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.     

Effects of resynchronization therapy on sympathetic activity in patients with depressed ejection fraction and intraventricular conduction delay due to ischemic or idiopathic dilated cardiomyopathy

This study assesses the effect of biventricular pacing on sympathetic nerve activity (SNA) in patients with depressed ejection fraction and intraventricular conduction delay (IVCD). Biventricular pacing has been shown to result in hemodynamic improvement in patients with depressed ejection fraction and IVCD. The effect of biventricular pacing on SNA, however, remains unclear. A total of 15 men with a mean ejection fraction of 25 +/- 4% were enrolled. Arterial pressure, central venous pressure and SNA were recorded during 3 minutes of right atrial (RA) pacing and RA-biventricular pacing. Pacing was performed at a rate 5 to 10 beats faster than sinus rhythm, with an atrioventricular interval equal to 100 ms during RA-biventricular pacing. RA-biventricular pacing resulted in greater arterial pressures (p <0.05) than RA pacing (146 +/- 15/83 +/- 11 vs 141 +/- 15/80 +/- 10 mm Hg). There were no differences in central venous pressures between the 2 pacing modes (p = 0.76). SNA was significantly less during RA-biventricular pacing (727 +/- 242 U) than during RA pacing (833 +/- 332 U) (p <0.02). Furthermore, there was a positive correlation between baseline QRS duration and the decrease in SNA noted with RA-biventricular pacing (r = 0.58, p = 0.03). Biventricular pacing results in improved hemodynamics and a decrease in SNA compared with intrinsic conduction in patients with left ventricular dysfunction and IVCD. If the current findings are also present with chronic biventricular pacing, then this form of therapy may have a positive impact on mortality.     

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.