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Molekularny mechanizm dzialania bisfosfonianow i ich zastosowanie w praktyce klinicznej

100%

Mytnik E., Kuryszko J., Chmielewska E., Kafarski P.

Medycyna Weterynaryjna

2010

tom 66

nr 05

307-310

Bisphosphonates are a unique class of drugs. As a family they are characterized pharmacologically by their ability to inhibit bone resorption, whereas, pharmacokinetically, they are classified by their similarity in absorption, distribution and elimination. Bisphosphonates have become the most important class of antiresorptive drugs, not only for the treatment of Paget’s disease, but also for other diseases that involve excessive osteoclast-mediated bone resorption, such as tumor-induced osteolysis and hypercalcemia as well as osteoporosis. Although all bisphosphonates have similar psychochemical properties, their antiresorbing activities differ substantially. The structure of the R2 side chain is the major determinant of antiresorptive potency, both phosphonate groups are also required for the drugs to be active. Activity is dramatically increased when the amino group is contained in the aliphatic carbon chain. They act by inhibiting the enzyme farnesyl diphosphate synthase. Despite this, the molecular mode of their action is still not clear. There is substantial evidence that BPs can have a direct effect on osteoclasts by mechanisms that may lead to osteoclast cell death by apoptosis. BPs can also inhibit proliferation and cause cell death in macrophages in vitro. It has been shown that the toxic effect of BPs on macrophages is also due to the induction of apoptotic, rather than necrotic, cell death. Bisphosphonates may inhibit osteoclast-mediated bone resorption by several routes, although a direct effect on mature osteoclasts is the most likely. Bisphosphonates perturb cellular metabolism and induce osteoclast apoptosis. The molecular mechanisms by which these effects are brought about are only now becoming clear. The simple bisphosphonates that closely resemble pyrophosphonates (such as clodronate, etidronate and tiludronate) can be metabolically incorporated into non-hydrolysable analogues of ATP that accumulate intracellularly in osteoclasts, resulting in the induction of osteoclast apoptosis. The more potent, nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signaling proteins. Loss of bone-resorptive activity and osteoclast apoptosis is primarily due to the loss of geranylgeranylated small GTPases.

Use of calcium sulfate as a biomaterial in the treatment of bone fractures in rabbits – preliminary studies

100%

Szponder T., Mytnik E., Jaegermann Z.

Bulletin of the Veterinary Institute in Puławy

2013

tom 57

nr 1

The paper presents preliminary results of the implantation of calcium sulfate type Hartform HF1 developed at the Institute of Glass and Ceramics in Warsaw. The study was conducted on 10 New Zealand White rabbits, in which after tibial osteotomy the biomateriał was implanted directly into the fracture site. The animals were divided into two groups based on the method of fracture stabilisation: intramedullary pinning using Kirschner wires in one group and acrylic external fixator in the other. After 12 weeks, bone union was observed in all animals as estimated by clinical and radiological findings. Histological tests revealed resorption of the biomateriał into the bone fracture area. It was concluded that type Hartform 1 calcium sulfate can be used as a biomateriał in veterinary orthopedics. Due to the lack of observable side effects during implantation and resorption, the material can be considered as a valuable ingredient in composite biomaterials containing calcium sulfate.

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Experimental osteoporosis in sheep - mechanical and histological approach

64%

Kielbowicz Z., Piatek A., Kuropka P., Mytnik E., Nikodem A., Biezynski J., Skrzypczak P., Pezowicz C., Kuryszko J., Reichert P.

Polish Journal of Veterinary Sciences

2016

tom 19

nr 1

The implementation of new methods of osteoporotic therapy requires tests on animal model. The use of sheep as model has numerous advantages over other animals. The aim of this study was to describe the change in parameters in sheep with osteoporosis induced using steroids and ovariorectomy methods as opposed to the parameters in healthy sheep. The study was performed on female „merinos” breed sheep divided into the three groups: negative control (NC) – healthy animals, positive control (PC) – ovariorectomized animals and steroid control group (SC) – in which methylprednisolone was administered. This paper presents histological and ultrastructural examination with mechanical comparative tests for force/strength values as well as indentation tests of joint cartilage. The obtained results confirm the loss of bone mass associated with mineral composition content in bones, which has an influence on bone strength.

Ograniczanie wyników

1 Bulletin of the Veterinary Institute in Puławy

1 Medycyna Weterynaryjna

1 Polish Journal of Veterinary Sciences

3 Mytnik E.

2 Kuryszko J.

1 Biezynski J.

1 Chmielewska E.

1 Jaegermann Z.

1 Kafarski P.

1 Kielbowicz Z.

1 Kuropka P.

1 Nikodem A.

1 Pezowicz C.

1 Piatek A.

1 Reichert P.

1 Skrzypczak P.

1 Szponder T.

1 2016

1 2013

1 2010

Wyniki wyszukiwania

Molekularny mechanizm dzialania bisfosfonianow i ich zastosowanie w praktyce klinicznej

Use of calcium sulfate as a biomaterial in the treatment of bone fractures in rabbits – preliminary studies

Experimental osteoporosis in sheep - mechanical and histological approach