Optic Neuropathy, Ischemic

Common Surgical Procedures in Geriatric Patients

Demographic studies show that life expectancy for people in the USA has been trending upwards for the past several decades. As the population ages, the number of geriatric patients who will require surgery has also increased. Information from the National Hospital Discharge Survey reported that in 2006, 35.3% of all inpatient procedures and 32.2% of all outpatient procedures were in patients aged 65 and older. Common elective surgeries in elderly patients include cataract and lens procedures, spinal fusions and laminectomies, and total or partial hip and knee replacements. Common urgent surgeries in this population include thoracic and abdominal cancer resections, breast and prostate cancer resections, and cholecystectomies. Finally, common emergency surgeries in the elderly population include hip fracture repairs and other geriatric traumas.

Neurological Examination

A neurological exam, also called a neuro exam, is an evaluation of a person's nervous system that can be done in the physcians. It may be done with instruments, such as lights and reflex hammers. It usually does not cause any pain to the patient. The nervous system consists of the brain, the spinal cord, and the nerves from these areas. There are many aspects of this exam, including an assessment of motor and sensory skills, balance and coordination, mental status (the patient's level of awareness and interaction with the environment), reflexes, and functioning of the nerves. The extent of the exam depends on many factors, including the initial problem that the patient is experiencing, the age of the patient, and the condition of the patient.

Application of Nanomaterials in the Medical Field: A Review

Nanomaterials are particles in sizes from 1-100 nm. Nanomaterials have a wide field of applications in aviation and aerospace, chemical industries, optics, solar hydrogen, fuel cell, batteries, sensors, power generation, aeronautic industry, buildingconstruction industry, automotive engineering, consumer electronics, thermoelectric devices, pharmaceuticals, paints, and cosmetics. Also, efforts are being made to develop friendly alternate energy sources using nanomaterials. In this chapter, the main focus will be on the application of nanomaterials in various aspects of the medical field. Nanomaterials are used in various medical devices. Some of the nanomaterials used in the area of optical imaging are quantum dots, and in MRI are superparamagnetic iron oxide nanoparticles. Also, nanomaterials are applied in ultrasound imaging and radionuclide imaging. Due to the small size of batteries (e.g., for pacemakers) or electronic circuits and sensors utilized in medical devices presently made using nanomaterials. New ceramics consisting of materials derived from sintered nanopowders (comparable to 3D-printing) or having a specially designed surface are made from so-called nanostructures for teeth filling or screws for dental implants. For bio-detection of pathogens, detection of proteins, and phagokinetic studies, nanomaterials are also used. For fluorescent biological labels, drug and gene delivery, probing of DNA structure, tissue engineering, tumour destruction via heating (hyperthermia), separation and purification of biological molecules and cells, MRI contrast enhancement, osteoporosis treatment, infection prevention, bone regeneration are some of the applications of nanomaterials used in medicines. Cancer therapy, neurodegenerative disease therapy, HIV/AIDS therapy, ocular disease therapy, respiratory disease therapy, sight-restoring therapy, and gene therapy are various therapies nanomaterials are used Nanomaterials used in various surgeries are surgical oncology, thoracic surgery, replacement of heart with an artificial heart, vascular surgery, neurosurgery, radiosurgery, ophthalmic surgery, plastic and reconstructive surgery, maxillofacial surgery, orthopedic surgery, intracellular surgery by nanorobots. Although all applications of nanomaterials have pros and cons, care should be taken so that the cons can be minimized.

Tinospora cordifolia in Neurodegeneration: A Strong Antioxidant and Anti-inflammatory Phytotherapeutic Drug Candidate

Tinospora cordifolia is a Rasayana herb of Ayurveda, commonly known as “Heavenly Elixir” or “Amrita”, and one of the most exploited herbs in herbal medicines. T. cordifolia is well reported for its various pharmacological properties, such as anti-diabetic, anti-inflammatory, antipyretic, immunomodulatory, anti-cancer, cardioprotective, neuroprotective, and hepatoprotective activities. The prevalence of neurodegenerative diseases and other neurologic disorders is increasing worldwide. Oxidative stress and neuroinflammation are among the major pathologic mechanisms underlying neurodegenerative diseases. This chapter discusses the pieces of scientific evidence of the beneficial effects of T. cordifolia in various brain-related ailments. Various research groups have demonstrated the ability of T. cordifolia and its extracts to normalize oxidative stress and suppress the inflammatory response against various causative agents, and thus suggested that T. cordifolia has the potential to be a neurotherapeutic drug candidate in the future.

