Effects of Acute Aerobic Exercise on Response Inhibition in Adult Patients with ADHD.

Previous studies suggest beneficial effects of aerobic exercise on executive functions, which are a core deficit in ADHD. The aim of the present fMRI study was to investigate acute effects of aerobic exercise on inhibitory control and related brain activation in adult patients with ADHD. 23 patients and 23 matched healthy controls performed on a Go/No-go task in an MRI scanner, following both, an exercise condition involving 30 min of cycling at moderate intensity, and a control condition. ADHD patients compared to healthy controls showed increased brain activation during successful inhibition in the exercise compared to the control condition in parietal, temporal, and occipital regions. Exercise did not improve behavioral performance in either group, but in ADHD patients, exercise-related increases in brain activation and behavioral task performance (i.e., correct inhibition rate) negatively correlated with correct inhibition rate in the control condition. Thus, patients with worse inhibition performance showed stronger exercise-related enhancements, indicating that the lack of improvements on the behavioral level for the whole patient group could be due to ceiling effects. Our findings might be an important step in understanding the neural basis of exercise effects and could, in the long term, help in developing alternative treatment approaches for ADHD.

Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system.

STUDY QUESTION: Does the prewash total motile sperm count (TMSC) have a better predictive value for spontaneous ongoing pregnancy (SOP) than the World Health Organization (WHO) classification system? SUMMARY ANSWER: The prewash TMSC shows a better correlation with the spontaneous ongoing pregnancy rate (SOPR) than the WHO 2010 classification system. WHAT IS KNOWN ALREADY: According to the WHO classification system, an abnormal semen analysis can be diagnosed as oligozoospermia, astenozoospermia, teratozoospermia or combinations of these and azoospermia. This classification is based on the fifth percentile cut-off values of a cohort of 1953 men with proven fertility. Although this classification suggests accuracy, the relevance for the prognosis of an infertile couple and the choice of treatment is questionable. The TMSC is obtained by multiplying the sample volume by the density and the percentage of A and B motility spermatozoa. STUDY DESIGN, SIZE, DURATION: We analyzed data from a longitudinal cohort study among unselected infertile couples who were referred to three Dutch hospitals between January 2002 and December 2006. Of the total cohort of 2476 infertile couples, only the couples with either male infertility as a single diagnosis or unexplained infertility were included (n = 1177) with a follow-up period of 3 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: In all couples a semen analysis was performed. Based on the best semen analysis if more tests were performed, couples were grouped according to the WHO classification system and the TMSC range, as described in the Dutch national guidelines for male infertility. The primary outcome measure was the SOPR, which occurred before, during or after treatments, including expectant management, intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection. After adjustment for the confounding factors (female and male age, duration and type of infertility and result of the postcoital test) the odd ratios (ORs) for risk of SOP for each WHO and TMSC group were calculated. The couples with unexplained infertility were used as reference. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 514 couples did and 663 couples did not achieve a SOP. All WHO groups have a lower SOPR compared with the unexplained group (ORs varying from 0.136 to 0.397). Comparing the couples within the abnormal WHO groups, there are no significant differences in SOPR, except when oligoasthenoteratozoospermia is compared with asthenozoospermia [OR 0.501 (95% CI 0.311-0.809)] and teratozoospermia [OR 0.499 (95% CI: 0.252-0.988)], and oligoasthenozoospermia is compared with asthenozoospermia [OR 0.572 (95% CI: 0.373-0.877)]. All TMSC groups have a significantly lower SOPR compared with the unexplained group (ORs varying from 0.171 to 0.461). Couples with a TMSC of <1 × 10(6) and 1-5 × 10(6) have significantly lower SOPR compared with couples with a TMSC of 5-10 × 10(6) [respectively, OR 0.371 (95% CI: 0.215-0.64) and OR 0.505 (95% CI: 0.307-0.832)]. LIMITATIONS, REASON FOR CAUTION: To include all SOPs during the follow-up period of 3 years, couples were not censured at the start of treatment. WIDER IMPLICATIONS OF THE FINDINGS: Roughly, three prognostic groups can be discerned: couples with a TMSC <5, couples with a TMSC between 5 and 20 and couples with a TMSC of more than 20 × 10(6) spermatozoa. We suggest using TMSC as the method of choice to express severity of male infertility. STUDY FUNDING/COMPETING INTERESTS: None.

