Podcasts about timps

BUFFALO, NY - March 3, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 28, 2025, titled “Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells." Elham Taheri and Maryam Raeeszadeh-Sarmazdeh from the University of Nevada, Reno, explored a new approach to slowing the spread of glioblastoma multiforme (GBM), the most aggressive and deadly form of brain cancer. Their study highlights the potential of both natural and engineered molecules to block cancer cell movement, offering a promising strategy to combat this challenging disease. Glioblastoma multiforme is difficult to treat because it quickly spreads into healthy brain tissue, making complete surgical removal nearly impossible. A major driver of this invasive behavior is a group of enzymes called matrix metalloproteinases (MMPs), which break down surrounding tissue and create space for cancer cells to spread. Among them, MMP-9 plays a particularly significant role in GBM progression and resistance to current treatments. To address this challenge, the researchers investigated tissue inhibitors of metalloproteinases (TIMPs), natural MMP blockers, and specially engineered versions designed for better effectiveness. The study used cell line models of GBM to test both TIMP-1 and TIMP-3 and their engineered counterparts (mTC1 and mTC3), specific blockers of MMP-9. “Our study focused on minimal TIMP variants, due to their small molecular size and potential in higher cellular uptake and delivery, to assess their potential in cell-based assays.” The results indicated that the engineered TIMPs were just as effective as, or even better than, the natural ones at reducing cancer cell migration and invasion. These findings are particularly promising because previous attempts to block MMPs with small-molecule drugs faced challenges such as poor selectivity and unwanted side effects. In contrast, these engineered TIMPs offer a more targeted and potentially safer approach. One of the greatest obstacles in treating brain cancer is delivering drugs across the blood-brain barrier, a protective layer that prevents many therapeutic compounds from reaching the brain. To address this, the researchers used cell-penetrating peptides to help the TIMP variants reach and enter cancer cells more effectively. Their results confirmed that the engineered TIMPs successfully reached tumor cells, further increasing their potential as a treatment. Additionally, the study found that these engineered TIMPs did not significantly affect healthy cells at lower doses, suggesting they could be used safely. This makes them strong candidates for further drug development. These findings could lead to new treatment options for GBM, a cancer with very few effective therapies. Future research will focus on testing these TIMP variants in animal models to evaluate their long-term effects and safety. Researchers also plan to investigate whether combining these engineered TIMPs with existing treatments, such as chemotherapy or immunotherapy, could improve outcomes. In summary, given the aggressive nature of GBM and the urgent need for better therapies, this study represents an important step forward. If further research confirms these results, engineered TIMPs could become a valuable tool in the fight against brain cancer, offering new hope for improved treatments and patient survival. DOI - https://doi.org/10.18632/oncotarget.28691 Correspondence to - Maryam Raeeszadeh-Sarmazdeh - maryamr@unr.edu Video short - https://www.youtube.com/watch?v=tdBlkOX50D8 To learn more about Oncotarget, please visit https://www.oncotarget.com. MEDIA@IMPACTJOURNALS.COM

Episode 78: Infantile Hemangioma. Dr Shelat discusses with Dr Schlaerth and Dr Arreaza the definition, pathophysiology, diagnosis and treatment of infantile hemangioma.___________________________Infantile Hemangioma. By Tejal Shelat, MD (Lady Hardinge Medical College). Discussed with Katherine Schlaerth, MD; and Hector Arreaza, MD.   This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. What is infantile hemangioma?Infantile hemangioma is vascular overgrowth that leads to tangled blood vessels that appear as a reddish plaque on the skin as early as days to weeks after birth.  It is the most common benign vascular tumor in infants, with a prevalence of 4-5% in mature neonates and is about 2.5 times more common in female (ratio female:male is 3:1) and Caucasian children.  