Dose and time dependent cerebrovascular and metabolic effects of ethanol

The purpose of these experiments was to determine the effect of ethanol dose and time of administration on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2). CBF and CMRO2 were measured in Sprague-Dawley rats 30 and 90 minutes after intraperitoneal injections of ethanol. Blood alcohol concentrations ranged from 1 to 3 mg/ml and were equivalent at both time periods. Ethanol produced small but significant increases in CBF and CMRO2 with blood alcohol concentrations. The above changes were not time dependent and were similar between 30 and 90 minute testing periods. The dose dependent effects of ethanol on cerebral metabolism are consistent with in vitro studies suggesting a dose related effect of ethanol on neuronal metabolism. The time of application appears to have little effect on the cerebral metabolic effects of alcohol.     

Induction of chromosomal aberrations and spindle disturbances in Chinese hamster epithelial liver cells in culture by pyrene and benzo[a]pyrene quinones

Regioisomers of pyrene and benzo[a]pyrene quinones were testedfor their ability to induce structural and numerical aberrationsand spindle disturbance in Chinese hamster epithelial liver(CHEL) cells in culture. All quinones tested were clastogenicPyrene-1,8-quinone (P-1,8-Q) and benzo[a]pyrene–3,6–quinone(BP-3,6-Q) induced strikingly high levels of triradials. Inaddition, dicentrics and ring chromosomes were very common inBP-3,6-Q-treated cultures. Isomers of these compounds, pyrene-1,6-quinone(P-1,6-Q) and benzo[a]pyrene-1,6-quinone (BP-1,6-Q), inducedunobtrusive patterns of chromosomal aberrations. We suspectthat the P-1,8-Q and BP-3,6-Q moieties bound to the DNA werestill reactive, and formed crosslinks and/or underwent redoxcycling leading to high local concentrations of reactive oxygenspecies. In addition, P-1,8-Q and BP-3,6-Q induced c-mitoses,hyperdiploidies and polyploidies, in particular endoreduplications.These effects were not seen with the other two test compounds,or they were only detected at the highest concentrations used,which were strongly cytotoxic (c-mitoses with P-1,6-Q, polyploidieswith BP-1,6-Q). ⁶To whom correspondence should be addressed at: European Centre for the Validation of Alternative Methods (ECVAM), Joint Research Centre (JRC), TP58O, 1–21020 Ispra, Italy     

Outpatient anterior chamber lens implantation

100 outpatient and 143 inpatient intracapsular cataract extractions with anterior chamber lens implantation were examined 6 months post-operatively. 74 (74%) in the former and 107 (75%) in the latter achieved visual acuity greater than or equal to 0.5. Excluding non-surgical pathology, 93% in the outpatient group and 98% in the inpatient group had a visual acuity greater than or equal to 0.5 (P = 0.12). There were no significant differences in post-operative complications except for the incidence of cystoid macular edema. Six (6%) of the outpatient and 1 (0.7%) of the inpatient procedures had cystoid macular edema that resulted in a visual acuity below 0.5 (P = 0.02).     

IFN-alpha-induced murine B16 melanoma cancer vaccine cells: induction and accumulation of cell-associated IL-15.

Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and natural killer (NK) cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Long-term IFN-alpha treatment of B16alpha vaccine cells induced both interleukin-15 (IL-15) mRNA and IL-15 protein. The bulk of the induced IL-15 remained cell associated, either cytoplasmic or associated with the cell membrane. Immunofluorescence microscopy studies showed that the cell-associated IL-15 was broadly distributed throughout the cytoplasm. These observations suggest that long-term IFN-alpha treatment may induce primarily the truncated isoform of IL-15. Vaccination with irradiated B16alpha vaccine cells may promote tumor immunity by releasing high levels of cell-associated IL-15 when spontaneously lysed or directly killed by innate immune cells. The release of accumulated cell-associated IL-15 may then trigger a host T cell response to tumor antigens and cause host development of immunity to the B16 tumor cells.     

Oral administration of taurolidine ameliorates chronic DSS colitis in mice.

Taurolidine (TRD) has antimicrobial and anti-inflammatory properties. However, the anti-inflammatory effects of TRD in inflammatory bowel diseases (IBD) have not been investigated. Here, we have analyzed the toxicity of TRD after oral long-term application in mice and examined the impact of oral TRD in a dextran sulfate sodium (DSS) model of experimental colitis. Female C57/BL6 mice received TRD in various concentrations (0.1% to 0.4%) for 60 days. Toxicity was evaluated by use of a disease activity index (DAI) and histological examination of major metabolic organs. Furthermore, the impact of 0.2% TRD on a chronic DSS colitis was examined by daily DAI, histological crypt damage score (CDS), bacterial translocation into mesenteric lymph nodes (MLN), and colonic expression of tumor necrosis factor (TNF) alpha, transforming growth factor (TGF) beta, interleukin (IL)-1beta, IL-6, cytochrome oxidase (COX)-2, and monocyte chemotactic protein (MCP)-1 by real-time polymerase chain reaction (PCR). Oral TRD administration for 60 days was well tolerated by the animals and did not show any toxic effects in terms of DAI and histological changes. TRD treatment of DSS colitis led to increased survival of 100%, compared to 33% in the untreated colitis group (p < or = .005). Clinical amelioration was mirrored by significantly reduced DAI and CDS in the TRD treated colitis. Colonic cytokine expression and bacterial translocation into MLN showed no differences between both groups. We thus report for the first time that oral application of TRD results in amelioration of an experimental IBD model. We hypothesize direct intraluminal antimicrobial effects of TRD as well as anti-inflammatory effects during the acute phase of DSS colitis.     

Orbital CT in the management of blow-out fractures of the orbital floor

The CT-examinations of 15 patients with blow-out fractures of the orbital floor were reviewed. All patients were examined with coronal/semicoronal CT-imaging, and 7 patients also were evaluated with semisagittal projections. Only in one case the semisagittal images gave more information than coronal sections when using the classification of Gilbard et al. (1985) of the inferior rectus muscle/fracture relationship. The anterior and posterior fracture margins were better delineated with semisagittal imaging. Two patients exhibiting positive traction tests with hooked, and not entrapped muscles on CT still had diplopia 5 1/2 and 12 weeks after the trauma.     

Substance P augments the rate of vasodilation induced by calcitonin gene-related peptide in porcine ophthalmic artery in vitro.

Peptides may function as neurotransmitters liberated antidromically by sensory nerve fibres, provoking vascular responses having potential importance in some neurological disorders. Dose-response relaxation curves induced by substance P (SP) and calcitonin gene related peptide (CGRP) have been studied in porcine ophthalmic arteries in vitro. Both peptides induced vasodilation when tested separately (CGRP much greater than SP). Because of the putative interactions between such peptides in this vascular territory, a computerised system was also used for analysing over time the response to a single addition of either 10(-8) M CGRP, 10(-8) M SP or a combination of 10(-8) M SP + 10(-8) M CGRP. SP did not augment the maximum relaxation induced by CGRP alone, but increased significantly the rate of relaxation during the initial phase of the response. The effect induced by the SP+CGRP combination was stronger than the sum of the individual SP and CGRP-induced relaxations during the first 4 min of the response, which suggests a SP-CGRP synergism in this artery.