Effects of crude oil and ultraviolet radiation on immunity within mouse skin

Previous studies indicate that crude oil leads to increased pigmentation and erythema (sunburn) in response to sunlight in exposed individuals. However, no information is currently available concerning whether crude oil exposure might enhance the immunosuppressive effects of solar ultraviolet radiation (UVR) on the skin. In order to address this question, the back skin of shaved, female C3H/HeN mice was exposed to crude oil with or without subsequent treatment with medium-wavelength (UVB) (200 J/m2) or long-wavelength (UVA) (20,000 J/m2) UVR. Immune function was assessed in treated mice by measuring their ability to mount contact hypersensitivity responses to a hapten (2,4-dinitro-1-flyorobenzene, DNGFB) applied to the site of crude oil and UVR treatment as determined by ear swelling upon subsequent challenge. Since Langerhans cells represent an important component of immunity within the skin and because suppression of contact hypersensitivity following UVR treatment is often accompanied by disappearance of Langerhans cells from the epidermis, the impact of these agents on epidermal Langerhans cell density was also analyzed. This was accomplished by enumerating IA-positive cells within the epidermis of treated skin. In these studies, crude oil alone induced inhibition of contact hypersensitivity but had no effect on epidermal Langerhans cells. In contrast, combined treatment with crude oil and UVA led to suppression of contact hypersensitivity, which was accompanied by depletion of epidermal Langerhans cells.     

Effect of CNTF on low-affinity NGF receptor expression by cultured neurons from different rat brain regions.

Our previous work indicated that in E14 embryonic rat spinal cord cultures ciliary neuronotrophic factor (CNTF) exerted (1) a survival-promoting effect on motor neurons and on a large population of unidentified neurons, and (2) a regulatory role on the expression of ChAT and low affinity NGF receptor (LNGFR) in a population of small/medium-sized neurons. In the present study, we examined the effect of CNTF on the expression of LNGFR in cultures of different regions from the E18 embryonic rat brain, namely cortex, septum, striatum, mesencephalon, hippocampus, brainstem, and cerebellum. The number of LNGFR-positive neurons (stained with the 192-IgG monoclonal antibody) was determined in untreated cultures and in cultures treated for 6 days (0-6) with human recombinant CNTF. To distinguish between effects on survival and on LNGFR expression, experiments were performed in which CNTF was administered only for the last 48 h of the culture (from days 4-6). LNGFR positive neurons were found in the cultures of all the regions examined. In each one of them, CNTF increased the number of LNGFR-positive neurons by three- to fourfold after 6 days of treatment. In the striatum, septum, mesencephalon, and cerebellum, the effect of CNTF was shown to be on the regulation of LNGFR expression and not on survival. In cultures from the cortex, hippocampus and brainstem, a survival-promoting role of CNTF could be demonstrated. The effect of CNTF was dose dependent, with half-maximal effects (ED50) achieved at 2-4.5 TU/ml for all the brain regions. Maximal effects were reached at 100-250 TU/ml. From these results, we conclude that (1) there exists a wide spectrum of CNTF-responsive neurons in the central nervous system, and (2) CNTF plays an important and widespread role in regulating the expression of the LNGFR in neurons.     

The effects of a reduced exercise duration taper programme on performance and muscle enzymes of endurance cyclists

Summary The influence of tapering on the metabolic and performance parameters in endurance cyclists was investigated. Cyclists (n = 25) trained 5 days · week^–1, 60 min·day^–1, at 75–85% maximal oxygen consumption (VO_2max) for 8 weeks and were then randomly assigned to a taper group: 4D (4 days;n = 7), 8D (8 days;n = 6), CON (control, 4 days rest;n = 6), NOTAPER (non-taper, continued training;n = 6). Muscle biopsy specimens taken before and after training and tapering were analysed for carnitine palmityltransferase (CPT), citrate synthase, ß-hydroxyacyl CoA dehydrogenase (HOAD), cytochrome oxidase (CYTOX), lactate dehydrogenase, glycogen and protein. Significant increases inVO_2max (6%), a 60-min endurance cycle test (34.5%), oxidative enzymes (77–178%), glycogen (35%) and protein (34%) occurred following training. After the taper, HOAD and CPT decreased 25 % (P<0.05) and 26% respectively, in the CON. Post-taper CYTOX values were different (P<0.05) for 4D and 8D compared with CON. Muscle glycogen levels were increased (P<0.05) after tapering in the 4D, 8D and CON, but decreased in NOTAPER. Similarly, power output at ventilation threshold was significantly increased in the 4D (27.4 W) and 8D (27 W) groups, but decreased (22 W) in the NOTAPER. These findings suggest that tapering elicited a physiological adaptation by altering oxidative enzymes and muscle glycogen levels. Such an adaptation may influence endurance cycling during a laboratory performance test.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Effects of phenytoin, carbamazepine, and clonazepam on cortex- and amygdala-evoked potentials in partially kindled rats

