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At least 811 records · Page 45Linked to original sources
PubMed1995

An in vivo/in vitro method for assessing micronucleus and chromosome aberration induction in rat bone marrow and spleen. 1. Studies with cyclophosphamide.

The mouse micronucleus assay has long been used as an indicator of in vivo genotoxicity. Recently, it was shown that no single protocol is adequate to detect all clastogens. As a first step in developing a potentially more sensitive assay, micronucleus induction by cyclophosphamide (CP) was assessed in an in vivo/in vitro system using rat bone marrow and spleen cells. In each of two independent experiments, two rats/dose were treated i.p. with 0, 20, or 40 mg CP/kg and killed 6 h later. Cultures were then established in the presence of growth stimulants (interleukin-3 and granulocyte-macrophage colony stimulating factor for bone marrow; lipopolysaccharide and concanavalin A for spleen) and cytochalasin B, a cytokinesis inhibitor. Bone marrow cells were harvested and slides prepared 24 h after initiation, while spleen cells were harvested at 48 h. One thousand cells/tissue/group were scored for cell cycle kinetics and 1000 binucleate (BN) cells were scored for micronuclei. In addition, spleen cells were concurrently assayed for chromosome aberrations. A dose-related cell cycle delay was observed in both tissues in both experiments. Bone marrow showed a 6% average background frequency of micronucleated BN cells, while the low dose induced an average of 20%, and the high dose 31%. For spleen, the average control frequency of micronucleated BN cells was 3%, the low dose induced a 40% average frequency, and the high dose 65%. Also in splenocytes, a dose-dependent increase in chromosome aberrations was observed, with an almost 40-fold increase observed over the control value at the high dose. Thus, the in vivo/in vitro approach described here shows great potential in detecting drug induced genotoxicity. Also, spleen appears more sensitive than bone marrow to CP.

Animals↗
PubMed1994

Contents of corticotropin-releasing hormone and arginine vasopressin immunoreactivity in the spleen and thymus during a chronic inflammatory stress.

We have previously found that proopiomelanocortin (POMC) mRNA and levels of adrenocorticotropin (ACTH) and beta-endorphin peptides are increased in the spleen and thymus of rats with adjuvant-induced arthritis (AA), and immunologically mediated inflammatory disease. To determine whether alterations in immune tissue POMC during AA are also accompanied by changes in immune tissue corticotropin-releasing hormone immunoreactivity (ir-CHR) and arginine vasopressin (AVP), we measured ir-CRH and AVP by radioimmunoassays in spleen and thymic extracts 14 days following injection of adjuvant. Ir-CRH was detectable in all extracts of spleen and thymus. Total contents of ir-CRH in the spleen and thymus were not altered following arthritis, although a significant decrease was observed in splenic extracts from arthritis rats (40.0 +/- 4.2 fmol/g tissue) compared to controls (69.5 +/- 8.4 fmol/g tissue) when contents were expressed as amount per weight of tissue. Low levels of AVP were also detected in immune tissues, with contents significantly increased in spleens from arthritis animals (17.4 +/- 1.6 fmol/g tissue) compared to controls (10.6 +/- 1.9 fmol/g) but thymic contents of AVP were not altered by arthritis (10.6 +/- 1.3 fmol/g) compared to controls (9.2 +/- 0.7 fmol/g). Control levels of AVP were significantly higher in spleens and thymuses from female rats (53 +/- 5 and 25 +/- 4 fmol/g tissue, respectively) compared to males. G-50 chromatography revealed that the principal form of splenic ir-CRH is CRH(1-41), although in non-arthritic animals some ir-CHR eluted in a position indicating a slightly larger form.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

The effect of some antirheumatic drugs in vivo on the response of spleen cells to concanavalin A in rats with chronic inflammation.