Role of Artificial Intelligence in Medicine and Health Care

With the passing decades, Artificial Intelligence (AI) is gaining high popularity in various domains. In this chapter, we aim to present the current scenario of the application of AI in the field of medical science. Firstly, we will introduce the early and basic role of AI in the medical field. We preceded the chapter with a summary of the most current applications of AI in various areas of medicine and health care. In this review, we have discussed the latest developments of applications of AI in biomedicine while predicting the risk of disease. Estimating the success ratio of the therapy also manages or reduces the severity of complications, taking care of ongoing patients, living assistance, biomedical information processing, biomedical research, and medical imagining. We also present a survey on AI techniques, which were used by many authors with different objectives in medical science. Furthermore, we showcase the effects of the usage of AI by highlighting the reduction in the rate of mortality, and fast and accurate diagnostics which help in decreasing errors related to human fatigue and lessening medical costs. Finally, we draw attention to some of the possible weaknesses, apprehensions, and uncertainties in using AI in medical science. We briefly review the efforts being made to improve the healthcare industry by offering various AI-based healthcare products.

Mitochondrial Dysfunction in Leprosy: Shedding Light on the Neurodegenerative Consequences

Leprosy is a chronic infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis. Dermal tissue macrophages and Schwann cells from peripheral nerves are the main host cells for the pathogen. The clinical manifestations of this disease depend basically on the host’s immune response to M. leprae. However, genes relevant to both innate and adaptive immune responses also seem to contribute to leprosy acquisition and to determine its clinical forms. The crucial clinical problem in leprosy is represented by episodes of intense inflammation. They represent a major problem in the course of leprosy, as reactional episodes can be responsible for permanent damage to nerves, causing deformities. Among bacterial pathogens, infection of peripheral nerves is a unique property of M. leprae. The intensity of the inflammatory reaction in response to tissue damage caused by pathogens is strongly associated with mitochondria and their respective mitochondrial DNA, since this organelle and its constituents act as potent ligands for several innate immunity receptors. In this chapter, we will first describe the general context of leprosy and its various clinical forms, diagnosis and treatment, highlighting episodes of acute inflammatory response during this pathology and, finally, we will outline some cellular mechanisms that lead to neurodegenerative consequences in leprosy. The literature partially attributes these to cytokines and, mainly, to TNF-α, as well as to changes in mitochondrial dynamics, especially mitochondrial DNA, when mitochondrial dysfunction seems to be involved in the pathogenesis of neuritis in leprosy.

Anesthetic Considerations for the Critically Ill Pediatric Patient

In comparison to adults, critical illness is relatively uncommon in the pediatric population. Many facilities may be unprepared or ill-equipped for treating these rare conditions. The conventional anesthesiologist may not be familiar with the common pathologies of critical illness in children. These patients may need complex and life-saving urgent procedures to stabilize them. It is logistically challenging to have pediatric trained personnel readily available at all hospitals and care centers. These patients have special perioperative needs that the anesthesiologist should consider. They may potentially present to the operating room, emergency department, or pediatric intensive care unit. Here, we offer a direct and practical approach to managing the care of these younger patients.

