scholarly journals DIABETIC NEUROPATHY: MOLECULAR MECHANISMS OF DEVELOPMENT AND POSSIBILITIES FOR PATHOGENETIC THERAPY

2019 ◽  
pp. 8-12
Author(s):  
N.V. Hudiakova ◽  
N.V. Ivanov ◽  
I. Yu. Pchelin ◽  
A.N. Shishkin ◽  
N.V. Vorokhobina ◽  
...  

The present review summarizes the results of global studies and assesses contribution of hyperglycemia towards formation of neurologic complications in diabetic patients. Hyperglycemia is believed to play a leading role in the formation of neurological complications in diabetes mellitus. However, the achievement of normalization of glycemia level does not ensure the cessation of their development and progression, which indicates a lack of knowledge about the pathogenetic relationships in diabetic neuropathy. Limited understanding of these issues entails the absence of treatment options that effectively affect the course of this complication. Based on the analysis of experimental and clinical studies of recent years, data on the molecular-biological relationships of hyperglycemia with the formation of neurological complications in diabetes mellitus are summarized. The influence of the oxidative and nitrosative stress, advanced glycation end products, the activation of the polyol and hexosamine pathways on the state of the nerve fiber is analyzed. The data on molecular mechanisms of development of diabetic neuropathy are contradictory. On the basis of recent experimental and clinical data we review possibilities for pathogenetic therapy. The problem of oppositely directed effects of treatment is discussed. Clinical rationale is given for declared direction of further studies.

Author(s):  
Pedro Henrique Abreu da Silva ◽  
Andressa Santos Garcia ◽  
Fábio Aguiar Alves ◽  
André Luis Souza dos Santos ◽  
Cátia Lacerda Sodré

: The COVID-19 pandemic turned the SARS-CoV-2 into the main target of scientific research all around the world. Many advances have already been made, but there is still a long way to go to solve the molecular mechanisms related to the process of the SARS-CoV-2 infection, as well as the particularities of the disease, its course and the complex host-pathogen relationships. However, a lot has been theorized and associated with COVID-19, like the worst prognosis of the disease among individuals with some comorbidities, like diabetes mellitus. In this perspective, diabetic patients are repeatedly associated with more severe cases of COVID-19 when compared to non-diabetic patients. Even though ACE2 (angiotensin-converting enzyme 2) was recognized as the host cell receptor for both binding and entering of SARS-CoV-2 particles, it was also pointed out that this enzyme plays an important protective role against pulmonary damage. Therefore, paradoxically as it may seem, the low baseline level of this receptor in people with diabetes is directly linked to a more expressive loss of ACE2 protective effect, which could be one of the possible factors for the worst prognosis of COVID-19. Still, COVID-19 may also have a diabetogenic effect. From this point of view, the main topics that will be highlighted are (i) the mechanism of the viral entry, with special attention to the cellular receptor (ACE2) and the viral binding protein (spike), (ii) the relationship among the renin-angiotensin system, the infection process and the patients' prognosis, (iii) the glucose control and the medicines used in this event, and (iv) a brief analysis on diabetes triggered by COVID-19.


2020 ◽  
Vol 11 (5) ◽  
pp. 218-222
Author(s):  
Laura George

Diabetes mellitus is a common endocrinopathy diagnosed in small animal patients, and once stable can be managed and well controlled in the home environment. Complications can occur, however, when unexpected factors arise which can cause destabilisation of the patient. This article will provide a brief review of diabetes mellitus in canine and feline patients before describing some of the common complications that may be observed including hypoglycaemia, diabetic ketoacidosis, urinary tract infection, diabetic neuropathy and cataracts. The aim is to ensure the veterinary nurse has a good understanding of these complications, for them to be aware of the clinical symptoms that may be displayed, and for them to appreciate the different treatment options available allowing them to be efficient advocates for their patients should the need arise.


Author(s):  
Joel Ramírez-Emiliano ◽  
Martha E. Fajardo-Araujo ◽  
Ismael Zúñiga-Trujillo ◽  
Victoriano Pérez-Vázquez ◽  
Cuauhtémoc Sandoval-Salazar ◽  
...  

