Maximum degradation of diacerein was observed in alkaline

Maximum degradation of diacerein was observed in alkaline cisplatin mechanism of action medium, followed by decomposition under thermal degradation and photolysis. The drug was stable to acid hydrolysis and oxidative conditions. Percent degradation of diacerein under all stressed conditions and retention time of the degradation products are included in Table 1. Separation of diacerein from its degradation products has been performed on an RP C18 column. Initially water and acetonitrile in various proportions were tried. However, good resolution between peaks was not obtained. Different ratios of orthophosphoric acid in water (pH 2.9) and acetonitrile were tried. Increasing the acetonitrile ratio was accompanied by a decrease in retention time of the different components; however, separation was still achieved.

In order to ensure complete separation and high resolution, the chosen ratio was 50 : 50 (% v/v). Simultaneous monitoring with the PDA detector was carried out at a range of wavelength between 200 �C 400 nm. Detection was carried out at 257 nm, where maximum sensitivity was observed. The specificity of the method is illustrated in all the chromatograms of the degradation studies. Validation of the method The method was validated with respect to parameters like linearity, precision, accuracy, specificity, and robustness. The LOD and LOQ concentrations were found to be 0.10 and 0.50 ��g/ml. Results from the regression analysis with system-suitability data are listed in Table 2. Results of precision and accuracy are listed in Table 3.

Influences of small changes in chromatographic conditions, such as, change in flow rate (�� 10%), organic content in the mobile phase (�� 2%), wavelength of detection (�� 5%), and pH of buffer in the mobile phase (�� 0.2%) were studied, to determine the robustness of the method. The RSD was < 2% in all cases. The RSD values of the assay of diacerein during solution stability experiments Cilengitide were < 2%. No significant changes were observed during solution stability. The solution stability data confirms that the sample solutions were stable for at least seven days. Table 2 Results from regression analysis and system suitability of diacerein Table 3 Precision and recovery data CONCLUSIONS The study concludes that diacerein is most labile to alkaline hydrolysis followed by thermal degradation and photolysis. It is stable to acid hydrolysis and oxidative stress conditions. The proposed method is sensitive, precise, accurate, and stability-indicating, resolving all the degradation products from the drug. Thus, the proposed method can have its application in the determination of diacerein in bulk drug, pharmaceutical formulation, as well as in the presence of all its degradation products.

Possible mis-assemblies were corrected with gapResolution

Possible mis-assemblies were corrected with gapResolution Tipifarnib Transferase inhibitor [40], Dupfinisher, or sequencing cloned bridging PCR fragments with subcloning or transposon bombing (Epicentre Biotechnologies, Madison, WI) [43]. Gaps between contigs were closed by editing in Consed, by PCR and by Bubble PCR primer walks (J.-F. Chang, unpublished). A total of 331 additional reactions were necessary to close gaps and to raise the quality of the finished sequence. Illumina reads were also used to correct potential base errors and increase consensus quality using a software Polisher developed at JGI [44]. The error rate of the completed genome sequence is less than 1 in 100,000. Together, the combination of the Illumina and 454 sequencing platforms provided 215.0 �� coverage of the genome.

The final assembly contained 327,738 pyrosequence and 15,336,223 Illumina reads. Genome annotation Genes were identified using Prodigal [45] as part of the Oak Ridge National Laboratory genome annotation pipeline, followed by a round of manual curation using the JGI GenePRIMP pipeline [46]. The predicted CDSs were translated and used to search the National Center for Biotechnology Information (NCBI) non-redundant database, UniProt, TIGR-Fam, Pfam, PRIAM, KEGG, COG, and InterPro databases. Additional gene prediction analysis and functional annotation was performed within the Integrated Microbial Genomes – Expert Review (IMG-ER) platform [47]. Genome properties The genome consists of a 3,406,739bp long chromosome with a GC content of 46.4% (Table 3 and Figure 3).

Of the 3,439 genes predicted, 3,370 were protein-coding genes, and 69 RNAs; 119 pseudogenes were also identified. The majority of the protein-coding genes (68.7%) were assigned a putative function while the remaining ones were annotated as hypothetical proteins. The distribution of genes into COGs functional categories is presented in Table 4. Table 3 Genome Statistics Figure 3 Graphical circular map of chromosome. From outside to the center: Genes on forward strand (color by COG categories), Genes on reverse strand (color by COG categories), RNA genes (tRNAs green, rRNAs red, other RNAs black), GC content, GC skew. Table 4 Number of genes associated with the general COG functional categories Acknowledgements We would like to gratefully acknowledge the help of Maren Schr?der (DSMZ) for growing S. glycolicus cultures.