During the course of adjuvant arthritis in rats adherent spleen cells inhibited the response of spleen lymphocytes to the T-cell mitogen concanavalin A (Con A). The effects of 14 days treatment with various antirheumatic drugs on spleen cell responsiveness to Con A were investigated. Two nonsteroidal anti-inflammatory drugs, indomethacin (1 mg/kg/day p.o.) and acetylsalicylic acid (200 mg/kg/day p.o.) did not modify the spleen cell response, whereas treatment with chloroquine (50 mg/kg/day p.o.) or levamisole (5 mg/kg/day p.o.) further increased the inhibitory effects of the adherent suppressive spleen cells. On the contrary, treatment with sodium aurothiomalate (10 mg/kg/day i.m.), D-penicillamine (50 mg/kg/day p.o.) or pyritinol (50 mg/kg/day p.o.) significantly enhanced the response of the lymphocytes to Con A. In addition to the effects on spleen cell responsiveness, the ability of the various drug treatments to modify the polyarthritic lesions of the disease was investigated. It is suggested that this model may provide a valuable approach for evaluating the effects of antirheumatic drugs in vivo on immunological responsiveness during chronic inflammatory disease.

Animals↗
PubMed1983

Activation of macrophages by culture fluid of antigen-stimulated spleen cells collected from chickens immunized with Eimeria tenella.

The effect of spleen cell factors on the activation of macrophages was investigated in chickens immunized with Eimeria tenella. The abilities of peritoneal macrophages obtained from normal chickens to kill sporozoites of E. tenella and to inhibit intracellular development of Toxoplasma gondii were enhanced by exposing them to 33 and 50% culture fluid of antigen-stimulated spleen cells of chickens immunized with E. tenella. The parasiticidal activity of normal macrophages was also distinctly enhanced by the treatment with culture fluid of phytohemagglutinin-stimulated normal spleen cells. On the other hand, the parasiticidal activity of normal macrophages could not be enhanced by the treatment with culture fluid of antigen-stimulated normal spleen cells under conditions similar to those of culture fluid of antigen-stimulated immune spleen cells. It thus appears that the macrophage activator was induced from immune spleen cells in response to the stimulation by the antigen.

Animals↗
PubMed1988

Neuropeptide Y- and alpha-adrenergic receptors in pig spleen: localization, binding characteristics, cyclic AMP effects and functional responses in control and denervated animals.

The localization of neuropeptide Y binding sites in the pig spleen, as revealed by [125I]Bolton-Hunter-labelled porcine neuropeptide Y and alpha 1-adrenergic receptor binding sites, as revealed by [125I](2-beta/4-hydroxy-phenyl/-ethylaminomethyl)-tetralone as radioligand, was compared with the distribution of neuropeptide Y and noradrenaline nerves, the latter revealed by tyrosine hydroxylase and dopamine-beta-hydroxylase, using immunohistochemistry. A large degree of codistribution was obtained between [125I]neuropeptide Y and alpha 1-binding sites in the capsule, trabeculae, blood vessels and the red pulp of the spleen. Neuropeptide Y and tyrosine hydroxylase as well as dopamine-beta-hydroxylase-positive nerves were identical in the spleen and had a similar gross distribution pattern as the [125I]neuropeptide Y and alpha 1 binding sites. In functional studies using the isolated blood-perfused spleen from pentobarbital-anaesthetized pigs, neuropeptide Y, noradrenaline and the alpha 1-selective agonist phenylephrine contracted the capsule and induced vasoconstriction in the spleen in vivo. However, the selective alpha 2-adrenoceptor agonists clonidine and azepexole had no effects on blood flow or perfusion pressure, suggesting that postjunctional alpha-receptors were of the alpha 1 type. Neuropeptide Y inhibited the forskolin-evoked, cyclic adenosine monophosphate formation in vitro. The [125I]neuropeptide Y binding, with an equilibrium-dissociation constant of 503 +/- 73 pM and a maximal number of specific binding sites of 23 +/- 3 fmol/mg protein, the neuropeptide Y-induced perfusion-pressure increase in vivo and the inhibition of forskolin-evoked cyclic adenosine monophosphate formation in vitro were dependent on the amidation of the C-terminal portion of the peptide molecule. Furthermore, the effects of neuropeptide Y were not changed by alpha- and beta-adrenoceptor blockade using prazosin and propranolol. Two weeks after postganglionic denervation the neuropeptide Y and the noradrenaline contents of the pig spleen were reduced by 97% and 99%, respectively. These changes were associated with a selective supersensitivity for the noradrenaline-induced perfusion-pressure increase in vivo compared with the effect of neuropeptide Y. However, a similar potentiation of the noradrenaline effect was induced by the monoamine-uptake blocker desipramine in the absence of denervation, and there was no change in the functional response to phenylephrine after denervation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

