No abstract

In patients with acute disseminated Lyme disease but without meningitis, oral doxycycline and parenterally administered ceftriaxone were equally effective in preventing the late manifestations of disease.

Highlights d IL-1b-driven increased intestinal permeability is observed in murine KD model d Blocking intestinal permeability or IgA production decreases murine KD vasculitis d IgA and IgA-C3 are observed in cardiovascular lesions of murine KD model d KD vasculitis may be a form of IgA vasculitis involving a gutvascular axis

Ceftriaxone for 14 days eradicated the signs and symptoms of late Lyme disease in the majority of evaluable patients. Although there were more failures in the 14-day group than in the 28-day group, this study did not have the power to determine if a clinical subset of patients may benefit from 28 days of therapy.

Nicotine directly regulates striatal dopamine (DA) neurotransmission via presynaptic nicotinic acetylcholine receptors (nAChRs) that are α6β2 and/or α4β2 subunit-containing, depending on region. Chronic nicotine exposure in smokers upregulates striatal nAChR density, with some reports suggesting differential impact on α6- or α4-containing nAChRs. Here, we explored whether chronic nicotine exposure modifies striatal DA transmission, whether the effects of acute nicotine on DA release probability persist and whether there are modifications to the regulation of DA release by α6-subunit-containing (*) relative to non-α6* nAChRs in nucleus accumbens (NAc) and in caudate-putamen (CPu). We detected electrically evoked DA release at carbon-fiber microelectrodes in striatal slices from mice exposed for 4-8 weeks to nicotine (200 μg/mL in saccharin-sweetened drinking water) or a control saccharin solution. Chronic nicotine exposure subtly reduced striatal DA release evoked by single electrical pulses, and in NAc enhanced the range of DA release evoked by different frequencies. Effects of acute nicotine (500 nm) on DA release probability and its sensitivity to activity were apparent. However, in NAc there was downregulation of the functional dominance of α6-nAChRs (α6α4β2β3), and an emergence in function of non-α6* nAChRs. In CPu, there was no change in the control of DA release by its α6 nAChRs (α6β2β3) relative to non-α6. These data suggest that chronic nicotine subtly modifies the regulation of DA transmission, which, in NAc, is through downregulation of function of a susceptible population of α6α4β2β3 nAChRs. This imbalance in function of α6:non-α6 nAChRs might contribute to DA dysregulation in nicotine addiction.