Crucell Terug naar discussie overzicht

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1. flosz 21 december 2009 13:10

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   Review
   Eleven years of Inflexal® V—a virosomal adjuvanted influenza vaccine
   
   Christian Herzog∗, Katharina Hartmann, Valérie Künzi, Oliver Kürsteiner, Robert Mischler,
   Hedvika Lazar1, Reinhard Glück
   Berna Biotech AG, Rehhagstrasse 79, 3018 Berne, Switzerland
   
   Contents
   1. Influenza viruses and epidemics
   2. Impact of influenza vaccination on health economics
   3. Virosomes as an adjuvant system
   4. Immunogenicity of Inflexal® V
   5. Safety of Inflexal® V
   6. Clinical experience with Inflexal® V
   6.1. Children
   6.2. Adults
   6.3. The elderly
   7. Conclusion
   Inflexal® V is the only virosomal adjuvanted influenza vaccine
   licensed for all age groups. During its 11 years on the market,
   Inflexal® V has shown an excellent tolerability profile due to its
   biocompatibility and purity. The vaccine contains no thiomersal or
   formaldehyde and very low levels of ovalbumin. It is completely
   biodegradable and highly efficacious by mimicking natural infection.
   Inflexal® V has a good immunogenicity in both healthy and
   immunocompromised elderly, adults and children.
   Acknowledgement
   References
   
   Volledig art. download.thelancet.com/flatcontentass...
   
2. MeawandMoo1 4 februari 2010 21:10

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   Development of a polishing step using a hydrophobic interaction membrane adsorber with a PER.C6-derived recombinant antibody.
   Kuczewski M, Fraud N, Faber R, Zarbis-Papastoitsis G.
   
   PERCIVIA LLC, Cambridge, Massachusetts 02139, USA. mkuczewski@percivia.com
   
   Membrane chromatography has already proven to be a powerful alternative to polishing columns in flow-through mode for contaminant removal. As flow-through utilization has expanded, membrane chromatography applications have included the capturing of large molecules, including proteins such as IgGs. Such bind-and-elute applications imply the demand for high binding capacity and larger membrane surface areas as compared to flow-through applications. Given these considerations, a new Sartobind Phenyl membrane adsorber was developed for large-scale purification of biomolecules based on hydrophobic interaction chromatography (HIC) principles. The new hydrophobic membrane adsorber combines the advantages of membrane chromatography-virtually no diffusion limitation and shorter processing time-with high binding capacity for proteins comparable to that of conventional HIC resins as well as excellent resolution. Results from these studies confirmed the capability of HIC membrane adsorber to purify therapeutic proteins with high dynamic binding capacities in the range of 20 mg-MAb/cm(3)-membrane and excellent impurity reduction. In addition the HIC phenyl membrane adsorber can operate at five- to ten-fold lower residence time when compared to column chromatography. A bind/elute purification step using the HIC membrane adsorber was developed for a recombinant monoclonal antibody produced using the PER.C6(R) cell line. Loading and elution conditions were optimized using statistical design of experiments. Scale-up is further discussed, and the performance of the membrane adsorber is compared to a traditional HIC resin used in column chromatography. 2009 Wiley Periodicals, Inc.
   
   www.ncbi.nlm.nih.gov/pubmed/19739096?...
3. de tuinman 4 februari 2010 23:24

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   ok hier begrijp ik dus helemaal niks meer van.
4. MeawandMoo1 23 maart 2010 22:06

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   quote:

   de tuinman schreef:

   ok hier begrijp ik dus helemaal niks meer van.
   

   Probeer deze eens. ;-)
   
   Macropinocytotic uptake and infection of human epithelial cells with species B2 adenovirus type 35.
   
   Kälin S, Amstutz B, Gastaldelli M, Wolfrum N, Boucke K, Havenga M, Digennaro F, Liska N, Hemmi S, Greber UF.
   
   Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland; Zurich PhD Program in Molecular Life Sciences, Crucell Holland BV, Leiden, The Netherlands; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
   
   The human adenovirus serotype 35 (HAdV-35, short Ad35) causes kidney and urinary tract infections, and infects respiratory organs of immunocompromised individuals. Unlike other adenoviruses, Ad35 has a low seroprevalence which makes Ad35-based vectors promising candidates for gene therapy. Ad35 utilizes CD46 and integrins as receptors for infection of epithelial and hematopoietic cells. Here, we show that infectious entry of Ad35 into HeLa, human kidney HK-2 cells and normal human lung fibroblasts strongly depended on CD46 and integrins but not heparan sulfate, and variably required the large GTPase dynamin. Ad35 infections were independent of expression of the carboxy-terminal domain of AP180 which effectively blocks clathrin-mediated uptake. Ad35 infections were inhibited by small chemicals against the serine/threonine kinase Pak1 (p21-activated kinase), protein kinase C (PKC), sodium-proton exchangers, actin and acidic organelles. Remarkably, the F-actin inhibitor jasplakinolide, the Pak1 inhibitor IPA-3 or the sodium-proton exchange inhibitor EIPA blocked the endocytic uptake of Ad35. Dominant-negative proteins or small interfering RNAs against factors driving macropinocytosis, including the small GTPase Rac1, Pak1 or the Pak1 effector C-terminal binding protein 1 (CtBP1) potently inhibited Ad35 infection. Confocal laser scanning microscopy, electron microscopy and live cell imaging showed that Ad35 colocalized with fluid phase markers in large endocytic structures that were positive for CD46, alpha v integrins and also CtBP1. Our results extend earlier observations with HAdV-3 (Ad3), and establish macropinocytosis as an infectious pathway for species B human adenoviruses in epithelial and hematopoietic cells
   
   www.ncbi.nlm.nih.gov/pubmed/20237079
5. de tuinman 24 maart 2010 09:20

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   quote:

   MeawandMoo1 schreef:

   [quote=de tuinman]
   ok hier begrijp ik dus helemaal niks meer van.
   [/quote]
   Probeer deze eens. ;-)
   
   Macropinocytotic uptake and infection of human epithelial cells with species B2 adenovirus type 35.
   
   Kälin S, Amstutz B, Gastaldelli M, Wolfrum N, Boucke K, Havenga M, Digennaro F, Liska N, Hemmi S, Greber UF.
   
   Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland; Zurich PhD Program in Molecular Life Sciences, Crucell Holland BV, Leiden, The Netherlands; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
   
   The human adenovirus serotype 35 (HAdV-35, short Ad35) causes kidney and urinary tract infections, and infects respiratory organs of immunocompromised individuals. Unlike other adenoviruses, Ad35 has a low seroprevalence which makes Ad35-based vectors promising candidates for gene therapy. Ad35 utilizes CD46 and integrins as receptors for infection of epithelial and hematopoietic cells. Here, we show that infectious entry of Ad35 into HeLa, human kidney HK-2 cells and normal human lung fibroblasts strongly depended on CD46 and integrins but not heparan sulfate, and variably required the large GTPase dynamin. Ad35 infections were independent of expression of the carboxy-terminal domain of AP180 which effectively blocks clathrin-mediated uptake. Ad35 infections were inhibited by small chemicals against the serine/threonine kinase Pak1 (p21-activated kinase), protein kinase C (PKC), sodium-proton exchangers, actin and acidic organelles. Remarkably, the F-actin inhibitor jasplakinolide, the Pak1 inhibitor IPA-3 or the sodium-proton exchange inhibitor EIPA blocked the endocytic uptake of Ad35. Dominant-negative proteins or small interfering RNAs against factors driving macropinocytosis, including the small GTPase Rac1, Pak1 or the Pak1 effector C-terminal binding protein 1 (CtBP1) potently inhibited Ad35 infection. Confocal laser scanning microscopy, electron microscopy and live cell imaging showed that Ad35 colocalized with fluid phase markers in large endocytic structures that were positive for CD46, alpha v integrins and also CtBP1. Our results extend earlier observations with HAdV-3 (Ad3), and establish macropinocytosis as an infectious pathway for species B human adenoviruses in epithelial and hematopoietic cells
   
   www.ncbi.nlm.nih.gov/pubmed/20237079
   

   Ja en?.... das toch logisch!!....
6. flosz 31 maart 2010 15:08

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   Rev Panam Salud Publica. 2010 Feb;27(2):117-24.
   A fully liquid DTPw-HepB-Hib combination vaccine for booster vaccination of toddlers in El Salvador.
   
