Synergistic Antibacterial Effects of Gallate Containing Compounds with Silver Nanoparticles in Gallate Crossed Linked PVA Hydrogel Films.

Currently available silver-based antiseptic wound dressings have limited patient effectiveness. There exists a need for wound dressings that behave as comfortable degradable hydrogels with a strong antibiotic potential. The objectives of this project were to investigate the combined use of gallates (either epi gallo catechin gallate (EGCG), Tannic acid, or Quercetin) as both PVA crosslinking agents and as potential synergistic antibiotics in combination with silver nanoparticles. Crosslinking was assessed gravimetrically, silver and gallate release was measured using inductively coupled plasma and HPLC methods, respectively. Synergy was measured using 96-well plate FICI methods and in-gel antibacterial effects were measured using planktonic CFU assays. All gallates crosslinked PVA with optimal extended swelling obtained using EGCG or Quercetin at 14% loadings (100 mg in 500 mg PVA with glycerol). All three gallates were synergistic in combination with silver nanoparticles against both gram-positive and -negative bacteria. In PVA hydrogel films, silver nanoparticles with EGCG or Quercetin more effectively inhibited bacterial growth in CFU counts over 24 h as compared to films containing single agents. These biocompatible natural-product antibiotics, EGCG or Quercetin, may play a dual role of providing stable PVA hydrogel films and a powerful synergistic antibiotic effect in combination with silver nanoparticles.

Exploring the use of a Ruthenium complex incorporated into a methacrylate-based dental material for antimicrobial photodynamic therapy.

OBJECTIVES: To evaluate the effects of a blue light photosensitizer (PS), Ruthenium II complex (Ru), on the chemical, physical, mechanical, and antimicrobial properties of experimental dental resin blends. METHODS: The experimental resin (BisEMA, TEEGDMA, HPMA, ethanol, and photoinitiator) was loaded with Ru at 0.00%, 0.07%, 0.14%, 0.28%, 0.56%, 1.12%, 1.2%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% w/w. Samples were evaluated for the degree of conversion (DC) after 30 and 60 s curing-time (n = 6). Selected formulations (0.00%, 0.28%, 0.56%, 1.12%) were further tested for shear bond strength (SBS) (n = 15); flexural strength (FS) (n = 12); and antimicrobial properties (CFUs), in dark and light conditions. These latter tests were performed on specimens stored for 24-h or 2-month in 37°C water. Water sorption (WS) and solubility (SL) tests were also performed (n = 12). Data were analyzed either by a one- or two-factor general linear model (α = 0.05). RESULTS: Overall, Ru concentration above 1.2% resulted in reduced DC. In SBS results, only the 1.12%Ru resin blend samples had statistically lower values compared to the 0.00%Ru resin blend at 24-h storage (p = 0.004). In addition, no differences in SBS were detected among the experimental groups after 2-month storage in water. Meanwhile, FS increased for all experimental groups under similar aging conditions (p < 0.001). Antimicrobial properties were improved upon inclusion of Ru and application of light (p < 0.001 for both) at 24-h and 2-month storage. Lastly, no detectable changes in WS or SL were observed for the Ru-added resins compared to the 0.00%Ru resin blend. However, the 0.28% Ru blend presented significantly higher WS compared to the 0.56% Ru blend (p = 0.007). CONCLUSIONS: Stable SBS, improved FS, and sustained antimicrobial properties after aging gives significant credence to our approach of adding the Ruthenium II complex into dental adhesive resin blends intended for an aPDT approach.

The Manufacture and Characterization of Silver Diammine Fluoride and Silver Salt Crosslinked Nanocrystalline Cellulose Films as Novel Antibacterial Materials.