This work was performed under the auspices of the US Department of Energy Office of Science, Biological and Environmental Research Brefeldin_A Program, and by the University of California, Lawrence Berkeley National Laboratory under contract No. DE-AC02-05CH11231, Lawrence Livermore National Laboratory under Contract No. DE-AC52-07NA27344, and Los Alamos National Laboratory under contract No. DE-AC02-06NA25396, UT-Battelle and Oak Ridge National Laboratory under contract DE-AC05-00OR22725, as well as German Research Foundation (DFG) INST 599/1-2.

0 min, 2 5 min, and 2 6 min, respectively [Figure 5] As it is ev

0 min, 2.5 min, and 2.6 min, respectively [Figure 5]. As it is evident from Figure 5, the peak area values of all main degradation products were growing in time. Besides the peaks of these degradation products, other small peaks were also found in the exposed samples, but none of them had the area value greater than 1% of concentration of SRT. Furthermore, the amount of these degradation products did not grow markedly during the time of the experiment. Figure 5 Chromatogram of SRT decomposition at 360 min in alkali hydrolysis condition The degradation of SRT in the solution of 3% H2O2 resulted in the formation of two major peaks [Figure 6]. The retention times indicated the agreement of oxidative degradation products with acid ones, but however, the decline of concentration of SRT was much higher than concentration fall in acid hydrolysis. As it is evident, acid, neutral, and oxidative hydrolysis led to the formation of the same degradation products. Figure 6 Chromatogram of SRT decomposition at 360 min in oxidative hydrolysis condition Degradation behavior The susceptibility of SRT to hydrolytic decomposition was determined as a fall of concentration of drug during the time of the experiment. The kinetic slopes are shown in Figure 7. The straight-line behavior was obtained for neutral, alkaline, and oxidative conditions with correlation coefficients R = 0.999, R = 0.998 and R = 0.996, respectively. This fact implies that the hydrolytic degradation followed pseudo-first-order kinetic behaviour. The correlation coefficient for acid hydrolysis was calculated to be R = 0.942. The rate constants were determined from the slope of kinetic curves and their values are: 4.85 �� 10�C2/min (acid condition), 3.40 �� 10�C2/min (neutral condition), 4.32 �� 10�C2/min (alkaline condition), and 8.35 �� 10�C2/min (oxidative condition). The values of rate constants determined that the susceptibility of SRT to hydrolytic decomposition increased in the following manner: Neutral condition < alkaline condition < acidic condition < oxidative condition. Figure 7 Kinetic curves of SRT decomposition CONCLUSION HPLC methods were developed and validated for the estimation of SRT in the presence of its degradation products. LOD and LOQ reported by this method are comparable to the reported one in previous literatures. The most striking feature of the developed method is its simplicity, accuracy, and rapidity. The behavior of SRT under the hydrolytic stress conditions in acid, neutral, alkaline, and oxidative media was studied. The information presented herein could be very useful for quality monitoring of bulk substance as well as the pharmaceutical preparation. ACKNOWLEDGMENT One of the authors, Md. A. Rahman, is highly grateful to the University Grant Commission (UGC), Government of India, for providing financial assistance in the form of Maulana Azad National Fellowship (MANF).

Medications included a proton-pump inhibitor (tablet Pantoprazole

Medications included a proton-pump inhibitor (tablet Pantoprazole 40mg twice a day) and a prokinetic agent (tablet Levosulpiride 75mg twice a day) given for a period of three months. Patients who improved symptomatically were continued on medical management. Those patients whose symptoms did not improve with conservative management and patients who required escalating doses of medications for symptom relief were subjected to laparoscopic Toupet’s fundoplication. Pneumoperitoneum was created by closed technique via a supraumbilical port. Dissection was carried out at hiatus, and fundus of stomach was mobilised and passed through a window created behind the gastroesophageal junction (shoe-shine technique). A 270�� posterior wrap was performed. Fundus was sutured to oesophagus by interrupted stitches.

