**Author details**

Hideo Orimo

Address all correspondence to: orimohd@nms.ac.jp

Division of Metabolism and Nutrition, Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan

#### **References**

[1] Whyte MP. Hypophosphatasia: Nature's Window on alkaline phosphatase function in man. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of Bone Biology. 2nd ed. San Diego, CA: Academic Press; 2002. p. 1229-1248

[2] Orimo H. Pathophysiology of hypophosphatasia and the potential role of asfotase alpha. Therapeutics and Clinical Risk Management. 2016;**12**:777-786

Once gene-transferred stem cells are transplanted, no other injection may be necessary [2]. Although gene therapy seems to be a promising procedure, results have so far only been obtained for mouse models, and its feasibility and safety in humans must be investigated.

HPP is a systemic skeletal disorder that is caused by TNAP deficiency. Human TNAP is one of the four isoenzymes of alkaline phosphatase and is expressed ubiquitously. The TNAP protein is linked to the outer membrane of cells via a GPI anchor and works as an enzyme in a homodimer state. TNAP is essential for biomineralization; it is located on the MV membrane and plays a role in the elongation of hydroxyapatite crystals into the extracellular space.

HPP is classified into six forms and clinical severity varies among the forms. Hypomineralization of hard tissues is a common feature of HPP. In the severe forms, patients show rickets and respiratory failure that cause death. Milder forms exhibit musculoskeletal disorder or teeth problems. Although low serum ALP activity and an elevated urine PEA value are characteristic of HPP, genetic diagnosis is the definitive diagnosis. ERT using a genetically modified enzyme (asfotase alfa) opens up a new vista in the therapy of HPP, especially for severe forms of HPP. Although asfotase alfa has drastically changed the treatment of HPP, there remain

The author has received honoraria from Alexion Pharmaceuticals, Inc. The author reports no

Division of Metabolism and Nutrition, Department of Biochemistry and Molecular Biology,

[1] Whyte MP. Hypophosphatasia: Nature's Window on alkaline phosphatase function in man. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of Bone Biology. 2nd ed.

still several problems with its use that need to be resolved.

**10. Conclusions**

112 Pathophysiology - Altered Physiological States

**Conflict of interest**

**Author details**

Hideo Orimo

**References**

other conflict of interest in this work.

Nippon Medical School, Tokyo, Japan

Address all correspondence to: orimohd@nms.ac.jp

San Diego, CA: Academic Press; 2002. p. 1229-1248


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**Chapter 7**

Provisional chapter

**Dynamic Properties of Skeletal Muscle Contraction in**

DOI: 10.5772/intechopen.70600

Dynamic Properties of Skeletal Muscle Contraction in

The study was conducted on 20 white nonlinear male rats, which were divided into 2 groups of 10 animals each. Rats in the first group were used as control. Rats in the second group were induced type I diabetes by intraperitoneal (i.p.) administration of streptozotocin (65 mg/kg). Diabetes in rats was confirmed by the presence of hyperglycemia. For the establishment of nociceptive pain sensation, mechanical nociceptive test and tail-flick test were conducted in rats. Further animals were anesthetized by i.p. administration of Nembutal (40 mg/kg). The study of dynamic properties of muscle contraction was performed under conditions of the tibia muscle activation by using the modulated stimulation of efferent n. tibialis. Streptozotocin (STZ) was injected in rats; as a result, the blood glucose level was increased by 4.4 times (p ≤ 0.001). Pain sensitivity in diabetic rats was suppressed, indicating the development of peripheral neuropathy. In rats with diabetes, biomechanical parameters of tibia muscle contraction such as the maximum force of contraction, the speed of maximum force of contraction, the retention time of maximum force of contraction and integrated power of muscle contraction (it is calculated on the total area of the received force curves) were violated. This prevents adequate implementation motor neuron pools muscular system, which will have significant consequences in accurate positional movements.

