Dry skin in dermatology: a complex physiopathology

Dry skin (xerosis) is a common dermatosis affecting people of varying skin types and ages and various areas of the body. It is associated with both skin thickening and skin thinning and is triggered by both exogenous (e.g. climate, environment, lifestyle) and endogenous (e.g. medication, hormone fluctuations, organ diseases) factors. Skin requires a water content of 10–15% to remain supple and intact. This water is either ‘static’ (i.e. bound) or ‘dynamic’. The predominance of hydrophobic substances in intercellular constituents is a means of regulating the humidity of the skin. Emollients, highly effective treatment adjuncts in the management of all dry skin disorders, help to restore damaged intercorneocyte lipid structures and increase the water content of the skin, helping to reduce scaling and improving its barrier function.     

The aging brain, a key target for the future: The protein kinase C involvement

The brain represents the primary centre for the regulation and control of all our body activities, receiving and interpreting sensory impulses and transmitting information to the periphery. Most importantly, it is also the seat of consciousness, thought, emotion and especially memory, being in fact able to encode, store and recall any information. Memory is really what makes possible so many of our complex cognitive functions, including communication and learning, and surely without memory, life would lose all of its glamour and purpose. Age-associated mental impairment can range in severity from forgetfulness at the border with pathology to dementia, such as in Alzheimer's disease. In recent years, one of the most relevant observations of research on brain aging relates to data indicating that age-related cognitive decline is not only due to neuronal loss, as previously thought; instead, scientists now believe that age-associated functional changes have more to do with the dysfunctions occurring over time. Within this context a prominent role is certainly played by signal transduction cascades which guarantee neuronal cell to elaborate coordinated responses to the multiple signals coming from the outside and to adapt itself to the environmental changes and requests. This review will focus the attention on protein kinase C pathway, with a particular interest on its activation process, and on the role of protein-lipid and protein-protein interactions to selectively localize the cellular responses. Furthermore, information is emerging and will be discussed on the possibility of mRNA stabilization through PKC activation. This review will also approach the issue on how alterations of these molecular cascades may have implications in physiological and pathological brain aging, such as Alzheimer's disease.     

Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood-brain barrier.

PURPOSE: The objective of the current study was to determine the ability of some antiemetic compounds to cross the blood-brain barrier (BBB) and thereby to determine possible side effects of compounds for the central nervous system (CNS). METHODS: We compared the brain penetration of some antiemetic compounds using an in vitro BBB model consisting in brain capillary endothelial cells co-cultured with primary rat glial cells. RESULTS: This study clearly demonstrated that the metopimazine metabolite, metopimazine acid, has a very low brain penetration, lower than metopimazine and even less than the other antiemetic compounds tested in this study. CONCLUSIONS: The poor brain penetration of metopimazine acid, metopimazine biodisponible form, seems very likely related to the clinically observed difference in therapeutic and safety profile.     

Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers

The expression of MHC isoforms in the skeletal muscles of nine patients with Duchenne muscular dystrophy (DMD) (from 2.5 to 15 yr of age) and three DMD carriers was studied using different specific anti-MHC MAbs. We also analyzed muscle fiber size and fiber reactivity with acridine orange and/or with a surface antigen marker. One-quarter of all fibers of DMD patients, or less with age, were of normal size and contained only adult slow MHC. Half of the muscle fibers contained adult and developmental MHCs. Only half of these fibers were representative of an active regenerative process. MHC co-expression also altered the proportion of normal fast or slow fibers. Adult fast MHCs were expressed as unique MHC only in small and very small fibers in the oldest DMD patients. In DMD carrier muscles, the greatest alterations in MHC expression were observed in patients with the most reduced dystrophin expression. However, MHC changes in dystrophin-positive fibers were similar to those observed in dystrophin-free fibers. In conclusion, disruptions or delays in the switching of all genes coding for adult fast and slow MHC and developmental MHC coincided with dystrophin deletion and with perturbations in its expression.     