Risk factors: There are several risk factors, including prematurity, low birth weight less than 1000g, family history of infantile hemangioma, placental anomalies, and eclampsia. Progression of infantile hemangioma. Hemangiomas typically undergo three phases:First is the proliferation phase that occurs between 0 to 6 months of age, with about 80% growing to their final size by age 3 months. During this time there is growth of a bright red, soft, raised, non-blanching plaque that is visible on the skin. This occurs to due proliferation of rapidly dividing endothelial cells in the blood vessels.This is followed by a plateau phase.Next is the involution phase, that occurs after 6 months of age. The lesion/s now turn deep red or violet and spontaneously begin to regress in size. Pathogenesis. Several hypotheses have been described to explain the reason behind the occurrence of hemangiomas. We now know that they occur due to dysregulation in angiogenesis and vasculogenesis.  The most likely trigger is thought to be hypoxia, which induces transcription of the Vascular Endothelial Growth Factor (VEGF) gene, leading to overexpression of angiogenic factors such as VEGF. This leads to differentiation of endothelial cells, influx of other cells such as mast cells, myeloid cells and also tissue inhibitors of metalloproteinases (TIMPs). Regression.  The mast cells produce interferon and transforming growth factor, which, along with the TIMPs that we just talked about all work together to halt the proliferation of endothelial cells. The endothelial cells then become senescent and that leads to passive involution of the hemangioma. Diagnosis. The diagnosis of infantile hemangiomas is clinical. If you are not familiar with how a hemangioma looks, search in your favorite dermatology atlas.  A hemangioma may be red if it involves the papillary dermis (called superficial strawberry hemangiomas), but they can also be purple, blue, or colorless if they involve the reticular dermis or subcutaneous fat (called deep, cavernous hemangiomas). Early white discoloration of infantile hemangioma may be an early sign of imminent ulceration. Additional workup.  Further investigation is also required in specific situations: If there are 5 or more cutaneous lesions, we would need a liver ultrasound to rule out involvement of the liverFor facial or segmental involvement, echocardiogram and MRI of the head are recommended to rule out posterior fossa malformations, hemangioma (usually localized on the face), arterial anomalies, cardiovascular anomalies, eye anomalies, sternal clefting and/or supraumbilical raphe  PHACE Syndrome: posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. By definition, PHACE is diagnosed when there is at least one hemangioma >5 cm on head/scalp PLUS one major or two minor criteria OR hemangioma of any size on neck, upper trunk and proximal upper extremity plus two major criteria.Major criteria include arterial anomalies such as anomaly of major cerebral or cervical arteries, retinal vascular anomalies, sternal defect. Minor criteria include cerebral artery aneurysm, ventricular septal defect, etc. Laryngoscopy should be done if there is cervicofacial involvement, i.e., beard distribution Spinal ultrasound should be performed if the hemangioma is in the lumbosacral region Management-Most hemangiomas will not require treatment, and most need observation only. -When treatment is needed, treatment is usually medical depending on severity, location, and extension of hemangioma/s, you may decide to go with topical or systemic therapy.-Topical therapies include beta blockers (propranolol 1% applied TID for 1 year), corticosteroids, and imiquimod, but data on efficacy is limited.-Systemic therapies: Beta blocker therapy (with propranolol by mouth) is indicated when there is concern for ulceration or scarring in large, facial, segmental and or rapidly growing hemangiomas, for visual impairment in periorbital involvement, high output heart failure in hepatic involvement and airway obstruction in subglottic involvement. The dose of propranolol is 1mg/kg to 3mg/kg in the form of an oral solution, depending on the response to therapy and weight of the child. Initiation of therapy may require hospital admission to watch for side effects to beta blockers.-Second-line treatments include systemic corticosteroids-Surgical intervention is rarely needed, and it´s usually avoided because surgical scars may be worse than the resulting lesion after spontaneous regression.  