Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

Differences between mentally retarded and nonretarded persons' efficiency of auditory sentence processing

Mentally retarded adolescents and MA-matched nonretarded children participated in three experiments designed to examine differences in language-processing efficiency. A compressed speech technique was used in Experiments 1 and 2. Experiment 3 relied on a sentence-picture verification procedure. Our results suggest that retarded and nonretarded individuals differ in the speed with which they are able to execute the semantic-analytic processes but not necessarily the phonological encoding processes that are involved in auditory language comprehension. In addition, the data suggest a possible group difference in the quality of the semantic representation encoded during sentence processing.     

Gallibacterium anatis-secreted metalloproteases degrade chicken IgG.

Gallibacterium anatis (previously named Pasteurella haemolytica-like) is considered a normal inhabitant of genital and upper respiratory tracts of healthy chickens, but it is also associated with different pathological conditions. Secreted metalloproteases from field and reference G. anatis cultures were obtained by methanol precipitation and were characterized. Proteins of molecular mass higher than 100 kDa showing proteolytic activity were observed in 10% polyacrylamide gels copolymerized with 1% bovine casein. They were active at alkaline pH, and inhibited by ethylenediamine tetraacetic acid. Their activity was stable at 50 degrees C, but partially inhibited at 60 degrees C, and totally inhibited at higher temperatures. Secreted proteins were able to degrade chicken IgG after 24 h of incubation, and cross-reacted with a polyclonal antibody against purified protease from Actinobacillus pleuropneumoniae. Secreted metalloproteases could play a role in infections caused by G. anatis.     

Glomeruloid haemangioma is not always associated with POEMS syndrome

Glomeruloid haemangioma is considered a specific marker of POEMS ( p olyneuropathy, o rganomegaly, e ndocrinopathy, M -protein and s kin changes) syndrome and it is usually but not always associated with multicentric Castleman's disease. We report a 78-year-old man who presented with a single, red-violet soft nodule with superficial telangiectases on the scalp. Histopathologically, the lesion consisted of lobules of coiled aggregated capillaries that involved the lumina of dilated vascular structures, mimicking renal glomeruli. A collagenous stroma separated the capillary lobules, and eosinophilic, periodic-acid–Schiff positive globules of varying sizes and shapes were seen within the cytoplasm of endothelial cells. Immunohistochemical studies with antibodies against IgA and IgG, and against the kappa and lambda light chains of immunoglobulins showed immunoreactivity within the eosinophilic globules. Results of complete blood count, liver, renal and thyroid function tests, fasting blood sugar measurement, serum levels of oestradiol, testosterone, prolactin and cortisol, serum protein electrophoresis, immunoelectrophoresis and immunofixation yielded normal or negative results. No Bence–Jones proteinuria was found in a sample from a 24-h urine collection. To our knowledge, only two cases of glomeruloid haemangioma have been previously reported in patients without POEMS syndrome. We describe the third case of glomeruloid haemangioma in a patient without features of POEMS syndrome.     

A comparative study of angiogenic and cytokine responses after laparoscopic cholecystectomy performed with standard- and low-pressure pneumoperitoneum

Background  Surgical procedures enhance production of pro- and anti-inflammatory cytokines and angiogenic factors that play a pivotal role in the immunological response to surgical trauma and take part in the pathogenesis of tumor growth and adhesions formation. The purpose of the study was to access the influence of low-pressure CO₂ pneumoperitoneum on the inflammatory and angiogenic responses during the postoperative period after laparoscopy. Methods  The study group consisted of 40 patients, operated on due to cholelithiasis using standard-pressure (n = 20) and low-pressure (n = 20) CO₂ pneumoperitoneum. Serum concentration of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF)-A, and endostatin were measured before and at 6, 24, and 48 h after surgery with commercially available enzyme-linked immunosorbent assay (ELISA). Results  Concentrations of IL-6 increased significantly after the operations in both groups. No differences were observed between the groups in regards to IL-6, IL-8, and IL-10 levels. Concentrations of VEGF-A measured at 6 and 48 h were significantly lower in patients who underwent laparoscopies performed with low-pressure pneumoperitoneum. No significant variations were observed in endostatin serum concentration. Concentrations of the studied parameters were not influenced by duration of surgery or by age, gender, or body mass index (BMI) of the patients. Conclusions  The results obtained in our study do not show any significant differences between studied operative procedures with regards to systemic inflammatory response. Changes in the concentrations of VEGF-A and endostatin observed in the studied population may suggest this technique is more favorable with regards to angiogenesis process intensity, along with all its consequences and implications.