Pyogenic brain abscess: findings from in vivo 1.5-T and 11.7-T in vitro proton MR spectroscopy.

BACKGROUND AND PURPOSE: Metabolites in pyogenic brain abscesses, as detected with in vivo proton MR spectroscopy, are different from those found in brain and can help differentiate pyogenic brain abscesses from necrotic neoplasms. We compared the findings of in vivo with those of in vitro MR spectroscopy and categorized the MR spectral patterns with respect to the causative organisms and abscess size. METHODS: Fifteen patients with pyogenic brain abscesses underwent in vivo 1.5-T (1)H MR spectroscopy and had findings of ring enhancement. The causative organisms were determined from cultures of aspirated pus. Single-voxel (1)H MR spectroscopy was performed with the point-resolved method (1600/270, 135 TR/TE). In six representative patients, in vitro 11.7-T (1)H MR spectra were obtained from the aspirated pus. RESULTS: Three in vivo MR spectral patterns were noted: A) presence of lactate at 1.3 ppm, cytosolic amino acids (leucine, isoleucine, and valine) at 0.9 ppm, alanine at 1.50 ppm, and acetate at 1.92 ppm, with the presence or absence of succinate at 2.4 ppm and lipids (0.8-1.3 ppm), representing mostly obligate anaerobes or a mixture of obligate and facultative anaerobes; B) presence of lactate at 1.3 ppm and cytosolic amino acids at 0.9 ppm, with the presence or absence of lipids but not acetate or alanine (0.8-1.3 ppm), representing mostly obligate aerobes or facultative anaerobes; and C) presence of lactate at 1.3 ppm alone, showing small abscess. Additional resonance peaks of lysine at 1.73 and 3.0 ppm, glutamate/glutamine at 2.09-2.36 ppm, taurine at 3.24 and 3.42 ppm, glycine at 3.55 ppm, and amino acids at 3.75 ppm could be observed in the in vitro MR spectra. CONCLUSION: Results from the in vivo observations were satisfactorily verified by the in vitro experiments. The in vitro measurements may offer complementary information that cannot be extracted from in vivo MR spectra. Determination of the three (1)H MR spectral patterns may be helpful in devising the best possible treatment plans for patients with pyogenic abscesses.

Effect of celecoxib on Ca2+ movement and cell proliferation in human osteoblasts.

In human osteoblasts, the effect of the widely prescribed cyclooxygenase-2 inhibitor celecoxib on intracellular Ca(2+) concentrations ([Ca(2+)](i)) and cell proliferation was explored by using fura-2 and the tetrazolium assay, respectively. Celecoxib at concentrations greater than 1microM caused a rapid rise in [Ca(2+)](i) in a concentration-dependent manner ( EC 50= 10 microM). Celecoxib-induced [Ca(2+)](i) rise was reduced by 90% by removal of extracellular Ca(2+), and by 30% by l-type Ca(2+) channel blockers. Celecoxib-induced Mn(2+)-associated quench of intracellular fura-2 fluorescence also suggests that celecoxib-induced extracellular Ca(2+) influx. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca(2+)](i) rise, after which the increasing effect of celecoxib on [Ca(2+)](i) was greatly inhibited. Conversely, pretreatment with celecoxib to deplete intracellular Ca(2+) stores totally prevented thapsigargin from releasing more Ca(2+). U73122, an inhibitor of phoispholipase C, abolished histamine (an inositol 1,4,5-trisphosphate-dependent Ca(2+) mobilizer)-induced, but not celecoxib-induced, [Ca(2+)](i) rise. Pretreatment with phorbol 12-myristate 13-acetate and forskolin to activate protein kinase C and adenylate cyclase, respectively, partly inhibited celecoxib-induced [Ca(2+)](i) rise in Ca(2+)-containing medium. Separately, overnight treatment with 1-100microM celecoxib inhibited cell proliferation in a concentration-dependent manner. These findings suggest that in human osteoblasts, celecoxib increases [Ca(2+)](i) by stimulating extracellular Ca(2+) influx and also by causing intracellular Ca(2+) release from the endoplasmic reticulum via a phospholiase C-independent manner. Celecoxib may be cytotoxic at higher concentrations.

Injury and strain-dependent dopaminergic neuronal degeneration in the substantia nigra of mice after axotomy or MPTP.

We studied the effects of axotomy or neurotoxin on the survival of substantia nigra pars compacta (SNpc) neurons in two strains of mice, FVB/N or C57BL/6. Fluoro gold (FG) was injected into both striata of the mice to retrogradely label the nigrostriatal neuronal population. Ten days later, these neurons were axotomized in the medial forebrain bundle (MFB) unilaterally or N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered intraperitonealy for 2 days to produce bilateral degeneration. MFB transection or MPTP administration produced a progressive loss of FG-labeled and tyrosine hydroxylase immunolabeled (TH+) neurons in both strains. Relative to control, 72% of SNpc neurons died 4 weeks after axotomy in C57BL/6 mice and 50% died after axotomy in FVB/N mice. MPTP resulted in death of 80% of SNpc neurons in C57BL/6 mice but only 40% in the FVB strain 4 weeks after MPTP administration. In this more sensitive strain, MPTP cell death was associated with positive staining for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and nuclear condensation. In contrast, no TUNEL staining was detected in SNpc after MPTP in FVB/N mice. Further, while similar kinetics and extent of cell death accompanied axotomy, axotomy-induced cell death was TUNEL negative in both FVB/N and C57BL/6 mice. Double staining for TUNEL and microtubule associated protein 2 confirmed that the majority of the TUNEL positive cells were neurons. These data indicate that genetic factors and the type of lesion play an important role in determining death of dopaminergic neurons after injury.

Brain abscess and necrotic brain tumor: discrimination with proton MR spectroscopy and diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Discriminating pyogenic brain abscesses from cystic or necrotic tumors is sometimes difficult with CT or MR imaging. We compared findings of proton MR spectroscopy ((1)H-MRS) with those of diffusion-weighted imaging to determine which technique was more effective for this differential diagnosis. METHODS: Fourteen patients (necrotic or cystic tumor [n = 7]; pyogenic abscess [n = 7]) who underwent 1.5-T (1)H-MRS and diffusion-weighted imaging and had findings of ring-shaped enhancement after contrast agent administration were enrolled in this study. Diffusion-weighted imaging was performed with a single-shot spin-echo echo-planar pulse sequence (b = 1000 s/mm(2)). The apparent diffusion coefficient and ratio were also measured. RESULTS: Spectra for two patients were unacceptable because of either poor shimming conditions or contamination from neighboring fat. Spectra in three of five patients with abscess had lactate, amino acids (including valine, alanine, and leucine), and acetate peaks; one of the three spectra had an additional peak of succinate. In one patient with abscess treated by antibiotics, only lactate and lipid peaks were detected. Spectra for four of seven patients with cystic or necrotic tumors showed only lactate peaks. Lactate and lipids were found in three patients with tumors. Hyperintensity was seen in all the pyogenic abscess cavities and hypointensity in all the cystic and necrotic tumors on diffusion-weighted images. CONCLUSION: (1)H-MRS and diffusion-weighted imaging are useful for differentiating brain abscess from brain tumor, but the latter requires less time and is more accurate than is (1)H-MRS. (1)H-MRS is probably more limited in cases of smaller peripheral lesions, skull base lesions, and treated abscesses.