[The importance of physical activity and fitness for human health]. / Körperliche Aktivität oder Fitness: Was ist wichtiger für die Gesundheit?

The decline of physical activity is considered to play an important role in the deterioration of health predictors, such as overweight, and the associated increase of cardiovascular and all-cause mortality. Therefore, most interventional strategies aim for increasing physical activity. Instead of physical activity, some studies use physical fitness as a key variable. Though physical fitness is influenced by genetic factors, physical fitness has to be developed by physical activity. As recent reports demonstrate the prospective associations between physical fitness and health and mortality, these associations are not reported for physical activity. Due to the fact that physical fitness-in contrast to physical activity-is evaluated with standardized laboratory measurements, it appears advisable to assess physical fitness for prospective health perspectives. Although physical fitness is determined by genetics, physical activity is the primary modifiable determinant for increasing physical fitness and should be aimed for to improve physical fitness in interventional strategies.

Diffraction contrast STEM of dislocations: imaging and simulations.

The application of scanning transmission electron microscopy (STEM) to crystalline defect analysis has been extended to dislocations. The present contribution highlights the use of STEM on two oppositely signed sets of near-screw dislocations in hcp α-Ti with 6wt% Al in solid solution. In addition to common systematic row diffraction conditions, other configurations such as zone axis and 3g imaging are explored, and appear to be very useful not only for defect analysis, but for general defect observation. It is demonstrated that conventional TEM rules for diffraction contrast such as g·b and g·R are applicable in STEM. Experimental and computational micrographs of dislocations imaged in the aforementioned modes are presented.

Severity of oligo-asteno-teratozoospermia no longer determines overall success rate in male subfertility.

In this longitudinal multicentre cohort study, the overall ongoing pregnancy rate after current evidence-based management in male subfertility was studied. All subfertile couples who visited the fertility clinic for the first time between 2002 and 2006, and had male subfertility as a single diagnosis (n = 762 of 2476 couples), were included in this study. Couples were grouped by the severity of male factor. Group I (n = 541) had a total motile sperm count (TMSC) 1-20 × 10(6). Group II (n = 161) had a TMSC <1 × 10(6). Group III (n = 60) had azoospermia. The overall ongoing pregnancy rate was 65.5% (500/762). The overall ongoing pregnancy rates in group I (69.3%) and group II (61.5%) were comparable (p = 0.06). However, group I and group II conceived significantly more frequently than group III (43.3%) (group I vs. group III p < 0.001 and group II vs. group III p = 0.02, respectively). Moreover, the spontaneous ongoing pregnancy rate in group I was 35.3%, in group II 22.4% and in group III, 1.7% (group I vs. group II p = 0.002; group I vs. group III p < 0.001; group II vs. group III p < 0.001). Thus, despite a significant difference in spontaneous ongoing pregnancy rates, except for azoospermia, the overall ongoing pregnancy rates, regardless of the severity of the male factor, were comparable. Couples with poorer sperm parameters, however, have to undergo more invasive treatment to reach the same goal.

Is the fertility treatment itself a risk factor for early pregnancy loss?

This longitudinal multicentre cohort study aimed to identify the role of the conception mode in infertile couples with an early pregnancy loss (EPL). All couples referred to the fertility clinic for the first time in the period 2002-2006 because of infertility were followed up to their first clinical pregnancy (n=1809). EPL was the outcome of 286 (15.8%) pregnancies. EPL rates for the different conception modes were as follows: spontaneous 14.5% (125/864), ovulation induction 15.8% (42/266), intrauterine insemination 25.0% (5/20), intrauterine insemination combined with ovarian stimulation 18.2% (37/203), IVF 16.3% (31/190), intracytoplasmic sperm injection (ICSI) 14.9% (30/202) and frozen embryo transfer (FET) 26.2% (16/61). After adjusting for female age, male age, hospital, obstetric history, female smoking habit, male alcohol use, menstrual cycle type and infertility diagnosis, the EPL rate after FET was significantly increased (odds ratio 2.2, 95% CI 1.14-4.19) compared with spontaneous conception. Embryo quality was comparable in fresh and frozen embryos. Other fertility treatments showed no increased miscarriage rate. Therefore, it is concluded that even after adjustment for confounding factors conception through FET remained an independent risk factor for EPL. Other modes of conception were not related with EPL.

