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Tissue-type plasminogen activator (t-PA) is a potent and efficacious mitogen for growth-arrested cultured human aortic smooth muscle cells, stimulating an increase in cell number at 0.3-30 nM concentration. Double-chain t-PA is as efficient as single-chain t-PA in stimulating smooth muscle cell mitogenesis, whereas single-chain urokinase-type plasminogen activator (u-PA) or u-PA and plasmin or plasminogen are ineffective. Plasminogen activator inhibitor-1, Pefabloc-TPA, diisopropyl fluorophosphate or alpha 1-anti-trypsin inhibit the mitogenic effect of t-PA for smooth muscle cells in a dose-dependent manner, showing that it is dependent on the enzymatic activity. t-PA activated phosphoinositide turnover in smooth muscle cells through a pertussis toxin-insensitive pathway and stimulated proto-oncogene c-fos and c-jun mRNA levels. These findings indicate that t-PA stimulates vascular human smooth muscle cell proliferation and suggest for the first time that it may contribute to intimal smooth muscle cell proliferation after vascular injury as a result of angioplasty or vascular compromise during atherogenesis.

An increasing number of brominated flame retardants and other brominated substances are being reported in herring gull eggs from the Laurentian Great Lakes basin. Yet, in extracts from gulls' eggs, numerous bromide anion response peaks in electron capture negative ion (ECNI) mass chromatograms remain unidentified. Using archived herring gull egg homogenates, we characterize the structures of three major and three minor, new and unique brominated substances. After extensive cleanup and separation to isolate these substances from the extracts, high-quality ECNI and electron impact (EI) mass spectra revealed fragmentation patterns consistent with congeners of methoxylated polybrominated diphenoxybenzene (MeO-PBDPB), where four congeners contained five bromines and the other two contain four and six bromines, respectively. Optimized, semiquantitative analysis revealed sum concentrations of the MeO-PBDBP congeners ranged from0.2 to 36.8 ng/g ww in pooled egg homogenates (collected in 2009) from fourteen herring gull colony sites across the Great Lakes, with the highest concentration being for Channel-Shelter Island in Saginaw Bay (Lake Huron). To our knowledge, there are no published reports on the environmental presence and sources of MeO-PBDPBs. We hypothesize that these MeO-PBDPBs are degradation products of the polybrominated diphenoxybenzenes, for example, tetradecabromodiphenoxybenzene (currently marketed as SAYTEX 120) or polybromo 3P2E. MeO-PBDPBs in Great Lakes herring gull eggs indicates their bioaccumulation potential, and raises concerns about their origin, environmental behavior and influences on wildlife and environmental health.

A large diversity of Mycobacterium spp. has been isolated from striped bass Morone saxatilis in Chesapeake Bay, USA. The new species M. shottsii and M. pseudoshottsii are the dominant isolates, while the classical fish pathogen M. marinum is found much less frequently. M. fortuitum and M. chelonae, other Mycobacterium spp. known to commonly infect fishes, have not yet been aseptically isolated from striped bass within Chesapeake Bay. While M. pseudoshottsii and M. shottsii have been phenotypically and genotypically characterized, other less common mycobacterial isolates have not. In the present study, we describe 17 photochromogenic isolates from Chesapeake Bay striped bass using phenotypic characterization and multilocus sequencing of 16S rRNA, hsp65 and rpoB genes. Genetic characterization reveals that these isolates are related to widely divergent portions of the mycobacterial phylogeny; however, some interesting trends are observed, such as a majority of isolates (10/17) belonging to the M. simiae-related grouping. Five additional isolates were assigned to the slow-growing mycobacteria (including 2 identified as M. marinum), while 2 are clearly shown to belong genetically to the fast-growing mycobacteria.

Lymphoceles are the most frequent complications following systematic lymphadenectomy in gynaecologic cancers. Some of them may have clinical significance with high morbidity. Through a review of literature, we describe surgical methods (way of surgery, lymphadenectomy type, sentinel lymph node, peritonization, drainages, lymphostasis, surgical patch) and medical methods (somatostatin analogs and nutrition treatment) which could prevent lymphoceles formation after pelvic and lumboaortic lymphadenectomy.

Some currently used brominated flame retardants (BFRs), such as hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), bis(2-ethylhexyl)tetrabromophthalate (BEHTBP), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE), are persistent organic contaminants detected in various environmental matrices, including wild birds. Data on potential toxicological and molecular responses to exposure of these BFRs are lacking for avian species. A combined in vitro/in ovo approach was used to determine the concentration-dependent effects of these BFRs on overt toxicity and hepatic messenger RNA (mRNA) expression levels of 11 transcripts in (1) primary cultures of chicken embryonic hepatocytes (CEH; all four BFRs) and (2) chicken embryos (HCDBCO and BTBPE only). Neither hepatocyte viability nor embryonic pipping success were affected by the BFRs at any of the administered concentrations (CEH: 0.001-30 μM, egg injection: 0.1-10 μg/g nominal dose). In CEH, 10 μM HCDBCO induced cytochrome P450 2H1 (CYP2H1) and CYP3A37, while CYP1A4/5 were down-regulated at all tested concentrations. In contrast, only transthyretin was down-regulated by HCDBCO in embryonic liver. There was concordance between the BTBPE-induced transcriptional responses in vitro and in ovo for CYP1A4/5 (up-regulated) and type III iodothyronine 5'-deiodinase (DIO3; down-regulated). DBDPE induced CYP1A4/5 29- and 59-fold at 0.2 μM in CEH and increased DIO1. None of the gene targets were responsive to BEHTBP exposure in CEH. The multi-tiered in vitro/in ovo screening approach was effective for assessing toxicological and molecular biological effects of these BFRs in an avian species.

The aim of this study was to describe the clinical features of vaginal melanoma and treatments available.This is a retrospective review of patients with primary vaginal melanoma operated from 2000 to 2010 at Gustave-Roussy Institute.Six patients had surgery for a vaginal melanoma out of 37 patients operated for vaginal cancer in our institute in the same period (13.6%). Median age was 53.5 years [48-66]. The melanoma presented as a macroscopically visible nodular tumor in all case. Median tumour size was 5.4cm [1.5-15]. Five of the six patients had a [18F] fluoro-deoxy-glucose positron-emission tomography combined with integrated computed tomography (FDG-PET/CT) before surgery. Initial management included two conservative treatments and four colpectomy with one anterior exenteration. Two sigmoidcolpoplasties were performed. Lymph node metastases were found in only one patient. Median progression free survival was 10.5 months [4-51]. All patients have relapsed, three of them in the 6 months following surgery. Recurrences were local in three patients and distant in three patients. Local recurrences were surgically treated. In one case, electrochemotherapy was performed. One patient with locoregional disease underwent a pelvic isolated perfusion. One patient had a KIT mutation. Two patients died at 12 and 83 months.Vaginal melanoma had a poor prognosis. The 5-year overall survival is under 20% from literature data. Local and/or distant recurrences are frequent and new local and adjuvant treatments are currently evaluated.