[Torsion of the spleen in children].

The wandering spleen is caused by congenital absence of fixating ligaments or abnormally long ligaments. It is an uncommon clinical entity, which rarely affects children. The clinical presentation of wandering spleen is variable, but the most dangerous complication is splenic torsion. A 7 year-old boy presented with abdominal pain and vomiting. The abdominal ultrasound scan discovered spleen ischemia. Volvulus of the spleen was evoked. Laparotomy was carried out and the patient underwent splenectomy. In this case the anatomical means of spleen fixity were absent. Because wandering spleen is uncommon in the paediatric population, a heightened awareness of the condition is required for accurate diagnosis and appropriate management. The treatment of choice is splenopexy, while if splenic necrosis is present, splenectomy is required.

Abdominal Pain↗
PubMed2006

Spleen plays an important role in the induction of accelerated blood clearance of PEGylated liposomes.

It is well known that steric stabilization of the surface of liposomes by a polyethyleneglycol (PEG) conjugated lipid results in reduced recognition of the liposomes by the cells of the mononuclear phagocyte system and consequently extended circulation times of the liposomes (t1/2 approximately 20 h in rat). Recently, we reported on the "accelerated blood clearance (ABC) phenomenon", causing PEGylated liposomes to be cleared very rapidly from the circulation upon repeated injection. We also reported that abundant binding of IgM, secreted into the blood stream after the first dose and, to PEGylated liposomes, plays an essential role in the induction of the ABC phenomenon. Spleen is well known to play a central role in the immune reaction and to produce IgM following a bacterial infection. The aim of the present study was to determine whether spleen contributes to the induction of the ABC phenomenon and to unravel its role in the phenomenon. In rats that were splenectomized (surgical removal of spleen) prior to the first injection of liposomes (0.001 micromol phospholipids/kg), the ABC phenomenon was totally abolished. In these rats serum IgM concentrations as well as the amounts of IgM bound to PEGylated liposomes were substantially reduced. Splenectomy attenuated the ABC phenomenon when performed until 3 days post-first injection. Removal of the spleen 4 days post-first injection left the ABC phenomenon unchanged. This finding indicates that the immune reaction in the spleen against the PEGylated liposomes occurs during at least 2-3 days following the first administration and then IgM reactive to PEGylated liposomes is produced. The present study proves that the spleen plays a critical role in the induction phase of the ABC phenomenon. For effective clinical application, many liposomal drug formulations will require multiple injections. The ABC phenomenon described in this and several preceding papers therefore has important implications for the development and evaluation of therapeutically useful liposomal formulations requiring multiple-dose administration.

Animals↗
PubMed2005

CD4-veCD8-ve CD30+ve T cells are detectable in human lung transplant patients and their proportion of the lymphocyte population after in vitro stimulation with donor spleen cells correlates with preservation of lung physiology.