Unexplained infertility: overall ongoing pregnancy rate and mode of conception.

BACKGROUND: Unexplained infertility is one of the most common diagnoses in fertility care. The aim of this study was to evaluate the outcome of current fertility management in unexplained infertility. METHODS: In an observational, longitudinal, multicentre cohort study, 437 couples were diagnosed with unexplained infertility and were available for analysis. They were treated according to their prognosis using standing national treatment protocols: (i) expectant management-IUI-IVF (main treatment route), (ii) IUI-IVF and (iii) directly IVF. Primary outcome measures were: ongoing pregnancy rate, patient flow over the strategies, numbers of protocol violation and drop out rates. A secondary outcome measure was the prediction of ongoing pregnancy and mode of conception. RESULTS: Of all couples 81.5% (356/437) achieved an ongoing pregnancy and 73.9% (263/356) of the pregnancies were conceived spontaneously. There were 408 couples (93.4%) in strategy-1, 21 (5.0%) in strategy-2 and 8 (1.8%) in strategy-3. In total, 33 (7.6%) couples entered the wrong strategy. There were 104 couples (23.8%) who discontinued fertility treatment prematurely: 26 on doctor's advice (with 4 still becoming pregnant) and 78 on their own initiative (with 33 still achieving a pregnancy). Predictors for overall pregnancy chance and mode of conception were duration of infertility, female age and obstetrical history. CONCLUSIONS: Overall success rate in couples with unexplained infertility is high. Most pregnancies are conceived spontaneously. We recommend that if the pregnancy prognosis is good, expectant management should be suggested. The prognosis criteria for treatment with IUI or IVF needs to be investigated in randomized controlled trials.

The relative contribution of IVF to the total ongoing pregnancy rate in a subfertile cohort.

BACKGROUND: Although in vitro fertilization (IVF) was introduced more than 30 years ago, its exact role in the spectrum of fertility treatments has never been studied in an unselected population. The aim of this study was to visualize the contribution of IVF to the ongoing pregnancy rates in a cohort of newly referred subfertile couples. MATERIALS: All new subfertile couples (n = 1391) that were referred to our fertility clinic by their general practitioner between January 2002 and December 2006 were included. Fertility care was provided according to the national Dutch fertility guidelines. Data on diagnosis, treatment, mode of conception and pregnancy outcome were documented. If follow-up data were missing, couples were contacted. Cumulative pregnancy curves were constructed for the whole cohort and per diagnostic group. RESULTS: As per December 2008 the overall ongoing pregnancy rate was 72.0% (n = 1001). Almost half of the pregnancies were conceived spontaneously (45.6%), 19.2% after ovulation induction (OI), 14.0% after intrauterine insemination (IUI) and 21.2% after IVF. A quarter (n = 349) of couples received IVF treatment, which was successful in 60% of cases. IVF had the largest contribution to ongoing pregnancies in patients with 'tubal factor', 'endometriosis' and 'male factor' (45, 45 and 37%, respectively) while in couples with 'unexplained subfertility' and 'ovulation disorders' the contribution to ongoing pregnancies of IVF was limited (13 and 4.5%, respectively). CONCLUSIONS: In a cohort of subfertile couples, most pregnancies were conceived spontaneously. The contribution of IVF to ongoing pregnancy rates was comparable to those of OI and IUI. Compared with the pre-IVF era, couples with 'endometriosis', 'tubal factor' and 'male subfertility' have benefited most from its introduction.

When and why do subfertile couples discontinue their fertility care? A longitudinal cohort study in a secondary care subfertility population.