There is an unmet need for biocompatible, anti-infective, and mechanically strong hydrogels. This study investigated the use of poly vinyl alcohol (PVA), polysaccharides, and nanocrystalline cellulose (CNC) to deliver silver in a controlled manner for possible use against oral or wound bacteria. Silver was included in solvent cast films as silver diammine fluoride (SDF) or as nitrate, sulphate, or acetate salts. Hydrogel formation was assessed by swelling determinations and silver release was measured using inductively coupled plasma methods. Antibacterial studies were performed using Gram-positive and negative bacteria turbidity assays. PVA formed homogenous, strong films with SDF and swelled gently (99% hydrolyzed) or vigorously with dissolution (88% hydrolyzed) and released silver slowly or quickly, respectively. CNC-SDF films swelled over a week and formed robust hydrogels whereas CNC alone (no silver) disintegrated after two days. SDF loaded CNC films released silver slowly over 9 days whereas films crosslinked with silver salts were less robust and swelled and released silver more quickly. All silver loaded films showed good antibacterial activity. CNC may be crosslinked with silver in the form of SDF (or any soluble silver salt) to form a robust hydrogel suitable for dental use such as for exposed periodontal debridement areas.

Effects of Smoking Cessation on Presynaptic Dopamine Function of Addicted Male Smokers.

BACKGROUND: There is evidence of abnormal cerebral dopamine transmission in nicotine-dependent smokers, but it is unclear whether dopaminergic abnormalities are due to acute nicotine abuse or whether they persist with abstinence. We addressed this question by conducting longitudinal positron emission tomography (PET) examination of smokers before and after 3 months of abstinence. METHODS: We obtained baseline 6-[(18)F]fluoro-L-DOPA (FDOPA)-PET scans in 15 nonsmokers and 30 nicotine-dependent smokers, who either smoked as per their usual habit or were in acute withdrawal. All smokers then underwent cessation treatment, and successful abstainers were re-examined by FDOPA-PET after 3 months of abstinence (n = 15). Uptake of FDOPA was analyzed using a steady-state model yielding estimates of the dopamine synthesis capacity (K); the turnover of tracer dopamine formed in living brain (kloss); and the tracer distribution volume (Vd), which is an index of dopamine storage capacity. RESULTS: Compared with nonsmokers, K was 15% to 20% lower in the caudate nuclei of consuming smokers. Intraindividual comparisons of consumption and long-term abstinence revealed significant increases in K in the right dorsal and left ventral caudate nuclei. Relative to acute withdrawal, Vd significantly decreased in the right ventral and dorsal caudate after prolonged abstinence. Severity of nicotine dependence significantly correlated with dopamine synthesis capacity and dopamine turnover in the bilateral ventral putamen of consuming smokers. CONCLUSIONS: The results suggest a lower dopamine synthesis capacity in nicotine-dependent smokers that appears to normalize with abstinence. Further investigations are needed to clarify the role of dopamine in nicotine addiction to help develop smoking prevention and cessation treatments.

MAOA-VNTR polymorphism modulates context-dependent dopamine release and aggressive behavior in males.

A recent [(18)F]FDOPA-PET study reports negative correlations between dopamine synthesis rates and aggressive behavior. Since dopamine is among the substrates for monoamine oxidase A (MAOA), this investigation examines whether functional allelic variants of the MAOA tandem repeat (VNTR) promotor polymorphism, which is known to modulate aggressive behavior, influences dopamine release and aggression in response to violent visual stimuli. We selected from a genetic prescreening sample, strictly case-matched groups of 2×12 healthy male subjects with VNTRs predictive of high (MAOA-High) and low (MAOA-Low) MAOA expression. Subjects underwent pairs of PET sessions (dopamine D2/3 ligand [(18)F]DMFP) while viewing a movie of neutral content, versus violent content. Directly afterwards, aggressive behavior was assessed by the Point Subtraction Aggression Paradigm (PSAP). Finally, PET data of 23 participants and behavioral data of 22 participants were analyzed due to post hoc exclusion criteria. In the genetic prescreening sample MAOA-Low carriers had significantly increased scores on the Buss-Perry Aggression Questionnaire. In the PET-study-group, aggressive behavior under the emotional neutral condition was significantly higher in the MAOA-Low group. Interestingly, the two MAOA-groups showed inverse dopaminergic and behavioral reactions to the violent movie: The MAOA-High group showed higher dopamine release and increased aggression after the violent movie; MAOA-Low subjects showed decreases in aggressive behavior and no consistent dopamine release. These results indicate a possible impact of the MAOA-promotor polymorphism on the neurobiological modulation of aggressive behavior. However, the data do not support approaches stating that MAOA-Low fosters aggression by a simple pro-dopaminergic mechanism.