INTRODUCTION: Survival following lung transplantation is less than 50% at 5 years, mainly due to immune-mediated chronic rejection. Recently a novel subset of T cells, CD4-veCD8-ve CD30+ve, so-called double negative (DN) CD30+ve T cells, has been described and shown to be responsible for tolerance in an animal model of skin transplantation. METHODS: We investigated 18 lung transplant recipients for the presence of DN CD30+ve T cells in resting peripheral blood and also following in vitro stimulation of recipient peripheral blood mononuclear cells (PBMCs) with donor spleen cells. RESULTS: Small percentages (0.2% to 6%) of DN T cells are detectable in resting PBMCs of human transplant patients (n = 18), but these did not correlate with allograft function, acute rejection episodes, HLA mismatch, or CMV status. On repeated stimulation of recipient PBMCs (two exposures) in vitro by donor spleen cells (2:1 ratio stimulators to responders) the percentage of DN CD30+ve T cells within the lymphocyte pool correlated with preservation of allograft lung function (both for FEV(1), P = .009, and FEF(25-75), P = .036) and was inversely correlated with grade of chronic rejection. On repeated exposure of recipient PBMCs to donor spleen cells with a 1:1 ratio the percentage of DN CD30+ve T cells correlated with the number of acute rejection episodes of grade 2 or greater. The total number of HLA mismatches correlated with the percentage DN CD30+ve T cells present after primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio). The number of mismatches at the B locus inversely correlated with the percentage of DN CD30+ve T cells after primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio; P = .031, n = 18). CONCLUSION: Percentages of DN CD30+ve T cells present following repeated stimulation of recipient PBMCs by donor spleen cells correlated with preservation of graft function following lung transplantation.

Antigens, CD↗
PubMed1997

Organ culture of human lymphoid tissue. II. Marked differences in cytokine production and proliferation between slice and suspension cultures of human spleen.

Recently, we have established a method for the culture of human spleen slices in vitro. The procedure allows thin slices (200-350 microns) of human spleen to be cultured for up to 7 days. Using this method, we have previously established that unstimulated spleen slices spontaneously synthesize and secrete considerably higher levels of immunoglobulin than suspension cultures of the same tissue run in parallel. In this study, we report that there are also marked differences in the cytokine secretion profile between slices and suspensions and in their proliferative response. In brief, control and PHA-stimulated spleen slices secrete high levels of IL-1 beta, IL-6, IL-8 and IL-11 while the levels found in suspension supernatants are appreciably lower. By way of contrast, high levels of IL-2, IL-4, IL-10 and TNF alpha are found in suspension culture supernatants following PHA stimulation while the response in slice cultures is extremely low. These differences are also reflected in the results obtained at the cellular (intracellular cytokine) level. Additional studies reveal that spontaneous immunoglobulin production observed in spleen slices can be inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha and that the bulk of the IL-6 and IL-1 beta detected in culture supernatants represents de novo synthesis. Finally, the background and mitogen-stimulated proliferative response of tissue slices is meagre compared with that observed in spleen suspensions suggesting that proliferation in the former is held under strict control. Collectively, we believe that the tissue slice procedure described provides us with a system for studying integrated events in lymphoid tissues in vitro and evaluating immunomodulatory substances of potential clinical importance.

Adolescent↗
PubMed1998

Laparoscopic splenopexy for pediatric wandering spleen.

Wandering spleen is an uncommon condition, showing a splenic hypermobility that results from laxity or maldevelopment of its suspensory ligament. This condition results in constant danger of splenic torsion and infarction. Wandering spleen was diagnosed in a 2-year-old girl who complained of intermittent abdominal pain, and viability of the spleen was confirmed by doppler ultrasound scan. Elective laparoscopic splenopexy was performed by anchoring the spleen wrapped in absorbable mesh. To our knowledge, this is the first reported case of laparoscopic splenopexy for wandering spleen. The authors believe that this approach is a safe and effective procedure for wandering spleen with the advantage of minimally invasive surgery.

Child, Preschool↗
PubMed1998

L-deprenyl-induced increase in IL-2 and NK cell activity accompanies restoration of noradrenergic nerve fibers in the spleens of old F344 rats.