BACKGROUND: A substantial number of subfertile couples discontinues fertility care before achieving pregnancy. Most studies on dropouts are related to IVF. The aim here is to examine dropout rates at all stages of fertility care. METHODS: We analysed a consecutive cohort of 1391 couples, referred to our secondary care hospital between January 2002 and December 2006. Discontinuation rates were studied at six stages. Stage I: immediately after first visit, Stage II: during diagnostic workup, Stage III: after finishing diagnostic workup but before treatment, Stage IV: during or after non-IVF treatment, Stage V: during IVF, Stage VI: after at least 3 cycles of IVF. Reasons to discontinue and spontaneous pregnancy rates after discontinuation were secondary outcomes. RESULTS: In our cohort 319 couples dropped out of fertility care, 76.8%, [95% confidence interval (CI): 72.2-81.4] on their own initiative and 23.2% (95% CI: 18.6-27.8) on doctor's advice. Percentage (95% CI) of couples discontinuing per stage were: Stage I 6.0% (3.4-8.6), Stage II 3.4% (1.5-5.5), Stage III 35.7% (30.5-41.0), Stage IV 23.5% (18.9-28.2), Stage V 17.9% (13.7-22.1) and Stage VI 13.5% (9.7-17.2). Main reasons for dropout (%, 95% CI) were 'emotional distress' (22.3%, 17.7-26.8), 'poor prognosis' (18.8%, 14.5-23.1) and 'reject treatment' (17.2%, 13.1-21.4). The spontaneous ongoing pregnancy rate after discontinuation was 10% (6.7-13.3). CONCLUSION: About half of the couples stopped before any fertility treatment was started and one-third stopped after at least one IVF cycle. The main reasons for withdrawal were emotional distress and poor prognosis. This insight may help to improve quality of patient care by making care more responsive to the needs and expectations of subfertile couples.

Physical activity levels after limb salvage surgery are not related to clinical scores-objective activity assessment in 22 patients after malignant bone tumor treatment with modular prostheses.

BACKGROUND: The aim of the present study was to objectively assess the physical activity levels of patients after tumor prosthesis implantation with two objective measurement devices. METHODS: The DynaPort ADL monitor permitted up to 24 hr monitoring of lower-extremity physical activities in daily life with respect to posture and locomotion. The step activity monitor (SAM) was worn for a whole week to collect the daily number of gait cycles. The devices were worn during the waking hours by 22 patients with knee prostheses after wide tumor resection. RESULTS: In the MSTS and TESS scores the patients achieved over 80% of the maximum score indicating a good clinical outcome. The most prominent activity was sitting which accounted for 54 +/- 18% of the recorded time, followed by standing (27 +/- 16%), locomotion (10 +/- 6%), and lying (8 +/- 6%). During locomotion, the average walking activity accumulated to 4,786 +/- 1,770 step cycles per day (range 2,045-8,135) corresponding to a yearly 1.75 million steps. There was no significant correlation between clinical scores and step count measures. CONCLUSIONS: Even though this activity level was lower than for a group of healthy adults it was comparable to the activity level for other patients, for example, with hip arthroplasty as reported in the literature.

Postpartum onset obsessive-compulsive disorder: diagnosis and management.

The postpartum period is associated with an increased risk of developing obsessive-compulsive disorder (OCD) in women. Postpartum onset OCD is often undiagnosed and untreated resulting in serious consequences for the patient, her family and the newborn. The symptoms of postpartum onset OCD may consist of obsessional intrusive thoughts about harming the newborn without compulsions or with both obsessions and compulsions. In this review, the phenomenology of postpartum onset OCD is described as well as strategies for screening and diagnosis. The review also characterizes the differences between postpartum onset OCD and postpartum depression and postpartum psychosis and explores strategies for managing postpartum onset OCD patients. Issues regarding pharmacologic treatment of OCD in breastfeeding mothers are also reviewed.

Hydroxyectoine is superior to trehalose for anhydrobiotic engineering of Pseudomonas putida KT2440.

Anhydrobiotic engineering aims to increase the level of desiccation tolerance in sensitive organisms to that observed in true anhydrobiotes. In addition to a suitable extracellular drying excipient, a key factor for anhydrobiotic engineering of gram-negative enterobacteria seems to be the generation of high intracellular concentrations of the nonreducing disaccharide trehalose, which can be achieved by osmotic induction. In the soil bacterium Pseudomonas putida KT2440, however, only limited amounts of trehalose are naturally accumulated in defined high-osmolarity medium, correlating with relatively poor survival of desiccated cultures. Based on the enterobacterial model, it was proposed that increasing intracellular trehalose concentration in P. putida KT2440 should improve survival. Using genetic engineering techniques, intracellular trehalose concentrations were obtained which were similar to or greater than those in enterobacteria, but this did not translate into improved desiccation tolerance. Therefore, at least for some populations of microorganisms, trehalose does not appear to provide full protection against desiccation damage, even when present at high concentrations both inside and outside the cell. For P. putida KT2440, it was shown that this was not due to a natural limit in desiccation tolerance since successful anhydrobiotic engineering was achieved by use of a different drying excipient, hydroxyectoine, with osmotically preconditioned bacteria for which 40 to 60% viability was maintained over extended periods (up to 42 days) in the dry state. Hydroxyectoine therefore has considerable potential for the improvement of desiccation tolerance in sensitive microorganisms, particularly for those recalcitrant to trehalose.