Crural stitches were placed in case the crura were far apart and the opening was too wide. Nasogastric tube was removed on postoperative day one and sips begun. Soft diet was begun on the evening of the first postoperative day and the patient was discharged the next day in case of an uneventful recovery. Medications (proton pump inhibitors and prokinetic drugs) were continued for one month postoperatively. All patients were followed up for a period of 9 months after diagnosis (6 months after surgery for operated patients). Outcomes after treatment were evaluated by both subjective and objective criteria. Improvement in symptoms (assessed by visual analogue scale) at 3 and 9 months after diagnosis. Improvement in quality of life (assessed by SF-36 questionnaire) at 3 and 9 months after diagnosis.

A score was obtained for eight specific areas of functional health status��physical functioning, role limitation due to physical health, role limitation due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health [2]. Changes in endoscopy findings at 9 months from diagnosis (6 months after surgery). Changes in manometry findings at 6 months after surgery. Patients managed surgically were also evaluated for complications: intraoperative bleeding requiring blood transfusion, diaphragmatic injury, pleural breach, splenic injury, esophageal perforation, gastric perforation, postoperative dysphagia, and wound infection. Results were analyzed using Student’s t-test, chi-square test, and Wilcoxon sign rank test. 3.

Batimastat Results and Discussion Fifty patients diagnosed to have gastroesophageal reflux disease (confirmed by endoscopy and esophageal manometry) were included in the study. 20 patients showed symptomatic improvement after three months and were thus managed conservatively, while 30 patients did not show any improvement in symptoms and were eventually operated. 88% of cases were in the age group of 20�C40 years while 12% cases were in the age group of 41�C50 years. Mean age of patients was 32.20 years.

A total of 80 additional reactions were necessary to close gaps,

A total of 80 additional reactions were necessary to close gaps, to improve the genome sequence quality and to ensure correct assembly and to resolve any remaining base-conflicts. Assembly validation was Sunitinib c-Kit confirmed by pulsed-field gel electrophoresis (Figure 3) [2]. Figure 3 Pulsed field gel electrophoresis of Methanobrevibacter sp. AbM4 genomic DNA digested with restriction endonucleases (A) and in silico restriction enzyme maps (B). Panel A: Lane 1, undigested genomic DNA; Lane 2, digested with ApaI; Lane 3, digested with … Genome annotation A GAMOLA/ARTEMIS [31,32] software suite was used to manage genome annotation. Protein-encoding open reading frames (ORFs) were identified using the ORF-prediction program Glimmer [33] and BLASTX [34,35].

A manual inspection was performed to verify or, if necessary, redefine the start and stop codons of each ORF. Assignment of protein function to ORFs was performed manually using results from the following sources; BLASTP [34] to both a non-redundant protein database provided by the National Centre for Biotechnology Information (NCBI) [36] and clusters of orthologous groups (COG) database [37]. HMMER [38] was used to identify protein motifs to both the PFAM [39] and TIGRFAM [40] libraries. TMHMM [41,42] was used to predict transmembrane sequences, and SignalP, version 4.1 [43] was used for the prediction of signal peptides. Ribosomal RNA genes were detected on the basis of BLASTN searches to a custom GAMOLA ribosomal database. Transfer RNA genes were identified using tRNAscan-SE [44].

Miscellaneous-coding RNAs were identified using the Rfam database [45] utilizing the INFERNAL software package [46]. The AbM4 genome sequence was prepared for NCBI submission using Sequin [47]. The adenine residue of the start codon of the Cdc6-1 replication initiation protein (Abm4_0001) gene was chosen as the first base for the AbM4 genome. The nucleotide sequence of the Methanobrevibacter sp. AbM4 chromosome has been deposited in Genbank under accession number “type”:”entrez-nucleotide”,”attrs”:”text”:”CP004050″,”term_id”:”509083678″,”term_text”:”CP004050″CP004050. Genome properties The genome of Methanobrevibacter sp. AbM4 consists of a single 1,998,189 bp circular chromosome Carfilzomib with an average G+C content of 29%. A total of 1,730 genes were predicted, 1,671 of which were protein-coding genes. A putative function was assigned to 1,258 of the protein-coding genes, while the remaining protein coding genes were annotated as hypothetical proteins. The properties and statistics of the genome are summarized in Tables 3 and and4,4, and are compared with genomes of other sequenced gut methanogens for the order Methanobacteriales in Table 5.

