Methamphetamine withdrawal induces activation of CRF neurons in the brain stress system in parallel with an increased activity of cardiac sympathetic pathways.

Methamphetamine (METH) addiction is a major public health problem in some countries. There is evidence to suggest that METH use is associated with increased risk of developing cardiovascular problems. Here, we investigated the effects of chronic METH administration and withdrawal on the activation of the brain stress system and cardiac sympathetic pathways. Mice were treated with METH (2 mg/kg, i.p.) for 10 days and left to spontaneous withdraw for 7 days. The number of corticotrophin-releasing factor (CRF), c-Fos, and CRF/c-Fos neurons was measured by immunohistochemistry in the paraventricular nucleus of the hypothalamus (PVN) and the oval region of the bed nucleus of stria terminalis (ovBNST), two regions associated with cardiac sympathetic control. In parallel, levels of catechol-o-methyl-transferase (COMT), tyrosine hydroxylase (TH), and heat shock protein 27 (Hsp27) were measured in the heart. In the brain, chronic-METH treatment enhanced the number of c-Fos neurons and the CRF neurons with c-Fos signal (CRF+/c-Fos+) in PVN and ovBNST. METH withdrawal increased the number of CRF+neurons. In the heart, METH administration induced an increase in soluble (S)-COMT and membrane-bound (MB)-COMT without changes in phospho (p)-TH, Hsp27, or pHsp27. Similarly, METH withdrawal increased the expression of S- and MB-COMT. In contrast to chronic treatment, METH withdrawal enhanced levels of (p)TH and (p)Hsp27 in the heart. Overall, our results demonstrate that chronic METH administration and withdrawal activate the brain CRF systems associated with the heart sympathetic control and point towards a METH withdrawal induced activation of sympathetic pathways in the heart. Our findings provide further insight in the mechanism underlining the cardiovascular risk associated with METH use and proposes targets for its treatment

Factors associated with pneumococcal immunisation among hospitalised elderly persons: A survey of patient\u27s perception, attitude, and knowledge

To investigate attitudes, perceptions and knowledge of elderly hospital patients in regard to vaccination in general and pneumococcal vaccination in particular. Setting: A hospital-based patient survey in Sydney, Australia. Participants: Patients aged 60 years and older who are admitted to selected wards in an 800-bed tertiary referral hospital in Sydney, Australia. Methods: A face-to-face interview administered to 200 inpatients. Results: Approximately half (49%) of the patients had a positive attitude to vaccination whereas 59% had less positive perception. There were 35% of the patients who were unvaccinated against influenza and pneumococcal disease. Positive perception (OR 2.9, 95% C.I. = 1.3–6.5) and attitude (OR 4.4, 95% C.I. = 2.0–9.4) significantly predicted vaccination with both vaccines. Similarly the odds of receiving pneumococcal vaccination for those who had a more positive attitude and more correct knowledge were significant (OR = 2.3, 95% C.I. = 1.0–5.4; OR = 2.7, 95% C.I. = 1.1–6.8). We explored reasons for non-vaccination. Physician recommendation was listed as an important factor by patients. Conclusions: Positive perception and attitude towards vaccination are significant factors associated with immunisation status. For the pneumococcal vaccination, having influenza vaccination is related to pneumococcal vaccination