Assessing chemical toxicity with the bioluminescent photobacterium (Vibrio fischeri): a comparison of three commercial systems.

The inhibition of light emitted by the bioluminescent bacterium, Vibrio fischeri, is the basis for several toxicity bioassays. The inhibitory effects of 81 chemicals, after 5 min contact time, were studied at eight concentrations using reagents from three commercial assay systems (ToxAlert 10, Microtox and LUMIStox). Solubility in water was the limiting factor in determining the selection of chemicals for study. The effective nominal concentrations (EC) resulting in 20, 50 and 80% inhibition were determined using Ln dose/Ln gamma plots and the results obtained for each system were compared by linear regression. The chemical concentrations producing 10-90% inhibition extended over 9 orders of magnitude and ranged from a minimum of 0.001 ppm to a maximum of 1,000,000 ppm. The toxicity of many chemicals was apparently related to their pH in solution and at high chemical concentrations, to osmotic imbalance. The fact that the same operator tested the same solutions simultaneously on three different systems reduced sources of error and variability and improved the consistency and reliability of the results. Only five compounds gave EC 50s that varied more than three-fold between assays. These data provide comparisons of toxicity that have not been previously available and demonstrate that, when used under standardised conditions, these bioluminescence-based toxicity assays produce very similar results.

Activation-dependent modulation of B lymphocyte migration to chemokines.

In this study we have examined the migration responses of human peripheral blood or tonsillar B lymphocytes to a selection of 27 chemokines. Freshly isolated (CD19(+)) B lymphocytes show greatly impaired in vitro chemotaxis which is overcome by overnight culture. The best responses of cultured B lymphocytes were observed with BCA-1, SLC, ELC and SDF-1, reaching 19-26% of total input cells that have migrated, followed by LARC and TECK with 5-10% of migrated cells, whereas no other chemokine was found to be active. Stimulation of B lymphocytes with lipopolysaccharide or anti-CD40 plus IL-4 resulted in marked enhancement of the migration response to BCA-1, SLC, ELC and SDF-1, reaching 30-60% migrated cells at 12 or 36 h of culture respectively. The activation-dependent increase in the migration efficacy was transient and declined to base level responses after 72 h of culture. Under no circumstances did we detect B lymphocyte chemotaxis to inflammatory chemokines. Also, mobilization of intracellular calcium ([Ca(2+)](i)), an otherwise typical response of leukocytes to chemokines, was not observed. The transient increase in B lymphocyte migration did not correlate with changes in chemokine receptor expression, as evidenced by cell surface staining with antibodies to CXCR4, CXCR5 and CCR6, and by receptor transcript analyses. BCA-1, SLC, ELC and SDF-1 are typical 'housekeeping' chemokines with prominent expression at discrete locations in lymphoid tissues. Modulation of migration to these chemokines may be a critical mechanism for the proper positioning of B lymphocytes during humoral responses in secondary lymphoid tissues.

Fluorescence of dental calculus from cats, dogs, and humans and of bacteria cultured from dental calculus.

Recently we reported that feline and canine dental calculus fluoresced pink to red under long wavelength ultraviolet light due to the presence of porphyrin. Here we report the observation of such fluorescence in 30 of 30 cats, 30 of 30 dogs, and 8 of 13 supragingival samples and 5 of 5 subgingival samples of humans. The fluorescence spectra of the calculus dissolved in 9 M HCl show that it is due to three distinct metal-free porphyrins. Similar fluorescence is obtained from bacterial cultures grown from calculus deposits of cats and dogs and bacteria grown on blood agar containing hemin and vitamin K1. The results of the bacterial culture study suggest that the metal-free porphyrin is produced by bacteria in the mouth. The clinical observation of fluorescence can be used for diagnosis.

Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages.