Anesthesia for Pediatric Patients with Common Comorbidities Part III

There have been dramatic improvements in the survival of neonates and children with many diseases and disorders due to advancements in medicine over the past several decades. These advances are attributed to the better understanding of these disease processes, the advent of multidrug combinations, molecularly targeted therapies, critical care and various surgical interventions. In the wake of this rapidly developing wide range of treatment protocols, the anesthesiologist needs to have a clear understanding of these disorders and their comorbidities, and stay abreast of the various treatment modalities, including their safety and toxicity profiles. This review attempts to emphasize some of the clinical conditions unique to these patients and special considerations for the conduct of anesthesia in this population. Some of the disease processes and comorbidities discussed here include anesthetic considerations for ex-premature infants, diabetes mellitus, obesity, childhood cancer, and children with congenital heart disease who present for non-cardiac surgery. The objective of this discussion is to provide an updated and comprehensive review of current perioperative anesthetic management of pediatric patients with these conditions. We also delineate the effects of anesthesia during the perioperative course, including major metabolic changes that may result in increased morbidity. We provide guidelines for any anesthesia provider involved in the care of these vulnerable patients. Special considerations need to be taken to promote the physical and mental wellbeing of these children and their families. Collaborative coordination with all providers involved in care is essential to provide safe and effective anesthesia to this subset of patients.

Subject Index

Updates on Pediatric Demyelinating Disorders

Myelin is a protective layer that enwraps the axonal terminals and is an essential component of the central nervous system white matter. Loss of myelin leads to conduction block in the axon leading to demyelinating disorders. Inherited poor formation of myelin is known as hypomyelination, and abnormally formed myelin is called dysmyelination. Demyelinating disorders exclude diseases where degeneration of the axon is the initial event and myelin is degraded secondarily. Most neurologists use the term demyelination only for acquired forms of loss of myelin with relative preservations of axons due to inflammation such as multiple sclerosis. Demyelinating disease in children may be monophasic (e.g., acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis) or chronic (multiple sclerosis and neuromyelitis optica). Pediatric multiple sclerosis is the most common demyelinating disorder in children. Recent genetic and clinical researches have significantly improved our understanding of the diverse spectrum of pediatric demyelinating disorders. In this chapter, an updated summary of the current knowledge on the categories, diagnosis, as well as management of pediatric demyelinating disorders has been presented.

Classification of Proliferative and Non- Proliferative Diabetic Retinopathy and its Implications

An understanding of the classification scheme of nonproliferative and proliferative diabetic retinopathy is essential for the proper management of diabetic eye disease. The level of retinopathy is based on clinical findings seen on fundus examination.

Diabetes, Cataract, and Glaucoma

Diabetes Mellitus (DM) affects many parts of the eye. While we traditionally associate vision loss from DM with diabetic retinopathy, it can affect various structures of the eye other than the retina. In this chapter, we will focus on the disease’s effects on the lens, and on the drainage apparatus of the eye. Specifically, we will look at cataract and glaucoma incidence in DM and its etiologic role, and then discuss treatment strategies.

Overview of Anterior and Posterior Segment Complications

Diabetic eye disease is a potential vision-threatening condition. The most well-known complication of uncontrolled diabetes is diabetic retinopathy, but diabetes can affect various structures of the globe other than the retina. Anterior segment complications include ocular surface disease, which includes Dry Eye Syndrome and diabetic keratopathy, cataracts, refractive changes, extraocular movement disorders, and neovascular glaucoma. Posterior segment complications include diabetic papillopathy and retinopathy. Diabetic retinopathy causes vision loss in multiple ways including macular edema and ischemia, vitreous hemorrhage, and retinal detachment. Tight glucose control can help to prevent these complications from occurring.

Neuro-Ophthalmic Complications of Diabetes Mellitus

Eye disease attributed to Diabetes can have devastating effects on all aspects of vision as all parts of the eyes are subject to damage including the optic nerve and cranial nerves. In this chapter, we will discuss the most common neuro-ophthalmic problems seen in diabetic patients.

Implication of Natural Compounds for the Prevention of Ocular Diseases

Our eyes are a window to this world and like other parts of our body are affected by various diseases and injuries. Prevalence of various ocular diseases is although very high, very few remedies are available. Diseases affecting eye and vision are on the rise particularly those associated with potentially blinding conditions such as diabetic retinopathy, age-related macular degeneration, and glaucoma. Prevention appears to be a better modality for most of the ocular diseases compared to that of the treatment options. Natural compounds have found its use in the prevention and treatment of many ocular diseases. Several natural compounds with properties such as anti-oxidative, anti-proliferative, immunomodulatory have been implicated in the prevention of various ocular diseases. However, there are many avenues left for the application of natural compounds for the prevention and treatment of various ocular diseases. Understanding of the probable mechanism responsible for the disease formation, identification of targets, evaluation of candidate molecules by in silico, in vitro and in vivo assays can strengthen the application of natural compounds for the prevention of ocular diseases. Besides disease prevention, natural compounds have also found its use in various ocular surgical procedures.