2019 ◽  
Author(s):  
Samuel Dagogo-Jack

The long-term complications of diabetes mellitus include those attributable to hyperglycemia-mediated small vessel (microvascular)and neuropathic complications and syndromes resulting from multifactorial large vessel disease (macrovascular complications). Diabetic patients with evidence of chronic complications are best managed in consultation with appropriate specialists. The microvascular and neuropathic complications, which are specifically related to hyperglycemia, include retinopathy, nephropathy, and diabetic neuropathy. This review contains 8 figures, 9 tables, and 83 references. Key Words: Hyperglycemia, hypoglycemia, macrovascular, microvascular, neuropathic


2009 ◽  
Vol 116 (9) ◽  
pp. 721-730 ◽  
Author(s):  
Visith Thongboonkerd ◽  
Wararat Chiangjong ◽  
Jan Mares ◽  
Jiri Moravec ◽  
Zdenek Tuma ◽  
...  

Sepsis is a systemic response to infection commonly found in critically ill patients and is associated with multi-organ failure and high mortality rate. Its pathophysiology and molecular mechanisms are complicated and remain poorly understood. In the present study, we performed a proteomics investigation to characterize early host responses to sepsis as determined by an altered plasma proteome in a porcine model of peritonitis-induced sepsis, which simulated several clinical characteristics of human sepsis syndrome. Haemodynamics, oxygen exchange, inflammatory responses, oxidative and nitrosative stress, and other laboratory parameters were closely monitored. Plasma samples were obtained from seven pigs before and 12 h after the induction of sepsis, and plasma proteins were resolved with two-dimensional gel electrophoresis (n=7 gels/group; before being compared with during sepsis). The resolved proteins were stained with the SYPRO Ruby fluorescence dye and subjected to quantitative and comparative analyses. From approx. 1500 protein spots visualized in each gel, levels of 36 protein spots were significantly altered in the plasma of animals with sepsis (sepsis/basal ratios or degrees of change ranged from 0.07 to 21.24). Q-TOF (quadrupole–time-of-flight) MS and MS/MS (tandem MS) identified 30 protein forms representing 22 unique proteins whose plasma levels were increased, whereas six forms of five unique proteins were significantly decreased during sepsis. The proteomic results could be related to the clinical features of this animal model, as most of these altered proteins have important roles in inflammatory responses and some of them play roles in oxidative and nitrosative stress. In conclusion, these findings may lead to a better understanding of the pathophysiology and molecular mechanisms underlying the sepsis syndrome.


2012 ◽  
Vol 49 (4) ◽  
pp. 284-290 ◽  
Author(s):  
Eleandro Aparecido Tronchini ◽  
Aline Rosa Trevizan ◽  
Cristiano Massao Tashima ◽  
Renata Virginia Ferreira Pereira ◽  
Jacqueline Nelisis Zanoni

CONTEXT: Diabetes mellitus is a disease characterized by hyperglycemia that, when allowed to progress long-term untreated, develops vascular and neurological complications, which are responsible for the development of alterations in the enteric nervous system in diabetic patients. In the gastrointestinal tract, diabetes mellitus promotes motor and sensory changes, and in the reflex function of this system, causing gastroparesis, diarrhea, constipation, megacolon, slow gastrointestinal transit, gastric stasis and dilation with decreased or increased peristaltic contractions. Several studies have shown that oxidative stress is the main responsible for the vascular and neurological complications affecting the enteric nervous system of diabetics. OBJECTIVE: The effects of 0.1% and 2% vitamin E on myosin-V- and nNOS-immunoreactive neurons in the jejunum of diabetic rats were investigated. METHODS: Thirty rats were divided into the groups: normoglycemic, normoglycemic treated with 0.1% vitamin E, normoglycemic treated with 2% vitamin E, diabetic, diabetic treated with 0.1% vitamin E, and diabetic treated with 2% vitamin E. The neuronal density and areas of neuron cell bodies were determined. RESULTS: Diabetes (diabetic group) significantly reduced the number of myosin-V-immunoreactive neurons compared with the normoglycemic group. The diabetic treated with 0.1% vitamin E and diabetic treated with 2% vitamin E groups did not exhibit a greater density than the D group (P>0.05). Nitrergic density did not change with diabetes (P>0.05). The areas of myosin-V- and nNOS-immunoreactive neurons significantly increased in the normoglycemic treated with 2% vitamin E and diabetic groups compared with the normoglycemic group. CONCLUSION: Supplementation with 2% vitamin E had a neurotrophic effect only in the area of myosin-V-immunoreactive neurons compared with the diabetic group.


