Nervous Systems Research Articles

Construction of the chronic temporomandibular disorder patients: the association between neural and psychological pathways.

Chronic temporomandibular disorder (cTMD) as a term based on the diagnostic criteria for temporomandibular disorders (DC/TMD) classification refers, in this paper, to the condition listed that has a non-mechanical association without any obvious organic cause. Specifically, this is the condition that falls under the International Classification of Diseases 11th revision (ICD-11) classification of chronic primary and chronic secondary pains. This implies that there is increased responsiveness of nociceptive neurons in the central nervous system, a phenomenon known as central sensitisation. cTMD patients may have their beginning with genetic susceptibility to pain. Although no single gene is exclusively linked to cTMD, various genes associated with nervous and musculoskeletal systems are believed to play a role. Environmental triggers and epigenetic changes are also thought to contribute to cTMD development. The biopsychosocial model emphasises the need to comprehensively address biological, psychological and social factors in cTMD assessment and management. In this study, we leverage the cyclic causation framework within the biopsychosocial model to illuminate the intricate interplay between biological and psychosocial factors in the context of cTMD. The conceptualisation of cTMD involves the dynamic evolution of genetic predispositions, influenced by life events and other biological susceptibilities. These factors collectively contribute to the emergence of nociplastic changes, ultimately manifesting as the distinctive features observed in individuals afflicted with cTMD.

A reduced proteomic signature in critically ill Covid-19 patients determined with plasma antibody micro-array and machine learning.

COVID-19 is a complex, multi-system disease with varying severity and symptoms. Identifying changes in critically ill COVID-19 patients' proteomes enables a better understanding of markers associated with susceptibility, symptoms, and treatment. We performed plasma antibody microarray and machine learning analyses to identify novel proteins of COVID-19. A case-control study comparing the concentration of 2000 plasma proteins in age- and sex-matched COVID-19 inpatients, non-COVID-19 sepsis controls, and healthy control subjects. Machine learning was used to identify a unique proteome signature in COVID-19 patients. Protein expression was correlated with clinically relevant variables and analyzed for temporal changes over hospitalization days 1, 3, 7, and 10. Expert-curated protein expression information was analyzed with Natural language processing (NLP) to determine organ- and cell-specific expression. Machine learning identified a 28-protein model that accurately differentiated COVID-19 patients from ICU non-COVID-19 patients (accuracy = 0.89, AUC = 1.00, F1 = 0.89) and healthy controls (accuracy = 0.89, AUC = 1.00, F1 = 0.88). An optimal nine-protein model (PF4V1, NUCB1, CrkL, SerpinD1, Fen1, GATA-4, ProSAAS, PARK7, and NET1) maintained high classification ability. Specific proteins correlated with hemoglobin, coagulation factors, hypertension, and high-flow nasal cannula intervention (P < 0.01). Time-course analysis of the 28 leading proteins demonstrated no significant temporal changes within the COVID-19 cohort. NLP analysis identified multi-system expression of the key proteins, with the digestive and nervous systems being the leading systems. The plasma proteome of critically ill COVID-19 patients was distinguishable from that of non-COVID-19 sepsis controls and healthy control subjects. The leading 28 proteins and their subset of 9 proteins yielded accurate classification models and are expressed in multiple organ systems. The identified COVID-19 proteomic signature helps elucidate COVID-19 pathophysiology and may guide future COVID-19 treatment development.

Presynaptic Adrenoceptors.

Presynaptic α2-adrenoceptors are localized on axon terminals of many noradrenergic and non-noradrenergic neurons in the peripheral and central nervous systems. Their activation by exogenous agonists leads to inhibition of the exocytotic release of noradrenaline and other transmitters from the neurons. Most often, the α2A-receptor subtype is involved in this inhibition. The chain of molecular events between receptor occupation and inhibition of the exocytotic release of transmitters has been determined. Physiologically released endogenous noradrenaline elicits retrograde autoinhibition of its own release. Some clonidine-like α2-receptor agonists have been used to treat hypertension. Dexmedetomidine is used for prolonged sedation in the intensive care; It also has a strong analgesic effect. The α2-receptor antagonist mirtazapine increases the noradrenaline concentration in the synaptic cleft by interrupting physiological autoinhibion of release. It belongs to the most effective antidepressive drugs. β2-Adrenoceptors are also localized on axon terminals in the peripheral and central nervous systems. Their activation leads to enhanced transmitter release, however, they are not activated by endogenous adrenaline.