Tumor recurrence in prostatic urethra following simultaneous resection of bladder tumor and prostate

A comparative retrospective study was performed on 100 patients who had undergone transurethral resection of a superficial bladder tumor (Ta-Tl) with no associated carcinoma in situ (group 1) and 100 patients who had undergone simultaneous transurethral resection of a superficial bladder tumor (Ta-Tl), with no associated carcinoma in situ, and benign prostatic hyperplasia (group II). Evaluation of the recurrences of prostatic urethral tumors in both groups showed that they appeared in 10 patients (12 recurrences) in group I and 10 patients (14 recurrences) in group II (p = not significant). These data enabled us to rule out the influence of simultaneous transurethral resection in cases of recurrences of prostatic urethral tumors.     

Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study.

We sought whether microdamage could rise in postmenopausal osteoporotic women on long-term bisphosphonates, as suggested by recent animal studies. We found few microcracks in iliac bone biopsies, despite a marked reduction in bone turnover. INTRODUCTION: Animal studies suggest that bisphosphonates (BPs) could increase microdamage frequency in a dose-dependent manner, caused by excessively suppressed bone turnover. However, there is limited data in humans receiving BP therapeutic doses for >3 yr. MATERIALS AND METHODS: We measured microcrack frequency and histomorphometry parameters on transiliac bone biopsies in 50 postmenopausal osteoporotic women (mean age = 68 yr) who had received BP therapy (3 on intravenous pamidronate, 37 on oral alendronate, and 10 on oral risedronate) for at least 3 yr (mean treatment duration = 6.5 yr). We compared these results with transiliac bone biopsies obtained from 12 cadavers. We used bulk staining with green calcein as a fluorochrome. The microcracks were quantified in three 100-microm-thick sections using optic microscopy and were confirmed by laser confocal microscopy. Microcrack frequency (number of microcracks/mm2 of bone tissue) was compared between treated women and controls using nonparametric tests. We also explored predictors of microcrack frequency, including age, duration of BP therapy, and activation frequency. RESULTS: Among treated women, cancellous bone microcrack frequency was low (mean, 0.13 microcracks/mm2) and did not differ significantly from that observed in controls (0.05 microcracks/mm2; p = 0.59). Of note, 54% of the treated women and 58% of the controls had no observable microcracks. There was no association between microcrack frequency and the duration of BP therapy (for microcracks/mm2 and duration, Spearman r = 0.04, p = 0.80) and between patients' ages and the number of microcracks (Spearman r = -0.09, p = 0.61). Although bone remodeling parameters were suppressed in treated women, we found no relationship between microcrack density and activation frequency (Spearman r = -0.003, p = 0.99). Also, microcrack frequency was not increased in women with prevalent vertebral fracture compared with those without fractures. CONCLUSIONS: Among postmenopausal osteoporotic women on long-term BPs, microcrack frequency in the iliac bone is low, despite a marked reduction of bone turnover.     

Interleukin-1 in alcoholic cirrhosis of the liver: the influence of nutrition.

Interleukin-1 (IL-1) is a cytokine produced by the macrophage-monocyte system that has important effects on immunological responses and inflammatory reactions. Several clinical studies have shown that severe protein energy malnutrition adversely effects cell-mediated immune responses and the functional state of macrophages. The objective of this study was to analyse IL-1 production by adherent cells stimulated in vitro with lipopolysaccharide B (LPS) from patients with alcoholic cirrhosis of the liver and its possible relationship with nutritional states. Forty-five patients with alcoholic cirrhosis and 28 healthy donors were investigated. A combined index of nine anthropometric and biochemical parameters was used to evaluate nutritional status of cirrhotic patients, allowing a distinction to be made between those patients with acceptable nutrition (group I: 40%), those with slight malnutrition (group II: 37.7%), and those with severe malnutrition (group III: 22.3%). IL-1 activity was significantly lower in the cirrhosis patients than in the controls (P less than 0.001). This activity also was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with acceptable nutrition (P less than 0.05); the combined index and the sole anthropometric index gave the same results, suggesting that malnutrition may play a role in the immunoregulatory disturbances in the pathogenesis of alcoholic liver disease.