Prognosis. The prognosis is very good for most uncomplicated hemangiomas, with about 50% undergoing complete involution by age 5 years and about 90% by age 9 years. Permanent cutaneous residua are seen for hemangiomas that involute slowly, after 6 years of age and hemangiomas involving the eyelid, nasal tip, ear and lip. Functional impairment or obstruction may occur when the hemangioma is located near natural orifices and/or in the head and neck area. In these cases, surgical intervention may be needed. Conclusion. You may find hemangiomas during routine physical exam of a newborn. It is important to remember the natural progression of uncomplicated hemangiomas. Make sure to educate parents about concerning features and how to determine if treatment is needed. In most cases, when treatment is needed, a dermatology evaluation is needed. ___________________________ [Music to end: JERUSALEMA]Now we conclude our episode number 78 “Infantile Hemangioma.” We learned about the natural progression of most hemangiomas. They grow for up to 3 years, then remain unchanged until around 6 years of age when they gradually regress without treatment. In most cases, monitoring is all what's needed. However, it's important to identify the hemangiomas with concerning features that require additional work up or early treatment. Treatment is mainly medical. Surgery is rarely recommended or required. Even without trying, every night you go to bed being a little wiser.Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Tejal Shelat. Audio edition: Suraj Amrutia. See you next week! _____________________References:Léauté-Labrèze, C., Harper, J. I., & Hoeger, P. H. (2017). Infantile haemangioma. The Lancet, 390(10089), 85-94.Kowalska, M., Dębek, W., & Matuszczak, E. (2021). Infantile Hemangiomas: An Update on Pathogenesis and Treatment. Journal of clinical medicine, 10(20), 4631.Metry D.W. Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications. UpToDate. Accessed December 5, 2021. https://www.uptodate.com/contents/infantile-hemangiomas-epidemiology-pathogenesis-clinical-features-and-complications#H22.Antaya R.J. Infantile Hemangioma. Medscape. Accessed December 5, 2021. https://emedicine.medscape.com/article/1083849-overview#a1.

Good morning lacrosse fans. Thank you for taking time out of your day for the Utah Lax Report. Don't forget to forward to a friend, it's the best way for the newsletter to grow. I originally had written this entire newsletter and was going to include this tweet at the bottom, but it belongs at the top. It belongs at the top because of the message Paul Carcaterra portrays about his friend, Rob Kavovit. It belongs at the top because as you listen to what Carc says, I'm sure someone will come to mind that has changed your life. It belongs at the top because I've been fortunate enough to have people change my life and most of them are in the lacrosse community. Kavovit was a Syracuse lacrosse legend and so much more. If you take away one thing from this newsletter, please let it be this: Interview with Walker BatemanOne of those people in my life who changed my life for the better is Walker Bateman. I don't want to spoil the podcast, but in essence, Walker came to my group of friends in Jan/Feb of 2000 in the halls of Highland High School and asked one of them, Paul Jones, if he was playing lacrosse this Spring. Paul said yes, and Walker asked Mark Hepworth if he was playing. Mark said he was and then Mark turned to me and told me I should play and that I would be good at defense. Well, that moment led to today. It led to you reading this newsletter and listening to this podcast. I'll never forget watching Walker win five consecutive face-offs and score five consecutive goals within about 50 seconds. Walker coaching at Highland in 2011Walker (left) in Japan with the USA West team with Justin Bokmeyer who played at Army. You can listen to the latest podcast above or on Apple Podcasts or Spotify. Don't forget to subscribe and leave a rating!While you're out and about at games, stop by Vessel Kitchen. You won't be disappointed. It's owned and operated by lacrosse players/coaches/fans and fuels the Utah Lax Report.Week 2 Coaches PollsNo.1 Corner Canyon continues to dominate on the field with a 20-6 win over Green Canyon on Wednesday followed by a 13-2 win over No. 5 (then No. 3) Mountain Ridge on Friday. This week will be the last non-region games for the Chargers as they take on No. 2 Park City on Tuesday and No. 8 Brighton on Friday. Their