The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents

Angiogenesis, the formation of new blood vessels, is essential for tumor growth, progression and metastasis. The development of agents that target tumor vasculature is ultimately dependent on the availability of appropriate preclinical screening assays. The chorioallantoic membrane (CAM) assay is well established and widely used as a model to examine angiogenesis, and anti-angiogenesis. This review 1) summarizes the currently used angiogenesis assays and the importance of CAM model among them; 2) summarizes the current knowledge about the development and structure of the CAM's capillary bed; 3) reports findings regarding the role played by molecular signaling pathways in angiogenesis process; 4) discusses the use, advantages and limitations of the CAM as a model for studying tumor angiogenesis and invasiveness, as well as development of angiogenic and/or anti-angiogenic agents; 5) discusses the importance of standardization of the major methodologies for all aspects of the use of the CAM in angiogenesis-related studies; 6) and finally, summarizes major findings regarding the agents developed by the use of CAM model in the study of tumor angiogenesis, invasion and development of anti-angiogenic agents.     

A validated capillary electrophoretic method for the determination of indacaterol and its application to a pharmaceutical preparation

Indacaterol is a new inhaled ultra-long acting ${\beta }_2$-agonist. It has been recently approved in the European Union for the treatment of chronic obstructive pulmonary disease. This paper reports, for the first time, a method for the determination and validation of Indacaterol (IND) using an internal standard in capsules. Capillary electrophoretic separation was performed on an uncoated fused-silica capillary (50 cm effective length, 75 μm i.d.) and background electrolyte composed of 20 mmol L^?1 of sodium tetraborate buffer, 15% (v/v) methanol (pH = 10.0) with the application of 20 kV of potential; 10 s at 5 × 10³ N m^?2 (50 mbar) of injection time; and wavelength of 200 nm and 25 °C of temperature. The linearity was evaluated in the range of 4.90 × 10^?6 mol L^?1 (2.50 μg mL^?1) and 3.94 × 10^?5 mol L^?1 (20.00 μg mL^?1), with R = 0.9993 for inter-day. LOD and LOQ values were 2.18 × 10^?8 mol L^?1 (0.011 μg mL^?1) and 7.25 × 10^?8 mol L^?1 (0.037 μg mL^?1) for inter-day, respectively. The precision values were 0.50–1.06% for intra-day and 2.12% for inter-day as RSD%. The accuracy was tested by the standard addition method with the recovery values being between 98.79 and 99.09 as percentages with RSD% interval of 0.01–0.80. The developed method was validated according to ICH guidelines. Indacaterol was successfully determined in Arcapta^® capsule dosage form by the validated CE method with a relative error of 0.28%. The result was within the requirements of the USP 34-NF29. Therefore, the validated method may be used for the determination of Indacaterol in its capsules in quality control laboratories.     

Secondary cold agglutinin disease associated with Hashimoto disease

Our case involves a 53 year old woman. Three years ago, she was investigated because of normal hemoglobin levels despite very a low erythrocyte count, which was revealed during the preoperative evaluation for ovarian cyst operation. The Direct Coombs test was found to be positive against complement and negative against IgG. Cold agglutinin titer was 1/448 (+). Due to the polyclonal IgM increase, secondary cold agglutinin disease (CAD) was considered but no factor could be found that would lead to cold agglutinin disease. During the post-operative follow-up, cold agglutinin titers increased with fluctuations in the patient. Twenty-four months after transabdominal hysterectomy and bilateral salpingooopherectomy operation, diagnosis of Hashimoto disease was made upon detection of subclinical hypothyroidism. No case of Hashimoto disease associated with CAD caused by polyclonal IgM has been reported until the present time.     

Spinal cavernous malformations: a report of 5 cases

BACKGROUND: This is a report of 5 patients treated surgically for SCMs. METHODS: During the period from 1998 to 2003, 5 patients (4 male and 1 female) harboring SCMs were treated surgically (all of them underwent complete surgical removal). Patients' ages ranged between 22 and 57 years (mean age, 46 years). Median duration of symptoms was 31 months (1-120 months). Diagnosis was made by MRI scan showing lesions in length of 1 to 6 cm in diameter (mean length, 2.9 cm). Three lesions were found in the cervical, one in the upper dorsal, and one in the lower dorsal cord. One of them was located extradurally, one of them intradural extramedullary, and 3 of them intramedullary. RESULTS: An MRI examination showing total removal was performed postoperatively in each patient (the postoperative MRI examinations revealed total removal in all cases). The follow-up period ranged from 1 to 4 years (mean, 27 months). All patients showed clinical improvement, with 3 of them worsening early in the postoperative period but doing better in long-term follow-up (although 3 of 5 patients had worse neurological examinations in the early postoperative period, all recovered in long-term follow-up and clinically improved relative to preoperative status). CONCLUSION: Neurological status of the patients can worsen in the early postoperative period, causing intramedullary operation; but it usually improves relative to preoperative status. Surgical removal seems to be a safe and a promising way of treatment of symptomatic SCMs.     

<Emphasis Type="Italic">Saccharomyces boulardii</Emphasis> prevents oral-poliovirus vaccine-induced IgA nephropathy in mice

Immunoglobulin A nephropathy (IgAN) is associated with mucosal IgA defect. Probiotics regulate specific and innate immunity. We evaluated the effect of Saccharomyces boulardii on experimental IgAN in mice. Four groups of BALB/c mice (eight for each) were formed. Group 1 was immunized by oral poliovirus vaccine (OPV) at 0, 14, and 28 days. Group 2 was also given S. boulardii in addition to OPV. Group 3 was given only S. boulardii, whereas group 4 received no treatment. At week 6, after urine and serum samples were obtained for urinalysis and serum creatinine and IgA measurements, all animals were sacrificed to get their kidneys for histopathological evaluation. Urinalysis and serum creatinine levels were normal in all groups. Serum IgA level was increased only in group 1. Whereas group 1 had mesangial proliferation, histology was normal in the other groups. Predominant IgA deposition was universal in group 1, whereas it was either not present or minimal in other groups. Three mice in group 1 also had C3 deposition, which was absent in other groups. Electron microscopy revealed mesangial proliferation, matrix expansion, focal glomerular basement membrane thickening and electron-dense deposits in group 1 only, whereas the other groups were normal. In conclusion, enteral S. boulardii prevented OPV-induced IgAN in mice.     

Fluid resuscitation of acute hemorrhage in uninephrectomized rabbits--effects on the early function of the remnant kidney

The aim of this study was to determine the effects of fluid resuscitation of acute hemorrhage on the early function and histopathology of the remnant kidney in uninephrectomized rabbits. Thirty-nine adult rabbits were studied in four groups. Group 1 (n = 8) included healthy controls; Group 2 (n = 10) healthy, bled animals; Group 3 (n = 10) uninephrectomized, non-bled animals; and Group 4 (n = 11) uninephrectomized, bled animals. In the hemorrhage groups, 8 mL kg(-1) of blood was drawn, and replaced with lactated Ringer's solution three times the volume of shed blood. Urine and blood samples were collected after 120-minutes of observation. None of the animals experienced hypotension during the study period. Serum and urinary electrolytes were similar between the Groups (p > 0.05). Urine output was lower in Groups 3 and 4 than in Group 1 (p = 0.001, both). Urinary microalbumin, NAG, fractional sodium excretion and creatinine clearance were similar in all four Groups. Light microscopic evaluation revealed only slight enlargement of the proximal tubule lumen in the renal medulla of the rabbits that were both uninephrectomized and bled. We observed no deleterious effects of well resuscitated hemorrhage on early function and histopathology of the remnant kidney in uninephrectomized rabbits.