Acute and sustained effects of methylphenidate on cognition and presynaptic dopamine metabolism: an [18F]FDOPA PET study.

Methylphenidate (MPH) inhibits the reuptake of dopamine and noradrenaline. PET studies with MPH challenge show increased competition at postsynaptic D2/3-receptors, thus indirectly revealing presynaptic dopamine release. We used [(18)F]fluorodopamine ([(18)F]FDOPA)-PET in conjunction with the inlet-outlet model (IOM) of Kumakura et al. (2007) to investigate acute and long-term changes in dopamine synthesis capacity and turnover in nigrostriatal fibers of healthy subjects with MPH challenge. Twenty healthy human females underwent two dynamic [(18)F]FDOPA PET scans (124 min; slow bolus-injection; arterial blood sampling), with one scan in untreated baseline condition and the other after MPH administration (0.5 mg/kg, p.o.), in randomized order. Subjects underwent cognitive testing at each PET session. Time activity curves were obtained for ventral putamen and caudate and were analyzed according to the IOM to obtain the regional net-uptake of [(18)F]FDOPA (K; dopamine synthesis capacity) as well as the [(18)F]fluorodopamine washout rate (kloss, index of dopamine turnover). MPH substantially decreased kloss in putamen (-22%; p = 0.003). In the reversed treatment order group (MPH/no drug), K was increased by 18% at no drug follow-up. The magnitude of K at the no drug baseline correlated with cognitive parameters. Furthermore, individual kloss changes correlated with altered cognitive performance under MPH. [(18)F]FDOPA PET in combination with the IOM detects an MPH-evoked decrease in striatal dopamine turnover, in accordance with the known acute pharmacodynamics of MPH. Furthermore, the scan-ordering effect on K suggested that a single MPH challenge persistently increased striatal dopamine synthesis capacity. Attenuation of dopamine turnover by MPH is linked to enhanced cognitive performance in healthy females.

Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

Neural dynamics of audiovisual synchrony and asynchrony perception in 6-month-old infants.

Young infants are sensitive to multisensory temporal synchrony relations, but the neural dynamics of temporal interactions between vision and audition in infancy are not well understood. We investigated audiovisual synchrony and asynchrony perception in 6-month-old infants using event-related brain potentials (ERP). In a prior behavioral experiment (n = 45), infants were habituated to an audiovisual synchronous stimulus and tested for recovery of interest by presenting an asynchronous test stimulus in which the visual stream was delayed with respect to the auditory stream by 400 ms. Infants who behaviorally discriminated the change in temporal alignment were included in further analyses. In the EEG experiment (final sample: n = 15), synchronous and asynchronous stimuli (visual delay of 400 ms) were presented in random order. Results show latency shifts in the auditory ERP components N1 and P2 as well as the infant ERP component Nc. Latencies in the asynchronous condition were significantly longer than in the synchronous condition. After video onset but preceding the auditory onset, amplitude modulations propagating from posterior to anterior sites and related to the Pb component of infants' ERP were observed. Results suggest temporal interactions between the two modalities. Specifically, they point to the significance of anticipatory visual motion for auditory processing, and indicate young infants' predictive capacities for audiovisual temporal synchrony relations.

Inactivated Orf virus (Parapoxvirus ovis) elicits antifibrotic activity in models of liver fibrosis.

