83 research outputs found
Penicillin kills chlamydia following the fusion of bacteria with Lysosomes and prevents genital inflammatory lesions in C. muridarum-infected mice
The obligate intracellular bacterium Chlamydia exists as two distinct forms. Elementary bodies (EBs) are infectious and extra-cellular, whereas reticulate bodies (RBs) replicate within a specialized intracellular compartment termed an âinclusionâ. Alternative persistent intra-cellular forms can be induced in culture by diverse stimuli such as IFNÎł or adenosine/EHNA. They do not grow or divide but revive upon withdrawal of the stimulus and are implicated in several widespread human diseases through ill-defined in vivo mechanisms. ÎČ-lactam antibiotics have also been claimed to induce persistence in vitro. The present report shows that upon penicillin G (pG) treatment, inclusions grow as fast as those in infected control cells. After removal of pG, Chlamydia do not revert to RBs. These effects are independent of host cell type, serovar, biovar and species of Chlamydia. Time-course experiments demonstrated that only RBs were susceptible to pG. pG-treated bacteria lost their control over host cell apoptotic pathways and no longer expressed pre-16S rRNA, in contrast to persistent bacteria induced with adenosine/EHNA. Confocal and live-video microscopy showed that bacteria within the inclusion fused with lysosomal compartments in pG-treated cells. That leads to recruitment of cathepsin D as early as 3 h post pG treatment, an event preceding bacterial death by several hours. These data demonstrate that pG treatment of cultured cells infected with Chlamydia results in the degradation of the bacteria. In addition we show that pG is significantly more efficient than doxycycline at preventing genital inflammatory lesions in C. muridarum-C57Bl/6 infected mice. These in vivo results support the physiological relevance of our findings and their potential therapeutic applications
SUICIDE ON THE PATERNAL AND MATERNAL SIDES OF DEPRESSED-PATIENTS WITH A LIFETIME HISTORY OF ATTEMPTED-SUICIDE
The computational model of Slater, based on the analysis of ancestral
secondary cases on the paternal and maternal sides of the subjects, was
applied to depressed patients with a lifetime history of attempted
suicide, either violent or nonviolent, in order to investigate possible
modes of transmission of suicidal behavior. Among 549 patients, 15 had 2
or more ascendant first- and second-degree relatives who committed
suicide. The results of the distribution of these cases were compatible
with polygenic inheritance of suicidal behavior in depressed patients
with a history of attempted suicide. In patients using violent methods,
a significantly greater loading of ancestral secondary cases of suicide
was observed on the maternal side and, in the nonviolent attempter
group, on the paternal side
Reconstruction of a attenuation map using Compton scattered radiation due to a radionucleide point source
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