The initial level of heart rate variability determines the dynamics of the neuropathy of the autonomic nervous system and temperature sensitivity in rats with streptozotocin diabetes

BACKGROUND: The development of diabetes mellitus (DM) is accompanied by hyperglycemia, which leads to the development of neuropathy. We assume that the individual characteristics of the organization of the autonomic nervous system (ANS) in humans affect not only the ability to withstand stress, but can determine the course of diseases, including diabetes. AIMS: The study of the dynamics of heart rate variability and temperature sensitivity in rats against the background of hyperglycemia depending on the organization of the initial regulation of the heart under ANS. MATERIALS AND METHODS: 70 male rats were randomized by weight and level of total heart rate variability (HRV) on animals with initially low and high levels of total HRV. Diabetes was modeled by a single i.p. injection of streptozotocin (STZ). The control group received a single i.p. injection of citrate buffer (CB). Before the induction of diabetes, as well as on 21, 42 and 70 days after the injection of STZ, a comprehensive examination of rats’ condition was carried out: 1) assessment of HRV; 2) analysis of temperature-pain sensitivity; 3) assessment of glucose and ketone bodies in the blood. Similarly, animals in the CB group were examined. RESULTS: The change in HRV and temperature-pain sensitivity in rats depends on the initial level of HRV. In rats with low variability, the reaction time in the pain test increased by 8–32% from the 28th day of the experiment, from 21 days the bradycardia increased and the decrease in individual HRV indices at rest, but not the response of these parameters to cold stress. CONCLUSION: The development of ANS’s lesion depends on the initial level of HRV. Low variability animals are more resistant to hyperglycemia: the normal ranges of CP reactions from the side of HR, the parameters of total HRV and the CVHS contribution to it are longer, but there is a loss of temperature sensitivity. Initially, highly variable rats with the development of diabetes do not lose temperature sensitivity, but demonstrate an imbalance in the regulatory circuits of heart rate and HRV

Keratinocytes differentiation and wound healing in rats with streptozotocin – induced diabetes and severe hyperglycemia

BACKGROUND: Diabetes mellitus leads to disruption of the skin repair processes, but the leading mechanisms of this pathology have not yet been identified. In this regard, in our work, we decided to check how hyperglycaemia affects the process of keratinocyte phenotype changes during wound healing. AIMS: To study the effect of hyperglycaemia on wound healing and differentiation of keratinocytes in a rat streptozotocin-induced diabetes model. MATERIALS AND METHODS: Diabetes mellitus was induced in rats by using streptozotocin, 65 mg / kg, intraperitoneally, once. The wound was applied in the supra-scapular region on the 42nd day, after which (after 8, 16, and 24 days) the repair process was evaluated using histological methods. Immunohistochemistry was used to evaluate the expression of cytokeratin-10 and cytokeratin-17. RESULTS: In rats with diabetes mellitus, wound healing slowed down in the later stages, compared with the control group. In general, wound healing was accompanied by an increase in the expression of cytokeratin-10 in its region compared with intact skin, and contractile keratinocytes activation was disrupted in diabetic rat wounds. CONCLUSIONS: Hyperglycaemia slightly slows wound healing in rats and impairs contractile keratinocytes activation

Dynamics of heart rate variability in rats with streptozotocin-induced diabetes

Background: Diabetes mellitus (DM) has a negative impact on all organs. This is due to insufficiency of blood supply and the disruption of the trophic function of the nervous system. One of the most serious complication of DM is diabetic foot caused be vascular and neurological reasons. Correction of vascular disorders is effectively treated by modern therapeutic approaches, but the damage of nervous system has been studied insufficiently. Aims: To investigate the dynamics of damage to the vegetative nervous system on the laboratory model of DM. Materials and methods: DM in rats was induced by injection of streptozotocin at a dose of 65 mg/kg in citrate buffer (DM group). The control group of rats received a citrate buffer equivalent (CB group). Rats with DM were given a maintenance therapy with insulin in a dose of 2 units/kg/day. On 42 days of experience, a round wound with a diameter of 2 cm on the back of the animals was observed. Before the DM simulation, then on the 42, 50, 58 and 66 days of its development, an electrocardiogram (ECG) was recorded in the rats at a frequency of 2 kHz digitising in a state of calm wakefulness and after cold exposure. For 5 minutes ECG fragments, heart rate and heart rate variability (HRV) in the temporal domain were calculated, characterising: 1) the total heart rate variability (tHRV) according to SDRR, SDHR, KVRR and KVHR; 2) the effect of the parasympathetic department of the autonomic nervous system (aANS) for RMSSD and pNN3; 3) the contribution of the sympathetic department of the ANS (sANS) by SDAvgRR, SDAvgHR. The spectral parameters were estimated in the frequency domain: the total power of the spectrum is TR (range: 0–2.5 Hz), the powers in the low and high frequency ranges are LF (range: 0.2–0.8 Hz) and HF (range: 0.8–2.5 Hz) LF/HF. Weekly, the tail withdrawal time was measured in a temperature pain test (55°C). Results: During the development of diabetes, the level of glucose in the blood increased 4–7 times compared with the normal level. The reaction time of the pain test in rats with DM increased by 20%–30% at the end of the experiment. At 42 days, the development of bradycardia (267 beats/min) was observed in rats with DM. The indicators of tHRV decreased by a factor of 2 due to a decrease in the contribution of sANS. The reaction to CP in the SD group differs from the norm by the severity of the individual components of the HRV structure, which indicates functional denervation of the heart and the development of diabetic neuropathy. Conclusions: As the diabetes progressed, signs of neuropathy were observed. The overall HRV parameters decreased, the ratio of the contributions of sANS and pANS to the regulation of heart rate changed, and the temperature sensitivity decreased