Dechlorane Plus (DP) is an additive chlorinated flame retardant comprising two major isomers, syn- and anti-DP, that is used in a variety of commercial/industrial products. It has been detected in biotic and abiotic matrices including the eggs of herring gulls collected from the Laurentian Great Lakes. However, data on potential toxicological and molecular responses to exposure are lacking, especially for avian species. A combined in vitro/in ovo approach was used to determine concentration-dependent effects of DP in chicken embryonic hepatocytes (CEH) and chicken embryos following injection of DP into the air cell of eggs prior to incubation. Overt toxicity (i.e. cytotoxicity and pipping success) and mRNA expression levels of transcripts previously determined to be responsive to a brominated flame retardant were assessed in CEH and hepatic tissue. DP was not cytotoxic up to a maximum concentration of 3 μM in CEH, and no effects on pipping success were observed up to the highest nominal dose group of 500 ng/g egg. A significant shift in isomeric content of syn- and anti-DP was detected between stock solutions of the commercial mixture and hepatic tissue; the proportion of the syn-DP isomer increased from 0.34 to 0.65 with a concomitant decrease of anti-DP from 0.66 to 0.35. None of the mRNA transcripts changed as a result of in vitro or in ovo exposure to DP indicating that, although there was concordance between the two approaches, DP may evoke its toxicity through other modes of action. At current environmental exposure levels, no adverse effects of DP on embryonic viability or pathways associated with the genes assessed are predicted.

We describe a case of right mammary homolateral recurrence with controlateral axillary invasion. The absence of occult involvement of the left breast was confirmed by MRI. A subsequent thoraco-abdomino-pelvic scan and bone scintigraphy did not reveal any metastases. Lymphoscintigraphy of the right breast, after periareolar injection, revealed lymphatic drainage from the right breast into the left contralateral axillary lymph node. Because of the changes in axillary drainage after mammary and axillary surgery observed by lymphoscintigraphy, contralateral axillary involvement could be considered as locoregional disease in the same way as homolateral lymph node involvement.

The present study demonstrates interleukin-1 (IL-1) production by human glioblastoma cells both in vitro and in vivo. The presence of IL-1 alpha and IL-1 beta transcripts was analyzed in 4 cell lines. IL-1 alpha mRNA was expressed constitutively in one cell line whereas constitutive IL-1 beta mRNA could not be detected in any of the cell lines. IL-1 alpha transcripts could be induced with phorbol myristate acetate (PMA) or PMA plus lipopolysaccharide (LPS) in 2 of 4 cell lines and IL-1 beta mRNA in 2 of 4 cell lines. Culture fluid from these cell lines was tested for the presence of IL-1 using a specific radio-immuno-assay for either IL-1 alpha or IL-1 beta. In agreement with the results on RNA, one of 4 cell lines was found to constitutively produce IL-1 alpha but not IL-1 beta. After treatment with PMA and LPS, IL-1 alpha was detected in the culture fluid from two other lines and IL-1 beta in the medium from three lines. That the IL-1 produced by these cell lines was biologically active was confirmed in a two step thymocyte proliferation assay. IL-1 like activity was detected in all samples that were positive in the radio-immuno-assay. Finally, immunohistological analysis on fresh frozen tumour sections provided evidence for IL-1 production by glioblastoma cells in vivo. Fourteen out of 28 glioblastomas were stained with an anti-IL-1 alpha monoclonal antibody while none of them was stained with an anti-IL-1 beta antibody.

Compounds possessing neurotrophic properties may represent a possible treatment for neurodegenerative disorders such as Alzheimer's disease. SR 57746A, 1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride, is a new compound with neurotrophic activity in a number of in vitro preparations. The neurotrophic effects of this compound have been evaluated in vivo using four distinct rat models of neurodegeneration: transient global ischaemia produced by a four-vessel occlusion; septohippocampal lesion produced by injection of vincristine sulphate into the medial septum; sciatic nerve crushing; and acrylamide-induced peripheral neuropathy. Rats were administered vehicle or 2.5-10 mg/kg p.o. SR 57746A, after initiation of the degenerative process, then once daily for 10 days in the first two models, 16 days in the third and 26 days in the fourth model. Median scores for ischaemia-induced neuronal damage were reduced by 30-40% by SR 57746A treatment in hippocampal CA1, CA2, and CA3 regions, and in the dorsal striatum. Twelve days after intraseptal vincristine administration, there was a marked loss of septohippocampal cholinergic neurons, as indicated by reduced choline acetyltransferase activity in both the septum and hippocampus. SR 57746A dose-dependently reversed this reduction in both areas. These results were confirmed by histoenzymological evaluation of hippocampal acetylcholinesterase content. SR 57746A also reversed the loss of hippocampal choline acetyltransferase induced by intraseptal vincristine in marmosets. Behavioral deficits in these models (exploratory behaviour in the former and short-term social memory in the latter) were also significantly reduced by SR 57746A treatment. In the sciatic crush model, sensorimotor function improved more rapidly in rats treated with 10 mg/kg SR 57746A. In this same model, SR 57746A (10 mg/kg/day) also significantly increased the length of regenerated nerve eight days after the crush, as measured using the pinch test. Finally, SR 57746A retarded the onset, reduced the amplitude and accelerated the recovery of acrylamide-induced peripheral neuropathy. Thus, SR 57746A possesses notable neurotrophic activity in a variety of neurodegenerative models in vivo, suggesting that the compound may possess therapeutic potential for the treatment of neurodegenerative diseases.

We present the case of a large yolk sac tumour of the ovary in a 14-year-old girl with high level of serum alpha-feto-protein (AFP). Multidisciplinary care is important to do appropriate surgical treatment with the aim of fertility preservation.

A bank of readily available, well characterized human hepatic microsomal fractions (29 samples from different livers) has been established. The enzymatic characteristics of each microsome sample were determined using three specific UDP-glucuronosyltransferase (UDPGT) substrates (p-nitrophenol for UDPGT(1), 4-hydroxybiphenyl for UDPGT(2)A and monodigitoxoside digitoxigenin (DT(1)) for UDPGT(7)). After characterization, the bank was used to study the phase II biotransformation processes of two drugs: an antiviral, zidovudine (AZT), and an intermediate metabolite of digoxin, monodigitoxoside digoxigenin (DG(1)). Results showed a wide interindividual variability for the glucuronidation rate of 4-hydroxybiphenyl, DT(1), AZT and DG(1). Surprisingly, this variability was lower for p-nitrophenol. No significant correlation was found between the various activities except between DG(1) and DT(1) UDPGT activities and 4-hydroxybiphenyl and AZT UDPGT activities. For AZT, further experiments showed that glucuronidation of this antiviral compound was inhibited by 4-hydroxybiphenyl and chloramphenicol but not by morphine, p-nitrophenol, acetaminophen, or bilirubin. Finally, the results strongly suggest the respective involvement of UDPGT(2)A and UDPGT(7) in the glucuronidation of AZT and DG(1).