This can be especially helpful during head and neck surgery and p

This can be especially helpful during head and neck surgery and pediatric surgery, because of the small size of the surgical field and the inability to maneuver the instruments and the camera within it. It can also help in distinguishing tissue types in oncological dissection [15]. 4.2. Elimination of Physiologic Tremors and Scale Motion sellckchem The surgical system eliminates the surgeon’s tremor through hardware and software filters. In addition, movements can be scaled, whereby large hand movements can be translated into micromovements inside the operative field, allowing the surgeon more precision [1]. 4.3. Multiarticulated Instruments EndoWrist instruments have 7 degrees of freedom, which improves dexterity, allowing maneuverability that approaches that of open surgery. 4.4.

Fatigue Reduction During the robotic portion of the surgery the surgeon is sitting with his/her forearms resting comfortably on a pad and the head resting against the console, therefore improving ergonomics. This results in reduced body fatigue. With the surgeon sitting at a remote workstation, it eliminates the need to physically twist and turn in awkward positions to move instruments within the operative field while simultaneously visualizing a monitor. In addition, hand muscle fatigue is reduced, which when considered together with improved visualization, makes tasks such as suturing substantially easier. Studies suggest (Berguer and Smith [16]) that robotic surgery is less stressful for the surgeon. 4.5.

Restore Proper Hand-Eye Coordination The robotic system eliminates the ��fulcrum effect�� [17] of endoscopic surgery and makes instrument and camera manipulation more intuitive, emulating another property of open surgery. 4.6. Telesurgery Since the inception of robotic surgery, the wish to overcome geographical constraints and the availability of specialists was an important goal. Marescaux and collaborators [18] described the feasibility and safety of a robot-assisted laparoscopic cholecystectomy at distance using high-speed connection between the surgical unit at Strasbourg, France, and the surgical console in New York. Telesurgery allows for these barriers to be overcome as well as offering new teaching and tutoring possibilities. 4.7. Training The robotic system provides some interesting tools and opportunities for teaching.

An experienced surgeon can use another console next to the trainee, which can be activated to command the main arms or auxiliary arms. The Vinci Skills Simulator (Intuitive Surgical Inc.) can be attached to the console, allowing a virtual training environment to be creating while maintaining the same robotic interface Batimastat [19]. However, there are currently no standardized residency curriculums that formally support the teaching of robotic surgical skills [20]. 5. Disadvantages of Robot-Assisted Surgery 5.1.

The TBS-soluble fraction was aliquoted, frozen

The TBS-soluble fraction was aliquoted, frozen selleck chem Regorafenib in liquid nitrogen and stored at ?80��C. The pellets were resuspended in 15 volumes of TBSX and kept on ice for 30 min, followed by a second centrifugation at 100,000��g for 1 h at 4��C. The TBSX soluble fraction was aliquoted, frozen and stored as for the TBS fraction. The TBSX-insoluble pellet was resuspended in 2 mL of 70% FA and centrifuged at 100,000��g at 4��C for 1 h. The FA extracts were neutralized by the addition of 20 volumes of 1 M Tris pH 11, aliquoted and stored at ?80��C. Total protein content in TBS- and TBSX-extracts was determined via BCA assay. Total protein in FA-extracts was determined by Bradford Protein Microassay (Bio-Rad, CA, USA). A�� Measurements The levels of intracellular A��1�C40 and A��1�C42 were quantified by using a sandwich ELISA as previously described by Durairajan et al.

[15],[24], with minor modification. Equal amounts of cell or brain lysates were used for A�� quantification by sandwich ELISA. The monoclonal antibody 6E10 was used as the capture antibody by adding to ELISA plates (0.2 ��g diluted in 0.1 M Na2CO3 (pH 9.6) per well) and incubated overnight at 4��C. The plates were washed with PBS (0.05% Tween 20) and blocked with 4% BlockAce (Serotec, Raleigh, NC, USA) for 2 h at room temperature. Equilibrated protein lysates from each treatment (a 100 ��L volume was adjusted in all treatment groups by using PBS) were applied in duplicate and incubated at room temperature for 2 h with constant rotation at 30 rpm.