The damages of the peripheral nervous system in patients with diabetes mellitus are recorded in 40–60% of cases and manifests itself in the form of diabetic polyneuropathy. The incidence of

> © The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

**Rats with Diabetes**

Rats with Diabetes

Tetyana Falalyeyeva and

Abstract

1. Introduction

Tetyana Volodymyrivna Beregova,

Tetyana Volodymyrivna Beregova, Dmytro Nozdrenko, Sergii Berehovyi, Natali Nikitina, Tetyana Falalyeyeva and

Liudmyla Ivanivna Ostapchenko

Liudmyla Ivanivna Ostapchenko

http://dx.doi.org/10.5772/intechopen.70600

Dmytro Nozdrenko, Sergii Berehovyi, Natali Nikitina,

Keywords: skeletal muscle, contraction, diabetes, neuropathy

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter


Provisional chapter

#### **Dynamic Properties of Skeletal Muscle Contraction in Rats with Diabetes** Dynamic Properties of Skeletal Muscle Contraction in

DOI: 10.5772/intechopen.70600

Rats with Diabetes

Hattori K, Yuba S, Ohgushi H, Yamaguchi S. Ex vivo expanded allogeneic mesenchymal stem cells with bone marrow transplantation improved osteogenesis in infants with severe

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[73] Yamamoto S, Orimo H, Matsumoto T, Iijima O, Narizawa S, Maeda T, Millán JL, Shimada T. Prolonged survival and phenotypic correction of *Akp2*−/− hypophosphatasia mice by len-

[74] Matsumoto T, Miyake K, Yamamoto S, Orimo H, Miyake N, Odagaki Y, Adachi K, Iijima O, Narisawa S, Millán JL, Fukunaga Y, Shimada T. Rescue of severe infantile hypophosphatasia mice by AAV-mediated sustained expression of soluble alkaline phosphatase.

[75] Iijima O, Miyake K, Watanabe A, Miyake N, Igarashi T, Kanokoda C, Nakamura-Takahashi A, Kinoshita H, Noguchi T, Abe S, Narisawa S, Millán JL, Okada T, Shimada T. Prevention of lethal murine hypophosphatasia by neonatal ex vivo gene therapy using lentivirally transduced bone marrow cells. Human Gene Therapy. 2015;**26**:801-881

bone disease. Scientific Reports. 2017;**7**:2233. DOI: 10.1038/s41598-017-02351-6

tiviral gene therapy. Journal of Bone and Mineral Research. 2011;**26**:135-142

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sia. Journal of Dental Research. 2011;**90**:470-476

images/pi.pdf [Accessed: 15 May 2017]

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2016;**101**:334-342

118 Pathophysiology - Altered Physiological States

2002;**91**:9-16

Tetyana Volodymyrivna Beregova, Dmytro Nozdrenko, Sergii Berehovyi, Natali Nikitina, Tetyana Falalyeyeva and Liudmyla Ivanivna Ostapchenko Tetyana Volodymyrivna Beregova, Dmytro Nozdrenko, Sergii Berehovyi, Natali Nikitina, Tetyana Falalyeyeva and

Additional information is available at the end of the chapter Liudmyla Ivanivna Ostapchenko

http://dx.doi.org/10.5772/intechopen.70600 Additional information is available at the end of the chapter

#### Abstract

The study was conducted on 20 white nonlinear male rats, which were divided into 2 groups of 10 animals each. Rats in the first group were used as control. Rats in the second group were induced type I diabetes by intraperitoneal (i.p.) administration of streptozotocin (65 mg/kg). Diabetes in rats was confirmed by the presence of hyperglycemia. For the establishment of nociceptive pain sensation, mechanical nociceptive test and tail-flick test were conducted in rats. Further animals were anesthetized by i.p. administration of Nembutal (40 mg/kg). The study of dynamic properties of muscle contraction was performed under conditions of the tibia muscle activation by using the modulated stimulation of efferent n. tibialis. Streptozotocin (STZ) was injected in rats; as a result, the blood glucose level was increased by 4.4 times (p ≤ 0.001). Pain sensitivity in diabetic rats was suppressed, indicating the development of peripheral neuropathy. In rats with diabetes, biomechanical parameters of tibia muscle contraction such as the maximum force of contraction, the speed of maximum force of contraction, the retention time of maximum force of contraction and integrated power of muscle contraction (it is calculated on the total area of the received force curves) were violated. This prevents adequate implementation motor neuron pools muscular system, which will have significant consequences in accurate positional movements.

Keywords: skeletal muscle, contraction, diabetes, neuropathy