Striped bass ( Morone saxatilis ) in the Chesapeake Bay are currently experiencing a very high prevalence of mycobacteriosis associated with newly described Mycobacterium species, Mycobacterium pseudoshottsii and M. shottsii. The ecology of these mycobacteria outside the striped bass host is currently unknown. In this work, we developed quantitative real-time PCR assays for M. pseudoshottsii and M. shottsii and applied these assays to DNA extracts from Chesapeake Bay water and sediment samples, as well as to tissues from two dominant prey of striped bass, Atlantic menhaden ( Brevoortia tyrannus ) and bay anchovy ( Anchoa mitchilli ). Mycobacterium pseudoshottsii was found to be ubiquitous in water samples from the main stem of the Chesapeake Bay and was also present in water and sediments from the Rappahannock River, Virginia. M. pseudoshottsii was also detected in menhaden and anchovy tissues. In contrast, M. shottsii was not detected in water, sediment, or prey fish tissues. In conjunction with its nonpigmented phenotype, which is frequently found in obligately pathogenic mycobacteria of humans, this pattern of occurrence suggests that M. shottsii may be an obligate pathogen of striped bass.

International audience; Imaging of the cerebral arterial circle (CAC) is essential in neurovascular diseases such as ischemic stroke for detecting arterial occlusions and evaluating arterial supply, and in subarachnoid or intralobar hemorrhage for detecting intracranial malformations. Multidetector computed tomography angiography (MD-CTA) is increasingly being used for the detection and treatment planning of intracranial aneurysm. For optimal interpretation and treatment planning, this method requires suitable post-processing equipment, and extensive knowledge of the relevant anatomy and anatomical variants. Anatomical variants of the CAC are common, particularly in the anterior CAC, the most common site of intracranial aneurysm. The aim of this review is to illustrate the normal anatomy and most common anatomical variants of the anterior CAC detected by MD-CTA, and to discuss the relevant embryological and technical considerations.

We report a case of placenta percreta with bladder invasion in a multiparous woman with five previous cesarean sections. At 25 weeks of gestation, because of severe hematuria, antenatal diagnosis was easy. A multidisciplinary management was carried out with conservative treatment. Three repeated artery embolizations were necessary because of placenta volume and collateral vessels. None surgical treatment was realized to avoid hemorrhage and morbidity secondary to hysterectomy and partial cystectomy.

Sternal cleft is a rare congenital abnormality. We report on a neonatal case of sternal cleft with median raphe with a follow-up of 3 years. We review the advantages of surgical repair in the neonatal period because the flexibility of the chest wall is maximal and compression of underlying structures is minimal.

✓ Adhesion molecules, a family of cell-surface molecules, are likely to be of central importance in mediating cell-extracellular matrix and specific cell-cell interactions within both neoplastic and inflammatory sites. The recently discovered expression of adhesion molecules on glioma cells, tumor-infiltrating lymphocytes, and endothelial cells within the tumor offers insight into the molecular basis of the interactions both between the glioma cell and surrounding heterologous cell types within the tumor environment, and between the tumor cell and the extracellular matrix. Such interactions suggest that these molecules may play roles in the homing of immune cells to these tumors and in regulating the extent of local tumor invasion. The ability to modulate adhesion molecule expression on either immune cells or their respective ligands on gliomas provides an approach to modify cell-cell interactions that may be used to increase tumor kill by the immune system. A similar approach in the modulation of adhesion molecules involved in tumor cell adhesion to the extracellular matrix or endothelial cells may be a method to limit local invasion in these lesions.

Electrokinetic transport of cylindrical cells under dc electric fields in a straight microfluidic channel is experimentally and numerically investigated with emphasis on the dielectrophoretic (DEP) effect on their orientation variations. A two-dimensional multiphysics model, composed of the Navier–Stokes equations for the fluid flow and the Laplace equation for the electric potential defined in an arbitrary Lagrangian–Eulerian framework, is employed to capture the transient electrokinetic motion of cylindrical cells. The numerical predictions of the particle transport are in quantitative agreement with the obtained experimental results, suggesting that the DEP effect should be taken into account to study the electrokinetic transport of cylindrical particles even in a straight microchannel with uniform cross-sectional area. A comprehensive parametric study indicates that cylindrical particles would experience an oscillatory motion under low electric fields. However, they are aligned with their longest axis parallel to the imposed electric field under high electric fields due to the induced DEP effect.

AIM: To document the feasibility and report the results of dosing darbepoetin-alpha at extended intervals up to once monthly (QM) in a large dialysis patient population. MATERIAL: 175 adult patients treated, at 23 Swiss hemodialysis centres, with stable doses of any erythropoiesis-stimulating agent who were switched by their physicians to darbepoetin-alpha treatment at prolonged dosing intervals (every 2 weeks [Q2W] or QM). METHOD: Multicentre, prospective, observational study. Patients' hemoglobin (Hb) levels and other data were recorded 1 month before conversion (baseline) to an extended darbepoetin-alpha dosing interval, at the time of conversion, and once monthly thereafter up to the evaluation point (maximum of 12 months or until loss to follow-up). RESULTS: Data for 161 evaluable patients from 23 sites were included in the final analysis. At 1 month prior to conversion, 73% of these patients were receiving darbepoetin-alpha weekly (QW) and 27% of the patients biweekly (Q2W). After a mean follow-up of 9.5 months, 34% received a monthly (QM) dosing regimen, 52% of the patients were receiving darbepoetin-alpha Q2W, and 14% QW. The mean (SD) Hb concentration at baseline was 12.3 +/- 1.2 g/dl, compared to 11.9 +/- 1.2 g/dl at the evaluation point. The corresponding mean weekly darbepoetin-alpha dose was 44.3 +/- 33.4 microg at baseline and 37.7 +/- 30.8 microg at the evaluation point. CONCLUSIONS: Conversion to extended darbepoetin-alpha dosing intervals of up to QM, with maintenance of initial Hb concentrations, was successful for the majority of stable dialysis patients.