Electrical activity in rat retina in a streptozotocin-induced diabetes model

Objectives: Diabetic retinopathy remains the major cause of blindness among the working-age population of developed countries. Considering this, experimental models of diabetes involving laboratory animals are important for assessing clinically significant methods to determine early pathologic alterations of the retina. The early detection of diabetic retinopathy in combination with a search for new pathogenetic targets will enable focusing on new strategies to limit the development of critical changes in the retina and to prolong retinal functioning during the development of diabetes mellitus. Aim: This study aimed to define parameters of electroretinography test that identifies changes due to retinal impairment in diabetes. Methods: Experimental diabetes was induced in Wistar rats by intraperitoneally injecting streptozocin (65 mg/kg; group DM). The control group (CB) received intraperitoneal injections of the vehicle, i.e. citric buffer. On each consecutive day of the experiment, all rats received insulin detemir (2 u/kg). Ophthalmoscopy and electroretinography were conducted before initiating the experiment and after 50, 58 and 66 days of injectin sptreptozocin. Results: Amid 2u\kg insulin injection the glucose level in venous blood in DM group amounted to 30-40 mM. The ophthalmoscopy showed that the optic nerve disk paled by the 50th day, with its line erasing. During electroretinography, wave amplitude in oscillatory potential test tended to decrease. -wave latency of photopic system increased with -wave latency of photopic system and - and -waves latency of scotopic system not altering. In addition, the amplitude of rhythmic stimulation of 8 and 12 Hz decreased. Conclusion: The most apparent parameters of electroretinography for modelling streptozocin-induced diabetes are wave amplitude during the oscillatory potential test, photopic B-wave latency and the amplitude of rhythmic stimulation. These results suggest that in diabetes, ischaemic injury is an important cause of early dysfunction of inner retinal layers

Classification of Acoustic Influences Registered with Phase-Sensitive OTDR Using Pattern Recognition Methods

This article is devoted to the development of a classification method based on an artificial neural network architecture to solve the problem of recognizing the sources of acoustic influences recorded by a phase-sensitive OTDR. At the initial stage of signal processing, we propose the use of a band-pass filter to collect data sets with an increased signal-to-noise ratio. When solving the classification problem, we study three widely used convolutional neural network architectures: AlexNet, ResNet50, and DenseNet169. As a result of computational experiments, it is shown that the AlexNet and DenseNet169 architectures can obtain accuracies above 90%. In addition, we propose a novel CNN architecture based on AlexNet, which obtains the best results; in particular, its accuracy is above 98%. The advantages of the proposed model include low power consumption (400 mW) and high speed (0.032 s per net evaluation). In further studies, in order to increase the accuracy, reliability, and data invariance, the use of new algorithms for the filtering and extraction of acoustic signals recorded by a phase-sensitive reflectometer will be considered

Triple drug therapy with GABA, sitagliptin, and omeprazole prevents type 1 diabetes onset and promotes its reversal in non-obese diabetic mice

Previous studies have reported that dual drug combinations consisting of γ-aminobutyric acid (GABA) together with a dipeptidyl-peptidase-4 inhibitor (DPP-4i), also a DPP-4i with a proton pump inhibitor (PPI), could improve pancreatic β-cell function and ameliorate diabetes in diabetic mice. In this study, we sought to determine if a triple drug combination of GABA, a DPP-4i and a PPI might have superior therapeutic effects compared with double drug therapies in the prevention and reversal of diabetes in the non-obese diabetic (NOD) mouse model of human type 1 diabetes (T1D). In a diabetes prevention arm of the study, the triple drug combination of GABA, a DPP-4i, and a PPI exhibited superior therapeutic effects in preventing the onset of diabetes compared with all the double drug combinations and placebo. Also, the triple drug combination significantly increased circulating C-peptide and serum insulin levels in the mice. In a diabetes reversal arm of the study, the triple drug combination was superior to all of the double drug combinations in reducing hyperglycemia in the mice. In addition, the triple drug combination was the most effective in increasing circulating levels of C-peptide and serum insulin, thereby significantly reducing exogenous insulin needs. The combination of GABA, a DPP-4i and a PPI appears to be a promising and easily scalable therapy for the treatment and prevention of T1D.De två första författarna delar förstaförfattarskapetDe två sista författarna delar sistaförfattarskapet</p