   Suárez E, Asturias EJ, Hilbert AK, Herzog C, Aeberhard U, Spyr C.
   Universidad de El Salvador, San Salvador, El Salvador.
   OBJECTIVES:To compare the safety and immunogenicity of a booster dose of a fully liquid diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HepB-Hib) vaccine to the separate administration of commercially available DTPw and Hib vaccines in healthy toddlers. METHODS:An open-label, randomized, parallel-group, Phase III study conducted at six centers in San Salvador, El Salvador, during February-June 2006. Toddlers (15-24 months of age) were eligible to participate if they had received primary immunization at 2, 4, and 6 months of age with a commercial DTPw-HepB/Hib vaccine requiring reconstitution. Participants received either one booster dose of DTPw-HepB-Hib fully liquid vaccine or DTPw and Hib vaccines administered separately. Blood samples were taken immediately prior to and at 1 month post-vaccination. For a 5-day period following vaccination, solicited adverse events were collected in subject diaries and assessed. RESULTS:The combined DTPw-HepB-Hib fully liquid vaccine was non-inferior to the separately administered DTPw and Hib vaccines, in terms of seroprotection/seroconversion rates for all antigens evaluated. The combination vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. The geometric mean concentrations (GMCs) of all antibodies in the DTPw-HepB-Hib group exceeded the seroprotection/seroconversion thresholds by very large margins, although for some antigens they were somewhat lower than the corresponding titers in the comparator group. With the combination vaccine, considerably fewer solicited local and systemic adverse events, such as fever and irritability, were reported than with the comparator vaccines.
   CONCLUSIONS:This study demonstrates that the fully liquid combined DTPw-HepB-Hib vaccine is highly immunogenic and has a favorable safety profile when given as a booster vaccination to toddlers who have received a primary vaccination course with a different pentavalent vaccine that requires reconstitution.
   PMID: 20339615
   www.ncbi.nlm.nih.gov/pubmed/20339615
   
   Volledig art.: journal.paho.org/uploads/1268236200.pdf
   
7. aossa 31 maart 2010 15:20

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   Leuk !
   
   Quinvaxem kan gebruikt worden als booster-vaccine voor andere merken pentavalent-vaccine...
   
   /quote
   The fully liquid DTPw-HepB-Hib vaccine
   is immunogenic and safe when used
   as a booster dose in children who have
   received primary vaccination with another
   pentavalent vaccine. The possible
   interchangeability of different manufacturers’
   primary and booster immunization
   products is important to demonstrate
   because frequent shortages and
   changes in the vaccine availability are
   often encountered and could be better
   addressed./
   
   Eentje voor boven het bed van C.Viehbacher ;-)
8. [verwijderd] 31 maart 2010 15:25

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   Dat kan toch geen toeval zijn, deze studie zou je zeggen...
   Heeft toch even geduurd om zo'n studie op te zetten en te analyseren, publiceren. Dus Crucell was al een aardig tijdje op de hoogte van het Shan5 gebeuren.
9. de tuinman 5 april 2010 13:25

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   Children Sacrifice for Bio-medical Research
   Posted: Kyoto, Japan [Jan 16, 2010]
   
   Last September infants in Bhutan were immunized using new life saving ‘5 in 1’ vaccine named ‘Pentavalent’. Gross of children succumbed to the vaccine and otherssuffered from acute side effects. The samples of vaccines were sent to advance laboratories for test. The result took unexpectedly long time to come out. In the mean time, the health minister who introduced the killer vaccine was conferred a distinguished award for the same.
   
   
   
   The health ministry received a dozen ambulances in gift. The parents who lost children are neither compensated, nor consoled. The entire episode was explained by the government as a “mere coincidence”. If people have digest it casually, the word “ethics” should get a new definition.Last September infants in Bhutan were immunized using new life saving ‘5 in 1’ vaccine named ‘Pentavalent’. Gross of children succumbed to the vaccine and others suffered from acute side effects. The samples of vaccines were sent to advance laboratories for test. The result took unexpectedly long time to come out. In the mean time, the health minister who introduced the killer vaccine was conferred a distinguished award for the same. The health ministry received a dozen ambulances in gift. The parents who lost children are neither compensated, nor consoled. The entire episode was explained by the government as a “mere coincidence”. If people have digest it casually, the word “ethics” should get a new definition.
   