Peripheral preprocessing in Drosophila facilitates odor classification

The mammalian brain implements sophisticated sensory processing algorithms along multilayered ("deep") neural networks. Strategies that insects use to meet similar computational demands, while relying on smaller nervous systems with shallow architectures, remain elusive. Using Drosophila as a model, we uncover the algorithmic role of odor preprocessing by a shallow network of compartmentalized olfactory receptor neurons. Each compartment operates as a ratiometric unit for specific odor-mixtures. This computation arises from a simple mechanism: electrical coupling between two differently sized neurons. We demonstrate that downstream synaptic connectivity is shaped to optimally leverage amplification of a hedonic value signal in the periphery. Furthermore, peripheral preprocessing is shown to markedly improve novel odor classification in a higher brain center. Together, our work highlights a far-reaching functional role of the sensory periphery for downstream processing. By elucidating the implementation of powerful computations by a shallow network, we provide insights into general principles of efficient sensory processing algorithms.

Sex Differences in Visceral Pain and Comorbidities: Clinical Outcomes, Preclinical Models, and Cellular and Molecular Mechanisms

Sexual dimorphism of visceral pain has been documented in clinics and experimental animal models. Aside from hormones, emerging evidence suggests the sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and the American College of Gastroenterology (ACG), up to 25% of the population have visceral pain at any one time, and in the United States 10–15 percent of adults suffer from irritable bowel syndrome (IBS). Here we examine the preclinical and clinical evidence of sex differences in visceral pain focusing on IBS, other forms of bowel dysfunction and IBS-associated comorbidities. We summarize preclinical animal models that provide a means to investigate the underlying molecular mechanisms in the sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems, and the communication of gut microbiota and neural systems all contribute to sex-dependent nociception and nociplasticity in visceral painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

Neuropsychological mechanisms of observational learning in human placebo effects.

Scientific evidence indicates that placebo effects are psychoneurobiological events involving the contribution of distinct central nervous systems and peripheral physiological mechanisms that influence pain perception and other symptoms. Placebo effects can occur without formal conditioning and direct prior experience because crucial information can be acquired through observational learning. Observation of benefits in another person results in placebo effects of a magnitude like those induced by directly experiencing an analgesic benefit. Understanding the psychological mechanisms of observationally induced placebo effects is a complex and multifaceted endeavor. While previous reviews have highlighted various frameworks and models to understand these phenomena, the underlying biological mechanisms have been overlooked. We summarize critically current understanding of its behavioral and neural mechanisms. Understanding the neural mechanisms of hypoalgesia driven by observation can serve as a foundation for future development of novel theoretical and methodological approaches and ultimately, applications.

Effect of a helium and oxygen mixture on physiological parameters of rats with cerebral arterial air embolism

Introduction: Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture.Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling.Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE.Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

Expression of ChAT, Iba-1, and nNOS in the Central Nervous System following Facial Nerve Injury

Expression of ChAT, Iba-1, and nNOS in the Central Nervous System following Facial Nerve Injury

Beta-Cyfluthrin-Induced Hepatic Alterations in Zebrafish: Enzymatic Profiles and Oxidative Stress Responses

Beta-Cyfluthrin is a widely used pesticide belonging to class of synthetic pyrethroids which affects the central and peripheral nervous systems. The current study investigates the impact of beta-Cyfluthrin on the biochemical parameters of liver of zebrafish (Danio sp.). Adult zebrafish were exposed to concentrations of 0.25, 0.5, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin for acute (96 hours) and chronic (21 days) exposure periods respectively (n=20). It was observed that exposure to beta-Cyfluthrin led to variations in biochemical markers in both acute and chronic exposure groups. Liver function tests revealed significant elevated activity of alanine transaminase (ALT) and aspartate transaminase (AST) at exposure concentrations of 2.0 and 4.0 µg/L of beta-Cyfluthrin in both acute and chronic groups, while acid phosphatase (ACP) and alkaline phosphatase (ALP) activity decreased significantly at concentrations of 1.0, 2.0 and 4.0 µg/L in the chronic group. Lipid peroxidation exhibited a concentration and time-dependent increase with significant difference at 1.0, 2.0 and 4.0 µg/L in both acute and chronic groups, while superoxide dismutase (SOD) and peroxidase (PER) levels declined significantly in both acute and chronic exposure groups at exposure concentrations of 1.0, 2.0 and 4.0 µg/L for SOD and 2.0 and 4.0 µg/L for PER. Catalase (CAT) initially increased significantly in acute groups of 1.0, 2.0 and 4.0 µg/L but decreased in chronic ones. Glutathione S-transferase (GST) levels exhibited a significant increase at lower concentrations of 0.25 µg/L but a decrease at higher concentrations, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin. The level of significance were considered at p&lt;0.05 and p&lt;0.01. This research suggests that exposure to beta-Cyfluthrin leads to hepatic damage in adult zebrafish. This indicates a potential risk to non-target aquatic fauna, through runoff where beta-Cyfluthrin is used as an agricultural pesticide.