closest margin of victory is currently 11 goals which is an incredible feat. Highlights from the Corner Canyon v. Mountain Ridge game below: No. 2 Park City hosts No. 1 Corner Canyon on Tuesday then heads to American Fork for a showdown against No. 10 American Fork. No. 3 Farmington moved up in the polls after beating No. 8 (then No. 3) Brighton on Monday, 10-8. Farmington then bested Skyline, 17-7 on Friday. Adding Davis Roche to the mix after an injury last year will help the Farmington offense. The Phoenix open region play against Box Elder and Viewmont this week. No. 4 Olympus bested Herriman, 22-4, on Tuesday then beat Westlake, 15-2, on Thursday. The Titan defense has allowed just 13 goals in 3 games. Olympus will travel to Skyridge on Tuesday then Sky View on Thursday. Mountain Ridge Defenseman Jacob WalshNo. 5 Mountain Ridge bested Timpview on Monday, 13-11, shutout Orem on Thursday, 21-0, then lost to Corner Canyon, 13-2, on Friday. I was really impressed with the Sentinels from the sidelines on Friday and suspect they could run the table until the last game of the season against No. 2 Park City on May 8th. No. 6 Lone Peak beat Brighton on Tuesday, 16-15, in overtime. Midfielder Garrett Haas had 13 goals including the game-winner in OT. Let that sink in for a minute. Ready for the next crazy stat? He only took 18 shots. 13 goals on 18 shots. Wow. I dug through the utahlax.org archives back to 2011 and found the closest effort was in 2018 when Box Elder attackman Jack Earley had 11 goals (and 4 assists) against Syracuse. There were plenty of games where point totals eclipsed 10 but Earley is the only one I could find with double digit goals. It's not like Lone Peak ran the score up, they literally needed overtime to win. If anyone has records from before 2011 let me know. I suspect it's a state record, and if not, certainly in the top 5. The Knights then beat Sky View on Friday, 17-0. Lone Peak will host Salem Hills on Tuesday.No. 7 Davis beat Roy, 16-5, on Tuesday then beat Northridge, 12-7, on Thursday. The Darts sit at 3-0 and travel to Fremont (also 3-0) on Tuesday for a key Region 1 showdown with the winner taking the top spot in-region. The Darts will host Clearfield on Thursday. No. 8 Brighton - It was a wild opening to the season for the Bengals when they played its first game on Friday, 3/12, a 8-7 win over Alta, then traveled to Farmington on Monday, losing 10-8, then on Tuesday went to Lone Peak and lost in OT, 16-15. The Bengals host Cedar Valley on Tuesday then gear up to host No. 1 Corner Canyon on Friday. The Bengals have one of the toughest (if not the toughest) schedules. As it sits today, the Bengals play No. 1 Corner Canyon (3/26), No. 2 Park City (4/27), No. 3 Farmington (L, 10-8), No. 4 Olympus (5/7, region game), No. 5 Mountain Ridge (4/23), No. 6 Lone Peak (L, 16-15 OT) and No. 9 Timpview (4/2). For the record, Region 6 only playing in-region teams once in a season allows them to do this, for better or worse. No. 9 Timpview had a great week which propelled it into the polls. On Monday, a 13-11 loss to No. 5 (then No. 3) Mountain Ridge was followed by a 21-6 win over Lehi on Thursday then a 12-10 win over American Fork on Friday. The T-Birds will host Alta on Tuesday and Timpanogos on Thursday. No. 10 American Fork beat Cedar Valley, 16-2, on Monday, then lost to Timpview, 12-10, on Friday. The Cavemen will head to East today in what should be a great matchup. American Fork then hosts No. 2 Park City on Friday. Boys ScheduleMondaySky View hosts Mountain Crest in a great Cache Valley/Region 11 matchup. Jonathan Higginbotham leads the charge for the Bobcats with 6 goals so far this season. TuesdayI'll be keeping my eye on No. 1 Corner Canyon at No. 2 Park City. The game will be streamed here. The other game to watch will be No. 7 Davis at Fremont in a battle of unbeaten teams for the top spot in Region 1. WednesdayBountiful hosts Viewmont at 5 p.m. Looks for the Braves to finally get in the win column after losses to No. 4 Olympus (15-7), Skyline (15-9) and No. 2 Park City (18-12). ThursdayCopper Hills travels to West Jordan for a rivalry game while the ‘Timps' take on each other at 7 p.m. (No. 9 Timpview @ Timpanogos)FridayI'm really intrigued by the Waterford @ Wasatch matchup at 7 p.m.No. 1 Park City beat then No. 4 Corner Canyon, 14-1, on Wednesday then beat Highland, 20-1, on Thursday. The Miners host No. 3 Herriman today then take on Springville on Wednesday. No. 2 Brighton beat