The production and use of nonpolybrominated diphenyl ether (non-PBDE), brominated flame retardant (BFR) alternatives have been on the rise, although their assessment in environmental samples is largely understudied. In the present study, several non-PBDE BFRs were found in the egg pools of herring gulls (Larus argentatus) from seven colonies in the five Laurentian Great Lakes (collected in 1982 to 2006). Of the 19 BFRs monitored, hexabromobenzene (HBB), 1,2-bis(2,4,6-tribromophe-noxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), and alpha-, beta-, gamma-, and delta-isomers of 1,2-dibromo-4-(1,2-dibromoeth-yl)cyclohexane (TBECH) were present in eggs from all the colonies with the highest detection frequencies of 100%, 54%, 9% and 97%, respectively. In 2005 and 2006 eggs, the concentrations of DBDPE were highest at three of the seven colonies (1.3 to 288 ng/g wet weight (ww)) and surpassed decabromodiphenyl ether (BDE-209). HBB (0.10 to 3.92 ng/g ww), BTBPE (1.82 to 0.06 ng/g ww), and Sigma-TBECH (0.04 to 3.44 ng/g ww; mainly the beta-isomer 52 to 100% of Sigma-TBECH) were detected at lower concentrations (and generallySigmaPBDE concentrations). Spatial trends were observed, although temporal trends were not obvious in most cases. Regardless, over the past 25 years non-PBDE BFRs have accumulated variably in female herring gulls and have been transferred during ovogenesis to their eggs, indicating that there has been continual exposure and bioaccumulation of several BFRs in the Great Lakes.

International audience; Neuroimaging studies investigating the neural correlates of verbal fluency (VF) focused on sex differences without taking into account behavioural variation. Nevertheless, group differences in this verbal ability might account for neurocognitive differences elicited between men and women. The aim of this study was to test sex and performance level effects and the combination of these on cerebral activation. Four samples of 11 healthy Students (N = 44) selected on the basis of sex and contrasted VF scores, high fluency (HF) versus low fluency (LF), performed a covert phonological VF task during scans. Within-nd between-group analyses were conducted. Consistent with previous studies, for each sample, the whole-group analysis reported activation in the inferior frontal gyrus (IFG), insula, anterior cingulate cortex (ACC), medial frontal gyrus (mFG), superior (SPL) and inferior parietal lobules (IPL), inferior visual areas, cerebellum, thalamus and basal ganglia. Between-group analyses showed an interaction between sexes and performances in the right precuneus, left ACC, right IFG and left dorsolateral prefrontal cortex (dlPFC). HF men showed more activation than LF ones in the right precuneus and left dlPFC. LF men showed more activation in the right IFG than HF ones and LF women elicited more activation in the left ACC than HF ones. A sex main effect was found regardless of performance in the left inferior temporal gyrus (ITG), cerebellum, anterior and posterior cingulate cortexes and in the right superior frontal gyrus (SFG) and dlPFC, lingual gyrus and ACC, with men eliciting significantly greater activations than women. A performance main effect was found for the left ACC and the left cerebellum regardless of sex. LF subjects had stronger activations than HF ones in the ACC whereas HF subjects showed stronger activations in the cerebellum. Activity in three discrete subregions of the ACC is related to sex, performance and their interaction, respectively. Our findings emphasize the need to consider sex and performance level in functional imaging studies of VF. (c) 2007 Elsevier Srl. All rights reserved.

Because of variability in histopathological interpretations in studies, it's difficult to elucidate the risk of non-sentinel lymph node involvement in case of sentinel node nanometastases (lesions not larger than 0.2 mm) and micrometastases (lesions not larger than 2 mm but larger than 0.2 mm) in breast cancer. In this study, we have evaluated this risk according to the European Working Group for Breast Screening Pathology (EWGBSP) recommendations.Among patients who underwent sentinel lymph node dissection between February 2001 and April 2008 in our unit, we reviewed the files of patients who had sentinel lymph node involvement smaller than 2mm. A second interpretation of all sentinel lymph node sections was made according to the EWGBSP recommendations. Each patient had complete axillary dissection.Among 608 patients who had sentinel lymph node dissection for breast cancer, 72 (11.84%) had sentinel lymph node involvement smaller than 2 mm (27 pN0i+ and 45 pN1mi). The percentage of pN1mi patients who had non sentinel involvement is 8.89%. None of pN0i+ patients had non sentinel involvement.After making a minimal sentinel lymph node involvement strict interpretation according to EWGBSP restrictive recommendations, nanometastases rate was smaller. Any non sentinel involvement was detected in case of sentinel lymph node nanometastases.

The striped bass (Morone saxatilis) is an economically and ecologically important finfish species along the Atlantic seaboard of the United States. Recent stock assessments in Chesapeake Bay (U.S.A.) indicate that non-fishing mortality in striped bass has increased since 1999, concomitant with very high (50%) prevalence of visceral and dermal disease caused by Mycobacterium spp. Current fishery assessment models do not differentiate between disease and other components of non-fishing mortality (e.g., senescence, predation); therefore, disease impact on the striped bass population has not been established. Specific measurement of mortality associated with mycobacteriosis in wild striped bass is complicated because the disease is chronic and mortality is cryptic. Epidemiological models have been developed to estimate disease-associated mortality from cross-sectional prevalence data and have recently been generalized to represent disease processes more realistically. Here, we used this generalized approach to demonstrate disease-associated mortality in striped bass from Chesapeake Bay. To our knowledge this is the first demonstration of cryptic mortality associated with a chronic infectious disease in a wild finfish. This finding has direct implications for management and stock assessment of striped bass, as it demonstrates population-level negative impacts of a chronic disease. Additionally, this research provides a framework by which disease-associated mortality may be specifically addressed within fisheries models for resource management.

Many cases of not life saving transplanted organs were described with the aim of improving quality of life. Uterus graft could be an alternative solution to adoption or surrogacy for women who have uterine factor infertility. Different animals' studies with mouse, sheep or monkey showed feasibility of the surgical technique with large vessels patch. One case of human uterine transplant has been reported but failed. Cold storage of the uterus in protective solution has been explored with mouse, sheep and human. Only pregnancy after uterus graft by syngenic mouse has been published. Results about pregnancy after allograft with sheep or monkey are necessary before pregnancy after human uterus graft becomes a reality.