AIM: Inactivated Orf virus (ORFV, Parapoxvirus ovis) demonstrates strong antiviral activity in animal models including a human hepatitis B virus (HBV)-transgenic mouse. In addition, expression of interferon (IFN)-γ and interleukin-10 (IL-10) was induced after administration of inactivated ORFV in these mice. IFN-γ and IL-10 are known to elicit antifibrotic activity. We therefore aimed to study antifibrotic activity of inactivated ORFV in models of liver fibrosis. METHODS: We characterized ORFV-induced hepatic cytokine expression in rats. We then studied ORFV in two models of liver fibrosis in rats, pig serum-induced liver fibrosis and carbon tetrachloride (CCL4 )-induced liver fibrosis. RESULTS: ORFV induced hepatic expression of IFN-γ and IL-10 in rats. ORFV mediated antifibrotic activity when administrated concomitantly with the fibrosis-inducing agents in both models of liver fibrosis. Importantly, when CCL4 -induced liver fibrosis was already established, ORFV application still showed significant antifibrotic activity. In addition, we were able to demonstrate a direct antifibrotic effect of ORFV on stellate cells. CONCLUSION: These results establish a potential novel antifibrotic therapeutic approach that not only prevents but also resolves established liver fibrosis. Further studies are required to unravel the details of the mechanisms involved.

Stimulation of soluble guanylate cyclase reduces experimental dermal fibrosis.

BACKGROUND: Fibrosis and vascular disease are cardinal features of systemic sclerosis (SSc). Stimulators of soluble guanylate cyclase (sGC) are vasoactive drugs that are currently being evaluated in phase III clinical trials for pulmonary arterial hypertension. OBJECTIVE: To study the antifibrotic potency of sGC stimulators. METHODS: The effect of the sGC stimulator BAY 41-2272 on the release of collagen from dermal fibroblasts was examined. The antifibrotic effects of BAY 41-2272 on prevention and regression of fibrosis in bleomycin-induced dermal fibrosis and in Tsk-1 mice were also studied. Telemetric blood pressure studies in conscious mice were used to study potential hypotensive effects of sGC stimulation. RESULTS: sGC stimulation with BAY 41-2272 dose-dependently inhibited collagen release in dermal fibroblasts from patients with SSc and healthy individuals. Furthermore, BAY 41-2272 stopped the development of bleomycin-induced dermal fibrosis and skin fibrosis in Tsk-1 mice, preventing dermal and hypodermal thickening, reducing the numbers of myofibroblasts and reducing the hydroxyproline content. In addition, BAY 41-2272 was highly effective in the treatment of established fibrosis in the modified models of bleomycin-induced skin fibrosis and Tsk-1 mice. Treatment with sGC stimulators was well tolerated. Relevant antifibrotic doses of BAY 41-2272 did not affect systemic blood pressure and heart rate in mice. CONCLUSIONS: These findings demonstrate potent antifibrotic effects and good tolerability of sGC stimulators in various experimental models of SSc. Given their potential vasoactive properties, sGC stimulators may be promising candidates for the dual treatment of fibrosis and vascular disease in SSc.

Comparison of ventricular tachyarrhythmia characteristics in patients with idiopathic dilated or ischemic cardiomyopathy and defibrillators implanted for primary prevention.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy for primary prevention is well established in ischemic cardiomyopathy (ICM). Data on the role of ICDs in patients with dilated cardiomyopathy (DCM) and no history of ventricular tachyarrhythmia (VT/VF) are more limited. HYPOTHESIS: DCM patients with an impaired left ventricular ejection fraction (LVEF) still represent a low arrhythmic risk subgroup in clinical practice. METHODS: ICD stored data of DCM patients with an LVEF ≤35% was compared to data of ICM patients meeting Multicenter Automatic Defibrillator Implantation Trial (MADIT) eligibility criteria. VT/VF occurrences and electrical storm (ES) events were analyzed. RESULTS: There were 652 patients followed for 50.9 ± 33.9 months. There were 1978 VT and 241 VF episodes analyzed in 66 out of 203 patients (32.5%) with DCM and in 118 out of 449 patients (26.3%, P = 0.209) with ICM. Freedom of appropriate ICD treatment due to VT/VF or ES events did not differ in both patient populations (log-rank, P>0.05). In patients presenting with VT/VF episodes, mean event rates were comparable in both patient populations (3.2 ± 14.1 for DCM and VT vs 3 ± 13.9 for ICM and VT [P = 0.855], 0.4 ± 1.3 for DCM and VF vs 0.4 ± 1.8 for ICM and VF [P = 0.763], and 0.2 ± 0.7 for DCM and ES vs 0.2 ± 1 for ICM and ES [P = 0.666]). CONCLUSIONS: DCM patients with prophylactic ICDs implanted due to heart failure and patients fulfilling MADIT criteria reveal comparable patterns of VT/VF/ES events during long-term follow-up. Incidence, mean number of events, and time to first event did not differ significantly. Findings support the current guidelines for prophylactic ICD therapy in DCM patients with heart failure.

