Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Gonadotropin levels in Turner's syndrome: correlation with breast development and hormone replacement therapy.

We conducted a study of the basal levels of gonadotropins in 38 patients with Turner's syndrome, 14 of whom were using hormone replacement therapy (HRT). The gonadotropin levels were compared with pubertal development and HRT. Seven patients had presented spontaneous menarche; five patients maintained their periods and normal gonadotropin levels, and two developed secondary amenorrhea and high gonadotropin levels. The majority of patients on HRT had high gonadotropin levels. Follicle stimulating hormone (FSH) levels were significantly lower (p = 0.001) in patients with breast development at stage 5, regardless of whether the patient had undergone a spontaneous or a hormonally induced puberty. We concluded that gonadotropin levels are normal in those patients with spontaneous periods, and are high in most patients on HRT; and that FSH levels are significantly lower in those patients with breasts at stage 5.     

Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Quantitative analysis of basal dendrites of prefrontal pyramidal cells after chronic alcohol consumption and withdrawal in the adult rat

The effects of chronic alcohol consumption and withdrawal on the organization of the basal dendrites of layer III pyramidal cells of the prelimbic cortex were studied in groups of rats fed on alcohol for 6 or 18 months, and in a group fed for 12 months, then switched to water for a further 6 months (withdrawal group). Three-dimensional analysis of the dendritic arborizations showed an age-dependent increase in several dendritic parameters, but a net stability was found in the metrical parameters between alcohol-fed and respective control rats. Conversely, a dendritic impoverishment occurred in the withdrawal group. The linear density of dendritic spines remained stable in all groups studied. Together with the previously found marked loss of the neurons after alcohol consumption and withdrawal, these findings point to a decrease in the available targets for afferents and therefore to the presence of probable functional alterations as a consequence of those in the connectivity patterns of the prelimbic area occurring under these conditions.     

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.     

A random clinical trial study to assess the efficiency of topical applications of podophyllin resin (25%) versus podophyllin resin (25%) together with acyclovir cream (5%) in the treatment of oral hairy leukoplakia.

OBJECTIVE: The objective of this study was to assess the efficiency of topical applications of podophyllin resin (25%) (P) versus podophyllin resin (25%) together with acyclovir cream (5%) (PA) in the treatment of oral hairy leukoplakia (OHL) in accordance with the following criteria: (1) number of applications necessary for the total clinical resolution of OHL; (2) correlation between the decrease of lesion size and the number of applications; (3) total clinical resolution of OHL; and (4) clinical reevaluation 12 months after the end of treatment. STUDY DESIGN: Forty-six OHLs were treated with P (P group) or with PA (PA group). Applications were performed weekly. Student t, Fisher exact, and Pearson correlation tests were used for statistical analysis. RESULTS: All 24 lesions from the PA group presented total clinical resolution while 4 lesions from the P group did not. The P group required up to 25 applications performed weekly while the PA group required up to 18. Observed was a negative significant association between the size of the lesions and the number of applications performed weekly in the PA group. CONCLUSIONS: The present study demonstrated the following: (1) P and PA topical treatments presented a similar average number of applications performed weekly; (2) both groups showed the same clinical response at 12 months post-therapy; and (3) PA presented a 100% clinical resolution and a continuous decrease in OHL size over the course of weekly applications.     

Saliva substitute in xerostomic patients with primary Sj?gren's syndrome: a single-blind trial.

OBJECTIVE: To evaluate the efficacy of oral moisturizing gel (Oral Balance) in xerostomic patients with primary Sj?gren's syndrome (SS). METHOD AND MATERIALS: Twenty-one xerostomic patients with primary SS were subjected to a single-blind trial in which the efficacy of Oral Balance gel in reducing xerostomia and xerostomia-related oral symptoms was compared with that of a placebo. Both gels were packaged identically and were indiscernible in appearance and taste. Xerostomia was confirmed for all the patients through measurement of stimulated whole saliva. Patients began using the Oral Balance gel three times a day for 90 days, and were then switched to a gel placebo to be used in the same way for the same length of time. Clinical response was evaluated through the patients' subjective assessment (improved, worsened, or unaltered) of both gels. RESULTS: Neither the Oral Balance gel nor the gel placebo affected the salivary output of the patients. The Oral Balance gel presented a substantial statistically significant advantage in the control of burning mouth, mastication, and swallowing. No statistically significant relief of the isolated sensation of oral dryness was established. CONCLUSION: Oral Balance is a useful tool in the management of dryness-related oral symptoms in primary SS, but there is room for enhancing the overall properties of topical preparations designed to reduce oral complaints in xerostomic patients.