, whatever their distance from amyloid plaques, but with an enhanced activity in the reactive astrocytes contacting amyloid plaques. Connexin43 was the main hemichannel contributor, however, a minor pannexin1 component was also identified in the subpopulation of reactive astrocytes in direct contact with plaques. Distinct regulatory pathways are involved in connexin and pannexin hemichannel activation. Inflammation triggered pannexin hemichannel activity, whereas connexin43 hemichannels were activated by the increase in resting calcium level of astrocytes. Importantly, hemichannel activation led to the release of ATP and glutamate that contributed to maintain a high calcium level in astrocytes placing them in the center of a vicious circle. The astroglial targeted connexin43 gene knocking-out in APPswe/PS1dE9 mice allowed to diminish gliotransmitter release and to alleviate neuronal damages, reducing oxidative stress and neuritic dystrophies in hippocampal neurons associated to plaques. Altogether, these data highlight the importance of astroglial hemichannels in AD and suggest that blocking astroglial hemichannel activity in astrocytes could represent an alternative therapeutic strategy in AD.

Influence of age, postmortem delay and freezing storage period on cannabinoid receptor density and functionality in human brain.

It has been suggested that cannabimimetic drugs could be of interest in the treatment of several nervous disorders. Thus, it is important to analyse the distribution and properties of cannabinoid (CB) receptors directly in human brain. As postmortem human tissue is subjected to the effects of several biological variables, we have analyzed by autoradiography the influence of age, postmortem delay and freezing storage period (at -25 degrees C) on two parameters corresponding to cannabinoid CB1 receptors in human frontal cortex: receptor density and degree of activation of G-proteins ([35S]GTPgammaS assays). A significant decrease in the amount of both receptor density and agonist-stimulated G-protein activity was observed with age, revealing a mean reduction of about 10% per decade. In contrast, no significant correlations were found with postmortem delay either for CB1 receptors density or functionality. Finally, both parameters (receptor density and [35S]GTPgammaS response) were significantly reduced with freezing storage period at -25 degrees C in frontal cortical layers. Non-linear analysis of these data yielded values between 12 and 24 months of storage for a 50% reduction. In conclusion, when studying CB1 receptor properties in human brain samples, a careful analysis (and matching) for variables such as age and freezing storage period has to be carried out.

Anemia and malaria in a Yanomami Amerindian population from the southern Venezuelan Amazon.

The prevalence and age distribution of anemia and malaria among Yanomami Amerindians undergoing sociocultural assimilation are described. Anemia and malaria proportions were determined in 103 individuals randomly selected from 515 villagers in Mavaca in the southern Venezuelan Amazon. The age and sex distribution reflected that of the entire village cluster. Anemia (hematocrit less than World Health Organization/Centers for Disease Control and Prevention reference values) was found in 91% of the study population. As a group, adults (> or = 15 years old) had the highest proportion of anemia (P=0.037). Adult females had lower mean hematocrit values than adult males (P=0.013). The anemia was predominantly hypochromic and microcytic (62%), a finding that could suggest a diagnosis of iron deficiency in the absence of known hereditary hemoglobinopathies in these Amerindians. Malaria was diagnosed in 14% overall. Children (< 10 years old) displayed the highest proportion of Plasmodium falciparum (17%) and P. vivax (14%) parasitemia, splenomegaly (94%), and fever (34%) (P=0.059, 0.039, 0.005, and 0.008, respectively). The high proportions of anemia and splenomegaly observed in the survey may be used as indicators of inadequately controlled malaria in this community. Further studies to assess the epidemiology of risk factors for the high prevalence of anemia, and predominance of P. falciparum infections in the area are urgently needed.