Predictors of electrical storm recurrences in patients with implantable cardioverter-defibrillators.

AIMS: To determine prevalence and predictors of electrical storm recurrences (ES-Rs) in patients with implantable cardioverter-defibrillators (ICDs) as electrical storms (ESs) represent serious clinical events carrying a high risk of mortality. METHODS AND RESULTS: Single-centre study analysing data of consecutive patients receiving an ICD between 1993 and 2008. Electrical storm was defined as ≥ 3 separate ventricular tachyarrhythmic (VT/VF) episodes ≤ 24 h. Nine hundred and fifty-five patients [mean left ventricular ejection fraction (LVEF) 35.7 ± 15.6%] were prospectively followed for 54.2 ± 35.5 months. In 274 of 955 patients (28.7%), 2871 VT/VF episodes were observed. One hundred and fifty-three ES episodes occurred in 63 of 955 patients (6.6%). Thirty-two of 63 patients (50.8%) experienced ≥ 2 ES episodes. Twenty-six of 32 patients (81.2%) with ES-Rs experienced the second ES episode within 1 year after the initial event. Cox regression analysis identified an LVEF ≤ 30% (OR 2.2; 95% CI 1.021-4.856; P = 0.044) and a patient's age >65 years (OR 3.5; 95% CI 1.207-10.176; P = 0.021) to be predictive for ES-Rs. Patients with angiotensin-converting enzyme (ACE) inhibitor therapy were less likely to experience ES-Rs (OR 0.39; 95% CI 0.187-0.817; P = 0.013). CONCLUSIONS: Electrical storm events are not rare in a 'real-world' patient population with ICDs (6.6% in 4.5 years). The risk for ES-Rs, especially within the first year after the initial event, is high. Left ventricular ejection fraction ≤ 30%, age >65 years, and a lack of ACE inhibitor therapy are independent predictors of ES-R.

Nitric oxide-independent activation of soluble guanylate cyclase by BAY 60-2770 in experimental liver fibrosis.

UNLABELLED: Liver cirrhosis is a chronic disease with high mortality rate and need for effective pharmacological intervention. The fibrotic remodelling of liver tissue is crucially dependent on hepatic stellate cell activation. Activation of hepatic stellate cells is reduced by an increase in cyclic guanosine monophosphate (cGMP). Stable cGMP analogues also reduce the contractile response of hepatic stellate cells. However, cGMP production is downregulated in the cirrhotic liver due to the reduced activity of the endothelial nitric oxide synthase. OBJECTIVE: Here we report that the novel activator of soluble guanylate cyclase (sGC), BAY 60-2770 (4-({(4-carboxybutyl) [2- (5-fluoro-2-{[4'-(trifluoromethyl) biphenyl-4-yl]methoxy}phenyl)ethyl] amino}methyl)benzoic acid), which increases the activity of sGC in a nitric oxide-independent manner, attenuates liver fibrosis in two rat models. METHODS: The compound was studied in the pig serum model and the carbon tetrachloride model. Fibrosis was assessed by estimating the increase in fibrous collagen by micromorphometry of histological sections stained with Sirius Red/Fast Green and by measuring total hepatic collagen. RESULTS: BAY 60-2770, on a recombinant sGC reporter cell line, stimulated the luminescence signals with an EC50 value of 5.4 +/- 1.2 nmol/L. In the presence of [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 pmol/L) the EC50 was shifted to 0.39 +/- 0.11 nmol/L. In both fibrosis models, once daily oral administration of BAY 60-2770 concomittantly with the fibrotic stimulus prevented 60-75% of fibrosis, the lowest effective dose being 0.1 mg/kg in the pig serum model and 0.3 mg/kg in the carbon tetrachloride model. The treatment was well tolerated by all animals. The doses used were devoid of any significant influence on systemic blood pressure. CONCLUSION: Nitric oxide-independent activation of sGC might be an innovative therapeutic approach for the treatment of liver fibrosis of necro-inflammatory and immunological origin.