Heart rate variability as a preictal marker for determining the laterality of seizure onset zone in frontal lobe epilepsy

Determining the laterality of the seizure onset zone is challenging in frontal lobe epilepsy (FLE) due to the rapid propagation of epileptic discharges to the contralateral hemisphere. There is hemispheric lateralization of autonomic control, and heart rate is modulated by interactions between the sympathetic and parasympathetic nervous systems. Based on this notion, the laterality of seizure foci in FLE might be determined using heart rate variability (HRV) parameters. We explored preictal markers for differentiating the laterality of seizure foci in FLE using HRV parameters. Twelve patients with FLE (6 right FLE and 6 left FLE) were included in the analyzes. A total of 551 (460 left FLE and 91 right FLE) 1-min epoch electrocardiography data were used for HRV analysis. We found that most HRV parameters differed between the left and right FLE groups. Among the machine learning algorithms applied in this study, the light gradient boosting machine was the most accurate, with an AUC value of 0.983 and a classification accuracy of 0.961. Our findings suggest that HRV parameter-based laterality determination models can be convenient and effective tools in clinical settings. Considering that heart rate can be easily measured in real time with a wearable device, our proposed method can be applied to a closed-loop device as a real-time monitoring tool for determining the side of stimulation.

Rabies death in a prisoner: necessity for medical history documentation

Rabies is a zoonotic illness with a high mortality rate that attacks mammals' central nervous systems. It is a viral illness that may be avoided with immunization. Up to 99% of the human rabies transmissions occur in dogs, making them the primary cause of rabies mortality in humans. It is a case-report of rabies death in a 55-years old male, a prisoner from Phulbani Jail (Kandhamal), who was presented to MKCG Medical College and Hospital casualty with with chief complaints of difficulty in breathing and difficulty in drinking water since last night on 17 July 2023, at 11:19 pm. The patient had a history of dog bite exposure four years ago, for which he had not received any post-exposure prophylaxis. The patient was identified as having a likely case of rabies based on his previous history of animal bite and clinical manifestations. Patient was declared dead on 18 July 2023 at 10:30 am. Rabies diagnosis was confirmed by pathological examination of brain sample which showed presence of Negri bodies. This case-report focuses on the importance of proper medical history information including any animal bite exposure especially for convicts before admitting in prison so as to avoid later morbidity and its legal consequences. Such kind of incident also shows that there is lack of awareness regarding rabies in community. In this instance, mortality may have been prevented if the patient had finished the anti-rabies vaccine regimen and made it to a higher center in time for immunoglobulin. Increasing rabies vaccination awareness among the general public can help reduce rabies-related deaths.

Anti-fatigue activity of methyl dihydrojasmonate and linalool in a rat model evaluated by a novel index for neuro-immune and oxidative stress interactions

Avoiding fatigue is a long-standing challenge in both healthy and diseased individuals. Establishing objective standard markers of fatigue is essential to evaluate conditions in spatiotemporally different locations and individuals and identify agents to fight against fatigue. Herein, we introduced a novel method for evaluating fatigue using nervous system markers (including dopamine, adrenaline, and noradrenaline), various cytokine levels (such as interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-10, IL-2, IL-5 and IL-17A), and oxidative stress markers (such as diacron-reactive oxygen metabolites [d-ROMs] and biological antioxidant potential [BAP]) in a rat fatigue model. Using this method, the anti-fatigue effects of methyl dihydrojasmonate (MDJ) and linalool, the fragrance/flavor compounds used in various products, were assessed. Our method evaluated the anti-fatigue effects of the aforementioned compounds based on the changes in levels of the nerves system markers, cytokines, and oxidative stress markers. MDJ exerted more potent anti-fatigue effects than linalool. In conclusion, the reported method could serve as a useful tool for fatigue studies and these compounds may act as effective therapeutic agents for abrogating fatigue symptoms.

Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders

The nervous and immune systems are highly developed, and each performs specialized physiological functions. However, they work together, and their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, and more general metabolites, are essential for the appropriate regulation of both systems. Tryptophan, an essential amino acid, is converted into functional molecules such as serotonin and kynurenine, both of which play important roles in the nervous and immune systems. The role of kynurenine metabolites in neurodegenerative and psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity of the kynurenine pathway is a critical risk factor for septic shock. In this review, we first outline neuroimmune interactions and tryptophan derivatives and then summarized the changes in tryptophan metabolism in neurological disorders. Finally, we discuss the potential of tryptophan derivatives as therapeutic targets for neuroimmune disorders.

Probabilistic risk assessment of dietary exposure to lead in residents of Guangzhou, China

Lead and its compounds can have cumulative harmful effects on the nervous, cardiovascular, and other systems, and especially affect the brain development of children. We collected 4918 samples from 15 food categories in 11 districts of Guangzhou, China, from 2017 to 2022, to investigate the extent of lead contamination in commercial foods and assess the health risk from dietary lead intake of the residents. Lead was measured in the samples using inductively coupled plasma mass spectrometry. Dietary exposure to lead was calculated based on the food consumption survey of Guangzhou residents in 2011, and the health risk of the population was evaluated using the margin of exposure (MOE) method. Lead was detected in 76.5% of the overall samples, with an average lead content of 29.4 µg kg−1. The highest lead level was found in bivalves. The mean daily dietary lead intakes were as follows: 0.44, 0.34, 0.25, and 0.28 µg kg−1 body weight (bw) day−1 for groups aged 3–6, 7–17, 18–59, and ≥ 60 years, respectively. Rice and rice products, leafy vegetables, and wheat flour and wheat products were identified as the primary sources of dietary lead exposure, accounting for 73.1%. The MOE values demonstrated the following tendency: younger age groups had lower MOEs, and 95% confidence ranges for the groups aged 3–6 and 7–17 began at 0.6 and 0.7, respectively, indicating the potential health risk of children, while those for other age groups were all above 1.0. Continued efforts are needed to reduce dietary lead exposure in Guangzhou.

Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.

Transient receptor potential canonical 3 (TRPC3) protein belongs to the TRP family of nonselective cation channels. Its activation occurs by signaling through a G protein-coupled receptor (GPCR) and a phospholipase C-dependent (PLC) pathway. Perturbations in the expression of TRPC3 are associated with a plethora of pathophysiological conditions responsible for disorders of the cardiovascular, immune, and central nervous systems. The recently solved cryo-EM structure of TRPC3 provides detailed inputs about the underlying mechanistic aspects of the channel, which in turn enables more efficient ways of designing small-molecule modulators. Pharmacologically targeting TRPC3 in animal models has demonstrated great efficacy in treating diseases including cancers, neurological disorders, and cardiovascular diseases. Despite extensive scientific evidence supporting some strong correlations between the expression and activity of TRPC3 and various pathophysiological conditions, therapeutic strategies based on its pharmacological modulations have not led to clinical trials. The development of small-molecule TRPC3 modulators with high safety, sufficient brain penetration, and acceptable drug-like profiles remains in progress. Determining the pathological mechanisms for TRPC3 involvement in human diseases and understanding the requirements for a drug-like TRPC3 modulator will be valuable in advancing small-molecule therapeutics to future clinical trials. In this review, we provide an overview of the origin and activation mechanism of TRPC3 channels, diseases associated with irregularities in their expression, and new development in small-molecule modulators as potential therapeutic interventions for treating TRPC3 channelopathies.

Neuroimmunological effects of omega-3 fatty acids on migraine: a review

Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.

Clinical Experience With Acute Phase Repair of Facial Nerve Dissections.

