Post-ischemic treatment with a lazaroid (U74389G) prevents transient global ischemic damage in rat hippocampus

Abstract

The ability of an experimental lazaroid, U74389G, to prevent damage to hippocampal CA 1 cytoarchitecture due to transient global ischemia was studied by light and electron microscopy. Post-ischemic rats were given a single i.p. dose of lazaroid (6 or 18 mg kg-¹) at 5 min after revival by cardiopulmonary resuscitation (CPR). Without lazaroid treatment the number of normal-appearing neurons in the CA1 region declined from a normal value of 75.49± 2.21 to 8.40± 10.08 per 100 μ,m² on day 7 after the ischemic episode, and there was extensive damage visible in the cytoarchitecture of this region. In lazaroid treated rats, the normal cytoarchitecture was retained and the number of normal-appearing cells was maintained at 15.1O± 2.22 per 100 ¼,m²? Ultrastructure studies indicated that pyknotic pyramidal cells laden with Pysosomal aggregates were common in untreated post-ischemic rats but rare in lazaroid-treated rats. These results indicate that U74389G maintained the structural integrity of this region of the brain after transient global ischemia and suggest that this lazaroid may be an effective neuroprotectant. [Neural Res 1997; 19: 431-434]     

The Impact of Hot Melt Extrusion and Spray Drying on Mechanical Properties and Tableting Indices of Materials Used in Pharmaceutical Development

The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (H_d) were determined along with Hiestand indices using compacts prepared at a solid fraction of ～0.85. HPMCAS and copovidone exhibited lower H_d, lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher H_d. Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BI_d) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development.     

A survey of knowledge, attitudes, and beliefs of house staff physicians from various specialties concerning antimicrobial use and resistance

BACKGROUND: Examination of knowledge, attitudes, and beliefs of house staff physicians will be important in developing interventions to improve antimicrobial use and prevent resistance. METHODS: A 75-item survey was distributed to house staff physicians on nonpediatric services in a university teaching hospital. Knowledge was assessed with a 10-question quiz. RESULTS: The survey was completed by 179 (67%) of 269 house staff physicians on 5 specialties. Outside and inside the intensive care unit, 21% and 25% of respondents, respectively, reported that they were using antibiotics optimally. Surgeons were significantly more likely than other physicians to report that they were regularly seeking input into antimicrobial selections (P<.001). Of the 170 physicians who completed the survey, 88% agreed antibiotics are overused in general and 72% also agreed this was the case at their institution (r = 0.56; P<.05); 96% agreed that hospitals in general face serious problems with antibiotic resistance and 93% agreed that their hospital faces these same problems (r = 0.57; P<.05); 97% agreed that better use of antibiotics would reduce resistance; 32% stated that they had not had formal teaching on antimicrobial agents in the last year (medicine residents reported significantly more formal teaching than others [P =.001]); and 90% wanted more education about antimicrobials and 67% wanted more feedback on antimicrobial selections. The mean antimicrobial quiz score was 28%, with medicine residents scoring significantly higher than others (P =.04). Upper-level residents did not perform better than interns. CONCLUSIONS: This survey (1) revealed that house staff are aware of the importance of antimicrobial resistance and believe better antimicrobial use will help this problem and (2) demonstrated differences between specialties with respect to antimicrobial use and knowledge. House staff at our hospital have suboptimal knowledge about antimicrobials, and this knowledge did not increase appreciably over the course of their training. Antimicrobial education is needed and is likely to be well received by house staff physicians in academic centers but may be more effective if it is tailored to specific specialties.     

Percutaneous high-speed rotational atherectomy (Rotablator™) of a restenosed ostial renal artery: A case report

This case report describes the feasibility and potential benefit of the use of a high-speed rotational atherectomy device (the Rotablator?) in the treatment of renovascular hypertension in a patient with a recorded restenosis of an ostial renal artery lesion following standard balloon angioplasty.