1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus

Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the (NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 ± 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 ± 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 ± 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 ± 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 ± 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A₁ receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A₁ receptors. On the other hand, under the conditions we assumed to be normoxic in our slices, DPCPX (50 nM) induced a much larger increase in the amplitude of the NMDA receptor-mediated fepsp compared to the increase in the fepsp, which suggest that endogenous adenosine is inhibiting predominantly the NMDA receptor-mediated fepsp under these conditions. Hypoxia markedly decreases the NMDA receptor-mediated fepsp in the hippocampal CA₁ area. The contribution of endogenous adenosine to the inhibition of the NMDA receptor-mediated fepsp may be fundamental for its neuroprotective effects.     

Evaluation of peripheral blood involvement of mantle cell lymphoma by fluorescence in situ hybridization in comparison with immunophenotypic and morphologic findings.

Mantle cell lymphoma is non-Hodgkin's B-cell lymphoma characterized by the t(11;14)(q13;q32) translocation. Peripheral blood involvement of mantle cell lymphoma is usually associated with a poor prognosis and therefore, its identification is clinically important. In this study, we performed cyclin D1/IgH-probe fusion fluorescence in situ hybridization analysis on 223 peripheral blood samples: 185 from 125 mantle cell lymphoma patients, and 38 normal controls. The cutoff values for the test were established using normal controls. Flow cytometry on peripheral blood and corresponding bone marrow samples was used to evaluate this test. In all, 26% of the 185 peripheral blood samples and 27% of the 161 corresponding bone marrow samples were flow cytometry positive for mantle cell lymphoma. The mean numbers of single and- double-fusion signals and the mean number of CD5/CD19-positive cells, absolute blood lymphocyte count, and white blood cell count were significantly higher in peripheral blood and corresponding bone marrow samples with mantle cell lymphoma-positive flow cytometry. Double-fusion signals were more specific than single-fusion ones. Fluorescence in situ hybridization was far more likely to be positive for mantle cell lymphoma when the peripheral blood and the corresponding bone marrow samples had positive flow cytometry results or morphology (P<0.01). Our study indicates that cyclin D1/IgH-fusion fluorescence in situ hybridization analysis could be used to determine the presence and character of circulating mantle cell lymphoma cells in peripheral blood, thus enhancing our ability to evaluate leukemic mantle cell lymphoma and minimum residual disease.     

A random clinical trial study to assess the efficiency of topical applications of podophyllin resin (25%) versus podophyllin resin (25%) together with acyclovir cream (5%) in the treatment of oral hairy leukoplakia.

OBJECTIVE: The objective of this study was to assess the efficiency of topical applications of podophyllin resin (25%) (P) versus podophyllin resin (25%) together with acyclovir cream (5%) (PA) in the treatment of oral hairy leukoplakia (OHL) in accordance with the following criteria: (1) number of applications necessary for the total clinical resolution of OHL; (2) correlation between the decrease of lesion size and the number of applications; (3) total clinical resolution of OHL; and (4) clinical reevaluation 12 months after the end of treatment. STUDY DESIGN: Forty-six OHLs were treated with P (P group) or with PA (PA group). Applications were performed weekly. Student t, Fisher exact, and Pearson correlation tests were used for statistical analysis. RESULTS: All 24 lesions from the PA group presented total clinical resolution while 4 lesions from the P group did not. The P group required up to 25 applications performed weekly while the PA group required up to 18. Observed was a negative significant association between the size of the lesions and the number of applications performed weekly in the PA group. CONCLUSIONS: The present study demonstrated the following: (1) P and PA topical treatments presented a similar average number of applications performed weekly; (2) both groups showed the same clinical response at 12 months post-therapy; and (3) PA presented a 100% clinical resolution and a continuous decrease in OHL size over the course of weekly applications.     

Sensitivity-encoded (SENSE) proton echo-planar spectroscopic imaging (PEPSI) in the human brain.

Magnetic resonance spectroscopic imaging (MRSI) provides spatially resolved metabolite information that is invaluable for both neuroscience studies and clinical applications. However, lengthy data acquisition times, which are a result of time-consuming phase encoding, represent a major challenge for MRSI. Fast MRSI pulse sequences that use echo-planar readout gradients, such as proton echo-planar spectroscopic imaging (PEPSI), are capable of fast spectral-spatial encoding and thus enable acceleration of image acquisition times. Combining PEPSI with recent advances in parallel MRI utilizing RF coil arrays can further accelerate MRSI data acquisition. Here we investigate the feasibility of ultrafast spectroscopic imaging at high field (3T and 4T) by combining PEPSI with sensitivity-encoded (SENSE) MRI using eight-channel head coil arrays. We show that the acquisition of single-average SENSE-PEPSI data at a short TE (15 ms) can be accelerated to 32 s or less, depending on the field strength, to obtain metabolic images of choline (Cho), creatine (Cre), N-acetyl-aspartate (NAA), and J-coupled metabolites (e.g., glutamate (Glu) and inositol (Ino)) with acceptable spectral quality and localization. The experimentally measured reductions in signal-to-noise ratio (SNR) and Cramer-Rao lower bounds (CRLBs) of metabolite resonances were well explained by both the g-factor and reduced measurement times. Thus, this technology is a promising means of reducing the scan times of 3D acquisitions and time-resolved 2D measurements.     

Chronic prostatitis/pelvic pain syndrome: A bladder dysfunction?

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is frustrating for both clinicians and patients. The prostate is not scientifically proven to cause the symptoms of CP/CPPS, yet the prostate continues to be the diagnosis of convenience in this complex syndrome in men. However, if the pain is not of prostatic origin, what causes it? A heterogeneous group of insults can result in a common neurogenic pain response, resulting in recurring pain and voiding or sexual dysfunction. To add to this dilemma, certain life-threatening diagnoses, such as carcinoma-in-situ, are in the differential diagnosis and must be excluded. Urodynamics may be useful in evaluating and treating patients whose voiding symptoms predominate, such as those with concomitant overactive bladder symptoms. However, many patients with CP/CPPS will not have measurable abnormalities by conventional methods and likely suffer from a functional somatic syndrome that is best treated with a multimodality approach.     

Clinical performance of non-contact tonometry by Reichert AT550® in glaucomatous patients

Measuring intraocular pressure (IOP) by non-contact tonometry (NCT) has been demonstrated to be a valid and reliable technique to be used in primary eye care; it is easier to use, it does not transmit infectious diseases, and it is not necessary to use anaesthetic or staining eye drops. Recently, a new NCT device has showed an excellent level of agreement with Goldmann tonometry, but there are no records of its performance in glaucomatous eyes. To rectify this, IOP was measured in twenty-two patients (44 eyes) receiving medical treatment to control elevated IOP, with AT550 and Goldmann tonometry. Mean values of IOP were 18.98 +/- 2.77 and 19.08 +/- 3.02 mmHg using Goldmann and AT550, respectively. Plots of differences against means displayed good agreement (mean difference +/- limits of agreement, -0.09 +/- 3.30); this value was not significantly different from zero (t-test for dependent samples, p = 0.709). In conclusion, IOP values as measured with the AT550 NCT are clinically comparable with those obtained with Goldmann tonometry in glaucomatous patients. This validates this NCT not only for screening of IOP but to follow-up glaucomatous patients with a rapid, non-invasive method.