then No. 4 Corner Canyon Friday, 16-6. (Deseret News recap) The Bengals will host Cedar Valley on Tuesday then travel to Juan Diego on Thursday. No. 3 Herriman lost to Skyridge on Wednesday, 14-10, then beat Jordan on Friday, 16-5. The Mustangs travel to No. 1 Park City today then host Copper Hills on Tuesday then face Bingham on Thursday. No. 4 Alta reeled off two great wins this week with a 22-1 win over Mountain View on Tuesday then a 13-9 win over American Fork on Thursday. The Hawks will host Timpview on Tuesday then face Mountain Ridge on Thursday in a great Region 7 matchup. Senior Eliza Johnson is second in total goals in the state with 21. No. 5 Lone Peak didn't play this week and moved up one spot in the polls. The Knights will face Wasatch on Wednesday and Highland on Thursday. No. 6 Waterford beat Provo, 20-2, on Friday and will take on No. 7 American Fork on Tuesday. The Ravens will travel to No. 9 Corner Canyon on Friday. No. 7 American Fork lost to then No. 3 Alta, 13-9, on Thursday. The Lady Cavemen will host No. 6 Waterford on Tuesday.No. 8 Skyridge beat then No. 6 Herriman, 14-10, on Wednesday. The Falcons will head to Westlake on Tuesday. Sophomore Haven Buechner leads the team with 14 goals and 3 assists. No. 9 Corner Canyon had a rough go last week with a 14-1 loss to No. 1 Park City and a 16-6 loss to No. 2 Brighton. The Chargers will look to rebound with two home games against Provo on Tuesday and No. 6 Waterford on Friday. No. 10 West Jordan took down fellow 6A schools West and Bingham, 28-1 and 19-7 respectively. The Jaguars will travel to Riverton on Tuesday and Copper Hills on Thursday. Skyline v. ViewmontGirls ScheduleMondayMountain Ridge @ Timpanogos should be a great region matchup. The Sentinels are averaging 19.7 goals per game and are 3-0. TuesdayLayton @ Syracuse will feature two 3-0 teams who are very similar on paper. Syracuse has a slight edge in goals per game at 14.3 but Layton has only allowed 12 goals in three games. WednesdayRidgeline @ Roy has the makings of an upset as Ridgeline enters 2-0 while Roy is 0-2. Both of the Riverhawks wins were by one goal: 11-10 over Box Elder and 12-11 over Judge. Roy lost to powerhouse Davis, 19-5, and Weber, 8-7. ThursdayLike the boys, the ‘Timps' (Timpview/Timpanogos) will face each other at 5 p.m. FridayNo. 6 Waterford @ No. 9 Corner Canyon is a great way to finish the week. Waterford Senior Jaimeson Meyer enters the week with 17 goals in two games and is certainly a candidate for the Player of the Year.CollegeMensWestminster hosted BYU on Saturday in a scrimmage and won 10-7. The Griffins will travel to Ohio on Friday for a showdown against Lake Erie College and No. 3 Mercyhurst on Saturday. BYU will host Dominican on Saturday in Provo. The game begins at 1 p.m. Dominican will stick around over the weekend and take on UVU on Monday at Noon. Utah State hosted Montana in a double-header and lost both games, 11-9 on Friday and 20-8 on Saturday. Utah will take on Mercer at 9 a.m on Saturday in Macon, Georgia. WomensWestminster will travel to Grand Junction, Colorado for an RMAC showdown with Colorado Mesa on Saturday. BYU will host Utah State on Saturday with an opening draw at 4 p.m.Utah State beat UVU, 14-4, on Saturday. The Wolverines will host Weber State on Saturday at Noon. Utah Lacrosse HistoryI posted these pics on Instagram and Twitter and they were well liked! These were sent to me by Matt Moffit, who played at Utah on the 1972-1974 teams. If you have old photos, send them my way! Utah v. BYU in Rice StadiumBe sure to follow us on Instagram, Facebook and Twitter. I try to posts scores on Instagram every night and Twitter is automated through a connection with MaxPreps so please enter your scores there as quickly as possible! Also, please enter your stats so I can write about your players.That's it for this week. — Tim Haslam This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit www.utahlaxreport.com

What are the future markets for growth Is it still the BRIC's (Brazil, Russia, India, China and South Africa) or the future belong to (A)TIMP's, Turkey, Indonesia, Mexico and the Philippines, or (B)MINT Mexico, Indonesia, Nigeria, Turkey, or (C)N11 Bangladesh, Egypt, Indonesia, Iran, Mexico, Nigeria, Pakistan, the Philippines, Turkey, South Korea, and Vietnam or (D)the Frontier Markets Whichever of these acronyms are the future growth markets, it is evident that centre of economic gravity is definitely shifting towards East.