1997 ◽  
Vol 18 (9) ◽  
pp. 575-577 ◽  
Author(s):  
Richard T. Laughlin ◽  
Fredrick Reeve ◽  
Douglas G. Wright ◽  
Jon T. Mader ◽  
Jason H. Calhoun

Plantar puncture wounds to the foot are a common injury. A small number (1.8%) of these puncture wounds become infected and progress to osteomyelitis. The purpose of this article is to report the cases of six patients who developed osteomyelitis of the calcaneus after a puncture wound to the heel caused by a nail. The characteristics of the patients, the pathogenic organism, and the outcome were studied. Patients who were healthy and had no systemic illness (N = 4) had only one pathogenic organism cultured, whereas patients who had systemic illness (diabetes mellitus, N = 2) had more than one pathogenic organism cultured. The only amputation in this group occurred in a patient with diabetes mellitus. It was concluded that diabetic patients who develop calcaneal osteomyelitis from a nail puncture wound are more likely to have multiple pathogens cultured. Furthermore, if a diabetic neuropathy is also present, the nail puncture wound may be the initial injury leading to a chronic ulceration, increasing the risk of amputation.


2015 ◽  
Vol 23 (6) ◽  
pp. 707-714 ◽  
Author(s):  
Kazuyoshi Nakanishi ◽  
Nobuhiro Tanaka ◽  
Naosuke Kamei ◽  
Takeshi Hiramatsu ◽  
Satoshi Ujigo ◽  
...  

OBJECT The occurrence of compressive cervical myelopathy (CCM) increases in adults over 50 years of age. In addition, diabetes mellitus (DM) is a frequent comorbidity for people of this age and may impact the severity of CCM. The authors assessed motor pathway function in diabetic patients with CCM to investigate the correlation between electrophysiological parameters and clinical symptoms. METHODS Motor evoked potentials (MEPs) were measured from the abductor digiti minimi muscle (ADM) and the abductor hallucis muscle (AH) following transcranial magnetic stimulation, as were M- and F-waves following electrical stimulation of the ulnar and tibial nerves, in 22 patients with CCM and diabetes mellitus (DM) who had not experienced symptomatic diabetic neuropathy (CCM-DM group), in 92 patients with CCM alone (CCM group), and in 24 healthy adults (control group). The peripheral conduction time (PCT; measured from the ADM and AH) was calculated as follows: (M-wave latency + F-wave latency −1)/2. The central motor conduction time (CMCT; measured from the ADM and AH) was calculated by subtracting the PCT from the onset latency of the MEPs. The Japanese Orthopaedic Association (JOA) score for cervical myelopathy was obtained before and 1 year after surgery as a clinical outcome measure. RESULTS MEP, PCT, and CMCT parameters in the CCM-DM and CCM groups were significantly longer than those in the control group (p = 0.000−0.007). The PCTs in the CCM-DM group were significantly longer than those in the CCM group (p = 0.001−0.003). No significant differences were detected in the MEP and CMCT parameters between the CCM-DM and CCM groups (p = 0.080–1.000). The JOA score before surgery in the CCM-DM group was 10.7 ± 2.0 points and was significantly lower than that in the CCM group (12.2 ± 2.5 points, p = 0.015). In the CCM-DM group, JOA scores before surgery correlated with MEP-AH (r = −0.610, p = 0.012) and PCT-AH (r = −0.676, p = 0.004) values, but not with CMCT values, while the JOA scores were related to both MEP and CMCT parameters in the CCM group. The JOA scores improved to 13.8 ± 2.2 points after surgery (p = 0.001) and correlated with MEP-AH (r = −0.667, p = 0.005) and PCT-AH (r = −0.611, p = 0.012) in the CCM-DM group. CONCLUSIONS The results suggest that MEP, PCT, and CMCT parameters each reveal abnormalities in the upper and lower motor neurons even in patients with DM. The results also show a prolonged PCT in CCM-DM patients, despite having no history of diabetic neuropathy. Corticospinal tract impairments are similar between CCM and CCM-DM patients, while the JOA score of the CCM-DM patients is lower than that in the CCM patients. The JOA score in CCM-DM patients may be influenced by additional impairments in peripheral nerves or other diabetic complications. These electrophysiological studies may be useful for screening motor pathway function for CCM in patients with DM.


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