DecaBDE is a current-use, commercial formulation of an additive, polybrominated diphenyl ether (PBDE) flame retardant composed of > 97% 2,2',3,3',4,4',5,5',6,6'-decabromoDE (BDE-209). Of the 43 PBDE congeners monitored, we report on the temporal trends (1982-2006) of quantifiable PBDEs, and specifically BDE-209, in pooled samples of herring gull (Larus argentatus) eggs from seven colonies spanning the Laurentian Great Lakes. BDE-209 concentrations in 2006 egg pools ranged from 4.5 to 20 ng/g wet weight (ww) and constituted 0.6-4.5% of sigma39PBDE concentrations among colonies, whereas sigma(octa)BDE and sigma(nona)BDE concentrations constituted from 0.5 to 2.2% and 0.3 to 1.1%, respectively. From 1982 to 2006, the BDE-209 doubling times ranged from 2.1 to 3.0 years, whereas for sigma(octa)BDEs and sigma(nona)BDEs, the mean doubling times ranged from 3.0 to 11 years and 2.4 to 5.3 years, respectively. The source of the octa- and nona-BDE congeners, e.g., BDE-207 and BDE-197, are the result of BDE-209 debromination, and they are either formed metabolically in Great Lakes herring gulls and/or bioaccumulated from the diet and subsequently transferred to their eggs. In contrast to BDE-209 and the octa- and nona-BDEs, congeners derived mainly from PentaBDE and OctaBDE mixtures, e.g., BDE-47, -99, and -100, showed rapid increases up until 2000; however, there was no increasing trend post-2000. The data illustrates that PBDE concentrations and congener pattern trends in the Great Lakes herring gull eggs have dramatically changed between 1995 and 2006. Regardless of BDE-209 not fitting the pervasive criteria as a persistent and bioaccumulative substance, it is clearly of increasing concern in Great Lake herring gulls, and provides evidence that regulation of DecaBDE formulations is warranted.

Eighty striped bass Morone saxatilis were obtained from Delaware Bay using commercial gill nets set adjacent to Woodland Beach (n = 70) and Bowers Beach (n = 10) in December 2003. Fish were examined for gross lesions. Total lengths (TLs) and eviscerated weights were determined to calculate condition factors (K). Portions of spleens were aseptically harvested for bacterial culture, and portions of spleens, kidneys (anterior and posterior), livers, and gonads were obtained for histological examination. The size distribution of the striped bass was relatively homogeneous; the mean TL was about 600 mm for all samples. Mean K exceeded 0.95 in all samples and was not significantly different (P0.05) among samples. Significant differences in mycobacterial infection prevalence (Por = 0.05) were observed among samples; samples obtained at Woodland Beach (WB) on December 10 (53.8%, n = 13) and December 17 (7.1%, n = 42) exhibited the most striking differences in prevalence. Mycobacterial infection intensity ranged from 1 X 10(2) to 1 X 10(7) colony-forming units per gram of spleen. Acanthocephalan infection prevalence and intensity, non-acid-fast bacterial infection prevalence, and fish sex ratio were also significantly different among the samples (Por = 0.05). Similar to the mycobacterial infections, differences in sex ratio, acanthocephalan infection, and non-acid-fast bacterial infection were observed between the WB samples taken on December 10 and 17. However, no significant associations (P0.05) were observed between sex ratio or these infections and mycobacterial infection. The differences in bacterial and parasite infection prevalence and intensity and fish sex ratio in some samples indicate that these fish had a different history and that the epizootiology of mycobacterial infection in striped bass from Delaware Bay may be relatively complex.

Kinetic properties of phosphofructokinase 2 (PFK2) and regulation of glycolysis by phorbol 12-myristate 13-acetate (PMA) and insulin were investigated in highly glycolytic HT29 colon cancer cells. PFK2 was found to be inhibited by citrate and, to a lesser extent, by phosphoenolpyruvate and ADP, but to be insensitive to inhibition by sn-glycerol phosphate. From these kinetic data, PFK2 from HT29 cells appears different from the liver form, but resembles somewhat the heart isoenzyme. Fructose 2,6-bisphosphate (Fru-2,6-P2) levels, glucose consumption and lactate production are increased in a dose-dependent manner in HT29 cells treated with PMA or insulin. The increase in Fru-2,6-P2 can be related to an increase in the Vmax. of PFK2, persisting after the enzyme has been precipitated with poly(ethylene glycol), without change in the Km for fructose 6-phosphate. The most striking effects of PMA and insulin on Fru-2,6-P2 production are observed after long-term treatment (24 h) and are abolished by actinomycin, cycloheximide and puromycin, suggesting that protein synthesis is involved. Furthermore, the effects of insulin and PMA on glucose consumption, lactate production, Fru-2,6-P2 levels and PFK2 activity are additive, and the effect of insulin on Fru-2,6-P2 production is not altered by pre-treatment of the cells with the phorbol ester. This suggests that these effects are exerted by separate mechanisms.

1. 1. Solubilization of mitochondrial bound hexokinase (HK), which represents 75–80% of the total enzyme activity in the cells, was investigated in freshly isolated mitochondria from undifferentiated (Glc+) or differentiated (Glc−) HT29 adenocarcinoma cells. In both models, the bound HK is almost completely released in vitro by 100 μM glucose 6-P (G 6-P). 2. 2. Free ATP (5 mM) or palmitate (800 μM) produce a partial solubilization of bound HK, more markedly in the case of Glc− mitochondria. 3. 3. Glucose or glucose 1-P are found unable to solubilize bound HK. Glucose 1,6-P2, 2-deoxyglucose 6-P or glucosamine 6-P can solubilize the enzyme but are less efficient than G 6-P. 4. 4. Mg2+ and Pi are found to counteract the glucose 6-P induced solubilization of HK in both types of mitochondria. Taking into account the intracellular concentrations of these ions, this could in part explain why, in HT29 cells, HK is predominantly bound to the mitochondria.

Several, unregulated, current-use brominated flame retardants (BFRs), including hexabromobenzene (HBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), pentabromoethylbenzene (PBEB), pentabromotoluene (PBT), and hexabromocyclododecane (as total-(alpha)-HBCD), were examined in egg yolk and plasma of male and female glaucous gulls (Larus hyperboreus) from the Norwegian Arctic. Also examined were BDE209 and 38 tri- to nona-BDE congeners and brominated biphenyl (BB) 101. The HBB, BTBPE, PBEB, and PBT had high detection frequencies and variability in male and female plasma and egg yolk samples, and their concentrations ranged from nondetectable (0.02-0.27 ng/g wet wt) to 2.64 ng/g wet wt. The detection frequencies and range of concentrations of non-BDE BFRs were generally highest in plasma of males relative to females. Total-(alpha)-HBCD concentrations were highest among the non-PBDE BFRs (up to 6.12 and 63.9 ng/g wet wt in plasma and egg yolk, respectively). Next highest was HBB with concentrations within a range comparable to the minor PBDEs monitored (e.g., BDE28, 116 and 155). Sum (sigma)38PBDE concentrations ranged from 2.49 to 54.5 ng/g wet wt in plasma and 81.2 to 321 ng/g wet wt in egg yolk. The BDE209 was virtually nondetectable, whereas six octa-BDEs (i.e., BDE196, 197, 201, 202, 203, and 205), as well as three nona-BDEs (i.e., BDE206, 207, and 208, and potential BDE209 debromination products) were found sporadically in plasma and egg yolk. The results from this study suggestthat in addition to PBDEs, several current-use, non-BDE BFRs undergo long-range atmospheric transport and bioaccumulate at low levels in and are maternally transferred (to eggs) in glaucous gulls from the Norwegian Arctic.