A very special HALLOWEEN episode of RAREFIED AIR! Hear vintage grooves to help get you in the Halloween spirit. All pieces featured here are library tracks originally written to be used in film and television productions during the 1960s, 70s, & 80s. For more details check out the complete show notes at www.rarefiedairpod.com   01. Hair Raiser, Keith Papworth; 00:22 (De Wolfe)   02. Perpetual Percussion, Sam Fonteyn; 04:23 (APM)   03. On the Graveside, Johnny Hawksworth; 06:11 (De Wolfe)   04. In a Panic Room, Ivan Kaslik; 08:06 (Megatrax)   05. Timps of Terror, Sam Fonteyn; 10:13 (APM)   06. Dirty Scream, Gert Wilden; 12:19 (Megatrax)   07. Suspense Musical Saw, Johnny Hawksworth; 12:54 (APM)   08. The Rat Race, Nick Ingman; 13:36 (APM)   09. Approaching Danger, Roger Roger; 17:18 (Firstcom)   10. Paper Chase, Eric Allen & Frank Reidy; 18:58 (De Wolfe)   11. Saturday Beat, Keith Papworth; 22:25 (De Wolfe)

Mesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity. METHODS AND FINDING: By modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-α and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-β1. TIMP-1-GPI stimulated rapid and efficient in vitro wound closure. The agent enhanced mesothelial cell proliferation and migration and was bioactive in the nanogram range. The application of TIMP-1-GPI may represent a new approach for limiting or repairing damaged mesothelium.

Metalloproteinases are secreted in response to a variety of inflammatory mediators and inhibited by tissue inhibitors of matrixmetalloproteinases (TIMPs). Two members of these families, MMP-9 and TIMP-1, were differentially expressed depending on clinical parameters in a previous genomewide mRNA analysis. The aim of this paper was now to evaluate the posttraumatic serum levels and the time course of both proteins depending on distinct clinical parameters. 60 multiple traumatized patients (ISS > 16) were included. Blood samples were drawn on admission and 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Serum levels were quantified by ELISA. MMP-9 levels significantly decreased in the early posttraumatic period (P < 0.05) whereas TIMP-1 levels significantly increased in all patients (P < 0.05). MMP-9 and TIMP-1 serum concentration kinetics became manifest in an inversely proportional balance. Furthermore, MMP-9 presented a stronger decrease in patients with severe trauma and non-survivors in contrast to minor traumatized patients (ISS

Die vorliegende Dissertation befasst sich mit den durch S-Lost-verursachten Symptomen in der Haut, die zunächst durch starke Blasenbildung und später durch eine verzögerte Wund-heilung charakterisiert sind. Bei S-Lost handelt es sich um einen chemischen Kampfstoff, der erstmals im ersten Weltkrieg zum Einsatz kam und bis heute in vielen internationalen Kon-flikten großen Schaden anrichtete, obwohl der Gebrauch schon 1925 durch die Genfer Konvention verboten wurde. Aktuell stellt S-Lost zudem eine Bedrohung durch terroristische Aktivitäten dar. Da für S-Lost-induzierte Verletzungen bislang keine spezifisch wirksamen Behandlungs-methoden verfügbar sind, besteht großes Interesse an der Aufklärung der dem Krankheitsbild zugrunde liegenden molekularen Pathomechanismen, um daraus Rückschlüsse auf besser ge-eignete therapeutische Maßnahmen ziehen zu können. In unseren ersten Experimenten wurden als mögliche Auslöser der Blasenbildung die Expression und Sekretion ausgewählter Matrix-Metalloproteinasen (MMPs) und deren endogenen Inhibitoren, den tissue inhibitors of matrix metalloproteinases (TIMPs) in einem 3D-Haut-modell und in verschiedenen Zelltypen der Haut (Keratinozyten, Fibroblasten, mikrovaskuläre Endothelzellen, mesenchymale Stammzellen, monozytäre Zellen, PMN-Granulozyten) sowohl in Mono- als auch in Mischkultur untersucht. Unter Verwendung von molekularbiologischen und proteinbiochemischen Methoden wie qRT-PCR, Zymographie