Nederlandse Organisatie Voor Toegepast-natuurwetenschappelijk Onderzoek Tno

Nederlandse Organisatie Voor Toegepast-natuurwetenschappelijk Onderzoek

Nederlandse Organisatie Voor Toegepast

Leids Universitair Medisch Centrum

Natuurwetenschappelijk Onderzoek Tno Leids Universitair Medisch Centrum

Johan Hendrikus Verheijen

Jan Roeland Occo Hanemaaijer

Robert Kleemann

Peter Ydo Wielinga

Reinout Stoop

Teake Kooistra

Michaela Diamant

Natascha Alexandra Van Lent

Johannes Hendrikus Nicolaas Lindeman

Mohamed Rahoef Daha

Johanna Roos

The invention relates to the surprising find that low density lipoprotein receptor-deficient mice (LDLr) mice when fed with high energy diets produce controllable and consistent diabetic complications, especially renal damage, similar to the human pathophysiology and biological response. The invention thus comprises a method for discovering a preventive or therapeutic regimen for the prevention or treatment of diabetic micro- or macrovascular complications, comprising the steps of: Specifically in such a method renal damage is assessed. Also use of said mice fed with a high energy diet for studying the diabetic micro- and macrovascular complications is part of the invention.

Animal model for non alcoholic steato hepatitis and liver fibrosis

The invention relates to the surprising find that low density lipoprotein receptor-deficient mice (LDLr&#x2212;/&#x2212;) mice when fed with high energy diets produce controllable and consistent diabetic complications, especially renal damage, similar to the human pathophysiology and biological response. The invention thus comprises a method for discovering a preventive or therapeutic regimen for the prevention or treatment of diabetic micro- or macrovascular complications, comprising the steps of: a. feeding LDLr&#x2212;/&#x2212; mice, which have not been treated with streptozotocin, with a high energy diet; b. before, during and/or after this diet treating the mice with the preventive or therapeutic regimen; c. checking whether any change in the micro- or macrovascular system of the animal occurs. Specifically in such a method renal damage is assessed. Also use of said mice fed with a high energy diet for studying the diabetic micro- and macrovascular complications is part of the invention.

Animal model for diabetic complications

The present invention relates to a method for determining if a subject having Type II diabetes has a kidney disorder by measuring the level of matrix metalloproteinase 8 (MMP-8) in the urine of a subject having Type II diabetes and comparing this level to a reference sample or a sample from a healthy subject and determining if the subject has a kidney disorder base on the presence of increased levels of MMP-8 in the urine compared to the reference values or reference sample.

Method for determining if a subject having type II diabetes has a kidney disorder

This invention relates to the field of determining, assaying or quantifying activity of components of the complement system. More particularly, the invention relates to methods for detecting the presence or level of activity in a sample of mannan-binding-lectin associated serine proteases (MASPs) or complexes of such proteases with lectins and to detection of the particular lectins themselves. Provided is a method for determining the activity of a MASP in a sample, comprising incubating the sample with a pro-urokinase comprising at its activation site the consensus sequence Arg/Leu/Gly-Yyy-Arg/Lys-Ile/Leu/Val-Zzz-Gly-Gly cleavable by a MASP, wherein Yyy can be any amino acid and Zzz is preferably an aliphatic amino acid, and determining proteolytic activation of said pro-urokinase.

Method for the functional determination of mannan-binding-lectin associated serine proteases (MASPs) and complexes thereof

A method for determining whether a urine sample has been obtained from a subject suffering from a kidney disorder involving kidney damage. The method is based on determining the level of a proteolytic enzyme in urine from the subject. Sample and optionally comparing this level with a reference value. The proteolytic enzyme preferably is a matrix metalloproteases, in particular MMP-2 or MMP-9. The method is particularly suitable for subjects with a condition or disorder that is associated with an increased risk of kidney disorders, such as diabetes. The method may adavnatageously be applied for early detection of kidney damage, in particular when the subject does not yet show any sign of microalbuminuria. The method may also be applied to a subject undergoing dialysis for determining whether the subject is suffering from remodelling of the peritoneal membrane. Thus, the method is particularly suited for patients undergoing continuous ambulatory peritoneal dialysis.

Proteolytic enzymes in urine as diagnostic parameters in diseases involving matrix remodelling

The present invention provides an improved protease assay in which the proteases are detected on basis of their capability to cleave a modified pro-caspase which will yield an activated caspase which can then further be detected. Also part of the invention are the modified pro-caspases and kits comprising said modified pro-caspases.

Method for the detection of proteolytic enzymes

A photometric measuring system comprising a holder (,) provided with at least one liquid storage chamber (,) having an open upper end (,) for holding liquid (,) to be measured; at least one light generator (,) for generating an incoming light beam (,) towards the liquid storage chamber, so that at least a portion of the incoming light beam (,) enters the liquid storage chamber (,) though the open upper end (,); and at least one light detector (,) for detecting, during operation, at least a portion of the light (,) which has interacted with the liquid present in the liquid storage chamber (,), wherein, at least a portion of the inner walls of the storage chamber has been provided with a reflective surface (,), so that at least a portion of the light which has entered the storage chamber to interact with the liquid in the storage chamber will be reflected towards the open upper end and will leave the storage chamber through the open upper end; and wherein the light detector detects at least a portion of said light which has left the storage chamber through the open upper end.

Photometric measuring system and a holder for such a system

The present invention relates to the use of non-bacterial plasminogen activators in the manufacture of a topical medical preparation for the treatment of slow- or non-healing wounds. In addition, the present invention relates to a composition comprising a physiologically acceptable carrier and an effective amount of a non-bacterial plasminogen activator, with the exclusion of t-PA. Finally, the present invention is directed to a method of treatment of slow- or non-healing wounds comprising the topical application of a non-bacterial plasminogen activator to the site of a wound.

Use of a preparation comprising a plasminogen activator to improve wound

Use of preparation comprising a plasminogen activator to improve wound

Detection or determination of a protease in a sample by incubating the sample with a substrate of the protease and observing proteolytic cleavage of said substrate. The substrate is a modified proenzyme containing a recognition site, e.g., an activation site, cleavable by said protease. Proteolytic cleavage of the modified proenzyme is detected by observing the resulting activity using a suitable substrate of the activated proenzyme. The protease may be e.g. an aspartic protease or a metalloprotease, and the modified proenzyme e.g. pro-urokinase having a mutant activation site which is cleavable by the protease to be determined.

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Berkel en Rodenrijs, Netherlands

Johan Hendrikus Verheijen