Interpretation and working through.

The function of insight is independent of content. Insight is the result of the assignment of meaning as distinct from finding meaning. Interpretation leads to insight which binds anxiety and lifts repression, thus providing relief of symptoms. Working is learning to apply the assigned meaning to new situations.     

Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248

Recent achievements in the development of multitargeted molecular inhibitors necessitate a better understanding of the contribution of activity against individual targets to their efficacy. SU11248, a small-molecule inhibitor targeting class III/V receptor tyrosine kinases, including the platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors, KIT and FLT3, exhibits direct effects on cancer cells as well as antiangiogenic activity. Here, we investigated the contributions of inhibiting individual SU11248 target receptors to its overall antitumor efficacy in tumor models representing diverse signaling paradigms. Consistent with previous results, SU11248 was highly efficacious (frequently cytoreductive) in all models tested. To elucidate the specific contributions of inhibition of PDGF and VEGF receptors to the in vivo efficacy of SU11248, we employed two selective inhibitors, SU10944 (VEGF receptor inhibitor) and Gleevec (PDGF receptor inhibitor). SU10944 alone induced a tumor growth delay in all models evaluated, consistent with a primarily antiangiogenic mode of action. In contrast, Gleevec resulted in modest growth inhibition in tumor models in which the cancer cells expressed its targets (PDGFRbeta and KIT), but was not efficacious against tumors not driven by these target receptor tyrosine kinases. Strikingly, in all but one tumor model evaluated, the antitumor efficacy of SU10944 combined with Gleevec was similar to that of single-agent SU11248, and was greatly superior to that of each compound alone, indicating that the antitumor potency of SU11248 in these models stems from combined inhibition of both PDGF and VEGF receptors. The one exception was a model driven by an activated mutant of FLT3, in which the activity of SU11248, which targets FLT3, was greater than that of SU10944 plus Gleevec. Moreover, SU10944 combined with Gleevec inhibited tumor neoangiogenesis to an extent comparable to that of SU11248. Thus, the potent efficacy of SU11248 in models representing diverse signaling paradigms results from simultaneous inhibition of individual target receptors expressed both in cancer cells and in the tumor neovasculature, supporting the hypothesis that multitargeted inhibitors have the cumulative antitumor efficacy of combined single-target inhibitors.     

Distribution of phenolic compounds and antioxidative activities in parts of sweet potato (Ipomoea batata L.) plants and in home processed roots

We measured six phenolic compounds by HPLC, the total phenolic content by Folin-Ciocalteu, and antioxidative activities by three methods in the sweet potato plant and in home processed roots. Total phenolic content was highest in the leaves. Eight root varieties were partitioned and analyzed for phenolics. The stem end of the root had significantly more phenolics. In all samples the predominant chlorogenic acids were 5-caffeoylquinic acid (5-CQA) and 3,5-diCQA. 3,4-diCQA was present in significant amounts in the leaves and the flower, and 4,5-diCQA in the leaves. Six home-processing/cooking techniques reduced phenolic content from 7% (baking) to ∼40% (deep frying/boiling). High correlations were observed between phenolic compounds determined by HPLC and Folin-Ciocalteu, radical scavenging activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH), and oxidative activity by ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. The results show that there is a large variation in phenolics among sweet potato varieties and different parts of the plant and that high-phenolic sweet potato leaves, widely consumed in Asian countries as a vegetable, should be considered for diets of other countries.     

Development of a US trust measure to assess and monitor parental confidence in the vaccine system

Objective

To develop a Vaccine Confidence Index (VCI) that is capable of detecting variations in parental confidence towards childhood immunizations centered on trust and concern issues that impact vaccine confidence.

Twelve cases of pituitary metastasis: a case series and review of the literature

Purpose

The pituitary gland is an unusual site for metastatic spread, but as patients with metastatic malignancy are living longer, it may become more prevalent. Compression of important anatomy adjacent to the sella may produce disabling symptoms and endocrine derangement, leading to significant morbidity.

Methods

An ambispective review of patient records between 2013 and 2017 from three neurosurgical centres was performed. After identifying cases, further investigation was performed to evaluate patient demographic, symptoms at presentation, radiological and histological findings, management, and outcome.

Results

Our investigation identified 12 patients with pituitary metastasis. The average age of the cases was 63.4 years, with breast (n?=?4) and lung (n?=?4) being the most common primary cancers. In half the cases there was a history of metastatic disease, while in one-quarter of cases, pituitary symptoms were the first sign of malignancy. Adenohypophyseal dysfunction (83%), diabetes insipidus (DI) (75%), headache (67%) and visual field defects (67%) were the most common findings at presentation. Glucocorticoid replacement increased the sensitivity for diagnosis of DI. All cases were contrast enhancing on MRI and the endoscopic trans-sphenoidal approach was preferred for biopsy and debulking.

Conclusions

The pituitary should not be overlooked as a site of metastasis and sellar symptoms may be the first presentation of neoplastic disease. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Moreover, the development of DI or ophthalmoplegia from any pituitary lesion is suggestive of metastatic disease even in patients with no known primary.

     

The effect of continuous intracerebroventricular infusion of satietin on ingestion, activity and body weight of rats

Satietin is a putative satiety agent when given either peripherally or intracerebroventricularly (ICV). In the present study male Sprague Dawley rats were fitted with chronic third ventricle cannulas. After recovery, Alzet seven day osmotic pumps were inserted subcutaneously and tubing was connected to the cannula. Rats were then infused ICV with saline or semi-purified human satietin (25 micrograms/day; 1 microliter/hr). In the satietin group, daily chow intake was reduced (p less than 0.05) on days 1 and 2, recovered to control levels on days 4 and 5 and again declined (p less than 0.05) on days 6-8. During this latter period the satietin treated animals appeared ill. The satietin group's water intake paralleled food consumption, whereas the groups' water/food intake ratios did not differ. Satietin infusions decreased (p less than 0.01) the rats' body weight 42 grams by day 4, whereas the control group's weight remained constant. Even during the period where the satietin group's food intake returned to control levels they continued to lose weight. Running wheel activity was reduced throughout the satietin infusion period even when food and water ingestion had returned to control levels. The data suggest that semi-purified human satietin, when tested in rats, is an anorexogenic agent, however, its continuous use quickly produces tolerance and later what may be a cross-species allergic reaction (due to the satietin itself or a contaminant). The appropriateness of testing semi-purified satietin in the rat model is questioned.     

Verletzungen und gewaltsamer Tod aus physikalischer Ursache

Ohne Zusammenfassung     

Verletzungen. Gewaltsamer Tod aus physikalischer Ursache

International Journal of Legal Medicine -