und Western Blot gelang der Nachweis, dass MMPs - insbesondere MMP-9 - nach Exposition der Zellen (v.a. Fibroblasten und monozytäre Zellen) mit S-Lost deutlich hochreguliert wurden. Zu Erhärtung der Annahme, dass MMP-9 durch Degradation der Basalmembran zwischen Epidermis und Dermis zur Blasenbildung beiträgt, konnte als Pathomechanismus nun erstmals eine parakrine Stimulation von Fibroblasten durch S-Lost-behandelte Keratinozyten identifiziert werden, als deren Folge eine vermehrte MMP-9-Sekretion resultierte. Darüber hinaus zeigte sich in weiteren Versuchen unter Verwendung des sog. Scratch-Assays und eines Transwell-basierten Invasionsassays, dass das Migrations- und Invasionsverhalten der Fibroblasten in Gegenwart des konditionierten Mediums der S-Lost-behandelten Keratinozyten positiv beeinflusst wurde. Aus klinischer Sicht sprechen diese Erkenntnisse für neue therapeutische Ansätze, die darauf beruhen sollten, die S-Lost-induzierte, auf proteolytischer Aktivität basierende Blasenbildung der Haut durch Applikation spezifischer MMP-Inhibitoren zu behandeln. In einem weiteren Projekt wurde die verzögerte Wundheilung als spätes Symptom der S-Lost-Vergiftung auf zellulärer Ebene untersucht, bei der eine eingeschränkte Re-Epithelialisierung der betroffenen Hautstellen beobachtet wird. Sowohl für den Prozess der Wundheilung als auch für die stetige Erneuerung der Haut werden epidermale Stammzellen benötigt, die für die Bildung von Keratinozyten verantwortlich sind. Diese unipotenten Progenitorzellen befinden sich in der basalen Schicht der Epidermis und sind in der Lage zu proliferieren und anschließend terminal zu differenzieren. Um eine Beeinflussung dieser Prozesse durch S-Lost zu untersuchen, wurden primäre unreife Keratinozyten (NHEK) verwendet und hinsichtlich ihres Differenzierungspotenzials untersucht. Dabei erwies sich S-Lost als potenter Induktor der Differenzierung von NHEK, was durch Bestimmung der Expression typischer Markerproteine wie Keratin-1, Involucrin und Loricrin gezeigt wurde. Die Induktion des Reifungsprozesses war sowohl von einem Rückgang der Proliferation als auch von einer verminderten Migrationsrate der Zellen begleitet. Die eingehende Analyse von mitogen-activated protein kinase (MAPK)-Signaltransduktionswegen führte zu der Erkenntnis, dass die Aktivitäten von p38 und ERK1/2 gegenteilige Rollen im Differenzierungsprozess einnehmen. Studien mit spezifischen Inhibitoren der MAPK be¬legten, dass p38 für den Reifungsvorgang in NHEK essentiell ist, während ERK1/2 diesem entgegen wirkt. So konnte durch Blockade von p38 die von S-Lost ausgelöste Differenzierung der Zellen verhindert werden. Ebenso war es durch diese Behandlung möglich, die von S-Lost stark beeinträchtige Migrationsfähigkeit der Keratinozyten wiederherzustellen, welche mit einer erhöhten MMP-1-Expression einherging. Davon abgeleitet erscheint es therapeutisch sinnvoll, selektive p38-Inhibitoren für die Behandlung von Wundheilungsstörungen nach Exposition der Haut mit S-Lost einzusetzen. Zusammenfassend erbrachten unsere Studien also den Nachweis, dass der S-Lost-induzierten Blasenbildung (als frühes Symptom) die spezifische Induktion der MMP-9 zugrunde liegt. Darüber hinaus konnte erstmals eine verfrühte Differenzierung in unreifen Keratinozyten der Haut (als mögliche Ursache für die verzögerte Wundheilung) nachgewiesen werden, wobei die MAPK p38 bei der Initiierung des Prozesses von entscheidender Bedeutung ist. Aufgrund dieser Resultate empfiehlt sich eine kombinierte Applikation von Inhibitoren der Aktivitäten von MMP-9 und p38, wobei der Einsatz jedoch zeitlich abgestimmt erfolgen sollte, um pathologische Effekte (Blasenbildung bzw. Differenzierungsinduktion in Keratinozyten) zu blockieren, ohne die positiven Auswirkungen von MMP-9 und p38 auf die Heilung (Migration von Immunzellen und Keratinozyten bzw. Reepithelialisierung) zu hemmen.

