Surface and transport properties of acrylic polymers influencing drug release from porous matrices

Three acrylic/methacrylic esters copolymers with different percentages of hydrophilic groups were used to prepare porous matrices containing aspirin as a drug model. The surface and transport properties of these matrices were studied by measuring the liquid/polymer contact angle and the liquid penetrability, whereas the porous structure was measured by mercury porosimetry. In the case of a non-wetting liquid, such as water, the penetration was found to be controlled by the intraparticle polymer diffusion, whereas for a wetting liquid the penetration was capillary driven.Consequently the drug release was dependent on the pore structure, i.e. the compaction pressure, in the case of a wetting liquid, whereas no pore structure influence was found in the case of water. Furthermore. whatever the copolymer used or the dissolution medium employed, the drug release was found √t -dependent suggesting a drug diffusion only through the interparticie pores.     

The activity of the hypothalamo-hypophysial Antidiuretic system in conscious dogs

Summary The influence of isoosmotic changes of blood volume on plasma vasopressin level, osmotic reactivity f the antidiuretic system, central venous pressure, arterial blood pressure and heart rate was examined in ten conscious dogs after left—sided cervical vagosympathectomy. A moderate decrease of the blood volume by 15% produced only a slight and transient rise of the plasma vasopressin level and heart rate. Mean arterial blood pressure decreased under the same conditions. A moderate increase of the blood volume by 15% influenced neither the spontaneous activity nor the osmotic reactivity of the antidiuretic system in the same dogs. An increase of central venous and mean arterial pressure was observed under these conditions.The result suggest that the most sensitive receptors susceptible to moderate blood volume changes and influencing the activity of the antidiuretic system are located in the region of distribution of the left vagosympathetic afferents.     

Effect of Hemodialysis on T Lymphocyte Subsets, Con-A-Activated Suppressor Cell Activity, and Interleukin-2 Receptor Expression on Lymphocytes in Chronic Uremic Patients

Effect of hemodialysis (HD) on some indices of immune response was studied in nine chronic uremics. Total lymphocyte, OKT4+, and OKT8+ cell numbers significantly decreased during the first 20 min of HD, and they were decreased till the third hour of the procedure, whereas the OKT4+/OKT8+ cell number ratio did not change significantly. Before HD, Con-A--activated suppressor cells exerted a stimulatory action on autologous responder cells measured in two-step culture. During HD, Con-A-activated suppressor cell activity transiently appeared, with its peak at 60 min after the start of HD. It was accompanied by a transient rise in lymphocyte count with spontaneous interleukin-2 (IL-2) receptor expression, whereas the number of cells expressing IL-2 receptor following phytohemaglutinin (PHA) stimulation was progressively decreased during HD. A significant correlation was found between the increment of Con-A-activated suppressor cell activity and the increment of spontaneous IL-2 receptor expression on lymphocytes during one single blood flow through the dialyzer. The results supply further evidence that HD may impose additional disturbances on immune regulation in chronic uremics.     

Structure of rat bile canaliculi as revealed by scanning electron microscopy

Bile canaliculi in the rat liver have been studied by scanning electron microscopy. They appear as half tubules carved out of the hepatocytes' surface. In several cases the bile channel bifurcates to form two or three long branches running on the same face of the cell. Therefore, by SEM it seems obvious that the same side of an hepatocyte may be used for bounding two or more bile canaliculi. Some bile canaliculi display a flexuous course and show lateral sacculations. Some of them are large and apparently similar to the short lateral branches of the bile canaliculus; others are smaller and arise obliquely from the subjacent cortical areas of the hepatocyte cytoplasm. These latter structures are best observed in stereo-views in which they appear as narrow intracellular projections bordered with a few microvilli, actually opening into the lumen of the bile canaliculus. The SEM results suggest that these sacculations probably correspond to short intracellular branches of the bile canaliculi. Zones of minimal distance (0.1 μ) between the space of Disse and the bile channel have been frequently observed. They are actually the zones where the intercellular clefts arising from the subendothelial space of Disse come into closest contact with the bile canaliculus and might serve as sites of simple diffusion of substances.     