Non-Compaction Cardiomyopathy from Infancy to Adulthood

Accepted as an unclassified cardiomyopathy by the American Heart Association or a genetic cardiomyopathy by the European Society of Cardiology, left ventricular non-compaction is an intriguing, but poorly understood condition characterized by the presence of a non-compacted extensive myocardial layer lining the cavity of the left ventricle which potentially leads to malignant arrhythmias, cardiac failure, and thromboembolism. Whether it is distinct cardiomyopathy or a morphological heterogeneous clinical condition with phenotypic morphologic traits often overlapping other types of cardiomyopathies remains very much debated. Ventricular trabeculation and compaction are two of the many essential steps for generating a functionally competent ventricular wall whereas, hyper trabeculation and the lack of ventricular wall compaction (non-compaction) are also one of the significant cardio-embryogenic defects associated with left ventricular noncompaction. This chapter aims to discuss in detail the current knowledge on embryology, epidemiology, clinical spectrum, genetics as both an isolated trait, and as part of other cardiac diseases or complex syndromes. It also explains the physiology, and the present pathophysiological concepts of non-compaction cardiomyopathy, provide an up-to-date view on imaging and also reevaluate the current diagnostic criteria and its impact on overdiagnosis of left ventricular non-compaction as well as the available data on prognosis, and therapy. The chapter will even go further to describe the challenges, and uncertainties facing the medical community, and the future directions in diagnosing left ventricular non-compaction.

Vasculitis

Vasculitis is inflammation in vessel walls leading to poor blood circulation and damage to vessels. The vasculitis are devided into large vessel vasculitis (Takayasu arteritis [TAK] and Giant cell arteritis [GCA]), medium vessel vasculitis (Polyarteritis nodosa and Kawasaki disease), small vessel vasculitis associated with antineutrophil cytoplasmic antibody (microscopic polyangiitis [MPA], granulomatosis with polyangiitis [GPA], eosinophilic granulomatosis with polyangiitis [EGPA]) and others. TAK affects patients younger than 50 years, and GCA after age 50. Clinical features include leg claudication, headaches, postural dizziness, visual disturbances and reduced or absent upper limb pulses. Management of TAK and GCA include high doses of GCS. Treatment of GCA can prevent blindness due to occlusion of optic arteries. New option is tocilizumab. Polyarteritis nodosa inflammation involves the skin, kidneys, peripheral nerves, muscles, and gut in patients between 40-60 years old. Management includes GCS, CYC and AZA. Kawasaki disease is an acute febrile mucocutaneous and lymph node disease affecting young children. Coronary arteries are often involved. Management includes IVIG and aspirin. GPA is necrotizing granulomatous inflammation involving the upper and lower respiratory tract, necrotizing glomerulonephritis, ocular vasculitis, pulmonary capillaritis with hemorrhage and granulomatous and nongranulomatous extravascular inflammation is common. c-ANCA is present in 98% of patients. Management is high doses of GCS, CYC, rituximab and AZA. EGPA is characterized by pulmonary and systemic small vessel vasculitis, granulomas and hypereosinophilia. Clinical features are atopic history, asthma, allergic rhinitis, pulmonary infiltrates, mono/polyneuropathy, mononeuritis multiplex, purpura and eosinophilia. Management is high doses of GCS, CYC and AZA.