Of the 13, current-use, non-polybrominated diphenyl ether (PBDE) flame retardants (FRs) monitored, hexabromobenzene (HBB), pentabromoethylbenzene (PBEB), pentabromotoluene (PBT), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and alpha- and gamma-isomers of hexabromocyclododecane (HBCD), and the syn- and anti-isomers of the chlorinated Dechlorane Plus (DP) were quantified in egg pools of herring gulls (Larus argentatus) collected in 2004 from six sites in all five of the Laurentian Great Lakes of North America. alpha-HBCD concentrations ranged from 2.1 to 20 ng/g (wet weight (ww)). Other "new" FR levels ranged from 0.004 to 1.4 ng/g ww and were much lower than those of the major BDE congeners that are in technical mixtures (namely BDE-47, -99, -100), where sigma3PBDE ranged from 186 to 498 ng/g ww. Nineteen hepta-BDEs (sigma(hepta) = 4.9-11 ng/g ww), octa-BDEs (alpha(octa) = 2.6-9.1 ng/g ww), and nona-BDEs (sigma(nona) = 0.12-5.6 ng/g ww) were detectible at all six colonies, while BDE-209 was low but quantifiable (0.1-0.21 ng/g ww) at two colonies. sigma-DP (syn- and anti-isomers) concentrations in eggs from all sites ranged from 1.5 to 4.5 ng/g ww. Our findings indicate that mother herring gulls are exposed to several, current-use flame retardants via their diet, and in ovo transfer occurred to their eggs. Given the aquatic diet of herring gull, this suggests that there are non-PBDE BFRs present in the gull-associated aquatic food web of the Great Lakes.

International audience; Two pressure probes and an intrusive bi-optical probe provide experimental data in the bubbling and turbulent regimes to improve our understanding of the bubbling to fast fluidization regimes transition. Pressure, voidage and bubbling properties assessment allows for new description of turbulent fluidization hydrodynamics. Appreciable changes in the hydrodynamics appear well below the transition criterion Uc determined based on pressure fluctuations: bubbles are fast bubbles below Uc, in bubble-emulsion equilibrium state at Uc, and then become slow bubbles for higher fluidizing velocity; the maximum of the total fluidizing gas fraction in the bubble-phase is reached below Uc and never exceeds 75-80 %. The fluidizing velocity at which major hydrodynamics modifications are observed is lower than Uc. This critical velocity is detected with pressure drop assessment or voidage fluctuations frequency analysis. Moreover, it can be theoretically calculated from the two-phase modeling correlations supplemented with a new criterion deduced from our experiments.

Mycobacteriosis in striped bass Morone saxatilis of Chesapeake Bay, USA, was first diagnosed in 1997 based on the presence of granulomatous inflammation and acid-fast bacteria in skin and spleen. To confirm histopathology, bacteriological detection and identification of mycobacteria were begun using splenic tissue from fish with and without skin ulcerations. On the basis of initial studies using a variety of selective and nonselective media, decontamination, homogenization and incubation conditions, a simple and quantitative recovery method using aseptic necropsy of splenic tissue was developed. Optimal recovery was obtained by spread-plating homogenates on Middlebrook 7H10 agar with incubation for 3 mo at 23 degrees C. Mycobacteria were recovered from 76% (n = 149/196) of fish examined. Mycobacterial densities exceeded 10(4) colony forming units x g tissue(-1) in 38% of samples (n = 63/168) that were examined using a quantitative approach. The most frequently recovered mycobacterium, present in 57% (n = 109/192) of characterized samples, was the recently named new species Mycobacterium shottsii. Polyinfections of M. shottsii and other mycobacteria were observed in 25% of samples (n = 47/192) with densities of M. shottsii usually 1 or more orders of magnitude higher than co-isolate(s). Other mycobacteria recovered included isolates that, based on phenotypic traits, resembled M. interjectum, M. marinum, M. scrofulaceum, M. szulgai and M. triplex. M. marinum, commonly associated with fish mycobacteriosis and human disease, was recovered infrequently (3%, n = 6/192). The presence of multiple mycobacterial types occurring at high densities suggests that a variety of mycobacteria could be causative agents of mycobacteriosis in striped bass from the Chesapeake Bay. Striped bass is the major recreational fish species in the Chesapeake Bay, and the significance of the current epizootic to human health and the potential adverse effects on fish stocks are not known.

Campylobacter jejuni is a common cause of serious food-borne illness. In an experimental model of human infection, germfree pigs were given C. jejuni, the whipworm Trichuris suis, dual infections with C. jejuni and T. suis, or no infection. In dual-infected pigs, a synergistic effect between C. jejuni and T. suis was observed 27 days after infection, when T. suis fourth-stage larvae were found in the proximal colon. In dual-infected pigs, lymphoglandular complexes (LGCs) in the distal colon were substantially enlarged, and C. jejuni was detected in cells of the follicle-associated epithelium (FAE) and in cells with macrophage morphology within these follicles. In the study reported here, cell types in colonic tissues from these pigs were analyzed by use of immunohistochemical and morphometric analyses for cell surface markers (IgM, IgG, IgA, CD4, CD8, MHC Class II, and macrophage SWC3a). To our knowledge, we provide the first description of cell types in mammalian LGCs, document that they have all elements necessary for antigen processing, and demonstrate the appearance of IgA germinal centers (GC) in LGCs from C. jejuni-infected pigs (single or dual infected). Ileocecal Peyer's patches (ICPP) and mesenteric lymph nodes (MLN) also had IgA GC development if C. jejuni was present, but LGCs had the greatest amount of anti-C. jejuni staining, and appreciable increase in overall follicle size and size and number of GCs committed to IgA production. LGCs are present in humans and other mammals and are important in other enteric infections.

The protozoan oyster parasite Perkinsus marinus releases a complex set of extracellular products (ECP) during in vitro culture. These products have been previously implicated in parasite virulence, and their expression can be altered by medium supplementation with oyster tissue homogenate. Little is known regarding ECP function, regulation, or mechanism of storage and release. Perkinsus marinus ECP were purified from a protein-free medium and used to produce a panel of five monoclonal antibodies. Several of the antibodies recognised series of proteins implying that the ECP may originate from comparatively few parental molecules. The ECP are secreted by several pathways, including the release of one product from an external cell layer, and two other products from two morphologically distinct intracellular compartments. Antibodies against separate epitopes on one protein provided information about possible protein structure. A sandwich ELISA format allowed sensitive quantification of that protein and showed significantly reduced protein expression in oyster tissue homogenate supplemented cultures. Immunopurification allowed tandem mass spectroscopic amino acid sequencing of that protein. Another antibody was used to characterise the P. marinus cell wall. This antibody specifically bound to trophozoite and tomont walls, and was used to investigate the morphological and antigenic changes in these walls during Ray's fluid thioglycollate medium-induced formation of hypnospores. It was also used to confirm that oyster tissue homogenate supplementation could induce formation of hypnospores. This antibody labeled P. marinus cells in fixed oyster tissue in a species-specific manner.