Taxol, a microtubule stabilizing agent, exhibits promise in the treatment of breast and ovarian tumors. Recently, this novel drug has been shown to activate murine macrophages to express TNF-alpha and to down-regulate TNF-alpha receptors, activities shared by bacterial LPS. Our study sought to determine if taxol could regulate gene expression in murine macrophages and to examine further the ability of taxol to generate an LPS-like signal. Toward this end, the ability of taxol to induce TNF-alpha mRNA and five other genes (IL-1 beta, IP-10, D3, D7, and D8) associated with LPS-activation of macrophages was examined by Northern blot analysis. Taxol alone (1-30 microM) induced murine C3H/OuJ macrophages to secrete bioactive TNF-alpha and express increased levels of each of the six genes under investigation. The magnitude and the kinetics of induction of each gene closely resembled that seen with Escherichia coli K235 LPS. Macrophages from LPS-hyporesponsive C3H/HeJ mice, however, failed to induce detectably any of the genes in response to taxol, despite being sensitive to the microtubule stabilizing effects of taxol as determined by immunofluorescence microscopy. The gene induction activity of taxol was in marked contrast to an alternative macrophage activator, heat killed Staphylococcus aureus, which induced a distinct gene profile in C3H/OuJ macrophages and which was equally active in C3H/OuJ and C3H/HeJ macrophages. These data are consistent with an ability of taxol to generate an LPS-like signal, possibly through a common signaling intermediate. As a first step toward identifying signal responses shared by taxol and LPS, we have shown that taxol, as shown previously for LPS, rapidly induces the tyrosine phosphorylation of a 41- and 42-kDa protein.

Autocrine and paracrine regulation of astrocyte function by transforming growth factor-beta.

Recent evidence indicates that astrocytes have a wide range of functions, usually attributed to cells of the immune system, which are critical for maintaining a balanced homeostatic environment in the central nervous system (CNS). Moreover, these cells are known to participate in inflammatory events within the CNS by secreting cytokines such as transforming growth factor-beta (TGF-beta). In this study we have investigated the ability of TGF-beta to influence astrocyte functions. TGF-beta 1 mRNA is constitutively expressed by astrocytes in vitro, and when cultures are stimulated with exogenous TGF-beta 1 an increase in the expression of this mRNA can be shown, suggesting both autocrine and paracrine regulation. In in vitro assays, TGF-beta 1 is chemotactic for astrocytes in a dose-dependent fashion and inhibits astrocyte proliferation. These results indicating signal transduction by TGF-beta 1-prompted studies to explore receptor-ligand interactions on isolated astrocyte populations. In a receptor binding assay, we demonstrate that astrocytes appear to express three distinct TGF-beta receptor subtypes with nearly 10,000 receptors per cell. Thus, TGF-beta may play an important role in regulating astrocyte functions pivotal to the evolution of intracerebral immune responses including recruitment and activation of glial cells at local inflammatory sites within the CNS.

Role of Kupffer cells in developing streptococcal cell wall granulomas. Streptococcal cell wall induction of inflammatory cytokines and mediators.

Hepatic granulomas are induced by intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats. Kupffer cells rapidly clear SCW from the blood, and the authors examined Kupffer cells further for a role in SCW-hepatic inflammation. Isolated Kupffer cells cultured with SCW secreted high levels of tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), transforming growth factor beta (TGF beta), and prostaglandin E2 (PGE2). SCW transiently induced increased steady-state levels of IL-1 beta and TNF alpha mRNA; in contrast, constitutive expression of TGF beta 1 mRNA in Kupffer cells was not affected by SCW. Low concentrations of SCW induced the accumulation of intracellular IL-1 and TGF beta bioactivity, with intracellular IL-1 bioactivity remaining high through at least 72 hours of culture. Kupffer cells isolated 1, 7, and 21 days after SCW injection did not express IL-1 beta or TNF alpha mRNA greater than control levels and exhibited marked hyporesponsiveness to secondary in vitro stimulation with SCW or LPS. SCW transiently induces Kupffer cells to secrete a variety of soluble mediators that contribute to hepatic inflammation by inducing leukocyte recruitment and activation and fibroproliferation. The transient nature of the Kupffer cell response and the hyporesponsiveness to secondary stimulation may be a mechanism by which the hepatic inflammation is negatively regulated.