Biotinylated monoclonal anti-A��40 5C3 (50 ng per well) and biotinylated monoclonal 8G7 (50 ng per well) antibodies were used for detection of A��1�C40 and A��1�C42, respectively, and were diluted in 1% BlockAce and incubated for 2 h at room temperature. Plates were thoroughly washed with PBS (0.05% Tween 20), and streptavidin conjugated HRP was added for 1 h at room temperature. Finally the plates were washed four times with PBST before adding the substrate TMB for 30 min. Absorbance at 450 nm was measured in duplicate wells after addition of 2 M H2SO4. All ELISA experimental data were from three different days. Synthetic A��40 and A��42 peptides were used for construction of calibration curves, and A�� was measured in lysates. SDS-PAGE and Western Blot Analysis For Western blot analysis from cell culture or mouse brain, 10�C30 ��g total protein was separated on 10% and 15% SDS�CPAGE gels and blotted onto PVDF membranes for the detection of full length APP (Fl-APP), CTFs, sAPP��, sAPP��-sw, ��-actin and phosphorylated APP (pAPPThr668). After blocking with 5% skim milk, the blots were incubated with primary antibodies overnight at 4��C with shaking. Blots were washed AV-951 and incubated with HRP-conjugated secondary antibodies.

46,47 Natural antibodies of the IgM isotype are predominantly pre

46,47 Natural antibodies of the IgM isotype are predominantly present in healthy individuals. Natural IgM has multiple roles in the immune system. They are key to the homeostasis of the immune system, particularly relating to B lymphocytes and autoimmunity. All the tumor-specific antibodies belong nearly exclusively to the IgM class. It makes sense Rapamycin AY-22989 that anti-tumor immunity seems to be a part of natural immunity, and immune memory is not needed and therefore not induced. The detection of natural IgM antibodies against tumor-specific antigens of angiogenesis, such as ANG in osteosarcoma, has raised the possibility of an auto-immune aspect to this disease.43,48,49 Investigators in the European Organization for Research and Treatment of Cancer have been studying marker�CIgM immune complexes, which play a role in diagnosis and prognosis in cancer.

We have recently discovered the occurrence of cancer markers associated with IgM in liver and colorectal cancer, and we have demonstrated that marker�CIgM immune complexes are a novel class of tumor markers with a greater diagnostic potential compared to the corresponding free biomarker (Fig. 3). When detected as IgM complexes, both alpha-fetoprotein (AFP; the conventional serological marker for the detection of hepatocellular carcinoma (HCC)) and squamous cell carcinoma antigen (SCCA; a novel HCC biomarker),50 improved our diagnosis of liver cancer.50�C52 Further evidence of the diagnostic relevance of IgM immune complexes in cancer was also provided by carcinoembryonic antigen (CEA), which is the serological gold standard for the diagnosis of colorectal cancer (CRC).

53 The assessment of CEA�CIgM levels in CRC patients allowed the identification of a much higher number of patients compared to free CEA, and co-determination of both biomarkers increased sensitivity without compromising assay specificity.53 Figure 3. Schematic illustration of the immune response to cancer and development of IgM immune complexes in the bloodstream. To our knowledge, no investigations have been reported on the occurrence of ANG�CIgM immune complexes in the serum of patients with osteosarcoma. It has been established that natural IgM antibodies are useful serological markers in the diagnosis of systemic autoimmune diseases54,55,66 and that their diagnostic value is related to their immunologic specificity.

Since natural IgM antibodies are prevalent in human sera and are part of the normal immune response,26,56 one important problem that is inherent to IgM-based methods for identifying tumor-related antigens is demonstrating their tumor relevance.27 Natural IgM antibodies to angiogenic proteins encoded by oncogenes Brefeldin_A and tumor suppressor have been thought to represent prime candidates for biomarkers for early diagnosis of osteosarcoma.

Furthermore, the results suggest that influences on this associat

Furthermore, the results suggest that influences on this association may vary across different depression symptom dimensions. Thus, it may be fruitful for future research to parse depressive symptoms into component subdimensions to avoid failing to model important phenotypic heterogeneity in Gemcitabine HCl depression that may differentially impact smoking behavior. Funding This research was supported by grant K08DA02504 from the National Institute on Drug Abuse and the Transdisciplinary Tobacco Use Research Center (grant 1 P50CA84735-01) from the National Cancer Institute, National Institute on Drug Abuse, and National Institute on Alcohol Abuse and Alcoholism. Declaration of Interests None declared.
Smoking remains a major source of morbidity and mortality in the United States and worldwide (Mokdad, Marks, Stroup, & Gerberding, 2004; World Health Organization, 2008).