Mycobacteriosis in Chesapeake Bay (USA) striped bass Morone saxatilis is an ongoing disease problem with important economic implications for a large commercial and recreational fishery. Additionally, striped bass serve as a reservoir of potential mycobacterial zoonoses. Recently, we described a striped bass gene homolog of the natural resistance-associated macrophage protein family (MsNramp), which is responsible for resistance to mycobacterial infections in mice. Striped bass MsNramp is strongly induced in peritoneal exudate cells (PE) in vivo after intraperitoneal injection with Mycobacterium spp. The purpose of the present study was to investigate short-term in vitro MsNramp expression and reactive oxygen intermediate (ROI) production in primary cultures of adherent PE after exposure to bacterial lipopolysaccharide (LPS), or live- or heat-killed (HK) Mycobacterium marinum. PE expressed significantly higher levels of MsNramp at 4 and 24 h post-treatment with live and HK M. marinum. MsNramp response to LPS was dose-dependent in these cells, with maximum expression at 4 h and 20 microg/ml LPS. Treatment of PE with LPS resulted in increased intracellular superoxide anion levels, whereas treatment with live M. marinum caused a significant depression. This study is the first report of induction of a teleost Nramp in vitro by mycobacteria, and supports findings of teleost Nramp induction by LPS.

Striped bass Morone saxatilis were infected intraperitoneally with approximately 10(5) Mycobacterium marinum, M. shottsii sp. nov., or M. gordonae. Infected fish were maintained in a flow-through freshwater system at 18 to 21 degrees C, and were examined histologically and bacteriologically at 2, 4, 6, 8, 17, 26, 36 and 45 wk post-infection (p.i.). M. marinum caused acute peritonitis, followed by extensive granuloma development in the mesenteries, spleen and anterior kidney. Granulomas in these tissues underwent a temporal progression of distinct morphological stages, culminating in well-circumscribed lesions surrounded by normal or healing tissue. Mycobacteria were cultured in high numbers from splenic tissue at all times p.i. Standard Ziehl-Neelsen staining, however, did not demonstrate acid-fast rods in most early inflammatory foci and granulomas. Large numbers of acid-fast rods were present in granulomas beginning at 8 wk p.i. Between 26 and 45 wk p.i., reactivation of disease was observed in some fish, with disintegration of granulomas, renewed inflammation, and elevated splenic bacterial densities approaching 10(9) colony-forming units g(-1). Infection with M. shottsii or M. gordonae did not produce severe pathology. Mild peritonitis was followed by granuloma formation in the mesenteries, but, with 1 exception, granulomas were not observed in the spleen or anterior kidney. M. shottsii and M. gordonae both established persistent infections in the spleen, but were present at densities at least 2 orders of magnitude less than M. marinum at all time points observed. Granulomas in the mesenteries of M. shottsii- and M. gordonae-infected fish resolved over time, and no reactivation of disease was observed.

Campylobacterjejuni, a leading cause of bacterial gastroenteritis, has different age distribution and disease expression in developing and developed countries, which may be due to the endemnicity of infection and the age of acquisition of immunity. Differences in disease expression are not solely dependent on the C. jejuni strain or virulence attributes. Another modulating factor in developing countries may be endemic nematode infections such as Trichuris, which drive type 2 cytokine responses and down-regulate type 1 immune responses. In this study, three-day-old germ-free pigs given dual infections with Trichuris suis and C. jejuni had more frequent, more severe diarrhea and severe pathology than pigs given no pathogens, only T. suis, or only C. jejuni. These pigs had significant hemorrhage and inflammatory cell infiltrates in the proximal colon where adult worms were found, and abscessed lymphoglandular complexes in the distal colon with intracellular C. jejuni. Pigs given only C. jejuni had mild clinical signs and pathology, and bacteria in feces or extracellular sites. Pigs given T. suis or no pathogens had no disease and minimal pathology. Thus, these agents synergized to produce significant disease and pathology, which was site specific.

Campylobacterjejuni, a leading cause of bacterial gastroenteritis, has different age distribution and disease expression in developing and developed countries, which may be due to the endemnicity of infection and the age of acquisition of immunity. Differences in disease expression are not solely dependent on the C. jejuni strain or virulence attributes. Another modulating factor in developing countries may be endemic nematode infections such as Trichuris, which drive type 2 cytokine responses and down-regulate type 1 immune responses. In this study, three-day-old germ-free pigs given dual infections with Trichuris suis and C. jejuni had more frequent, more severe diarrhea and severe pathology than pigs given no pathogens, only T. suis, or only C. jejuni. These pigs had significant hemorrhage and inflammatory cell infiltrates in the proximal colon where adult worms were found, and abscessed lymphoglandular complexes in the distal colon with intracellular C. jejuni. Pigs given only C. jejuni had mild clinical signs and pathology, and bacteria in feces or extracellular sites. Pigs given T. suis or no pathogens had no disease and minimal pathology. Thus, these agents synergized to produce significant disease and pathology, which was site specific.

Sera from 720 inhabitants of Baker Lake, Northwest Territories, a community with high rates of hepatitis A and B infection, were tested for antibody to hepatitis C virus by commercial enzyme-linked immunosorbent assay. Only two individuals (0.3%) were positive, a 63-year-old female and an unrelated 10-year-old male. Neither individual was at increased risk of hepatitis C virus exposure. The results of this study indicate that hepatitis C virus infection is no more common in this northern Canadian Inuit settlement than it is in the blood donor population of southern Canada.

Serodiagnosis of Lyme borreliosis in dogs is complicated by the use of commercially available Lyme disease vaccines that may cross-react with certain diagnostic assays. Western immunoblotting may be used to distinguish between dogs naturally exposed and those vaccinated against Borrelia burgdorferi. Because current vaccines are not 100% efficacious and dogs may be vaccinated after natural exposure, certain dogs may show serum antibody responses against both natural and vaccine exposure (dual status). In this study, samples from 17 nonexposed, 17 B. burgdorferi-bacterin vaccinated, 13 naturally exposed, and 8 dual-status dogs were tested by western immunoblot to determine if dual-status dogs could be reliably differentiated from naturally infected or vaccinated dogs. Reaction to outer surface protein A antigen of B. burgdorferi (31 kD) was a consistent marker for vaccination, appearing in all samples from vaccinate and dual-status dogs and in no samples from single-status naturally exposed dogs. Antibodies to 4 bands, at 80, 39, 29, and 28 kD, were present in all naturally infected and dual-status dogs. No samples from vaccinated or nonexposed dogs were reactive to all 4 of these bands simultaneously. Thus, vaccine and natural exposure produce differing antibody responses, whereas dual-status dogs produced the full antibody response of both types of exposure.