The kindling technique has been reported to produce a long-lasting enhancement in both the early and late phases of evoked potentials triggered from the kindled focus. It also alters paired-pulse facilitation and depression in the pathways which support these phenomena. The present experiment was designed to determine whether the drugs which antagonize secondary generalization in the kindling model also antagonize kindling-enhanced excitation in the pathways leading out of the focus. Multiple doses of phenytoin, carbamazepine, and clonazepam were therefore tested against single- and double-pulse evoked potentials triggered from the focus in rats that had been subjected to parital kindling from either the amygdala or the cortex. Responses were recorded in monosynaptic sites and in the mesencephalic reticular formation--a polysynaptic site thought to play an important role in secondary generalization. No drug-related effects were found on early evoked potential components, either in the single-pulse or the double-pulse paradigm. Kindling-enhanced late components ("late waves"), however, were clearly and selectively antagonized by clonazepam.     

The GABA hypothesis of kindling: Recent assay studies

The GABA (gamma-aminobutyric acid) hypothesis of kindling suggests that the permanent changes caused by the kindling procedure result from a loss of GABA-mediated inhibition. Pharmacological studies have generally supported this hypothesis: GABA-complex antagonists accelerate (or stimulate) kindling, whereas GABA-complex agonists retard (or reverse) it. Assay studies, however, have presented an inconsistent picture. Earlier studies found no GABAergic brain changes after kindling, whereas recent studies have reported postkindling changes in a number of GABA-related parameters. The crucial difference seems to be that earlier studies assayed GABA parameters in "whole tissue," whereas recent studies have concentrated on "synaptic" GABA. As indicated by recent studies, when the "metabolic pool" is excluded, kindled subjects show a variety of persistent abnormalities in the GABA system. These data are generally consistent with the GABA hypothesis of kindling.     

The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression.

Posttransplant lymphoproliferative disorders (PTLDs) were diagnosed in 43 patients from the Pittsburgh-Denver series between June 1980 and March 1987. This constitutes a detection rate of 1.7%. Major categories of clinical presentation included a mononucleosislike syndrome, gastrointestinal/abdominal disease, and solid organ disease. The median time of onset in patients initially immunosuppressed with cyclosporine-A (CsA)-containing regimens was 4.4 months after transplant, regardless of tumor clonality. A strong association of PTLD with Epstein-Barr virus (EBV) was observed. A histologic spectrum of lesions from polymorphic to monomorphic was observed. Whereas polymorphic lesions could be either clonal or nonclonal, monomorphic lesions appeared to be clonal in composition. The presence of large atypical cells (atypical immunoblasts) or necrosis did not appreciably worsen the prognosis. Twelve patients had clonal, 13 had nonclonal, and five had both clonal and nonclonal tumors. Clonality was indeterminate in 13 cases. Most patients were treated with a regimen based on reduced immunosuppression and supportive surgery. Almost all nonclonal and about half of the clonal lesions respond to this conservative therapy, indicating that it is an appropriate first line of treatment. This behavior suggests that a spectrum of lesions ranging from infectious mononucleosis to malignant lymphoma constitutes the entity known as PTLD. Some monoclonal tumors can undergo regression, however, apparently in response to host immune control mechanisms. Because of its short latency and strong association with EBV, PTLD is an important model for the study of virus-associated tumor progression in humans.     

Microsurgical anatomy of VII and VIII cranial nerves and related arteries in the cerebellopontine angle

Summary The relationships of VII and VIII cranial nerves and related arteries are reviewed in 26 preparations by microdissection techniques. These vessels may be grouped in large (AICA, PICA), medium (LA, SA, CSA, RPI) and small calibre (vasa nervorum, radicullar and medullar branches). The importance of these structures in acoustic neuroma surgery, vestibular neurectomy and cross-compression syndromes is discussed. Vascular loops and elongated arteries are normal structures present at birth.This work was supported by a grant from the AJ Roemmers Foundation