Bioactivity study of modified curcumin loaded polymeric nanoparticles

By Bably Khatun

Drugs are natural or synthetic substances which when taken into a living body alter the body functioning and are used to treat or prevent a disease [157]. Drugs cause temporary changes in the body thereby correcting imbalances. Drugs have been used since ages for the treatment of different types of diseases through various means like oral, nasal

• Language: English
• Publisher: brandontiminsky
• Release date: Jan 13, 2023
• ISBN: 9781805455295

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Design, Development and Analysis of a Nerve Conduction Study System: An Auto-Controlled Biofeedback Approach

Champak Talukdar

CONTENTS

CHAPTER I

Introduction to Research Problem

CHAPTER II

Experimental Setup for NCS Development

CHAPTER III

Biofeedback Based Auto-Controlled Neurostimulator for NCS Testing

CHAPTER IV

Modeling and Impedance Analysis of NCS Signals by System Identification

CHAPTER 1

Introduction to Research Problem

1.0 Introduction

The nerve conduction study (NCS) is becoming increasingly important in biomedical field for detection of nerve condition. Over the past decades, there has been increasing focus on research devoted to PC based NCS system for developing quick, accurate, reliable, simple and cost effective systems. Generally PC based commercially available NCS machines are used by the neurophysiologists to study nerve related diseases which are expensive, bulky as well as difficult to operate without a specialist. So design and development of an embedded μC based system is the salient concern for the researchers to acquire and study the NCS signal. However, considerable challenges still exists, therefore research pursuit on new measuring techniques and development of appropriate design could provide a viable solution for further analysis. In this research, such areas are investigated which were previously less unexplored than expected.

1.1. Human Nervous System

The human nervous system mainly consists of central nervous system (CNS) and peripheral nervous system (PNS), however PNS is further divided in to autonomic nervous system (ANS) and somatic nervous system (SNS) [70, 26, 47]. The CNS includes brain and spinal cord while PNS is the communication system between the CNS and the rest of the body with their sympathetic and parasympathetic network tools as well as somatic branches. The ANS is a 'self-regulating' system which influences the function of organs outside voluntary control, such as the heart rate, or the functions of the digestive system [5, 12]. However, it is to be mentioned that nerve cell or neuron performs the function of CNS and the PNS. The details of a human nervous system are shown in Fig.1.1. Since the research aims at development of electronic devices for NCS of PNS, the following sections discusses as PNS and neuropathy.

1.1.1 Peripheral Nervous System

PNS consists of nerves and ganglia outside the CNS i.e. brain and spinal cord. The main function of the PNS is to connect the CNS to the limbs and organs, like a relay between the brain and spinal cord as well as the rest of the body [17]. However, PNS is often exposed to toxins and mechanical injuries because it is not protected by the vertebral 1

Image 1

column and skull unlike CNS. PNS consists of large myelinated unipolar sensory neurons with the cell body off to one side of the single dendritic-axon process. On the other hand multipolar motor neurons are large myelinated neurons that have many dendrites off the cell body and an axon that may branch to affect many effectors. Nerve impulses are transmitted in three steps- i) neurotransmitters released from one neuron binds to the dendrites of the next neuron, ii) initiates genesis of action potentials and iii) it gets propagated down the axons and excites the next neuron when it crossed the threshold.

When a neuron sends a sufficiently strong signal to the next neuron, the neuron is excited to a threshold potential. Transporters on the cell membrane sends positive ions into the cell, causing a change in potential, which spreads to down to the axon. This electrical potential is called the action potential [71]. Satellite cells are present in the sensory neuron and schwann cell present in PNS and both have importance in conduction capacity of peripheral nerve fibers. The cells wrap themselves around neurons in the PNS to synthesise the myeline sheath.

Fig.1.1 Human nervous system [27]

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1.2. Neuropathy

Neuropathy refers to disease or any injury conditions that affect the working of nervous system smoothly. Neuropathy involves motor or sensory neurons, affecting fine and broad motor control. Neuropathy may be associated with varying combinations of weakness, autonomic changes and sensory changes like loss of muscle bulk or fasciculation’s, a particular fine twitching of muscle etc. may be seen. Symptoms depend on the type of nerves affected (motor, sensory, or autonomic) and where the nerves are located in the body however one or more types of nerves may be affected. Common symptoms associated with damage to the motor nerve are muscle weakness, cramps, and spasms more over loss of balance and coordination may also occur. Sensory symptoms encompass loss of sensation and positive phenomena including pain. Damage to the sensory nerve can produce tingling, numbness, and a burning pain. Pain associated with this nerve is described in various ways such as the following: burning, freezing, or electric like, extreme sensitivity to touch etc. [45]. Proper diagnosis of neuropathy can lead to a solution that reduces pain or can at least manage it more effectively.

1.2.1 Types of neuropathy

There are several types of neuropathy which are as follows-i) Peripheral Neuropathy: In peripheral neuropathy, the nerves related to PNS are affected i.e. the nerves of extremities like toes, hand, feet, arms, fingers etc. Physical trauma, repetitive, infection, metabolic problems and exposure to toxins and some drugs can all lead to peripheral neuropathy [81].

i ) Proximal Neuropathy: In proximal neuropathy, the damage of nerves related to specially shoulders, thighs, hips or buttocks.

iii) Cranial Neuropathy: There are two types of cranial neuropathy i.e. optic neuropathy and auditory neuropathy. The optic neuropathy refers to the dysfunction of the optic nerves that carry signals from the eye retina to the brain, whereas auditory neuropathy refers to malfunctioning of the nerves that carries signals from inner ear to the brain.

iv) Autonomic Neuropathy: In this type of neuropathy, the nerves of involuntary nervous system are affected. These nerves control the heart rate, blood pressure circulation, digestion, bowel and bladder function, sexual response and perspiration etc.

