Foods, diet, and skin diseases

Human skin is continuously exposed to internal and external influences that may alter its condition and functioning. As a consequence, the skin may undergo alterations leading to immune dysfunction, imbalanced epidermal homeostasis, or other skin disorders. New theories are developing that link food intake and health. The objective of this review is to evaluate current knowledge about the interrelation of food and skin, particularly the effect of nutrients on some cutaneous immune disorders and therapeutic actions of nutrients in skin disorders.     

Training physiotherapy students' abilities in scoring the motor assessment scale for stroke

The purpose of this study was to test the ability of students in scoring an observational tool for measuring physical disability, the Motor Assessment Scale (MAS) for stroke, before and after training in order to establish whether current training and testing procedures for students are adequate. Sixteen students were tested using items 1-8 of the MAS before and after training. The students were required to observe the videotaped performance of four patients with stroke being assessed using the MAS and to score the performance of each patient. After training, the students were retested. The percent exact agreement between students' scores and criterion scores was calculated for each student and for each item. They were then compared before and after training using Student t test. When compared with criterion, the students achieved a mean of 79.6% (standard deviation, 10.8%) exact agreement before training and 83.9% (standard deviation, 6.7%) after training. While this increase in percent exact agreement was not statistically significant (p = 0.10), all students reached at least 75% exact agreement after training. Percent exact agreement on the items increased significantly (p = 0.03) so that seven of the eight items reached at least 75% exact agreement after training. The results of this study suggest that training is important to ensure that all students reach an acceptable standard.     

Splenic marginal zone lymphoma with or without villous lymphocytes. Hematologic findings and outcomes in a series of 57 patients

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a well defined pathologic entity. However, questions regarding the bone marrow infiltration rate, the minimal diagnostic data set, and therapy remain unanswered. METHODS: Clinical-pathologic features and outcomes of 57 consecutive patients who had splenomegaly with no clinically significant lymphadenomegaly and who were diagnosed with SMZL with or without (+/-) villous lymphocytes (VL) were reviewed. RESULTS: SMVL +/- VL occurred mostly in elderly males (median age, 62 years +/- 10 years; male-to-female ratio, (1.85). Anemia was recorded in 49% of patients, and 30% of patients had moderate thrombocytopenia. Leukocytosis and leukopenia were found in 33% and 14% of patients, respectively, and typical VL were found in 84% of patients. Serology for hepatitis C virus infection was positive in 16% of patients, and a small monoclonal component was detected in 36% of patients. The bone marrow was infiltrated with an intrasinusoidal component in all patients. Thirteen patients were monitored using a watch-and-see policy, and they remained alive 1-5 years after diagnosis. Overall, 21 patients (36%) underwent splenectomy; and, in all patients, the diagnosis of SMZL was confirmed histologically in the surgical specimens. Twenty-five patients received single-agent therapy, which included either alkylators or pentostatine, and they achieved an overall response rate (ORR) of 65% and 87%, respectively: Polychemotherapy was administered to 6 patients (ORR, 83%). The median survival for all patients in the series was not reached, and it is expected that 70% of patients will be alive at 5 years. CONCLUSIONS: Up to 20% of patients who had SMZL +/- VL could be monitored using a watch-and-wait policy. The bone marrow intrasinusoidal infiltration pattern may be a valuable diagnostic hallmark, thus obviating diagnostic splenectomy. The issues regarding prognostic stratification and the best therapeutic strategy need to be addressed in properly designed, prospective trials.     

Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth

The insulin-like growth factor-1 receptor (IGF-1R) plays a pivotal role in transformation, growth, and survival of malignant cells, and has emerged as a general and promising target for cancer treatment. However, no fully selective IGF-1R inhibitors have thus far been found. This is explained by the fact that IGF-1R is highly homologous to the insulin receptor, coinhibition of which may cause diabetic response. The receptors are both tyrosine kinases, and their ATP binding sites are identical, implying that ATP inhibitors cannot discriminate between them. Therefore, the current strategy has been to identify compounds interfering with receptor autophosphorylation at the substrate level. In this study we investigated the effects of cyclolignans and related molecules on IGF-1R activity. We report that certain cyclolignans are potent and selective inhibitors of tyrosine phosphorylation of the IGF-1R. Of particular interest was picropodophyllin (PPP), which is almost nontoxic (LD(50) >500 mg/kg in rodents). PPP efficiently blocked IGF-1R activity, reduced pAkt and phosphorylated extracellular signal regulated kinase 1 and 2 (pErk1/2), induced apoptosis in cultured IGF-1R-positive tumor cells, and caused complete tumor regression in xenografted and allografted mice. PPP did not affect the insulin receptor or compete with ATP in an in vitro kinase assay, suggesting that it may inhibit IGF-1R autophosphorylation at the substrate level. This is also in agreement with our molecular model of how the cyclolignans may act on the IGF-1R kinase. Our results open the possibility to use PPP or related compounds with inhibitory effects on IGF-1R as lead compounds in development of anticancer agents.     

