Noninvasive assessment of pharmaceutical intervention during myocardial ischemia-reperfusion in a canine model using two-dimensional 31P chemical shift imaging

The metabolic effects during myocardial ischemia and sustained reperfusion of the antianginal agents diltiazem (n = 10) and propranolol (n = 10) were monitored with noninvasive phosphorus nuclear magnetic resonance spectroscopy to establish any correlation between metabolic changes and infarct size. Spectroscopy followed changes in high-energy phosphate concentrations and myocardial intracellular pH during 2 h of left anterior descending coronary artery occlusion and 3 subsequent weeks of reperfusion, in a closed chest canine infarct model. Gadolinium-DTPA enhanced magnetic resonance imaging was used to assess the extent of myocardial injury (infarct size). Microspheres were used to document the zone at risk and the success of reperfusion. Whereas diltiazem appeared to reduce the derangement in high-energy phosphates during coronary occlusion, there was no significant change in infarct size when compared with a previously studied control group. Propranolol, which produced a lesser decline in pH during occlusion and smaller pH changes during early reperfusion, was associated with a significant reduction in the degree of tissue necrosis (compared with controls). There was an inverse correlation (r = -0.51) between the change in myocardial pH (occlusion end to immediate reperfusion) and the recovery index (an index of myocardial salvage). By 1 h into reperfusion, there was a stronger inverse correlation between pH and infarct size (r = -0.75), implying a protective effect of delaying pH recovery during early reperfusion and indicating the potential use of this parameter as a predictor of tissue viability.     

Low density lipoprotein of synovial fluid in inflammatory joint disease is mildly oxidized

The histologic diagnosis of adult renal epithelial neoplasms with prominent eosinophilic cytoplasm (renal oncocytoma, chromophobe renal-cell carcinoma (RCC), eosinophilic variant of clear-cell RCC, eosinophilic variant of papillary RCC, and collecting duct carcinoma), could be problematic in some cases because of overlapping morphologic features. Precise diagnosis is essential, however, because it often connotes a distinct biologic behavior. Proliferative activity has not been specifically investigated in this spectrum of renal tumors, so we studied the MIB-1 proliferation index in 20 renal oncocytomas, 12 chromophobe RCCs, 9 eosinophilic variants of papillary RCCs, and 13 eosinophilic variants of clear-cell RCCs. Our purpose was to identify the biologic potential of these renal tumors on the basis of MIB-1 tumor proliferation index and to ascertain whether that index had diagnostic value. Overall, nuclear grade correlated with MIB-1 tumor proliferation index (P=.03). The mean proliferation index progressively increased from renal oncocytomas (0.3) to chromophobe RCCs (0.8) to eosinophilic variants of papillary RCCs (2.2) to eosinophilic variants of clear-cell RCCs (4.1) (P=.002). None of the renal oncocytomas or chromophobe RCCs had an index greater than 2, whereas 8 of 13 eosinophilic variants of clear-cell RCCs had an index greater than 2; in 5 of these, it was more than 3. Thus, in the differential diagnosis between renal oncocytoma/chromophobe RCC and eosinophilic variant of RCC, an MIB-1 index of greater than 3 with appropriate morphologic correlation would strongly support the diagnosis of the latter. We also concluded that the progressive increase in MIB-1 tumor proliferation index across the spectrum of granular renal-cell neoplasms parallels the emerging data in the current literature concerning the biologic potential of adult renal epithelial tumors and justifies histologic categorization of adult renal epithelial neoplasms.     

