Sympathetic skin response in peritoneal dialysis patients

To determine if there is any difference in nerve conduction studies or sympathetic skin response (SSR) between patients on peritoneal dialysis and those on regular hemodialysis, we did a cross-sectional observational study. The study group consisted of 24 patients on peritoneal dialysis (PD) (12 men, aged 45 +/- 17 years) and 20 patients on hemodialysis (HD) (11 men, aged 50 +/- 22 years). All of these patients were in stable clinical condition, they were receiving adequate dialysis, and none of them had systemic diseases. Motor and sensory nerve conduction studies of the common and medial peroneal nerve and SSR were performed in all patients. There were no differences in motor and sensory nerve conduction velocities between PD and HD patients. All PD patients had detectable SSR. However, six patients on HD (30%) failed to show SSR (p < 0.05). Mean SSR amplitude was higher in PD patients than in HD patients (1233 +/- 843 vs. 605 +/- 771 microv, p < 0.05). There were no differences in mean SSR latency between PD and HD patients. PD modality (continuous ambulatory PD vs. automated PD) or the presence of residual renal function did not influence nerve conduction studies or SSR. In conclusion, using standard nerve conduction studies, no differences could be found between HD and PD. However, a higher proportion of patients on HD showed an impaired SSR, suggesting that subclinical neuropathy may be more common in HD than PD patients.     

Cytotoxic cucurbitacin constituents from Sloanea zuliaensis

A new cucurbitacin D analogue, 2-deoxycucurbitacin D (1), as well as cucurbitacin D (2) and 25-acetylcucurbitacin F (3) were isolated from Sloanea zuliaensis. Compound 1 was found only in the young leaves of the plant and not in the mature leaves, and its structure was established using spectroscopic means. Compounds 1-3 demonstrated potent cytotoxic activity against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines.     

Endobronchial foreign body extraction: a new interventional approach

Endobronchial foreign bodies are often difficult to diagnose as the cause of obstructive pneumonias and atelectasis, but once discovered, they can generally be removed, leading to immediate and dramatic resolution of symptoms. The use of flexible fiberoptic and rigid bronchoscopy to extract foreign bodies is well-known. Thoracotomy is generally reserved as a last resort due to the inherent risks of the procedure. We describe a new technique for foreign body removal utilizing steerable hydrophilic guidewires, standard sheaths, and a snare device commonly utilized in intravascular foreign body retrieval.     

In vitro infection of human primary adipose cells with HIV-1: a reassessment

We reassessed the infection ability of human primary preadipocytes. The use of X4, R5 or VSV-G-pseudotyped viral particles indicated that viral entry is the limiting step. However, transfection with HIV-1 receptors restored efficient infection. Analyses of CD4, CXCR4 and CCR5 expression on preadipocytes and adipocytes revealed that receptor co-expression levels did not permit HIV-1 entry into adipose cells from all biopsies tested. We concluded that adipose tissue cannot be infected with HIV-1 in vivo.     

Role for M5 muscarinic acetylcholine receptors in cocaine addiction

Muscarinic cholinergic receptors of the M5 subtype are expressed by dopamine-containing neurons of the ventral tegmentum. These M5 receptors modulate the activity of midbrain dopaminergic neurons, which play an important role in mediating reinforcing properties of abused psychostimulants like cocaine. The potential role of M5 receptors in the reinforcing effects of cocaine was investigated using M5 receptor-deficient mice in a model of acute cocaine self-administration. The M5-deficient mice self-administered cocaine at a significantly lower rate than wild-type controls. In the conditioned place preference procedure, a classic test for evaluating the rewarding properties of drugs, M5-deficient mice spent significantly less time in the cocaine-paired compartment than control mice. Moreover, the severity of the cocaine withdrawal syndrome (withdrawal-associated anxiety measured in the elevated plus-maze) was significantly attenuated in mice lacking the M5 receptor. These results demonstrate that M5 receptors play an important role in mediating both cocaine-associated reinforcement and withdrawal.     

Behavioral effects of severe and moderate early malnutrition

Rats with a history of prenatal and early postnatal undernutrition (6 or 8% casein diets) were "nutritionally rehabilitated" at weaning, and were compared to well-fed animals (25% casein) at maturity. The severely-malnourished (6%) animals were hyperactive in the open field and when tested in a stabilimeter. They also appeared to be highly active during the early trials in 8-arm radial maze testing where they made more arm entries and re-entry errors than the well-fed rats. In terms of trials to criterion, however, their scores on the radial maze and on a spatial alternation task fell within normal limits. The moderately-malnourished (8%) rats tended to perform at control levels on the learning measures, but these rats were not as active as the 6% rats on the measures of activity. Brain size and weight differences among the three groups of rats also are presented and discussed.     

Immunohistochemical overexpression of platelet-derived growth factor receptor-beta (PDGFR-β) is associated with PDGFRB gene copy number gain in sarcomatoid non-small-cell lung cancer

Introduction

Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We hypothesized that the PDGF-B/PDGF-Rβ pathway may be dysregulated in sarcomatoid lung cancer.

Methods

We conducted immunohistochemical (IHC) and gene copy number gain studies of PDGF-B/PDGFR-β on archived surgically resected specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and stage-matched. Biomarkers were correlated to patient demographics, tumor characteristics, and survival.

Results

Sarcomatoid tumors had higher PDGFR-β IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No difference was seen between the two groups of PDGF-B IHC expression; and neither PDGF-B nor PDGFR-β IHC levels correlated with gender, age, clinical or pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated by FISH using three ways: presence of amplification, gene copy number gain, and gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013). Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher gene copy ratios above 1.83. Higher PDGFR-β IHC expression in tumor cells was associated with gene copy number gain (P = 0.021) and higher gene copy ratio status (P = 0.005).

Conclusion

This is the first study to demonstrate high PDGFR-β IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and suggests that further studies are warranted to determine whether PDGFR-β is a feasible therapeutic target in this population.     

Alterations in dendritic morphology of the prefrontal cortical and striatum neurons in the unilateral 6-OHDA-rat model of Parkinson's disease

We have studied the morphological changes of the dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and the medium spiny neurons of the caudate-putamen (CPu) and nucleus accumbens (NAcc) induced by the injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). The unilateral 6-OHDA-induced lesion of the SNc was made in Wistar rats to produce the Parkinson model lesion. Two weeks after the injection, the testing of rotational behavior caused by amphetamine injection was done to assess the animals with lesions. Four weeks after the 6-OHDA injection, the morphology of the pyramidal cells of Layer 5 of the PFC and the medium spiny neurons of the CPu and NAcc were quantified by modified Golgi-Cox staining. The results showed that the length of dendrites, the branching, and the density of dendritic spines on the medium spiny neurons of the same side of the caudate-putamen lesion were significantly decreased in rats with the unilateral 6-OHDA-induced lesion of the SNc. The pyramidal neurons of the PFC and medium spiny neurons of the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. Our data suggest that the SNc lesion with the 6-OHDA, Hemiparkinsonism animal model may lead to altered neuronal plasticity in the CPu, NAcc, and PFC that may have participated in the emergence of the behavioral changes observed in these animals.