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Following are most common morphology of neuropathy -

• Carpal tunnel syndrome

• Cubital Tunnel Syndrome

• Central pain syndrome

• Chronic inflammatory demyelinating polyneuropathy

• Guyon Canal Syndrome

• Cumulative trauma disorders

• Spinal disc herniation

• Guillain-Barre syndrome

• Tarsal Tunnel Syndrome

• Ulnar neuropathy

• Locked-In syndrome

1.3 Nerve Conduction Study

Nerve conduction study (NCS) measures how well and fast the nerves can send electrical signals. NCS is a medical diagnostic test commonly used to evaluate the nerve functioning, especially the ability of electrical conduction by the motor and sensory nerves of the human body [73, 7]. Nerve conduction velocity (NCV) is a common measurement made in NCS.

In NCS, the nerve is electrically stimulated by using a stimulating electrode circuit and the electrical impulse travelling from the point of stimulus is measured and recorded with a pair of electrodes that are placed on the skin over the nerve at various locations. The distance between the stimulating and recording electrodes positions are measured as well as the time for the stimulating impulse to travel from stimulating electrode to recording electrodes is also measured [8]. Finally the conduction velocity is measured by dividing the distance i.e. distances between stimulating and recording electrodes by the time [9]. A decreased value of NCV (m/sec) with the standard range of NCV of a healthy subject indicates nerve disease or abnormal pressure on the nerve i.e. neuropathy.

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Image 2

1.3.1 NCS parameters

The NCS signal with different parameters is shown in the Fig. 1.2 -

Fig. 1.2 NCS signal with different parameters [88]

The parameters responsible for NCS analysis are-

a) Compound muscle action potential (CMAP)

The CMAP is the summation of all underlying individual muscle fiber action potentials

[6]. Furthermore, the height of the evoked response i.e. CMAP is measured from baseline to negative peak [29] as shown in the Fig.1.2. Amplitudes are semi quantitative measure of the number of axons conducting impulses from stimulating to the recording points.

CMAP amplitudes are indicative of the efficiency of neuromuscular transmission.

Furthermore, the numbers of muscle fibers composition of the recorded muscles generate the action potentials [32, 38]. CMAP is one of the most important parameters of the NCS.

If a response is unelicitable i.e., has zero amplitude, then none of the other measurements can be performed [87].

b) Latency

The latency defines the time it takes for the action potential to travel from the stimulation site to the recording site and depends mainly on the conduction time in the peripheral axons. Moreover, if the electrodes are not over the end plates, the latency also includes the conduction time through the muscle fiber to the recording electrodes. There are two types of latencies i.e. distal and proximal based on stimulation site as shown in Fig 1.2.

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Image 3

Distal latency is the onset of a CMAP at the distal site of stimulation and it is measured from the stimulus to the onset of depolarization of the wave response, however, for proximal latency the stimulation site is the proximal position and the mechanism is same as the distal latency [7]. These two latencies are used to calculate the conduction velocity of the nerve. The motor latencies reflect the time required not only for passage of impulses along motor nerves, but also for neuromuscular transmission, and for the initiation of muscle action potentials [38].

c) Duration

This is the time interval during which the evoked response occurs after stimulation, expressed in milliseconds (ms). For CMAPs the duration typically is that period extending from the beginning to the end of the initial negative phase shown in Fig. 1.2.

The durations of the CMAPs mainly reflect the relative conduction rates of the impulses as they travel along the various axons between the stimulating and recording points.

Duration and amplitude are closely related; as the duration becomes more prolonged (i.e., the response becomes dispersed), the amplitude decreases.

Fig. 1.3 NCV calculation details [32]

d) Conduction Velocity

Conduction velocity (CV) is a measure of the velocity of impulse conduction through the nerves. This parameter is used to detect signs of nerve injury that makes it most important parameter of NCS signal. Most often, CVs are obtained by stimulating the nerve at two points along its course, subtracting the distal latency from the proximal latency, and then dividing that difference by the distance (as determined by surface measurements) between 6

the two stimulating points [7]. Therefore conduction velocity is the rate of conduction which is expressed as the distance travelled per unit of time, in m/sec (Fig. 1.3).

e) Area

Area is a function of both the amplitude and duration of the evoked response, it is measured in mVmsec (motor NCS). Compared to amplitude, it more accurately reflects the number of axons being activated. Nonetheless, it requires more technically sophisticated equipment and it can be compromised, just as the amplitude can be, by such factors as interphase cancellation i.e. when negative and positive phases of different motor unit action potentials overlap, they cancel each other because of temporal dispersion [38].

1.3.2 Types of NCS

There are four types of nerve conduction study techniques-

• Motor nerve conduction study (MNCS)

• Sensory nerve conduction study (SNCS)

• F wave study

• H-reflex study

Motor NCS are performed by applying an electrical stimulation to a peripheral nerve and CMAP responses are recorded