Functionalization of C–H bonds in acetophenone oximes with arylacetic acids and elemental sulfur

Fused thieno[3,2-d]thiazoles were synthesized via a coupling of acetophenone ketoximes, arylacetic acids, and elemental sulfur in the presence of Li₂CO₃ base. Functionalities including chloro, bromo, fluoro, trifluoromethyl, and pyridyl groups were compatible with reaction conditions. High yields and excellent regioselectivities were obtained even if meta-substituted ketoxime acetates were used. Ethyl esters of heteroarylacetic acids were competent substrates, which is very rare in the literature. Our method would offer a convenient protocol to afford polyheterocyclic structures from simple substrates.

Annulation of acetophenone oxime acetates, arylacetic acids or esters, and elemental sulfur in absence of transition metals is reported.     

Hospitalized osteoporotic vertebral fracture increases the risk of stroke: A population‐based cohort study

The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age‐ and sex‐matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed‐up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan‐Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person‐years; 95% confidence interval [CI], 27.5–51.2) was significantly higher than in the comparison group (14.0 per 1000 person‐years; 95% CI, 12.0–16.4, p < 0.001). Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2.68, 95% CI 1.89–3.79, p < 0.001; adjusted HR 2.71, 95% CI 1.90–3.86, p < 0.001). In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies. © 2013 American Society for Bone and Mineral Research.     

Association between initial morphine intake and body weight change,acoustic startle reflex and drug seeking in rats

Rationale

Although chronic use of opiates can induce physical dependence and addiction, individual differences contributing to these symptoms are largely unknown.

Objectives

Using intravenous morphine self-administration (MSA), we investigated whether individual differences in drug intake are associated with weight change, acoustic startle reflex (ASR), pre-pulse inhibition (PPI), and drug seeking during spontaneous withdrawal.

Methods

Male Sprague-Dawley rats self-administered morphine (0.5 mg/kg/infusion) or saline for 3 weeks (4–6 h/day, 5 days/week) and drug intake and body weight were monitored daily. The ASR and the PPI (baseline, 1 day and 1 week) and drug seeking (1 week) were measured during spontaneous withdrawal.

Results

Morphine animals did not gain weight (101 %?±?0.69), while the control animals did (115 %?±?1.06) after 3 weeks of self-administration. The ASR and the PPI were not significantly different between morphine and saline animals in 1-day or 1-week withdrawal. However, individual differences in initial (first 10 min), but not total (4–6 h), morphine intake of the daily sessions were positively correlated with weight change (r?=?0.437, p?=?0.037) and drug seeking (r?=?0.424, p?=?0.035) while inversely correlated with the ASR (r?=??0.544, p?=?0.005) in 1-week withdrawal from chronic morphine.

Conclusions

A subgroup of animals that self-administered a larger amount of morphine at the beginning of the daily sessions exhibited subsequent weight gain, reduced ASR, and enhanced drug seeking in morphine withdrawal. Thus, individual differences in initial morphine intake may reveal a novel behavioral phenotype in opioid addiction.     

Size Effects in Internal Friction of Nanocrystalline Aluminum Films

Al thin film is extensively used in micro-electromechanical systems (MEMS) and electronic interconnections; however, most previous research has concentrated on their quasi-static properties and applied their designs on larger scales. The present study designed a paddle-like cantilever specimen with metal films deposited on the upper surface to investigate the quasi-static properties of Al thin film at room temperature under high vacuum conditions at microscopic scales. Energy loss was determined using a decay technique in the oscillation amplitude of a vibrating structure following resonant excitation. Grain size and film thickness size were strictly controlled considering the quasi-static properties of the films. This study found that the internal friction of ultra-thin and thin Al films was more dependent on the grain boundaries than film thickness.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.