1. Zound Delta (21:52) 2. Bells & Timps (5:30) 3. BuchBel (11:54) Zound Delta was made at a residency with the European Sound Delta Project in 2009. The sounds were recorded from the mouth of the Danube River at the Black Sea, - to about 200km upstream, at Russe Bulgaria. In Russe, there was a festival, and the finished piece was played. There were boats (Belgian barges outfitted as living boats) starting at the mouth of the Danube and the Rhine Rivers, with changing residents, for several months. Bells and Timps was made using church bells in Gent Belgium, recorded by Godfried Willem Raes of Logos Foundation, in 1986. I modified the time by stretching vastly, and some changes in pitch as well. BuchBel was recorded during an overnight train ride from Bucharest to Belgrade. All sounds are from the train, with many layerings. The train trip was immediately after the festival in Russe, Bulgaria, in 2009. All of the pieces were made in ProTools.

Purpose: Ileal carcinoids are gut epithelial tumors originating from serotonin-containing enterochromaffin (EC) cells. Therapeutic options for effectively inhibiting the growth and spread of metastatic carcinoids are still limited. We aimed to identify the role of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) during tumor development and metastasis. Patients and Methods: Tissue samples were obtained from surgically treated patients. Expression of the EC-cell marker, vesicular monoamine transporter-1 (VMAT-1), was used to verify ileal carcinoids. We investigated the differential expression of MMP-2, 7, 9, 11, and 13 and their endogenous inhibitors (TIMP-1, 2, and 3) by quantitative real-time RT-PCR in 25 primary tumors, their corresponding lymph node metastases and/or liver metastases and matched normal mucosa. Results: Significantly increased expression of VMAT-1, MMP-2, MMP-11, TIMP-1 and TIMP-3 was determined by quantitative RT-PCR in EC-cell carcinoids compared to normal intestinal mucosa (p < 0.05). In contrast, MMP-2 and MMP-9 as well as TIMP-1, TIMP-2, and TIMP-3 expression in primary tumors of patients with liver metastases (M1) was significantly lower than in patients lacking liver metastases (M0). EC-cell tumors were significantly larger in the M1 group of tumors, while VMAT-1 expression was significantly decreased. We found an inverse correlation between tumor size and prognosis. Univariate analysis further revealed that decreased expression of VMAT-1, MMP-2 and TIMP-3 in primary tumors was significantly associated with a reduced survival time of the patients. Conclusion: Our data reveal that MMP-2 and TIMP-3 expression together with VMAT-1 expression are of potential prognostic and clinical value in ileal carcinoids. Copyright (C) 2008 S. Karger AG, Basel

We monitored serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) before and during intravenously applied immunoglobulin (IVIG) therapy in 33 patients with chronic immune-mediated neuropathies and myopathies and 15 controls. Baseline MMP-2 and TIMP-2 serum levels were lower and MMP-9 and TIMP-1 serum levels higher in all patients compared to age-matched controls. Eight days after IVIG treatment, MMP-2, TIMP-2, and TIMP-1 serum levels increased, while MMP-9 serum levels decreased, indicating tissue repair. After 60 days, MMP-9 levels increased, MMP-2 approached normal levels, while TIMP-1 and TIMP-2 serum levels were below day 8 levels, indicating relapsing tissue damage. Comparing the MMP/TIMP results with the clinical courses, IVIG treatment tended to change MMP/TIMP levels in a way that paralleled clinical improvement and relapse. In sum, during a distinct time period, IVIG therapy seems to be able to modulate VIMP-mediated tissue repair. Copyright (c) 2006 S. Karger AG, Basel.