Retinal Angiogenesis: Towards a Cure

Retinal angiogenesis is evident in a number of different pathological and degenerative conditions including proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. There have been numerous attempts to control retinal angiogenesis but the fragility of the tissue and the presence of the blood retinal barrier limiting the transport of pharmacological agents has proved problematic in the therapeutic regulation of this process. This chapter presents the structure of the retina in relation to the structure of the eye. In addition, the molecular initiators of angiogenesis are discussed and in particular how the hyperglycaemic environment leads to oxidative stress in proliferative diabetic retinopathy. The lack of perfusion due to damage from the diabetic milieu, the impaired retinal development in the case of retinopathy of prematurity and the aging of the retinal pigment epithelial cells are characteristics that are associated with angiogenesis. The consequent reduction in oxygen level that follows impaired perfusion creates an hypoxic environment that stabilises hypoxia inducible factor type 1 alpha and precipitates the activation of hypoxia inducible factor type 1. The activation of this transcription factor leads to the increased expression of a number of genes including vascular endothelial growth factor and this is central to the angiogenic process. The development of specific pharmacological inhibitors of aldose reductase, protein kinase Cβ, advanced glycatedend products, hypoxia inducible factor type 1 alpha and vascular endothelial growth factor are reviewed. Inhibition using small interfering RNAs to inhibit specific pathways and the use of cell replacement is discussed in terms of their therapeutic potential.

Current Therapeutic Situation

Craniopharyngiomas are benign midline tumors that have a propensity for local recurrence and are ideally curable via total surgical resection. Many survivors suffer from behavioral, cognitive, endocrine, hypothalamic, and visual disturbances. Optimal management remains highly controversial. In this chapter, we reviewed the therapy strategies for Craniopharyngiomas including surgery, radiotherapy and chemotherapy. Complete resection is even more important in children, especially those younger than 3 years, because of the additional morbidity associated with radiotherapy during early childhood. The aim of radiotherapy is to achieve long-term disease control in patients lacking complete removal or with recurrent tumors. Systemic chemotherapy has rarely been reported in terms of craniopharyngioma management. Local intratumoral chemotherapy for craniopharyngioma was used to treat difficult, recurrent cystic tumors and has subsequently been employed as a strategy to avoid late-term effects of surgery or radiotherapy. The roles of all therapies should be balanced according to factors such as the patient’s age, the tumor size and location, and prior treatment.

The Endocrinology and Iatrogenesis

Iatrogenicity is inherent to endocrinology, being a consequence of treatment (e.g., use of thyroid hormones in large doses to suppress thyroid stimulating hormone [TSH] in thyroid cancer) or occurring due to a lack of patient compliance (e.g., lack of adequate controls in chronic diseases, such as Hashimoto’s chronic thyroiditis). Quite often, it is induced as a side effect of medicines (e.g., long-lasting use of antithyroid agents or glucocorticoids). In this chapter, we review the most important iatrogenic effects, according to the main features of endocrinology. We present certain drugs that can trigger particular syndromes, such as the syndrome of inappropriate antidiuretic hormone secretion (SIAHS), along with preparations with pitressin and complications of treatment performed for pituitary adenomas, potential complications of drugs used to treat pituitary insufficiency in children and other specific features constituting required knowledge for medical practitioners. All therapeutic modalities of hyperthyroidism (medical, surgical, radioiodine) can cause iatrogenic pathology. For example, the euthyroid state is a sine qua non condition of thyroid surgery (except the thyrotoxic storm in advanced stages). Radioiodine treatment, in turn, has its own contraindications. Iodine-containing preparations can activate thyroid autonomies and aggravate autoimmune thyroiditis and overt hyperthyroidism. In hypothyroid elderly and cardiac patients, the thyroid hormone substitution must be applied only after initial cardiovascular treatment, in small, gradually increasing doses. In Addison’s disease, indication of dietary salt reduction alongside glucocorticoid substitution, or the lack of increase in glucocorticoid dose in acute injuries, are serious iatrogenic complications.