   
   
   GAVI
   Global alliance for vaccines and immunization (GAVI), an alliance of government, UN agencies, vaccine makers and charities was formed in 2000 AD with a globally appreciated altruistic motive. The motive was to provide life saving vaccines at subsidized cost to people in poor countries. Three prong approaches were adopted to fulfill the noble mission. Firstly, it was to raise awareness among people in the poor countries to make them seek the vaccines and increase the demands. Secondly, it was to encourage more vaccine makers to get into competition. Lastly and subsequently, it was to reduce the cost of vaccines.
   
   The public private partnership, GAVI, based in Geneva was set up with a seed fund of US$ 750 million from Bill and Milinda Gates Foundation. When it began in 2000, there was only one company producing Pentavalent. Today there are at least four companies reaping profits from the alliance. The price has come down from $3.65 to $ 3.0 per dose, and profit swollen to 10 digits.
   
   Two Indian vaccines makers, Shantha Biotechnics Ltd acquired by French drug maker Sonofi Aventis SA, and Panacae Biotech limited joined the competition in 2008. Two more Indian companies, Serum Institute of India Ltd and Bharat Biotech International Ltd are knocking at the door of World Health Organization (WHO) for pre-qualification approval. Unicef buys drugs from companies which have pre-qualification approval from WHO. Unicef then gives to GAVI, which in turn supplies to member countries at subsidized rates. The vaccine is supplied to 72 countries chosen on the basis of their low economic standards.
   
   Children sacrifice
   Without a pilot test or with no means to test, immunization using GAVI’s subsidized vaccine Pentavalent was started nationwide in Bhutan on September 1, 2009. Within a month 8 children were reported killed by the vaccine. The parents of all these children are highly educated, who could track the cause. The actual deaths within this period are yet to be known. An unpublished draft mentions that the ministry of health has registered at least 31 cases of deaths and hundreds of children immunized during this period sick.
   
   Bhutan government responded very fast to the deaths, suspended the vaccines and resorted to previous doses. It ensured total collection of the unused and used veils to prevent possible test by private groups. Though fast, Bhutan is not the first country to suspend the immunization using Pentavalent. Sri Lanka and Pakistan had stopped, too. However, despite reports of deaths in their countries, Afganinthan, Bangladesh, Nepal and many more countries are continuing with it.
   
   Even if all the Pentavalent immunized children did not succumb to injection, they are not out of other dangers. The actual antigens used in the vaccines are unknown and protected by patents. The vaccine comes in a solution with aluminium thimerosal, a mercury based compound, and formaldehyde as preservatives. These cause inflammation of brain, cancer, encephalitis, etc. Either when a child is in poor health condition or when the amount of these preservatives crosses a certain threshold level, the chemicals show their effect.
   
   Pentavalent is an untested vaccine hypothetically meant to protect children against five killer diseases, Haemophilus influenza type B(Hib) disease, DPT( diphtheria, pertussis and tetanus) and Hipatitis B. Pentavalent replaces the separate use of DPT, Hib and Hepatities B. But the numbers of time parents need to visit clinic remain the same as Pentavalent is given thrice; after 6, 10 and 14 weeks. This is independent of BCG and measles vaccines.
   
   Child sacrifice brings awards to ministers
   During the third week of November, GAVI partners’ forum awarded health ministers from the GAVI recipient countries. They were conferred various awards and titles. The Bhutan’s minister for health Professor Zangley Drukpa was recognized for obtaining over 95 percent immunization in four years. While statistics (95 percent) is fiction based, the minister was in this job for a little more than a year. This was a month after the killer vaccine was suspended from use in Bhutan. The award ceremony in Hanoi, Vietnam on November 19, 2009 was grander than any of the past Oscar film award ceremonies. The event was moderated by singer Yvonne Chaka Chaka from South Africa. The purpose was to make the event more of entertainment than of purpose. In the grand program no mention was made regarding the children who lost their life to the vaccines and no prayers were offered. No leader raised a word on the compensation to the grieved parents. The ministers retuned with heavy medals.
   
   The Pentavalent recipient countries have no access or techniques to verify the constituent and quality of the vaccines. The recipients accept them on the trust and mercy of the donors, makers and the governments. While it was introduced in many countries Bhutan was a fore runner to suspend and withdraw the use and go for a cross check. There are many chances for Bhutan’s health minister to fall under the influence of the drug dealers.
   
