Thresholds for ultrasonically induced lung hemorrhage in neonatal swine

The threshold for generation of lung hemorrhage in adult mice by pulsed ultrasound has been shown to be approximately 1 MPa at the surface of the lung (10-microseconds pulse and a carrier frequency of 2 MHz). This investigation used neonatal swine to determine if the findings for mice can be generalized to other species. After exploratory observations, the inverse sampling method was used in a primary study (22 animals, 88 exposure sites) to determine the threshold for lung hemorrhage in neonatal swine. The primary study was followed by a separate confirmation study (13 animals, 48 exposure sites), testing the conclusions of the first study and comparing damage at subthreshold levels with sham-exposed animals. A separate investigation explored the histological nature of tissue damage at suprathreshold levels. A 2.3-MHz focused transducer (10 microseconds at 100-Hz pulse-repetition frequency) was incremented vertically for a distance of 2 cm over the chest of the subject for a total exposure period of 16 min. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.5 MPa peak positive pressure in water at the surface of the animal or, at the surface of the lung, 1.1 MPa peak positive pressure, 1 MPa fundamental pressure, 0.9 MPa maximum negative pressure, 25 W cm-2 pulse average intensity or a mechanical index of 0.6. These values are essentially the same as those reported for adult mice.     

Vascular protection with newer antihypertensive agents

ROLE OF CALCIUM: Alterations in the structure and function of small arteries may contribute to elevated blood pressure in patients with essential hypertension and the cardiovascular complications of this disease. Angiotensin II, endothelin 1, and other peptides, as well as catecholamines, may contribute to the altered structure and function of small arteries, in part through their effects on intracellular calcium. Intracellular calcium is implicated in signal transduction pathways that result in smooth muscle cell growth and contraction and in the release of endothelium-dependent agents involved in the regulation of vascular function. VASCULAR EFFECTS OF NEWER ANTIHYPERTENSIVE AGENTS: The newer antihypertensive agents that affect intracellular calcium pathways either directly or indirectly, such as calcium antagonists or angiotensin converting enzyme (ACE) inhibitors, may exert vascular protective effects, partly by regressing vascular remodeling and by correcting endothelial dysfunction. A double-blind trial comparing the effects of the ACE inhibitor cilazapril and the beta-blocker atenolol on media: lumen ratio of small gluteal subcutaneous arteries, which was significantly higher in hypertensive patients before treatment than in normotensive subjects, was corrected after treatment with cilazapril. In contrast, no improvement was seen in the media: lumen ratio of small arteries in the patients receiving atenolol, even after 2 years of treatment. In another study, treatment with the intrinsically long-acting calcium antagonist amlodipine resulted in a reduction in forearm minimal vascular resistance. Patients treated with amlodipine also showed normalized responses of forearm blood flow to nitric oxide synthase inhibition. Furthermore, patients treated with a slow-release formulation of nifedipine exhibited normal media: lumen ratio of small arteries and normal endothelium-dependent relaxation. CONCLUSIONS: These findings appear very promising; however, it remains to be demonstrated whether the apparently beneficial effects of treatment with long-acting calcium antagonists and ACE inhibitors will lead to reductions in the cardiovascular morbidity and mortality associated with hypertension.     

Studies of the denaturation patterns of bovine alpha-crystallin using an ionic denaturant, guanidine hydrochloride and a non-ionic denaturant, urea

The effects of non-ionic and ionic denaturation and denaturation/renaturation on the native structure of alpha-crystallin at room temperature were examined. Native alpha-crystallin, at concentrations above and below the previously reported critical micelle concentration (CMC) range, was denatured by varying concentrations of urea and guanidine hydrochloride. The resulting denatured samples were examined by gel filtration fast performance liquid chromatography (FPLC), circular dichroism spectropolarimetry (CD), and transmission electron microscopy. Elution peak samples from gel filtration chromatography with sufficiently high concentrations were examined for subunit composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The studies presented herein demonstrate that the denaturation and renaturation of alpha-crystallin via non-ionic urea denaturation results in different renaturation species, depending upon the initial concentration of alpha-crystallin which is denatured and the concentration of urea, including certain species which, by gel filtration FPLC, have an apparent molecular weight greater than the native 800 kD aggregate. Transmission electron microscopy has also demonstrated the existence of a high molecular weight aggregate form for denatured samples. Ionic dissociation, in contrast, proceeds much in the same manner above and below the CMC range, the major difference occurring at 2 M guanidine hydrochloride. alpha B-crystallin is preferentially removed from the native alpha-crystallin aggregate upon treatment with 2 M guanidine hydrochloride indicating, once again, differences between the two subunits. Above and below the CMC range, dissociation with guanidine hydrochloride appears to plateau after 4 M guanidine hydrochloride as indicated by the presence of two apparent homotetrameric species and no further dissociation of these species with increasing guanidine hydrochloride concentrations. CD demonstrates that some secondary structure, which is lost with lower concentrations of alpha-crystallin, is still present when concentrations of alpha-crystallin, well above the critical micelle concentration range, are treated with high concentrations of urea at room temperature. In contrast, concentrations both above and below the CMC range demonstrate a significant loss of secondary structure upon treatment with 2 M guanidine hydrochloride. Finally, ionic denaturation and subsequent renaturation results in the formation of a species which is functionally incapable of protecting gamma-crystallin from heat-induced aggregation.     