Iatrogenic Lesions in Neurology

Iatrogenic neurological disorders can be induced by several factors, such as pharmacological agents prescribed for treatment or prevention (drug-induced neurological disorders [DIND]), complications of diagnostic and treatment procedures, like cerebral angiography or lumbar puncture, organ transplantation (related to the surgical procedure of transplantation, post-transplant immunosuppression, opportunistic infection or the inherent disorders that lead to transplantation), radiation therapy, etc. Iatrogenic neurological effects may be devastating due to the higher potential irreversibility of central nervous system, peripheral nervous system, neuromuscular junction (NMJ) and/or muscular system involvement. DIND represent the majority of iatrogenic neurological disorders. Drugs may directly induce neurological damage (through primary neurotoxicity, such as damage to the bloodbrain barrier [BBB], disturbances of brain energy metabolism, ion channels/neurotransmitters disturbances, mitochondrial dysfunction, metabolitemediated toxins, drug-induced selective cell death) or do so indirectly (cardiovascular, hematological or renal effects). Identification of DIND is important because early recognition and drug withdrawal can prevent irreversible damage. The numerous intrinsic risk factors for DIND should be well known by medical practitioners.

Iatrogenic Pathology of the Cardiovascular System

This chapter includes a synthesis of data regarding cardiovascular-related lesions induced by medical drugs or radiotherapy, and also relates to the specific injuries that can be caused by diagnostic and/or therapeutic interventions. The effects of chemotherapeutics and non-chemotherapeutic drugs on the myocardium are analyzed in detail, with a focus on anthracycline-induced cardiovascular effects in children. Some of the disorders are illustrated using representative pictures taken during autopsies. Although a common technique, insertion of prosthetic grafts can lead to complications, such as thrombosis, aberrant neointimal hyperplasia or dehiscence. Percutaneous vascular intervention complications can be related to the catheter or to the intervention itself. The differences between in-stent restenosis and postoperative thrombosis are also presented. The final part of this chapter is dedicated to open heart surgical intervention complications.

Genetic Causes of Ischemic Stroke

The pathogenesis of ischemic stroke remains unknown but a better knowledge of its pathogenetic mechanism may help us in identifying more effective therapies to reduce the the disease burden. Family and twin studies support the role of genetic factors in stroke pathophysiology. A number of monogenic conditions presenting with stroke have been described. They account for only a small proportion of strokes, but it is believed they are underestimated and the study of these diseases may provide insight in the pathogenic pathways of stroke, given also the existence of animal models in which examine disease mechanisms. However, in most cases, stroke is believed to be a multifactorial disorder. A number of genetic association studies using the candidate gene approach have failed in demonstrating reliable associations between stroke and genetic variants. Although several molecular variants resulted from GWAS strongly associated with ischemic stroke risk, they account for only a small part of the risk of ischemic stroke. Moreover, the pathogenic significance of many of these genetic variants has yet to be determined by functional studies so that the significance of these findings in clinical practice has been limited. Interestingly, the studies conducted so far demonstrated that the majority of the identified genetic variants found were associated with specific stroke subtypes, supporting the hypothesis that distinct genetic architecture and pathophysiological mechanisms underlie specific stroke subtypes.

Central Retinal Vein Occlusion

Uncommon Cause of Stroke: Diagnosis and Treatment (Part I)

This chapter contains detailed, up-to-date information about the nature, diagnosis, and treatment of those relatively uncommon types of cerebrovascular disease that cause strokes. Although many of the conditions discussed are rare, the chapter covers the causes of up to 10% to 15% of all strokes and of up to 40% of strokes in young adults. This chapter may be an essential resource to help physicians diagnose and treat stroke patients who do not fit well into the usual clinical categories.

Discussed within are the dissection of carotid and vertebral arteries, the more relevant cause of stroke in the young. The collagen vascular disorders causing stroke as a consequence of dissection , occlusion and, more rarely, rupture of extracranial and intracranial arteries are reported in detail. Various forms of cerebral angiitis, with focus on the primary central system vasculitis and reversible cerebral vasoconstriction syndrome are discussed.

Treatment of Diabetic Neuropathy - Current Possibilities and Perspectives

Diabetic neuropathy (DN), characterized by nerve damage associated with diabetes mellitus, belongs among the earliest and most frequent chronic diabetic complications. It may occur in clinical form (as peripheral sensory/motor, autonomic, proximal, painful or focal) or in subclinical form detectable just by sensitive diagnostic methods. The etiology of DN is complex and not fully understood, untill now. Longterm hyperglycemia triggers a variety of interacting pathways such as production of advanced glycation end products (AGEs), products of oxidative stress and polyol pathway, protein kinase C activation, decrease activity of Na+K+ATP-ase, changed concentration of neural growth factor and production of proinflammatory cytokines. These pathomechanisms may target directly on nerve cells or on endothelial cells causing the microangiopathy of vasa nervorum.