   Health minister of Bhutan
   Academically, Professor Zanglay Drukpa comes from education management background. Beside a few interactions with his family physicians, he had hardly any time and opportunity to know anything related to health and medicine, until he became health minister a year ago. He was convinced to save state’s budget when vaccines costing $ 3.65 per dose were given to him at $ 0. 23 per dose. He accepted without a second thought. A dose of Pentavalent vaccine costs US$3.65 to Unicef when it buys from companies. Through GAVI initiative Bhutan received at a subsidized rate of $0.23 per dose. The huge difference adds to the suspicion that the vaccines are being used for test. Research companies bribe influential people for favors. Economically Professor Zanglay lives with a silver spoon in his mouth. However, chances th
10. de tuinman 5 april 2010 13:33

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    Kan iemand mij hier bij helpen. Ik heb hierboven een bijzonder bericht geplaatst die ik vond met googelen.
    
    Hierin wordt het 5 in 1 vaccin verdacht gemaakt. Er zouden kinderen zijn omgekomen en bijwerkingen zijn. In dit geval komt het produkt van Panacea.
    
    Vreemd verhaal..
    
    Ik zie dat niet het hele artikel is gekopieeerd. Ik zal de rest hieronder zetten.
11. de tuinman 5 april 2010 13:35

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    Health minister of Bhutan
    Academically, Professor Zanglay Drukpa comes from education management background. Beside a few interactions with his family physicians, he had hardly any time and opportunity to know anything related to health and medicine, until he became health minister a year ago. He was convinced to save state’s budget when vaccines costing $ 3.65 per dose were given to him at $ 0. 23 per dose. He accepted without a second thought. A dose of Pentavalent vaccine costs US$3.65 to Unicef when it buys from companies. Through GAVI initiative Bhutan received at a subsidized rate of $0.23 per dose. The huge difference adds to the suspicion that the vaccines are being used for test. Research companies bribe influential people for favors. Economically Professor Zanglay lives with a silver spoon in his mouth. However, chances that he walked an extra mile to rescue his debt ridden party from bankruptcy, cannot be ruled out. If so, it is not just the health minister who is acknowledgeable, the entire cabinet and the DPT’s top members are aware, informed and under influence.
    
    Ethics in biomedical research
    Biomedical tests or test of drugs and vaccines on humans are highly sensitive protocols often provoking human right issues. Drugs are tested for their effects and side effects starting from small animals like bacteria, nematodes, mice, rabbits, etc. When they pass all these stages they are tested in primates like monkeys and chimpanzees, which are closer to humans. However, their actual effects cannot be specified without testing in humans. There are various protocols to be followed to test any drugs in humans. The human must be a volunteer, fully informed of the test and consequences, and free from expectations of any forms of rewards and benefits. Legally, bio medical test on humans is next to impossible. Moreover, Pentavalent is meant for the infants, their tests and report of tests in informed volunteer adults give no meaning. Thus somehow or the other, illegally or Para-legally they are tested through the influence of authorities. The common practice is that the drugs are tested on prisoners, refugees, soldiers, street dwellers, beggars and ignorant people. For the test either authorities, where absolute authorities exist like in army, or politicians who influence large masses are taken into confidence through various means.
    
    For the test, drugs or vaccines with different combinations of constituents are mixed and the samples are identified using codes. The code of the Penatvalent used in Bhutan was ‘EasyFive’ a trade name used by Panacae Biotec, India. Each vial of vaccine has an identifier encoded in the barcode. Since different combinations are used, some of which are placebo, different receipient get different symptoms. Some are not given any treatment. When the dose is completed in an area, epidemic is spread. After the epidemic like the recent H1N1 swine flue epidemic, recipients susceptible to disease are noted and compared against the dose they received. After the tests are successfully carried out, the drugs with best results are replicated and sold in developed countries, which have reliable techniques to test and verify drugs. These selected drugs are usually a bit expensive.
    
    Vial in file
    Bhutan government took a bold step by sending the collected samples to test to different undisclosed laboratories. If the result from the test prove the vaccines faulty, it shall be the worlds’ first most notorious scandal of the 21st century. To resist it Bhutanese people have to tighten their belt.
    
