Effects of 7-nitroindazole, NG-nitro-L-arginine, and D-CPPene on harmaline-induced postural tremor, N-methyl-D-aspartate-induced seizures, and lisuride-induced rotations in rats with nigral 6-hydroxydopamine lesions

The present behavioral study was undertaken to investigate whether neuronal nitric oxide (NO) synthase mediates the abnormal consequences of increased NMDA receptor-mediated synaptic transmission in models of postural tremor, Parkinson's disease and epilepsy. We used 7-nitroindazole, a selective inhibitor of neuronal NO synthase, and NG-nitro-L-arginine (L-NAME), an unspecific NO synthase inhibitor, and compared their action with that of the competitive NMDA receptor antagonist 3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid (D-CPPene). In both mice and rats, 7-nitroindazole, L-NAME and D-CPPene dose dependently reversed the harmaline-induced increase of cerebellar cyclic guanosine-5'-monophosphate (cGMP) levels. For subsequent behavioral experiments we used doses of 7-nitroindazole, L-NAME and D-CPPene which were equipotent in preventing harmaline-induced cGMP increase. Harmaline-induced tremor in mice and rats was suppressed by D-CPPene, but not by 7-nitroindazole or by L-NAME. This effect of D-CPPene was not due to unspecific suppression of motor activity, since D-CPPene did not affect locomotor activity at doses which reduced tremor. D-CPPene, but not 7-nitroindazole and L-NAME potentiated the antiparkinsonian action of the dopamine agonist lisuride in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. D-CPPene antagonized seizures induced by intracerebroventricular injection of NMDA in mice. In contrast, 7-nitroindazole and L-NAME had only a tendency to prevent seizures and to delay the latency to onset of seizures. We conclude from these results that neuronal NO synthase does not serve as a major mediator of increased NMDA receptor-mediated synaptic transmission in animal models of Parkinson's disease, postural tremor and epilepsy. The novel observation that D-CPPene suppresses harmaline-induced tremor leads us to suggest that NMDA receptor antagonists should be considered as novel therapeutics for postural tremor.     

Re-face stereospecificity at C4 of NAD(P) for alcohol dehydrogenase from Methanogenium organophilum and for (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans as determined by 1H-NMR spectroscopy

The two diastereotopic protons at C4 of NAD(P)H are seen separately in 1H-NMR spectra. This fact was used to determine the stereospecificity at C4 of NAD(P) for the NADP-dependent alcohol dehydrogenase from Methanogenium organophilum and for the NAD-dependent (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans. The reduction of NADP+ with [2H6]ethanol was found to yield (4R)-[4-2H1]NADPH and the oxidation of (4R)-[4-2H1]NADH with 2-oxoglutarate to yield unlabelled [4-1H]NAD+. These results indicate that both enzymes are Re-face stereospecific at C4 of the pyridine nucleotides.     

Repair kinetics in pig epidermis: an analysis based on two separate rates of repair

Pig skin was irradiated using 90Sr/90Y plaques and the dose-related incidence of induced moist desquamation was determined. The repair of radiation-induced sublethal damage (SLD) was studied by fitting these response data to the generalized LQ equation for incomplete repair using quasilikelihood methods with binomial statistics, and either a Poisson or logistic link to relate the probability of response to the covariates. A Poisson response analysis based on the assumption that SLD was governed by two repair processes gave estimated repair half-times of 0.20 [(95% confidence limits) 0.12, 0.34] and 6.6 [4.3, 10.0] h. The estimates of the short and long repair half-times were significantly different, although there was no significant difference between the results using the Poisson and logistic modes of analyses. The partition coefficient for the longer repair process was 0.5 [0.34, 0.71] indicating that about 33% of SLD-derived lethal damage is associated with the longer repair process in the case of 'complete repair' protocols. However, this proportionation is, in general, protocol dependent for incomplete repair protocols. A chi2 test on the residual deviance showed that the assumption of two repair processes for SLD gave a superior fit to the data than a single repair process at a significance level >99%. The radiation dose to the assumed target cell population depends upon their depth from the skin surface, due to the relatively short range of the electron emission from the 90Sr/90Y plaques. However, further modelling analyses have shown that the estimated repair half-times were independent of the assumed target cell distribution in the skin. This is in contrast with the alpha/beta ratio, where different (clinically significant) estimates can be obtained depending upon the assumed target cell distribution. If the target cells were at 16 micrometer depth from the surface of the skin, the estimated value for the alpha/beta ratio using the biphasic repair model would be 4.6[3.6, 5.6] Gy(Poisson analysis). However, the estimates decrease with the assumed depth (distribution) of the target cells.     

Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to the 7.9-kDa peptide showed reactivity by western blot analysis and suppressed its in vitro chemotactic activity. Cross-desensitization chemotaxis experiments suggested that the chemotactic responses elicited by MIP-2 and the related chemokine, cytokine-induced neutrophil chemoattractant, may be mediated through a common receptor. Also, chemotactic responses to human GRO-alpha were blocked by exposure of human neutrophils to either GRO-alpha or rat MIP-2, suggesting conservation of this receptor-mediated response. After LPS instillation into rat lung, mRNA for MIP-2 was up-regulated in a time-dependent manner, peaking at 6 h. MIP-2 protein was detected in bronchoalveolar lavage fluids of these animals and a significant amount of chemotactic activity present in these fluids was attributed to MIP-2. On the basis of intrapulmonary instillation of Ab to MIP-2, neutrophil accumulation in lungs after airway instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils.     