Change in colony morphology influences the virulence as well as the biochemical properties of the Mycobacterium avium complex

Factors that influence colony morphology are of crucial importance for drug development as well as for understanding the virulence of Mycobacterium avium complex (MAC) strains. The MAC 101 strain used in the present study grows as smooth transparent (SmT) colonies that tend to become opaque and pigmented when incubated for long periods of time. However, when MAC was passaged in animals, two types of colonies were recovered. The new rough transparent (RgT) colony morphology appeared more flat and transparent, having a central spot, irregular edges at times, and a dry, granular appearance like that of the rough mutants. In animal studies, the RgT bacilli multiplied at a much faster rate than that of the SmT bacilli, causing 60-80% mortality compared with the 10% mortality observed in mice infected with SmT. In vitro studies indicated that the SmT MAC did not grow and multiply as well in resident peritoneal macrophages as the RgT MAC did. The two morphotypes did not differ in their growth ratesin vitro but the RgT MAC failed to reduce dimethylthiazol-diphenyltetrazolium bromide (MTT), alamar blue and neutral red, suggesting that there might be significant changes in the cell wall or elsewhere causing changes in cellular permeability. These two morphotypes could serve as models for studying the biochemical markers or the identification of factors responsible for the virulence of the MAC.     

Thalidomide analogs and PDE4 inhibition

N-Phthaloyl 3-amino-3-arylpropionic acid analogs of thalidomide that are potent inhibitors of tumor necrosis factor-alpha are reported. These compounds were found to be potent inhibitors of phosphodiesterase 4.     

Stability of vancomycin in an extemporaneously compounded ophthalmic solution

The stability of vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution at -10, 4, 25, and 40 degrees C was studied. Vancomycin power was reconstituted with sterile water for injection to a concentration of 50 mg/mL. Artificial tears solution containing 0.3% hydroxypropyl methylcellulose, 0.1% dextran 70, 0.01% benzalkonium chloride, and 0.05% edetate disodium was used to produce a final concentration of 31 mg/mL. Triplicate solutions for each storage temperature and sampling time were prepared. The solutions were stored at -10, 4, 25, and 40 degrees C. Samples were taken initially and at 3, 7, 10, 21, 30, 45, and 60 days for visual inspection and analysis by high-performance liquid chromatography. All solutions remained clear and colorless at -10, 4, and 25 degrees C throughout the study period. By day 3, crystalline particles formed in the solutions stored at 40 degrees C. No substantial change in pH was observed at any time. At -10 degrees C, the solutions retained more than 90% of their initial vancomycin concentrations throughout the study period. The solutions retained a mean of at least 90% of the initial drug concentration for 21 days at 4 degrees C and for 7 days at 25 degrees C. For the solutions stored at 25 or 40 degrees C, less than 85% of the initial vancomycin concentration remained after 10 and 3 days, respectively. Vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution was stable for 45 days at -10 degrees C, 10 days at 4 degrees C, and 7 days at 25 degrees C in the tears solution's original container.     

TFF1 gene expression in human medullary thyroid carcinoma

This epidemiological study investigated the reasons why children in Northern Ireland who need orthodontic treatment do not receive treatment even when it is provided free by the state. A total of 1584 15- and 16-year-olds were examined in 23 high schools with the Index of Orthodontic Treatment Need. The characteristics of the adolescents who had received orthodontic treatment were compared with those who had a definite need for treatment and yet did not receive treatment or advice. One in 10 of the adolescents examined had an unmet need for orthodontic treatment. Logistic regression analysis was used to assess the influence of 11 variables including socioeconomic status, religion, and standard of dental health on the uptake of orthodontic care. This analysis revealed that the only significant predictors of whether an adolescent received orthodontic treatment was the dental attendance pattern of the adolescent, the adolescent's dental health, and the dental attendance pattern of the adolescent's mother. Those adolescents who had good dental health, who regularly attended a dentist, and whose mother regularly attended a dentist were more likely to receive orthodontic treatment.     

Characterization of DNA sequences encoding a novel isoform of the 55 kDa B regulatory subunit of the type 2A protein serine/threonine phosphatase of Arabidopsis thaliana

We have identified a novel gene (AtB beta) encoding a previously uncharacterized isoform of the B regulatory subunit of the type 2A serine/threonine protein phosphatase (PP2A) of Arabidopsis, and show that mRNA derived from the AtB beta gene accumulates in all Arabidopsis organs. In addition, we examined the expression of the three genes encoding the A regulatory subunit of Arabidopsis PP2A and show these genes are expressed in all organs as well. Taken together, our results suggest a myriad of PP2A subunit combinations, possibly with distinct substrate specificities, may occur within each Arabidopsis cell.