    However as the symptoms show, the government is ready to subside the issue proclaiming that the killer vaccine and death from the injection were coincidental. The government cannot hide the mal practice so easily; the people of Bhutan know exactly when the iron is hot. Delay in releasing the laboratory reports is an unexpected event taking place. Any good laboratory can analyze chemical composition of vaccines in a day. However, it takes long time to study the effects, which is not expected from them. It has been a month already that the samples were dispatched for test. The reports are still in the file.
    
    Gift diplomacy
    Easy five, the Pentavalent received by Bhutan was the product of Panacea Biotech Ltd in New Delhi. The company must not be waiting with fingers crossed for the lab results. The government seems seriously evaluating the pros and cons of the report and its release. When the lab result is still in the file and peoples’ eyes are focused on it, there was a distraction. Bhutan received a dozen ultra sophisticated ambulances from New Delhi as gift with promises of some more such gifts soon.
    
    The addition of ambulances will certainly ease the people’s trouble, and save many who would otherwise breath their last, untimely, on the way to hospitals. But it cannot bring the children sacrificed to illegal vaccines back to life.
    
    Mission ahead
    GAVI’s noble mission to keep the future population healthy should continue. They should see that their altruism adds, not subtract, health and life to the children. They should buy only those drugs and vaccines that are accepted in developed countries.
    
    Bill and Melinda Gates Foundation have spent billions of dollars in charities to improve health and agriculture. They should ensure that their charities are used for the just cause and not to siphon dollars into billionaires eyeing to take up Bill Gates position in Forbex index.
    
    Not every government can follow Bhutan, Sri Lanka or Pakistan to act fast to save lives, but they should not be tempted by low prices, rewards and gifts.
    
    Unicef, WHO, PAHO, etc. are globally trusted, international organizations to which people and governments resort to at times of need and controversies. All the people working in these organizations may not be immunized against corruption and unethical partnership with drug makers and testers.
    
    The government of Bhutan must be confident that people will support them if they stand with the actual result of the test even if it mean losing cost subsidized vaccines, ambulances and awards, and will not support the fabrication for a vein glory.
    
    The civil societies must be bold enough to ensure that all the parents who lost their children get proper compensation and other children who survived the killer vaccine get medical supervision for good.
    
    By Govinda Rizal
    
    Source & Copyright © 2010, APFA News
    
12. [verwijderd] 5 april 2010 13:41

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    Hier schieten woorden tekort. Voorlopig heb ik alleen maar pijn.
13. flosz 5 april 2010 13:41

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    Beste tuinman, gelieve ook even hier te schoffelen:
    15 mrt 10, 13:41
    www.iex.nl/forum/topic.asp?forum=228&...
    
    the Pentavalent received by Bhutan was the product of Panacea Biotech Ltd in New Delhi.
    www.investorvillage.com/smbd.asp?mb=2...
    Dit ter voorkoming van alweer een hoop onzinnige insinuaties.
14. de tuinman 5 april 2010 13:49

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    quote:

    flosz schreef:

    Beste tuinman, gelieve ook even hier te schoffelen:
    15 mrt 10, 13:41
    www.iex.nl/forum/topic.asp?forum=228&...
    
    the Pentavalent received by Bhutan was the product of Panacea Biotech Ltd in New Delhi.
    www.investorvillage.com/smbd.asp?mb=2...
    Dit ter voorkoming van alweer een hoop onzinnige insinuaties, LET op mod: eerst even de ik-ben-wakker-knop activeren: anti-CRUCELL-insinuaties!
    
    

    Bedankt voor de snelle reactie, alleen dat laatste zinnetje begrijp ik niet. Sarcasme?
15. flosz 5 april 2010 13:54

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    quote:

    de tuinman schreef:

    alleen dat laatste zinnetje begrijp ik niet.
    

    Dit is het CRXL-Pubmed-draadje!
16. josti5 5 april 2010 18:16

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17. [verwijderd] 5 april 2010 18:40

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    Probeer eens na te denken, wat dit draadje inhoudt Josti5, dan zou je zoiets nalaten!!
    Zij probeert het overzichtelijk te houden, snap je??
18. de tuinman 5 april 2010 18:40

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    Meester, meester. De tuinman is stout geweest!!!!!
    
    
19. josti5 5 april 2010 19:27

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20. [verwijderd] 5 april 2010 19:33

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    weissheiss