Impact of placing a conduit from the right ventricle to the pulmonary arteries as the first stage of further palliation in the Norwood sequence for hypoplasia of the left heart.

OBJECTIVE: We describe the experience from a single institution with the Norwood sequence of palliation for hypoplasia of the left heart, emphasizing complications related to placement of a conduit from the right ventricle to the pulmonary arteries and their management. METHODS: Between November, 2002 and January, 2006, we palliated 32 patients with hypoplastic left heart syndrome or its variants by placing a conduit from the right ventricle to the pulmonary arteries. We reviewed retrospectively the charts and angiograms from these patients. RESULTS: Hospital survival after construction of the conduit was 90.6%. There were 3 interstage deaths, of which 2 were likely due severe obstruction of the conduit. Stents were implanted into the proximal or medial portions of the conduits of 3 patients. Early revision of the distal anastomosis, and shortening the conduit, was performed early postoperatively in 2 patients. So far, 24 out 26 survivors of the first stage underwent a bi-directional cavopulmonary anastomosis after a mean interval of 4.3 plus or minus 1.4 months. Of these, 3 required a semi-urgent second stage of palliation because of worsening cyanosis, with one patient dying after the second stage. Completion of the Fontan circulation by insertion of an extracardiac conduit was performed in 8 patients at the mean age of 19.8 plus or minus 2.2 months. We were able to achieve biventricular repair in 1 patient, with aortic atresia, hypoplastic arch and ventricular septal defect, 4.3 months after the initial palliative procedure. Overall survival of the whole cohort of 32 patients was 78.9%, plus or minus 7.8%, at 5 months, and 74.3%, plus or minus 8.6%, up to 25 months. CONCLUSIONS: The introduction of the conduit placed from the right ventricle to the pulmonary arteries has led to an improved outcome in the complex entity of hypoplastic left heart syndrome and its variants. Stenosis of the conduit, nonetheless, may account for significant interstage morbidity, and often requires intervention or early installation of the second stage of palliation.

Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats.

Liver fibrosis is characterized by increased synthesis, and decreased degradation, of extracellular matrix (ECM) within the injured tissue. Decreased ECM degradation results, in part, from increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which blocks matrix metalloproteinase (MMP) activity. TIMP-1 is also involved in promoting survival of activated hepatic stellate cells (HSCs), a major source of ECM. This study examined the effects of blocking TIMP-1 activity in a clinically relevant model of established liver fibrosis. Rats were treated with carbon tetrachloride (CCl(4)), or olive oil control, for 6 weeks; 24 days into the treatment, the rats were administered a neutralizing anti-TIMP-1 antibody derived from a fully human combinatorial antibody library (HuCAL), PBS, or an isotype control antibody. Livers from CCl(4)-treated rats exhibited substantial damage, including bridging fibrosis, inflammation, and extensive expression of smooth muscle alpha-actin (alpha-SMA). Compared to controls, rats administered anti-TIMP-1 showed a reduction in collagen accumulation by histological examination and hydroxyproline content. Administration of anti-TIMP-1 resulted in a marked decrease in alpha-SMA staining. Zymography analysis showed antibody treatment decreased the activity of MMP-2. In conclusion, administration of a TIMP-1 antibody attenuated CCl(4)-induced liver fibrosis and decreased HSC activation and MMP-2 activity.

Influence of the alternative sigma(28) factor on virulence and flagellum expression of Legionella pneumophila.

The fliA gene of Legionella pneumophila encoding the alternative sigma(28) factor was inactivated by introducing a kanamycin resistance cassette. Electron microscopy and Western blot analysis revealed that the fliA mutant strain is aflagellate and expresses no flagellin. Reporter gene assays indicated that the flaA promoter is not active in the fliA mutant strain. The fliA mutant strain multiplied less effectively in coculture with amoebae than the wild-type strain and was not able to replicate in coculture with Dictyostelium discoideum.