Performance qualification of a new hypromellose capsule: part I. Comparative evaluation of physical, mechanical and processability quality attributes of Vcaps Plus, Quali-V and gelatin capsules.

This Part I paper describes the qualification of a new high performance hypromellose (hydroxypropyl methylcellulose, HPMC) capsule shell which contains no gelling agent and is dissolution friendly. The development history and the test results for a series of quality attributes including scanning electron microscopy, hygroscopicity, machineability, weight variation, powder leakage, mechanical strength, stability, cross-linking, animal and human pharmacokinetic results are reported. Comparisons to gelatin and HPMC capsule containing carrageenan showed the new HPMC capsule is superior in terms of mechanical strength, hygroscopicity and compatibility with a wide range of drugs.

Blockade of cytosolic phospholipase A2 alpha prevents experimental autoimmune encephalomyelitis and diminishes development of Th1 and Th17 responses.

Cytosolic phospholipase A2 alpha (cPLA2 alpha) is the rate-limiting enzyme for release of arachidonic acid, which is converted primarily to prostaglandins via the cyclooxygenase (COX) 1/2 pathways, and leukotrienes via the 5-lipoxygenase (LO) pathway. We utilized inhibitors of cPLA2 alpha, COX-1/2 and 5-LO to determine the potential roles of these enzymes in development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Blocking cPLA2 alpha prevented EAE development and greatly reduced antigen-induced production of Th1-type cytokines and IL-17.

Indole cytosolic phospholipase A2 alpha inhibitors: discovery and in vitro and in vivo characterization of 4-{3-[5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoic acid, efipladib.

The optimization of a class of indole cPLA 2 alpha inhibitors is described herein. The importance of the substituent at C3 and the substitution pattern of the phenylmethane sulfonamide region are highlighted. Optimization of these regions led to the discovery of 111 (efipladib) and 121 (WAY-196025), which are shown to be potent, selective inhibitors of cPLA 2 alpha in a variety of isolated enzyme assays, cell based assays, and rat and human whole blood assays.

Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha.

The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) are described. Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed.

Thiourea inhibitors of herpes viruses. Part 2: N-Benzyl-N'-arylthiourea inhibitors of CMV.

A series of highly potent thiourea inhibitors of cytomegalovirus (CMV) with improved stability properties was prepared and evaluated. Compound 29 inhibited the virus in cultured HFF cells with IC50 of 0.2 nM.

Osteoid osteoma. Computed tomography guided percutaneous excision.

The authors' experience with computed tomography guided excision of osteoid osteoma in an outpatient setting using an Einhorn biopsy set and a power drill in 21 patients is described. In the last 5 years, 21 patients aged 7 to 51 years who had radiographic findings and symptoms of osteoid osteoma were included in the study. The nidus of the tumor was excised successfully in all cases using a coaxial technique with a power drill.

Dedifferentiated parosteal osteosarcoma with rhabdomyosarcomatous differentiation.

Dedifferentiated parosteal osteosarcomas are characterized histologically by the combination of low-grade fibroblastic osteosarcoma admixed with a high-grade component that typically has the appearance of malignant fibrous histiocytoma or osteosarcoma. Herein we report a case of dedifferentiated parosteal osteosarcoma of the distal femur, in which the high-grade component consisted of rhabdomyosarcoma. To our knowledge, a rhabdomyosarcomatous component has not been described previously in a dedifferentiated parosteal osteosarcoma.

Metastatic prostate carcinoma to the foot with magnetic resonance imaging and pathologic correlation.

Metastases to the bones of the foot from prostate carcinomas are rare and usually are associated with diffuse metastatic disease. The authors encountered a patient who presented with prostate carcinoma metastases limited to the right foot. Magnetic resonance imaging correlation in this case demonstrated normal marrow signal in the surrounding bones of the foot and increased vascularity of the foot.

Intraosseous ganglion cyst associated with neuropathy.

We present a case of expansile intraosseous ganglion of the fibular head with cortical breakthrough, which has not been previously reported. Also associated with this case, and not previously reported, is peroneal nerve compression, causing foot drop caused by the large expansile nature of the lesion.

Osseous manifestations of bacillary angiomatosis.

We report a case of bacillary angiomatosis in a 32-year-old HIV-positive black Haitian male. Radiologic and pathologic features are presented.

Hemorrhagic prepatellar bursitis.

Simple prepatellar bursitis is easily diagnosed both clinically and by MRI. MRI shows the typical T1 and T2 lengthening of fluid within the bursa. However, because of complex MRI appearance of hemorrhage, chronic hemorrhagic bursitis and the size of the prepatellar mass the clinical and MRI appearance can be very different.

Collaboration projects between nursing education and nursing service: a case study.

Collaboration refers to a variety of efforts to blend nursing education and nursing service. A regional planning agency in Southwestern Pennsylvania assumed a strategic role in developing a collaboration action plan which was expressed in three pilot demonstration projects involving an associate degree, a baccalaureate, and a diploma program with their respective service partners. The purpose of this 2 year evaluation case study was to assess the extent to which the three demonstration projects met their stated goals and objectives.

Pseudoaneurysm of common iliac artery mimicking colonic metastasis on double-contrast barium enema.

We describe a patient with a pseudoaneurysm of the right common iliac artery that on a double-contrast barium enema mimicked the appearance of metastatic tumor involving the sigmoid colon, including a mass effect and spiculated, tethered mucosal folds. In the appropriate clinical setting, computed tomography, magnetic resonance imaging, and aortography help to distinguish a pseudoaneurysm from metastatic tumor involving the bowel.