Pyogenic hepatic abscess. Changing trends over 42 years

OBJECTIVE: The authors document changes in the etiology, diagnosis, bacteriology, treatment, and outcome of patients with pyogenic hepatic abscesses over the past 4 decades. SUMMARY BACKGROUND DATA: Pyogenic hepatic abscess is a highly lethal problem. Over the past 2 decades, new roentgenographic methods, such as ultrasound, computed tomographic scanning, direct cholangiography, guided aspiration, and percutaneous drainage, have altered both the diagnosis and treatment of these patients. A more aggressive approach to the management of hepatobiliary and pancreatic neoplasms also has resulted in an increased incidence of this problem METHODS: The records of 233 patients with pyogenic liver abscesses managed over a 42-year period were reviewed. Patients treated from 1952 to 1972 (n = 80) were compared with those seen from 1973 to 1993 (n = 153). RESULTS: From 1973 to 1993, the incidence increased from 13 to 20 per 100,000 hospital admissions (p < 0.01. Patients managed from 1973 to 1993 were more likely (p < 0.01) to have an underlying malignancy (52% vs. 28%) with most of these (81%) being a hepatobiliary or pancreatic cancer. The 1973 to 1993 patients were more likely (p < 0.05) to be infected with streptococcal (53% vs. 30%) or Pseudomonas (30% vs. 9%) species or to have mixed bacterial and fungal 26% vs. 1%) infections. The recent patients also were more likely (p < 0.05) to be managed by percutaneous abscess drainage (45% vs. 0%). Despite having more underlying problems, overall mortality decreased significantly (p < 0.01) from 65% (in 1952 to 1972 period) to 31% (in 1973 to 1993 period). The reduction was greatest for patients with multiple abscesses (88% vs. 44%; p < 0.05) with either a malignant or a benign biliary etiology (90% vs. 38%; p < 0.05). Mortality was increased (p < 0.02) in patients with mixed bacterial and fungal abscesses (50%). From 1973 to 1993, mortality was lower (p = 0.19) with open surgical as opposed to percutaneous abscess drainage (14% vs. 26%). CONCLUSIONS: Significant changes have occurred in the etiology, diagnosis, bacteriology, treatment, and outcome patients with pyogenic hepatic abscesses over the past 4 decades. However, mortality remains high, and proper management continues to be a challenge. Appropriate systemic antibiotics and fungal agents as well as adequate surgical, percutaneous, or biliary drainage are required for the best results.     

Characteristics of secondary electrons produced by 6, 10 and 24 MV x-ray beams

Megavoltage x-ray beams generated by linear accelerators (linacs) deliver their maximum dose a few centimetres below the treatment or phantom surface. This skin-sparing effect is degraded by the generation of secondary electrons as the x-ray beam passes to the patient or phantom. This work measures the characteristics of these electrons. A light-weight electromagnet was constructed that could be mounted in the block-tray position, 58 cm from the x-ray source of a Varian Clinac 2100C or 2500 linac. A field strength as high as 0.1500 T was generated, which was strong enough to sweep secondary electrons out of a 10 cm x 10 cm field. For 6, 10 and 24 MV x-ray beams, secondary contamination electrons produced 18, 38 and 65% of the surface dose, corresponding to 3, 5 and 12% of the maximum dose, respectively. A parameterized depth-dose curve for the contamination electrons was produced and was valid for all the x-ray energies studied.     

Large-core biopsy guns: comparison for yield of breast tissue

PURPOSE: To compare seven large-core, long-throw, 14-gauge biopsy guns for yield and quality of breast tissue obtained. MATERIALS AND METHODS: A two-phase, randomized and blinded study was performed. In the first phase, four fully automated 14-gauge biopsy guns (BIP, Manan, Biopsy, and ASAP) and one semiautomated device (Temno) were used to obtain breast cores from a cadaver. Samples were assessed for volume, number of fragments, and crush artifact. In the second phase, seven biopsy guns (previously mentioned guns plus Monopty and Ultra-Cut guns) were used to obtain cores from a breast parenchyma model. These cores were then evaluated for weight, volume, and number of fragments. RESULTS: The mean specimen volume of cadaveric breast tissue obtained was 17.9 mm3 for the BIP gun, 17.8 for the Manan gun, 14.9 for the Biopsy gun, 14.1 for the ASAP gun, and 9.9 for the Temno gun. The Temno gun obtained statistically significantly smaller volumes than all other guns. For the breast parenchyma model, mean obtained volumes were 24.5, 24.1, 16.2, 21.7, 17.5, 20.0, and 15.2 mm3, respectively. The BIP and Manan guns yielded statistically significantly larger cores than all other guns except the ASAP. CONCLUSION: Yields of breast tissue provided by each biopsy device differed statistically significantly. BIP and Manan biopsy guns yielded the greatest volume of core tissue, which may facilitate histopathologic diagnosis from breast biopsies performed with imaging guidance.