One major determinant of tobacco consumption is the cost of cigarettes. For example, at the population level, health economic studies have revealed that cigarette taxation substantially influences consumption (e.g., Levy, Chaloupka, & Gitchell, 2004), and at the level of the individual smoker, behavioral economic studies have similarly revealed that the costs of cigarettes substantially affect consumption (e.g., Johnson & Bickel, 2006). Within behavioral economics, individual demand curve analysis is one methodology to quantify the relative value of commodities, including cigarettes. This refers to examining the relationship between a person��s consumption of a commodity and its cost.

As prices increase, demand typically decreases at a relatively low rate initially but then becomes more precipitous at higher prices, finally terminating altogether. Importantly, several indices of motivation can be generated from demand curves (Hursh & Silberberg, 2008; Murphy & MacKillop, 2006). For example, the start and the finish of the demand curve are referred to as intensity and breakpoint. Intensity is defined as consumption at zero or minimal cost, whereas breakpoint is defined as the first price that fully suppresses consumption to zero. In addition, a demand curve can be used to generate a measure of expenditure, termed Omax (i.e., maximum expenditure across prices), and a measure of overall price sensitivity, termed elasticity (i.e., the proportional slope of the demand curve or, more simply, how responsive the individual is to increases in price).

Together, these indices provide a multidimensional assessment of an individual��s relative value of cigarettes. A recent approach for conducting demand curve analysis is the use of a cigarette Brefeldin_A purchase task (CPT), which assesses individuals�� estimated consumption of cigarettes at varying levels of price. This typically starts at zero or very low prices and escalates to very high prices.

In the United Kingdom’s National Health

In the United Kingdom’s National Health somehow Service, interferon-�� and ribavirin treatment for chronic hepatitis C is only recommended for patients who show significant histological fibrosis or necroinflammation (National Institute for Clinical Excellence 2000). Interobserver variation in Knodell scoring has been shown to be only fair to moderate (Gr?nb?k et al. 2002); immunohistochemistry for activated caspase-3 could therefore provide a more reproducible method of measuring disease activity, making such treatment decisions more robust and the monitoring of treatment effects more accurate. Acknowledgments We thank Angela Gillies and Linda Potter for technical assistance and Dr Angus McGregor for helpful comments on the manuscript.

The hepatic parenchyma is composed of epithelial (hepatocytes) and endothelial cells, macrophages and perisinusoidal, mesenchymal cells called stellate cells (fat-storing cells), which are considered to be the major cell type responsible for fibrosis (Burt 1999). In a normal liver, these components are organized within the hepatic acini, where hepatocytes are separated from sinusoidal endothelium by the space of Disse. This space contains low amounts of extracellular matrix (ECM) components that maintain all the cell types of the liver under a functional state. However, once the liver becomes fibrotic, the ECM undergoes important quantitative and qualitative changes in its composition. The total content of collagens increases many fold, and the ECM becomes much more dense with fibril-forming collagens (Gressner 1998; Burt 1999).

Liver fibrosis is a defence mechanism of adult liver in response to injury that results in the encapsulation of the damaged tissue and stabilization of the remaining structure. Hepatic fibrogenesis represents the first step in how wound healing reverses tissue damage and can be induced by several conditions including viral hepatitis, alcohol abuse, metabolic disorders, auto immune hepatic disease or genetically inherited abnormalities (Friedman 2000). The development of fibrosis usually takes months and often will only develop when a significant amount of damaged tissue accumulates. Once fibrosis is established, the hepatic tissue can either revert to its previous status, or evolve to liver cirrhosis, which is the final, irreversible, consequence of chronic fibrosis.

Thus, comprehension of the molecular mechanisms underlying hepatic fibrosis is a major objective in finding therapies that could prevent or modulate its development. Transforming growth factor-�� (TGF-��) is a major profibrogenic molecule (Sanderson et al. 1995; Kanzler et al. 1999; Bauer & Schuppan 2001). TGF-�� overexpression induces fibrosis, and treatment with Drug_discovery TGF-��-specific antibodies reverts the fibrotic lesion (George et al. 1999; Qi et al. 1999).