SUMMARY We report a case of Yersinia enterocolitica 0:9 septicaemia complicating systemic lupus erythematosus in an elderly male patient. The infection gave rise to digital vasculitis, fevers and general malaise on top of pre-existing articular symptoms. Features of Yersinia septicaemia may mimic some of the signs of lupus. SYSTEMIC lupus erythematosus (SLE) commonly aAects young women between 20 and 40 yr of age. Nevertheless, many investigators have shown that in 10‐20% of cases, onset occurs after the age of 50. In the elderly, the presenting symptoms of lupus are often insidious and diagnosis may be delayed. In this paper, we describe a 75-yr-old patient who presented with lupus whose clinical course was complicated by Yersinia septicaemia which gave rise to digital vasculitis. Systemic Yersinia infections infrequently give rise to multisystemic chronic inflammatory disorders, some of the clinical features of which may mimic those seen in connective tissue diseases. Awareness of this condition should help to establish a correct diagnosis earlier, especially in the elderly patient who presents with an unexpected vasculitis in the context of an established rheumatological disease.

An increased incidence of visceral leishmaniasis in patients infected with the human immunodeficiency virus (HIV) is observed in areas in which both infectious diseases are endemic. Intensive worldwide traveling has also resulted recently in an increasing number of leishmanial and HIV coinfections in nonendemic areas. We describe the clinical, light microscopic, and ultrastructural features of two cases of imported, HIV-related, visceral leishmaniasis involving the alimentary tract, including the esophagus, the stomach, the duodenum, the ileum, the colon, and the rectum. We also discuss the differentiation of leishmanial infections from other HIV-related gastrointestinal opportunistic infections.

Recombinant interferon (r-IFN) is an antiviral agent used to treat patients with chronic viral hepatitis patients. Unfortunately, the use is often limited due to its myelosuppressive properties. Currently, there are two forms of r-IFN commercially available: r-IFN alpha-2a and rIFN alpha-2b. Although both are thought to be equally effective, a comparative study of their myelosuppressive properties has not been undertaken.In the present study, three groups of healthy adult volunteers (n = 6/group) were randomized to receive a two week course of either r-IFN alpha-2a or r-IFN alpha-2b (5 million units, subcutaneously, thrice weekly) or no treatment. All subjects were then followed for an additional two week post treatment; observation period.The results of the study revealed that both forms of r-IFN alpha caused a significant and similar decrease in white blood cell counts (maximum declines of 37.9 +/- 6.8% for alpha-2a and 39.5 +/- 6.0% for alpha-2b at day 4) and platelet counts (maximum declines of 19.5 +/- 8.6% for alpha-2a and 20.2 +/- 8.4% for alpha-2b at day 2) from baseline values. Following discontinuation of therapy, white blood cell and platelet counts returned to pretreatment levels. Hemoglobin levels remained unchanged throughout the study period.The results of this study indicate that r-IFN alpha causes a prompt and significant decrease in white blood cell and platelet counts. However, no differences exist between r-IFN alpha-2a and r-IFN alpha-2b in terms of their myelosuppressive properties in humans.

To determine whether the inhibitory effects of ethanol on hepatic regeneration could be prevented by ciprofloxacin, a fluroquinolone antibiotic with gamma-aminobutyric acid (GABAA), receptor antagonist properties, adult, male Sprague-Dawley rats (n = 6-8/group) received intraperitoneal injections of saline, putrescine (a hepatic growth promoter, 50 mg/kg), or ciprofloxacin (100 mg/kg), followed 1 hour later by gastric gavage with saline or ethanol (5 g/kg). One hour post-gavage, all rats underwent a 70% partial hepatectomy (PHx). Hepatic regenerative activity was documented 24 hours post-PHx by 3H-thymidine incorporation into hepatic DNA (DNA synthesis), proliferating cell nuclear antigen staining, and hepatic tissue putrescine levels. Compared with healthy controls, DNA synthesis rates were significantly lower in ethanol-gavaged/saline-treated rats (22.7 +/- 4.4 x 10(3) vs. 12.3 +/- 6.9 x 10(3) DPM/mg DNA, respectively, P.001) but unaltered in putrescine-(18.8 +/- 3.4 x 10(3) DPM/mg DNA) and ciprofloxacin-treated (18.3 +/- 2.6 x 10(3) DPM/mg DNA) rats. Hepatic proliferating cell nuclear antigen staining supported these findings. Hepatic putrescine levels also correlated with DNA synthesis data, being decreased in ethanol-gavaged/saline-treated rats (86 +/- 14 pmoles/mg tissue) compared with healthy controls (120 +/- 12 pmoles/mg, P.01), ethanol-gavaged/putrescine-treated (112 +/- 14 pmoles/mg, P.05) and ethanol-gavaged/ciprofloxacin-treated (125 +/- 17 pmoles/mg, P.05) rats. To determine whether these effects resulted from GABAA receptor-mediated changes in liver membrane potentials, intracellular membrane potentials were recorded before and 1 hour after PHx in healthy control, ethanol-gavaged/saline-treated and ethanol-gavaged/ciprofloxacin-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Although caffeine apparently plays a role in the modulation of pain perception in a variety of acute pain states, little is known about its effects on the experience of chronic pain. This exploratory study examined the relationship between dietary caffeine consumption and the symptoms reported by patients with chronic low back pain.A retrospective chart review was conducted of 131 patients with chronic low back pain (64 men and 67 women; mean age = 42.1 years; mean duration of pain = 6.1 years) referred to a multidisciplinary pain clinic over a 2-year period. Patients were classified as low (less than 100 mg; n = 34), moderate (100-400 mg; n = 68) or high (more than 400 mg; n = 29) caffeine users based on their self-reports of daily coffee, tea, and cola consumption.There were no significant differences among the low, medium, and high caffeine consumer groups on any self-report measure of pain severity, affective distress, anxiety-related symptoms, or sleeping behavior. High caffeine users were more likely to be tobacco smokers than low caffeine users (79% and 27%, respectively, p0.001).Our findings indicate that dietary caffeine consumption is not related to the global experience of pain and disability in patients with chronic low back pain, although high caffeine use may be embedded in a context of other unhealthy life-style behaviors.