Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa

Background  

Angiogenesis, a complex multistep process that comprehends proliferation, migration and anastomosis of endothelial cells (EC), has a major role in the development of pathologic conditions such as inflammatory diseases, tumor growth and metastasis. Brazilian flora, the most diverse in the world, is an interesting spot to prospect for new chemical leads, being an important source of new anticancer drugs. Plant-derived alkaloids have traditionally been of interest due to their pronounced physiological activities. We investigated the anti-angiogenic potential of the naturally occurring guanidine alkaloid pterogynidine (Pt) isolated from the Brazilian plant Alchornea glandulosa. The purpose of this study was to examine which features of the angiogenic process could be disturbed by Pt.     

Reward Cues in Space: Commonalities and Differences in Neural Coding by Hippocampal and Ventral Striatal Ensembles

Forming place-reward associations critically depends on the integrity of the hippocampal-ventral striatal system. The ventral striatum (VS) receives a strong hippocampal input conveying spatial-contextual information, but it is unclear how this structure integrates this information to invigorate reward-directed behavior. Neuronal ensembles in rat hippocampus (HC) and VS were simultaneously recorded during a conditioning task in which navigation depended on path integration. In contrast to HC, ventral striatal neurons showed low spatial selectivity, but rather coded behavioral task phases toward reaching goal sites. Outcome-predicting cues induced a remapping of firing patterns in the HC, consistent with its role in episodic memory. VS remapped in conjunction with the HC, indicating that remapping can take place in multiple brain regions engaged in the same task. Subsets of ventral striatal neurons showed a "flip" from high activity when cue lights were illuminated to low activity in intertrial intervals, or vice versa. The cues induced an increase in spatial information transmission and sparsity in both structures. These effects were paralleled by an enhanced temporal specificity of ensemble coding and a more accurate reconstruction of the animal's position from population firing patterns. Altogether, the results reveal strong differences in spatial processing between hippocampal area CA1 and VS, but indicate similarities in how discrete cues impact on this processing.     

Socio-demographic, health-related and psychosocial correlates of fear of falling and avoidance of activity in community-living older persons who avoid activity due to fear of falling

Background  

Fear of falling and avoidance of activity are common in old age and are suggested to be (public) health problems of equal importance to falls. Earlier studies of correlates of fear of falling and avoidance of activity did hardly differentiate between severe and mild levels of fear of falling and avoidance of activity which may be relevant from clinical point of view. Furthermore, most studies focused only on socio-demographics and/or health-related variables and hardly incorporated an extensive range of potential correlates of fear of falling including psychosocial variables. This study analyzes the univariate and multivariate associations between five socio-demographic, seven health-related and six psychosocial variables and levels of fear of falling and avoidance of activity in older persons who avoid activity due to fear of falling.     

A split microdrive for simultaneous multi-electrode recordings from two brain areas in awake small animals

Complex cognitive operations such as memory formation and decision-making are thought to be mediated not by single, isolated brain structures but by multiple, connected brain areas. To facilitate studies on the neural communication between connected brain structures, we developed a multi-electrode microdrive for chronically recording ensembles of neurons in two different brain areas simultaneously. The "split drive" contains 14 independently movable microdrivers that were designed to hold tetrodes and to permit day-to-day adjustment of dorsoventral position in the brain. The limited weight of the drive allowed rats to adjust well to the headstage after recovering from surgery and permitted stable recording sessions across at least several weeks. In addition to describing the design and assembly of the split drive, we also discuss some important individual parts of microdrives used for tetrode recordings in general. Furthermore, the split drive was applied to two widely separated and connected brain structures, the hippocampus and ventral striatum. From these two areas, stable ensemble recordings were conducted in rats performing a reward-searching task on a triangular track, yielding group sizes of about 15 and 25 units in the dorsal hippocampus and ventral striatum, respectively.     

Critical Appraisal on the Role and Outcome of Emergency Colectomy for Uncomplicated Right-sided Colonic Diverticulitis

Background Emergency colectomy is well accepted for treating complicated right-sided colonic diverticulitis. However, the role of colectomy for uncomplicated diverticulitis is not well defined. The aim of this study was to evaluate the short-term and long-term surgical outcome of uncomplicated right-sided diverticulitis in our locality. Patients and Methods Retrospective chart review of patients operated for right-sided diverticulitis over a 20-year period was conducted. Recurrent attacks of right-sided diverticulitis, re-operation rate and re-hospitalisation rate were the long-term parameters of interest. An updated telephone interview was carried out for all surviving patients. Results Seventy-four patients (35 males and 39 females), median age 35.5 (range 16–70) years, were operated for uncomplicated diverticulitis. Thirty patients underwent colectomy, whereas the others underwent appendectomy with diverticulectomy (n = 8) or appendectomy alone (n = 36). All short-term parameters were less favourable for the colectomy group, including higher complication rate, slower return of gastrointestinal function, higher requirement of parenteral analgesic and longer hospital stay. Without colectomy, only 2 patients developed recurrent diverticulitis necessitating hospitalisation, both of whom resolved on conservative treatment. On the other hand, 1 patient required re-operation after colectomy because of intestinal obstruction. The overall re-hospitalisation rate was comparable between the colectomy and the non-colectomy group (16.7% vs. 13.6%). Conclusions Emergency colectomy can eradicate suspicious lesions and eliminate risk of recurrent diverticulitis but at the expense of higher morbidity rates. As the natural course of uncomplicated right-sided colonic diverticulitis is usually benign, conservative treatment with minimal surgery may be a better therapeutic option.     