The purpose of this study was to evaluate the facial nerve recovery of patients with traumatic facial nerve transections after tension-free end-to-end nerve epineural anastomosis during the acute phase. A total of 11 patients with traumatic facial nerve transections during the acute phase were surgically treated in the authors' department from November 2016 to August 2022. The case data and imaging data were collected from the patients, and the House-Brackman evaluation system of the facial nerve was applied to assess the recovery of facial nerve function, and the higher the grade, the worse the facial nerve function. Of the patients, 90.9% recovered to H-B grade II or below, and there were differences in the degree of recovery of the facial nerve function among the branches, and the ones that recovered to H-B grade II or below after surgery were 100% of the zygomatic branch, of which 80% were H-B grade I, 100% of the buccal branch, of which 44.4% were H-B grade I, 88.9% of the marginal mandibular branch, and 66.7% of the temporal branch. The study showed that the recovery rate of young patients was better than that of middle-aged and old people, and the best recovery of each branch of the facial nerve was the zygomatic branch, followed by the buccal branch, the marginal mandibular branch, and the worse was the temporal branch.

Copper Poisoning with Emphasis on Its Clinical Manifestations and Treatment of Intoxication

Background. Copper is an essential trace element found in the human body in an oxidized (Cu II) and reduced (Cu I) form. It plays a crucial role in the integrity and function of proteins and enzymes. Short-term and long-term exposure to copper can result in harmful effects and lead to clinical manifestations in multiple bodily systems, including the gastrointestinal tract, liver, kidneys, eyes, respiratory, cardiovascular, central nervous, endocrine, and hematopoietic systems. Objective. The purpose of this study is the importance of early recognition and diagnosis of copper poisoning immediate and necessary measures and the use of chelators. Materials and Methods. In this review article, authors from Pub Med, Scopus, and a toxicologic emergencies reference book from 1996 to 2024 are used. Result. An excessive increase in copper level produces reactive oxygen species that can cause lipid peroxidation in cell membranes, direct oxidation of proteins, and the breakdown of DNA and RNA molecules. All of these can generally be reasons for cell death. Conclusion. Assessing levels of copper in whole blood, free serum copper, 24-hr urine copper, liver biopsy for copper concentration, and ceruloplasmin play a crucial role in the diagnosis. The blood copper concentration is directly related to the severity of poisoning. Treatment for copper poisoning typically involves removing the source of exposure and administering medications to help remove the excess copper from the body. Supportive care for copper intoxication usually includes managing vomiting, correcting fluids and electrolytes, and stabilizing vital signs. Chelators like D-penicillamine, succimer, trientine, tetrathiomolybdate, and PBT-2 have been utilized in treatment.

A Design and Construction of the Vibration Perception Threshold Measurement Device for Diabetes

A Design and Construction of the Vibration Perception Threshold Measurement Device for Diabetes

Influence of peripheral nerve system on proliferation and migration of keratinocytes on site of the wound edges

AIM: to assess proliferation and migration of keratinocytes at the nonhealing edges of neuropathic wounds.MATERIALS AND METHODS: 25 patients with neuropathic ulcers and 5 patients without diabetes with decubitus were enrolled. Diabetic foot (DF) patients were underwent to standard treatment including debridement, atraumatic dressing, offloading, antibacterial therapy if it needs. Severity of peripheral neuropathy was assessed according to the NDS scale. Histo­logical (hematoxylin and eosin) and immunohistochemical (Ki-67 , α7nAChR markers) examination of wound edge were done during treatment (0, 10, 24 days).RESULTS: All patients have severe neuropathy according to NDSm (&gt;8). The average size of DF ulcers before and on 10th day of treatment was of 4 cm2 and 2,5 cm2, respectively (p&lt;0,004). Neuropathic ulcers were characterized by hyperproliferative epidermis. Mitotically active keratinocytes reside throughout the suprabasal layers. Ki-67 expressed all layers of the epidermis, but a greater staining density was detected in the basal layer. The density of a7nAChR-positive cells increased from 0 to 24 days (p=0,031).THE CONCLUSION: The data shows that neuropathy is one of the possible mechanisms of keratinocyte cell cycle disruption: proliferative activity and ability to migrate. Identification of new signaling pathways regulating the physiological repair of tissues and the study of their disorders in diabetes mellitus opens the prospect of developing an optimal therapeutic strategy.