Unusual radiological presentation of a primary CNS lymphoma

The Authors report a case of primary cerebral lymphoma occurred in a 62 years old lady, who came to observation for headache and mood alterations. An enhanced CT showed a lesion recalling a meningeal sarcoma. Points of interest in this case are the unusual radiological appearance and the infrequent localization. Main anatomical and clinical characteristics of primary CNS non-Hodgkin lymphomas are recalled, even with regard to modern immunohistochemical tecniques.

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Sommario Gli Autori descrivono un caso di linfoma primitivo cerebrale occorso in una paziente di 62 anni, presentatasi per cefalea ed alterazioni dell'umore. Alla TC la lesione si presentava con un aspetto che richiamava il sarcoma meningeo. I punti d'interesse di questo caso sono l'aspetto radiologico inusuale e la localizzazione infrequente. Vengono richiamate le principali caratteristiche anatomo-cliniche dei linfomi primitivi del SNC, alla luce anche delle moderne tecniche immunoistochimiche.

     

Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

PURPOSE: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). METHODS AND MATERIALS: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. RESULTS: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. CONCLUSION: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL.     

Cyclin-dependent kinase 2 expression in human melanomas and benign melanocytic skin lesions

Cyclin-dependent kinase 2 (CDK-2) is strongly involved in regulating the progression of the cell cycle through G1/S checkpoint and S phase. Numerous studies demonstrated increased levels of CDK-2 (and also of its regulatory cyclins E and/or A) in different types of human tumours. Correlations found between the expression of those cell cycle regulators and progression and/or invasiveness of some tumours indicated the importance of CDK-2 as a potential prognostic marker. At the same time, in vitro studies of melanoma cell lines revealed melanocyte-specific regulation of CDK-2. The present study was aimed at examining levels of CDK-2 in human melanomas and benign pigmented lesions to evaluate whether it might be considered a potential molecular marker of melanoma progression. Expression of CDK-2 was determined immunohistochemically in formalin-fixed paraffin-embedded specimens comprising 76 lesions including 41 primary cutaneous melanomas, 15 lymph node melanoma metastases (in eight cases correlated with primary tumours), three melanoma recurrences (two cases correlated with both primary and metastatic melanomas) and 17 nevi. Our results demonstrate that development and progression of melanoma are associated with changes in CDK-2 expression level. Statistical significance of the observed correlations indicates that CDK-2 may be a suitable prognostic marker for melanoma and perhaps also a target for chemotherapeutic drugs.     

GnRH agonists and antagonists decrease the metastatic progression of human prostate cancer cell lines by inhibiting the plasminogen activator system

Prostate cancer (PCa) growth initially depends on circulating androgens. Gonadotropin-releasing hormone (GnRH) agonists are currently used for the treatment of PCa. However, after an initial responsiveness to hormonal deprivation, PCa progresses and metastasizes. Recently, also GnRH antagonists have been used for clinical trials in patients with PCa and the results seem promising. The components of the plasminogen activator (PA) system (urokinase-type PA, uPA; PA inhibitors, PAI-1/2; uPA receptor, uPAR) have been implicated in the local degradation of the extracellular matrix (ECM) and PCa progression. The aim of this study was to test the possible effects of the treatment with an agonist (Leuprolide, GnRH-A) and an antagonist (Cetrorelix, GnRH-ANT) of GnRH on the expression and activity of uPA and PAI-1 in the conditioned media of DU145 and PC3, two PCa androgen-independent cell lines. The involvement of the PA system in the control of cellular migration was also investigated. The results obtained in DU145 and PC3 cells show that both GnRH-A and GnRH-ANT: i) inhibit cell proliferation; ii) significantly decrease the enzymatic activity and the secretion of uPA; iii) significantly increase the protein levels of PAI-1; iv) induce a significant decrease of the migratory and invasion PCa capabilities. This study suggests that GnRH analogues exhibit not only an antiproliferative effect, but also an anti-metastatic action exerted through the inhibition of the activity of PA system and might provide a rational basis for the development of clinical strategies for those tumours that progress towards an androgen-independent condition characterized by a higher metastatic potential.