According to multicentric studies, duration and poor compensation of diabetes are the principal risk factors associated with the development of chronic diabetic complications, so the basis for the management is to maintain adequate metabolic compensation. Intensified insulin regimen is the most effective in the treatment of patients with type 1 diabetes. In patients with type 2 diabetes, administration of selected peroral antidiabetics or insulin therapy is considered. Physical activity, lifestyle and dietary management also contribute to euglycemia. Currently used management of DN includes supportive (alpha-lipoic acid, vitamins, antioxidants) and symptomatic treatment (painkillers, beta blockers, magnetotherapy). Other therapeutic possibilities are experimental so far. These drugs interfere with the pathophysiological processes and few of them have been shown to be beneficial in clinical studies (inhibitors of aldose reductase, selective inhibitor of protein kinase C beta, C peptide substitution), however, the effect of other medicines seems to be controversial (vascular endothelial growth factor, erythropoietin). This chapter brings comprehensive review about current possibilities and future perspectives in the management of diabetic neuropathy.

Myocardial Ischemia, Myocardial Infarction

In this chapter, we address the basic notions of myocardial ischemia and myocardial infarction. Cardiac ischemia changes the electrical activity and the genesis of the action potential and of the resting potential. It can be divided into 3 forms; ischemia, lesion and necrosis. Modification of the QRS complex, the ST segment and T wave is observed. Ischemia is a biochemically reversible anomaly. Moreover, it is mainly ionic, notably potassium disturbances which underlie ST and T wave changes. Lesion is a more severe form of cardiac ischemia but is still reversible, with interstitial oedema and biochemical disturbances. Essentially, it is the ST segment, which is modified, in that it becomes displaced from the isoelectric baseline. The ST segment vector is determined in the same manner as that of the QRS complex: it allows for better localization of the site of the stenosis or obstruction of the culprit artey. The more leads exhibit ST changes, the bigger the territory at risk. A sum total of ST depression or elevation greater than 12 mm in the different leads implies widespread ischemia. The most severe stage of cardiac ischemia is necrosis since there is cellular death with cessation of electrical activity. Neither the action potential nor the resting membrane potential exists anymore and the conduction capability has ceased. The start of depolarisation (QRS) is modified with the apparition of an \"electrical hole\" (Q waves), which could progress as far as the total disappearance of the positive forces (R waves) and a QS morphology; the necrosis is transmural affecting therefore the full thickness of the myocardium. Acute coronary syndrome includes STEMI and non-STEMI. STEMI (ST Segment Elevation Myocardial Infarction) is the acute coronary syndrome with ST segment elevation and non-STEMI is associated with other ST segment changes (negative T waves or ST segment depression) but not ST segment elevation. Electrocardiographically, the electrical changes recorded in the different territories differ according to the coronary artery involved. There is a good correlation between the ischemic zone and the coronary artery affected. Ischemia is recorded by the electrode \"exploring\" the territory implicated. Involvement of the right coronary artery gives rise to inferior wall ischemia and this is characterized on the ECG as changes in leads II, III and aVF. Involvement of the left coronary artery gives rise to anterior wall ischemia and this is characterized on the ECG as changes in precordial leads.