Previously, we have hypothesized a causal relationship between some measures of immunosenescence and the age-related decline in sympathetic noradrenergic (NA) nerve fibers in spleen and lymph nodes of F344 rats. In the present study, we investigated this interrelationship further by measuring NK cell activity, Con A-induced IL-2 production, norepinephrine (NE) concentration, and morphological localization of NA and neuropeptide-Y (NPY) nerve fibers in the spleens of old (21 months old) male F344 rats after 10 weeks of daily treatment with low doses of L-deprenyl, an irreversible monoamine oxidase-B inhibitor, followed by a 9-day wash-out period. NK cell activity and Con A-induced IL-2 production were increased in deprenyl-treated old rats in comparison to untreated and saline-treated old rats. Deprenyl treatment did not alter the percentage of CD5+ T-cells, but moderately increased the percentage of sIgM+ B-cells in the spleens of old rats. In addition to changes in immune responses, NE content and the volume density of NA and NPY nerve fibers were partially augmented in the spleens of deprenyl-treated old rats. In a separate study, various concentrations of deprenyl were added in vitro to spleen cells from young and old F344 rats to examine the direct effects of the drug on Con A-induced IL-2 production. In contrast to in vivo treatment, in vitro addition of deprenyl did not alter the Con A-induced IL-2 production by splenocytes from old rats. Together, these results suggest that the ability of deprenyl to enhance certain immune responses are interlinked to the restoration of sympathetic NA and NPY nerve fibers in the spleens of old rats.

Aging↗
PubMed1997

Exposure of tilapian fish to the pesticide lindane results in hypocellularity of the primary hematopoietic organ (pronephros) and the spleen without altering activity of phagocytic cells in these organs.

Tilapia were dosed by intraperitoneal injection for 5 consecutive days with either 20 or 40 mg/kg of the environmental contaminant hexachlorocyclohexane (lindane). The effects of this organochlorine pesticide on morphology and total cellularity of the spleen and pronephros were examined on the second day following termination of dosing. The functional capacity of phagocytic cells isolated from both spleen and pronephros was also evaluated as possible additional indicators of chemical-induced immunotoxicity. A dose-related reduction was found in spleen and pronephros total white blood cell counts in the fish exposed to lindane. In addition, hypocellularity of lymphoid regions in the spleen and pronephros was evident in chemical-exposed animals upon histopathological examination. However, phagocytosis of fluorescent microspheres by phagocytic cells isolated from the spleen and pronephros was not inhibited by the exposure to lindane. Similarly, no decrease in phorbolmyristate acetate (PMA)-stimulated hydrogen peroxide production was observed in phagocytic cells collected from lindane-exposed fish. These results suggest that cellular depletion in tilapia spleen and pronephros may represent a more sensitive indicator of lindane exposure than does the functional capacity of phagocytic cells isolated from these hematopoietic organs. Ultrastructural observations support this hypothesis and, further, suggest that lymphocytic cells may be targeted at the present exposure levels.

Animals↗
PubMed2001

Effects of ageing and increased haemolysis on the levels of dolichol in rat spleen.

Dolichol is a long-chain polyisoprenoid. No enzyme pathway for dolichol degradation was discovered. Dolichol accumulates in human and rodent tissues during ageing. Red blood cells contain a larger amount of dolichol and red blood cell life span is shorter in older rats. The effects of age and of the load of dolichol from red blood cell degradation on the ageing-associated accumulation of dolichol in spleen were studied in 2, 6, 12, 18 and 24 month-old male Sprague Dawley rats fed ad libitum (AL) or on an anti-ageing dietary regimen (EOD). Tissue dolichol was extracted and assayed by HPLC [J. Gerontol. 53A (1998) B87]. Levels of dolichol increased in spleen, liver, kidney and muscle in parallel fashion from the age of 2 to 12 months. Unexpectedly, spleen dolichol decreased in older rats whereas liver, kidney and muscle dolichol increased significantly. The effects of haemolysis on spleen dolichol were tested by the administration of phenylhydrazine. Results show that haemolysis does not increase, but rather decreases the levels of dolichol in erythroclastic organs. It is concluded that the levels of spleen dolichol may decrease in the absence of any known enzymatic degradative pathway if the spleen and its resident phagocytes are forced to cope with a higher number of red blood cells to be cleared. Free-radical mediated decomposition of dolichol by phagocytic cells during erythrophagocytosis might be involved in the process.