Psychosocial impact of Von Hippel–Lindau disease: levels and sources of distress

Lammens CRM, Bleiker EMA, Verhoef S, Hes FJ, Ausems MGEM, Majoor‐Krakauer D, Sijmons RH, Luijt van der RB, Ouweland van den AMW, Van Os Tam, Hoogerbrugge N, Gomez‐Garcia EB, Dommering CJ, Gundy CM, Aaronson NK. Psychosocial impact of von Hippel–Lindau disease: levels and sources of distress. Von Hippel–Lindau disease (VHL) is a hereditary tumor susceptibility syndrome, characterized by an increased risk of developing multiple benign and malignant tumors at various sites and ages with limited preventive options. This study evaluates the prevalence of distress among VHL family members and factors associated significantly with such distress. Forty‐eight families with a VHL mutation were identified via the nine family cancer clinics in the Netherlands. In total, 171 family members (carriers, 50% at‐risk, non‐carriers) were approached, of whom 123 (72%) completed a self‐report questionnaire. Approximately 40% of the VHL family members reported clinically relevant levels of distress, approaching 50% among the carriers and, possibly even more striking, 36% among the non‐carriers. Having lost a first degree relative due to VHL during adolescence (OR 11.2; 95% CI 1.4–86.9) was related significantly to heightened levels of distress. Approximately, only one‐third of those who reported heightened levels of distress had received professional psychosocial support. A substantial percentage of family members experience clinically relevant levels of distress. We would recommend the introduction of a procedure for screening for distress in this vulnerable population. Special attention should be paid to those individuals who have lost a close relative due to VHL during adolescence.     

How to determine life expectancy change of air pollution mortality: a time series study

Background  

Information on life expectancy (LE) change is of great concern for policy makers, as evidenced by discussions of the "harvesting" (or "mortality displacement") issue, i.e. how large an LE loss corresponds to the mortality results of time series (TS) studies. Whereas loss of LE attributable to chronic air pollution exposure can be determined from cohort studies, using life table methods, conventional TS studies have identified only deaths due to acute exposure, during the immediate past (typically the preceding one to five days), and they provide no information about the LE loss per death.     

Emphysema on imaging is associated with quality of life in elderly patients with chronic obstructive pulmonary disease

Background:   Limited data are available on the association between the severity of emphysema or airway narrowing, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD), which has been seen to be more prevalent among elderly subjects. The aim of this study was to examine the association between HRQOL, physical parameters and structural alterations in lung of COPD patients.
Methods:   Stable COPD patients ( n  = 125; mean age 71.0) were studied. Both the severity of emphysema, which was expressed as the extent of the low-attenuation area (LAA%), and percentage of the large airway wall area (WA%) on high-resolution computed tomography (HRCT) were compared with various parameters of the generic and HRQOL, respectively, together with pulmonary function tests and exercise capacity.
Results:   The predicted value of forced expiratory volume in 1 s was significantly associated with both LAA% and WA%, but the diffusion capacity was strongly correlated with LAA% alone. Parameters of the generic and HRQOL, and almost all other parameters appeared to be significantly associated with LAA% alone, whereas no association was observed between WA% and QOL.
Conclusion:   We concluded that the severity of emphysema, but not that of large airway narrowing on HRCT, is associated with both generic and health-related QOL and reduced diffusion capacity. This notion might provide useful information in practice among elderly subjects who are unable to perform a spirometry.     

In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: a case report

Background

The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium.

Methods

The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations. The removal of the urothelial layer was affirmed microscopically.

Results

After the swabbing, the smaller contractions were evoked by electrical as well as by chemical stimulation (50 μM carbachol or 50 μM α, β meATP). Electrical stimulation, carbachol and substance P (5 μM) evoked lower release of ATP in the swabbed strips than in intact strips. Although release of NO evoked by electrical stimulation or substance P was not changed, release of NO evoked by carbachol was significantly less in the swabbed preparations.

Conclusion

Since swabbing removes only the urothelium, the presence of the suburothelial layer may explain the difference between our findings and those of others who found an increase in contractility. Evoked release of ATP is reduced in swabbed strips, indicating that ATP derives solely from the urothelium. On the other hand, electrical stimulation and substance P evoke identical degrees of NO release in both intact and swabbed preparations, suggesting that NO can be released from the suburothelium. Conversely, carbachol-induced release of NO is lower in swabbed strips, implying that the cholinergic receptors (muscarinic or nicotinic) are located in the upper layer of the urothelium.