Subpopulations of rat dorsal root ganglion neurons express active vesicular acetylcholine transporter

The vesicular acetylcholine transporter (VAChT) is a transmembrane protein required, in cholinergic neurons, for selective storage of acetylcholine into synaptic vesicles. Although dorsal root ganglion (DRG) neurons utilize neuropeptides and amino acids for neurotransmission, we have previously demonstrated the presence of a cholinergic system. To investigate whether, in sensory neurons, the vesicular accumulation of acetylcholine relies on the same mechanisms active in classical cholinergic neurons, we investigated VAChT presence, subcellular distribution, and activity. RT-PCR and Western blot analysis demonstrated the presence of VAChT mRNA and protein product in DRG neurons and in the striatum and cortex, used as positive controls. Moreover, in situ hybridization and immunocytochemistry showed VAChT staining located mainly in the medium/large-sized subpopulation of the sensory neurons. A few small neurons were also faintly labeled by immunocytochemistry. In the electron microscope, immunolabeling was associated with vesicle-like elements distributed in the neuronal cytoplasm and in both myelinated and unmyelinated intraganglionic nerve fibers. Finally, [(3)H]acetylcholine active transport, evaluated either in the presence or in the absence of ATP, also demonstrated that, as previously reported, the uptake of acetylcholine by VAChT is ATP dependent. This study suggests that DRG neurons not only are able to synthesize and degrade ACh and to convey cholinergic stimuli but also are capable of accumulating and, possibly, releasing acetylcholine by the same mechanism used by the better known cholinergic neurons.     

Reevaluation of mortality risks from leukemia in the formaldehyde cohort study of the National Cancer Institute

OBJECTIVE: To determine whether the National Cancer Institute's (NCI) recent suggestion of a causal association between formaldehyde exposure and mortality from leukemia and myeloid leukemia (ML) is robust with respect to alternative characterizations and categorizations of formaldehyde exposure and to alternative methods of data analysis. METHODS: The original authors provided the cohort data. We computed US and local county rate-based standardized mortality ratios (SMRs) and internal cohort rate-based relative risks (RR) by categories of four formaldehyde exposure metrics (highest peak, average intensity (AIE), cumulative, and duration), using both NCI categories and an alternative categorization based on tertiles of deaths from all leukemia among exposed subjects. For highest peak exposure, we computed RRs by the duration of time worked in the highest peak category and the time since highest peak exposure. For AIE, we computed RRs by the duration of exposure and the time since first exposure. RESULTS: Our external comparisons revealed that the elevated leukemia and ML RRs and associated trends reported by NCI for highest peak and AIE occurred because null (or slight) to moderate mortality excesses were compared with statistically significant baseline category deficits in deaths. Our alternative categorization of AIE yielded leukemia and ML SMRs close to 1.0 in the highest exposure category, and revealed weaker evidence of a trend in RRs for leukemia and ML. We corroborated NCI's finding of no association for cumulative and duration of formaldehyde exposure. We found no consistent evidence that leukemia or ML risks increased with increasing duration of time spent in a given highest peak exposure (or for AIE, duration of exposure in a given AIE category). We also found no consistent evidence that leukemia or ML risks were greater in the more relevant shorter (less than 20 years) versus longer (20+ years) periods of time from the first highest peak exposure (or for AIE, first exposure). CONCLUSIONS: Our reanalysis provided little evidence to support NCI's suggestion of a causal association between formaldehyde exposure and mortality from leukemia and ML. NCI's key findings for highest peak exposure and AIE do not adequately account for the inordinately large deficits in deaths in the categories used as the baselines for internal rate-based RRs. The NCI findings also do not adequately account for the duration of time subjects spent in the highest peak category (or for AIE, duration of exposure) or the time since their first peak exposure (or for AIE, time since first exposure). Our finding that NCI's suggestion of a causal association is not robust with respect to alternative categorizations of formaldehyde exposure and methods of data analysis casts considerable additional uncertainty regarding the validity of this suggested association.     

Intracerebroventricular injection of the terminal complement complex causes inflammatory reaction in the rat brain

To investigate the effect of the terminal complement complex (TCC) on the central nervous system, we injected both the cytolytically active and the inactive complexes into the lateral ventricle of rats. Both complexes promoted accumulation of leukocytes into the cerebrospinal fluid at 4-6 h post-injection. The cells recovered at this time were mostly polymorphonuclear leukocytes (PMN) that were partially replaced by mononuclear cells at 12 h. A direct contribution of the complexes to the in-vivo migration of leukocytes was ruled out by their inability to be chemotactic for rat PMN. Contaminating C5a is unlikely to be responsible for the effect of TCC because it failed to mobilize leukocytes when injected into the lateral ventricle. Histological analysis of rat brains 6 hours after injection of TCC revealed marked leukocyte infiltration of the choroid plexus, increased expression of intercellular adhesion molecule-1 and egression of leukocytes out of the meningeal vessels. The cerebrospinal fluid of rats treated with TCC exhibited chemotactic activity for rat PMN and increased levels of growth related oncogene/cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1 preceding the accumulation of leukocytes. Elevated concentration of IL-1 beta was also found in the cerebrospinal fluid and in periventricular areas of rats treated with TCC.