The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid dispersions of Itraconazole.

Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no Itraconazole peaks were visible; the polymer on the other hand appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly the physical mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.     

Radiation therapy of benign diseases. What's new eight years after?]

The authors present an update version of the indications for radiotherapy in the management of benign diseases. This is based on available randomized trials and recent international meetings. Validated indications remain the prevention of resected heterotopic bone ossifications, kelo?ds scars and pterygium and also treatment of arteriovenous malformations; the place of radiotherapy for malignant exophtalmia is more and more restricted. Randomized trials have demonstrated the efficacy of endobrachytherapy in the prevention of restenosis after angioplasty but the use of embedded stent has replaced this indication. Macular degeneration is no more an indication of radiotherapy. Quality requirements for radiotherapy are identical for benign or malignant indications.     

Comparison between ankle and toe index in patients with peripheral arterial disease

In contrast to the systolic blood pressure at the posterior tibial artery, the evaluation of pressure at the digital artery of the foot before and after exercise in patients with peripheral arterial disease is not well known. Twenty three patients with peripheral vascular disease were examined. The systolic pressure was measured by means of an ultrasound velocity detector at the brachial and posterior tibial artery. Digital artery pressure was determined with photoplethysmography. Pressures were measured before and within 5 and 10 minutes after a treadmill test. Ankle and toe index was calculated. At rest the toe index is lower than the ankle index and after a treadmill test the decrease in toe index occurs in parallel to the ankle index.     

Ultrastructure of aberrant serotonin-immunoreactive fibers in the caudate putamen complex of the aged rat

Degeneration of neurons in the central nervous system is associated with morphological changes. Previous observations made at the light microscopical level indicated degeneration of serotonin-immunoreactive (IR) fibers in the aged rat brain. In this study, a comparison at the ultrastructural level was made between serotonin-IR normal thin and aberrant swollen varicose fibers in the caudate-putamen complex of the aged rat. Ultrastructural features such as the size and content of the thin varicose fibers resembled those in the caudate-putamen complex of the young rat as reported by others. The aberrant profiles were swollen, reaching a size of 6 microns. Their vesicles varied in size and were no longer uniformly round. Moreover, distorted mitochondria and membrane-filled vacuolelike structures were a common feature of the aberrant profiles. These changes are indicative of a degenerative process and give further evidence that, whereas many serotonergic fibers are preserved at high age, other serotonergic fibers are degenerating in the caudate-putamen complex of the aged rat.     

Male subfertility induced by acute scrotal heating affects embryo quality in normal female mice

The aim of this experiment was to design a suitable mouse model for male subfertility in which to study the effect of decreased sperm quality on embryo quality in vivo and in vitro. To achieve male subfertility, testes of adult male mice were immersed in water at either 42 degrees C (heated) or 33 degrees C (controls) during 20 min. Twenty-eight days after treatment, all heat stressed males showed a significant decrease in relative testis weight [384.7 mg in controls (286.7-460.6) versus 323 mg in stress heated groups (117.9-405.6); P < 0.001], sperm concentration [3.75 x 10(6)/ml (2.75-7.25) versus 1.00 x 10(6)/ml (0-4.00); P < 0.001] and progressive sperm motility [57.5% (48.0-79.0) versus 42.5% (14.0-66.0); P < 0.001]. Moreover, after mating to heat exposed males, not only the number of pregnant females (20/22 versus 18/30) but also the weight of their embryos [275.4 mg (78.7-339.4) versus 261.8 mg (68.1-339.0); P < 0.001] was significantly lower at 14.5 days post coitum when compared to controls. Neither the number of resorption sites nor the number of viable embryos per pregnant female was significantly different between groups. Also, the in-vitro fertilization rate of oocytes, fertilized by spermatozoa collected from heat stressed males, was significantly lower (44.9%; P < 0.0001) when compared to controls (65.1%; P < 0.0001). In conclusion, the results of this study suggest that male subfertility induced by acute scrotal heating may result in impaired sperm quality, reduced embryo weight in vivo and decreased fertilization rate in vitro.      

Treatment of nasopharyngeal inlet stenosis following uvulopalatopharyngoplasty with the co2 laser

This report looks at outpatient treatment of nasopharyngeal inlet stenosis, a more commonly seen postoperative complication of uvulopalatopharyngoplasty (UPPP). It does not study the effectiveness of the UPPP for treatment of obstructive sleep apnea syndrome (OSAS). The authors evaluated six patients who had a UPPP for OSAS, all of whom developed stenosis in the nasopharyngeal inlet ranging from 14 mm to complete closure. Two patients had failed rotation flap repairs. The carbon dioxide laser was used to treat these patients in the office under a local anesthesia in a staged manner. We now have patients from 3 months to 12 months follow-up who have had stenosis treated successfully. We believe that the postoperative complication of nasopharyngeal inlet stenosis after UPPP can be treated in a safe and cost-effective manner in the office setting.     

Hypophyseal Non-Hodgkin's Lymphoma presenting with clinical panhypopituitarism successfully treated with chemotherapy

Summary A patient is described with a testicular Non-Hodgkin's Lymphoma (NHL) presenting with panhypopituitarism caused by a hypophyseal localization. A⁶⁷Gallium scintigraphy showed avid uptake in the hypophyseal region. Obviously⁶⁷Gallium could reach the tumor, by the intravenous route, which was the reason to treat the patient with intravenous chemotherapy. A complete remission was induced, which seems to be lasting (+ 25 months). As far as we know this is the first report of panhypopituitarism caused by a hypophyseal NHL in the hypophysis and successfully treated by intravenous chemotherapy.     

MRP8 and MRP14, S-100-like proteins associated with myeloid differentiation, are translocated to plasma membrane and intermediate filaments in a calcium-dependent manner

MRP8 and MRP14 are two Ca(2+)-binding proteins of the S-100 family expressed by myelomonocytic cells. Both proteins assemble to noncovalently associated complexes in a Ca(2+)-dependent manner. Members of the S-100 family are known to play a role in cytoskeletal- membrane interactions; therefore, we investigated the subcellular distribution of MRP8/MRP14 and their complexes in human monocytes. Using differential centrifugation and subsequent Western blot or enzyme- linked immunosorbent assay analysis, we found that MRP8/MRP14 were almost completely translocated from the cytoplasma to membrane and cytoskeletal structures in a Ca(2+)-dependent manner. Using a cross- linking technique, complexed forms of MRP8/MRP14 were found to be associated with the plasma membrane. Analysis of MRP-transfected L132 cells showed that the MRP8 as well as the MRP14 component of the MRP8/MRP14 complex may independently bind to membrane and cytoskeletal structures. Furthermore, immunogold electron microscopy showed a colocalization of MRP8/MRP14 and the intermediate filament type III protein vimentin in A23187-treated monocytes. Our data indicate that, in analogy to other S-100-like proteins, MRP8 and MRP14 play a role in Ca(2+)-dependent cytoskeletal-membrane interactions. Restriction of MRP8/MRP14 expression to distinct stages of myelomonocytic differentiation suggests that these proteins are involved in highly specific pathways of intracellular signaling in phagocytes.