Cell Encapsulation Technology: An Alternative Biotechnological Platform for the Treatment of Central Nervous System Diseases

Cell encapsulation technology is based on the immobilization of cells that secrete active therapeutic agents, in structures made from different biomaterials and surrounded by a semipermeable membrane that protects the cells from the host immune response and the mechanical stress. This technology has proven to be a suitable treatment strategy for different kinds of diseases such as diabetes, heart failure, anemia, cancer or central nervous system (CNS) diseases since promising results have been obtained in numerous works that have been carried out in this field. For this last application, cell encapsulation technology presents exceptional features as it allows direct, continuous and long-lasting release of the desired therapeutic product, next to the affected tissue and without crossing the blood-brain-barrier (BBB). Numerous studies have been carried out using this technology, in different animal models of CNS diseases, in which encouraging results have been obtained. Moreover, the rapid developments achieved in recent years, have allowed the application of these strategies in several advanced clinical trials, reflecting the potential of these techniques. However, there are still some features that must be optimized before cell encapsulation technology can be applied in clinical practice. This chapter will focus on the application of cell encapsulation technology in the treatment of CNS diseases, such as epilepsy, different neurodegenerative disorders- Parkinson, Alzheimer, Amyotrophic lateral sclerosis or Huntington-, pathologies caused by traumas or ischemic processes and brain tumors.

Targeted Delivery of Short Interfering RNAs - Strategies for In Vivo Application

During the last decade, an increased amount of oligonucleotides have been developed as promising therapeutic agents for treatment of diseases. siRNA/shRNA is one promising example of therapeutic oligonucleotides which can inhibit target gene expression by degrading mRNA in a highly sequence-specific manner. Although, siRNA shows potential therapeutic properties, the specific delivery remains a major barrier for clinical development of siRNA-based drugs. In this chatper, we provide an overview of current progress in the field of siRNA/shRNA delivery and discuss recent patents and technical advances in the development of efficient small RNA delivery vehicles including strategies to enhance their pharmacokinetic properties, to promote their cellular uptake, and to foster corresponding clinical trials.

miRNAs in Myocardial Infarction

The aim of this chapter is to provide an overview on the role of miRNAs in myocardial ischemia, ischemia/reperfusion injury and ischemic preconditioning. Myocardial ischemia due to occlusion of coronary arteries constitutes the major cause of mortality and morbidity of humans worldwide by causing an array of injuries. Timely myocardial reperfusion remains the most effective treatment strategy for reducing myocardial infarct size, preventing left ventricular remodelling, preserving left ventricular systolic function and improving clinical outcomes. However, the full benefits of myocardial reperfusion are not realized, given that the actual process of reperfusing ischemic myocardium can independently induce myocardial injury. On the other hand, heart has endogenous cardioprotective capability against myocardial/reperfusion injury, called ischemic preconditioning. Recent studies indicate that miRNAs are implicated in all these different aspects of myocardial ischemia. This chapter describes the role of miR-1 and mR-133 in myocardial ischemia, miR-21, miR-29 and miR-320 in ischemia/reperfusion injury, and miR-21 and miR-199a in preconditioning.

Recent Patents on Therapeutic Agents for Cancer

Cancer is one of the most dreaded diseases with a complex pathogenesis, which threats human life greatly. Multidisciplinary scientific investigations are making best efforts to combat this disease and put to the identification of novel anticancer agents. Patent anticancer agents registered in China are therefore increasing dramatically during the past ten years, which will be reviewed briefly in this article.

I. Platinum complexes

II. Anthracycline analogs (including doxorubicin derivatives)

III. Quinoline analogs

IV. Podophyllotoxins analogs

V. Taxane analogs

Neurological Complications of Antiangiogenic Therapy

Since the discovery of the principles of angiogenesis and the drugs with antiangiogenic properties, the science has evolved greatly in understanding the pathophysiology of several diseases like cancer and the development of drugs that act in the cascade of mechanisms related to angiogenesis. Due to the systemic action of antiangiogenic therapy, patients may experience several side effects, among them those related to the nervous system. Several neurological complications have been described in patients treated with antiangiogenic therapy. The neurological side effect profile of the new agents is largely unknown and may include central (reversible posterior leukoencephalopathy, strokes, encephalopathy, seizures) and peripheral neurotoxicity (autonomic, sensory or sensorimotor neuropathy) depending on the specific agent. The peripheral neurotoxicity of relatively older agents such as bortezomib and thalidomide is well described and health care professionals dealing with patients treated with such medications need to be aware of these complications. Further research is necessary to understand the mechanisms and foster prevention and treatment of these neurological complications.