Aging↗
PubMed1999

MR imaging of the liver and spleen: a comparison of the effects on signal intensity of two superparamagnetic iron oxide agents.

We compared the effects of two superparamagnetic iron oxide (SPIO) contrast agents, ferumoxides and SHU-555A, in MR imaging of the liver and spleen. Thirty-six patients with known malignant lesions of the liver underwent T2W turbo spin-echo (TSE) and T1WGRE FLASH opposed-phase imaging before and after SPIO injection on a 1.0 T MR system. Post-ferumoxides images were obtained in 18 patients 90 min after infusion of 15 micrommol Fe/kg of the agent. In 18 other patients SHU-555A was administered as a rapid bolus at a dose of 7.0-12.9 micrommol Fe/kg. T1WGRE FLASH images were obtained immediately, 30 s and 480 s and T2WTSE images 10 min after injection. Signal intensity of the liver, spleen, and malignant liver lesions before and after SPIO was measured with operator-defined regions of interest. The effects of ferumoxides and SHU-555A were measured as the percentage signal intensity change (PSIC) and in the malignant liver lesions additionally as changes in lesion-to-liver contrast-to-noise ratio (deltaDCNR). On T2W TSE images, there was no significant difference between the two agents in signal loss of liver parenchyma (p > 0.05). The signal loss in the spleen produced by ferumoxides was greater than with SHU-555A (p < 0.05). Both SPIO agents produced a significant increase in the CNR of malignant liver lesions. Delta CNR was slightly greater with ferumoxides than with SHU-555A (p < 0.05). On T1WGRE FLASH images, a slight decrease of liver SI induced by both agents was found on late post-SPIO images. No significant difference of liver PSIC between the two SPIO agents was noted on T1W images. The SI of spleen was significantly increased with both agents on T1W images and no difference in PSIC of spleen was noted (p > 0.05). The T1 and T2 effects produced by ferumoxides and SHU-555A were comparable in the liver although ferumoxides produced a stronger T2 effect in the spleen.

Contrast Media↗
PubMedDate not supplied

The Wilms tumor suppressor gene wt1 is required for development of the spleen.

The Wilms tumor suppressor gene WT1 (wt1 in mouse) is unique among tumor suppressors because, in addition to its involvement in cancer [1] [2] and various other diseases [3] [4] [5] [6], it has an essential role in the development of certain organs. This is revealed by the phenotype of mice with inactivated wt1 alleles [7]. These animals exhibit a complete failure of kidney and gonad development as well as abnormalities of the heart and mesothelial structures. On a C57BL/6 genetic background, wt1(-/-) animals die between day 13.5 (E13.5) and 15.5 (E15.5) of embryonic development [7]. We report here that crossing of the wt1 mutation onto different mouse backgrounds delayed embryonic lethality until birth. In wt1(-/-) mice on these different genetic backgrounds, we observed a dramatic failure of spleen development, in addition to the well characterized phenotypic abnormalities. The spleen anlage formed at around E12 to E13 and involuted by the E15 stage, before the invasion of hematopoietic cells. The absence of proper spleen development in these wt1(-/-) embryos correlated with enhanced apoptosis in the primordial spleen cells. The expression of hox11, a gene that also controls development of the spleen [8] [9], was not altered by the inactivation of wt1. In situ hybridization revealed that the two genes are regulated independently. These findings demonstrate that the penetrance of the wt1(-/-) phenotype depends on the existence of one or more modifier gene(s) and that wt1 plays a pivotal role in the development of the spleen, thereby extending its role in organogenesis.

Animals↗
PubMed2001

[Torsion of the accessory spleen: an atypical etiology for acute abdomen].