Synthesis and structure elucidation of estrogen quinones conjugated with cysteine, N-acetylcysteine, and glutathione

A micromechanical model for predicting the densification of particulate matter under hydrostatic loading was developed to account for the time-dependent response of materials to applied loads. Viscoelastic material response used in the analysis was based upon a standard three-parameter rheological model. Compaction data under closed die conditions were collected using an Instron analyzer for different rates of applied load. Densification during the loading phase of PMMA/coMMA powder, a pharmaceutical polymeric coating material, was well predicted by the proposed algorithm, which contrasts with the prediction implied through a static indentation model. Secondary factors which affect compaction such as die-wall friction are also briefly discussed.     

A prospective study of dietary fiber types and symptomatic diverticular disease in men

To examine prospectively dietary fiber calculated from food composition values based on analytic techniques and specific dietary fiber types in relation to risk of diverticular disease, we analyzed data from a prospective cohort of 43,881 U.S. male health professionals 40-75 y of age at base line; subjects were free of diagnosed diverticular disease, colon or rectal polyps, ulcerative colitis and cancer. The insoluble component of fiber was inversely associated with risk of diverticular disease relative risk (RR) = 0. 63, 95% confidence interval (CI), 0.44-0.91, P for trend = 0.02, and this association was particularly strong for cellulose (RR = 0.52, 95% CI, 0.36-0.75, P for trend = 0.002). The association between diverticular disease and total dietary fiber intake calculated from the AOACstandards method was not appreciably different from results using the Southgate or Englyst method [for AOAC method, RR = 0.60, 95% CI, 0.41-0.87; for Southgate method, RR = 0.61, 95% CI, 0.42-0. 88; for Englyst method, RR = 0.60, 95% CI, 0.42-0.87, for the highest quintiles]. Our findings provide evidence for the hypothesis that a diet high in dietary fiber decreases the risk of diverticular disease, and this result was not sensitive to the use of different analytic techniques to define dietary fiber. Our findings suggest that the insoluble component of fiber was significantly associated with a decreased risk of diverticular disease, and this inverse association was particularly strong for cellulose.     

Runt determines cell fates in the Drosophila embryonic CNS

BACKGROUND AND PURPOSE: Our purpose was to evaluate the ability of transcranial color-coded Doppler sonography (TCCD) to 1) identify Guglielmi detachable coils (GDCs) within intracranial aneurysms, 2) show endovascular aneurysmal occlusion and patency of parent and branch arteries, 3) determine the flow velocities within parent arteries and major branches before and after treatment, and 4) assess persistence of aneurysmal occlusion. METHODS: The sonographic appearance of GDCs was established experimentally by TCCD (2 to 2.5 MHz), which was then performed in 40 patients with 43 aneurysms occluded by GDCs. The patency of parent arteries and major branches was assessed qualitatively and compared with the immediate posttherapeutic angiographic appearance in every patient. Flow velocities were selectively measured and compared before and after treatment in 21 parent arteries and 24 major branches. Follow-up TCCD studies performed in 26 patients were compared with angiographic (16 cases) and MR angiographic (10 cases) findings for signs of recanalization of the treated aneurysms. RESULTS: The GDCs were identified experimentally and in the patients as hyperechoic structures of the size and shape, and in the location of, the treated aneurysm in 41 of 43 cases. TCCD in accordance with angiography showed a lack of flow in 42 aneurysms and the presence of flow signal in one large aneurysm. Patency of the parent artery was shown in 40 aneurysms and in all branches. Follow-up TCCD showed the coils unchanged in 23 of 26 cases. In three large aneurysms, TCCD indicated recanalization and reappearance of a flow signal separate from the parent artery. CONCLUSION: TCCD is a reliable, noninvasive means to assess parent artery and major branch patency and to reveal a lack of hemodynamic compromise in the vicinity of aneurysms after endovascular therapy. On follow-up examinations, TCCD was able to detect signs of aneurysmal recanalization.     

Prevention of acute allograft rejection by antibody targeting of TIRC7, a novel T cell membrane protein

The in vitro activity of trovafloxacin, a new fluoroquinolone, was compared with that of ciprofloxacin, ofloxacin, fleroxacin, ceftazidime, piperacillin/tazobactam, and meropenem against 613 consecutively recovered blood isolates from recently hospitalized patients. Susceptibility testing was performed by agar dilution according to NCCLS guidelines. Test strains included Acinetobacter species (n = 26), Escherichia coli (n = 137), Enterobacter species (n = 27), Klebsiella species (n = 42), Proteus species (n = 16), Pseudomonas aeruginosa (n = 28), Serratia marcescens (n = 13), Stenotrophomonas maltophilia (n = 7), enterococci (n = 54), coagulase-negative staphylococci (n = 38), Staphylococcus aureus (n = 137), Streptococcus pneumoniae (n = 27), beta-haemolytic streptococci (n = 13), and viridans group streptococci (n = 48). The overall respective MICs at which 50% and 90% of isolates were inhibited (MIC50s and MIC90s) were as follows: trovafloxacin, 0.06 and 1 mg/l; ciprofloxacin, 0.25 and 4 mg/l; ofloxacin, 0.5 and 4 mg/l; fleroxacin, 0.5 and 16 mg/l; ceftazidime, 2 and 128 mg/l; piperacillin/tazobactam, 2 and 8 mg/l; meropenem, 0.06 and 4 mg/l. For the quinolones, the rank order of activity against gram-negative microorganisms was ciprofloxacin > trovafloxacin > ofloxacin = fleroxacin, against gram-positive organisms, trovafloxacin > ciprofloxacin = ofloxacin > fleroxacin. Data obtained showed the similar activity of trovafloxacin and ciprofloxacin against gram-negative pathogens and the superior activity of trovafloxacin against gram-positive bacteria thus making it a potential candidate for the empiric treatment of patients with suspected bacteremia and sepsis.