SYNTHESIS AND CYTOTOXICITY OF NOVEL LIGNANS

In this study the syntheses of 11 novel lignans are described. Their cytotoxicities are studied in GLC4, a human small cell lung carcinoma cell line, using the microculture tetrazolium (MTT) assay. Ten of these compounds were substituted with a menthyloxy group on the 5-position of the lactone. These compounds can easily be prepared in (novel) ‘one-pot’, three- or four-step syntheses. In addition, methods for controlling the stereogenic centers are described. Furthermore, five naturally occurring podophyllotoxin-related compounds were tested. The cytotoxicities of all lignan compounds, and of three non-lignan intermediates originating from the syntheses, were compared with the clinically applied anticancer agents etoposide, teniposide, and cisplatin. Most compounds showed moderate to high activities against GLC4, and two of the compounds containing a menthyloxy group showed activities comparable to the reference cytotoxic agents.

Relative effectiveness and adverse effects of cervical manipulation, mobilisation and the activator instrument in patients with sub-acute non-specific neck pain: results from a stopped randomised trial

<p>Abstract</p> <p>Background</p> <p>Neck pain of a mechanical nature is a common complaint seen by practitioners of manual medicine, who use a multitude of methods to treat the condition. It is not known, however, if any of these methods are superior in treatment effectiveness. This trial was stopped due to poor recruitment. The purposes of this report are (1) to describe the trial protocol, (2) to report on the data obtained from subjects who completed the study, (3) to discuss the problems we encountered in conducting this study.</p> <p>Methods</p> <p>A pragmatic randomised clinical trial was undertaken. Patients who met eligibility criteria were randomised into three groups. One group was treated using specific segmental high velocity low amplitude manipulation (diversified), another by specific segmental mobilisation, and a third group by the Activator instrument. All three groups were also treated for any myofascial distortions and given appropriate exercises and advice. Participants were treated six times over a three-week period or until they reported being pain free. The primary outcome measure for the study was Patient Global Impression of Change (PGIC); secondary outcome measures included the Short-Form Health Survey (SF-36v₂), the neck Bournemouth Questionnaire, and the numerical rating scale for pain intensity. Participants also kept a diary of any pain medication taken and noted any perceived adverse effects of treatment. Outcomes were measured at four points: end of treatment, and 3, 6, and 12 months thereafter.</p> <p>Results</p> <p>Between January 2007 and March 2008, 123 patients were assessed for eligibility, of these 47 were considered eligible, of which 16 were allocated to manipulation, 16 to the Activator instrument and 15 to the mobilisation group. Comparison between the groups on the PGIC adjusted for baseline covariants did not show a significant difference for any of the endpoints. Within group analyses for change from baseline to the 12-month follow up for secondary outcomes were significant for all groups on the Bournemouth Questionnaire and for pain, while the mobilisation group had a significant improvement on the PCS and MCS subscales of the SF-36_v2. Finally, there were no moderate, severe, or long-lasting adverse effects reported by any participant in any group.</p> <p>Conclusions</p> <p>Although the small sample size must be taken into consideration, it appears that all three methods of treating mechanical neck pain had a long-term benefit for subacute neck pain, without moderate or serious adverse events associated with any of the treatment methods. There were difficulties in recruiting subjects to this trial. This pragmatic trial should be repeated with a larger sample size.</p

Relationship between self-reported weight change, educational status, and health-related quality of life in patients with diabetes in Luxembourg

&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;The aim of this study was to assess the relationship between self-reported weight change, socio-economic status, and health-related quality of life (HRQOL) in patients with diabetes, 5 years after they underwent coronary angiography.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Between 2013 and 2014, 1873 of 4391 patients (319 with diabetes) who underwent coronary angiography between 2008 and 2009 participated in a follow-up study. Three out of four domains of the World Health Organization Quality of Life (WHOQOL)-BREF (physical health, psychological health and social relationships) were surveyed during the follow-up period. To assess the relationship between weight change and HRQOL, generalized linear models were constructed for every dimension of the WHOQOL-BREF, with educational level as a predictor and sex, age, marital status, smoking status, hypertension, cholesterol, ischemic heart disease, acute myocardial infarction, and stable angina pectoris as covariates.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;The mean age of the patients was 70 years and almost three-quarters of the patients (72.7 %) were men. During the 12 months preceding the follow-up survey, 22.6 % of the patients reported weight loss, 20 % reported weight gain, and 57.4 % reported no weight change. There were significant differences in the HRQOL scores between patients who reported weight loss and those who reported either weight gain or unchanged weight. The most affected domains were physical and psychological health, with higher scores for patients who reported weight loss (54.7 and 67.2, respectively) than those who reported weight gain (46.3 and 58.5, respectively). The generalized linear model confirmed higher HRQOL scores among patients who reported weight loss and revealed an association between the HRQOL score and education level.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;Weight change and education level were associated with HRQOL in patients with diabetes. Self-reported weight loss and no weight change were positively associated with HRQOL in patients with diabetes, while weight gain was negatively associated with HRQOL.&lt;/p&gt;</p

A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease

Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory adipokine, functions via leptin receptors, signaling via the long isoform of receptor, LepRb. Leptin promotes DC maturation and increases CCR7 expression on blood DC. Increased mesenteric fat and leptin occur early in Crohn's disease (CD), suggesting leptin-mediated change in intestinal CCR7 expression on DC as a pro-inflammatory mechanism. We have demonstrated CCR7 expression and capacity to migrate to its ligand macrophage inflammatory protein 3β in normal human ileal DC but not colonic or blood DC. In CD, functional CCR7 was expressed on DC from all sites. Only DC populations containing CCR7-expressing cells produced LepRb; in vitro exposure to leptin also increased expression of functional CCR7 in intestinal DC in a dose-dependent manner. In conclusion, leptin may regulate DC migration from gut, in homeostatic and inflammatory conditions, providing a link between mesenteric obesity and inflammation