The accessory spleen is often a incidental discovery. The accessory post-accidental spleen are unusual. The torsion of a movable spleen is possible and represent about 0.2 to 0.3% of splenectomy. But the torsion of an accessory spleen is exceptional. A case of acute torsion of an accessory spleen is reported. In a 26-year-old women was admitted with acute abdominal pain. The abdominal ultrasound and the abdominal X-Ray are no specific. In the face of the acute pain, a laparoscopy was necessary. At laparoscopy, the patient was found to have torsion and infarction of an accessory spleen in the pelvis. The treatment was a splenectomy and the evolution was favorable.

Abdominal Pain↗
PubMed1999

Hypoxia induces free radical damage to rat erythrocytes and spleen: analysis of the fluorescent end-products of lipid peroxidation.

Several studies have shown that hypoxia induces alterations in the lipid membranes of many cell types. The mechanism of these changes might consist in membrane lipid peroxidation. Lipid peroxidation in erythrocytes and spleen is easily detected by measurement of the concentration of fluorescent end-products. Exposure of rats to hypoxia for various time periods induced formation of lipophilic fluorescent products both in erythrocytes and spleen. A new kind of fluorophore was found in chloroform extracts from erythrocytes with excitation maximum at 270 nm and emission maximum at 310 nm. Additionally, two minor fluorophores were observed, emitting at 360 nm and in the region of 415-440 nm. Only one type of fluorophore was detected in spleen, emitting at 445 nm after excitation at 315 nm. The concentration of fluorophores was dependent on the time of hypoxic exposure both in erythrocytes and spleen. In erythrocytes there was a decrease of the predominant fluorophore after 3 hours (54%, P < 0.05) and 21 days (54%, P < 0.05) of hypoxia in relation to normoxic controls, accompanied by changes in spectral patterns of tridimensional fluorescence spectra. There was also a significant increase in the concentration of fluorophore in spleen (to 164%, P < 0.05, after 3 h, and to 240%, P < 0.05, after 21 days). The fluorophores, both in erythrocytes and spleen, were resolved into several distinct fractions with HPLC. The presented results support the hypothesis of hypoxia-induced lipid peroxidation and create a basis for further characterization of the fluorescent products.

Animals↗
PubMed2003

Cytokine release by murine spleen cells following multiple low dose streptozotocin-induced diabetes and treatment with a TNFalpha transcriptional inhibitor.

We recently reported that administration of 9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine (MDL 201,449A), a transcriptional inhibitor of TNFalpha, decreased hyperglycemia in murine diabetes induced by multiple low doses of streptozotocin (MLDSTZ). In the present study, we first investigated if in vivo administration of MDL 201,449A in the MLDSTZ model affects cytokine release from cultured spleen cells. Secondly, we studied how MDL 201,449A affects cytokine release from normal cultured spleen cells. In all experiments, the mitogen concanavalin A (2 micro g/ml) was added to the cultured spleen cells in order to enhance cytokine release. MLDSTZ treatment in vivo caused increased IFNgamma secretion, a decreased/retarded rate of increased TNFalpha accumulation, whereas IL-10 production was not altered compared to vehicle-treated mice. MDL 201,449A treatment of MLDSTZ mice did not affect cytokine release from spleen cells subsequently cultured in the absence of MDL 201,449A. We also studied cytokine release from normal spleen cells in the presence or absence of MDL 201,449A. Production of TNFalpha, IFNgamma and IL-10 was all suppressed by the drug. In groups where exposure to MDL 201,449A was discontinued, cytokine levels increased promptly and in the case of TNFalpha secretion, it exceeded the production from control cells. Our data suggest an enhanced Th1 cytokine secretion from spleen cells derived from MLDSTZ-treated mice. MDL 210,449A may be a potent inhibitor of cytokine secretion, albeit not completely selective for TNFalpha. However, when MDL 201,449A is withdrawn, there may be a rebound phenomenon of increased TNFalpha secretion.

Adenine↗