Postsynaptic potentials of soleus motor neurons produced by transspinal stimulation: a human single-motor unit study.

Transspinal (or transcutaneous spinal cord) stimulation is a noninvasive, cost-effective, easily applied method with great potential as a therapeutic modality for recovering somatic and nonsomatic functions in upper motor neuron disorders. However, how transspinal stimulation affects motor neuron depolarization is poorly understood, limiting the development of effective transspinal stimulation protocols for rehabilitation. In this study, we characterized the responses of soleus α motor neurons to single-pulse transspinal stimulation using single-motor unit (SMU) discharges as a proxy given the 1:1 discharge activation between the motor neuron and the motor unit. Peristimulus time histogram, peristimulus frequencygram, and surface electromyography (sEMG) were used to characterize the postsynaptic potentials of soleus motor neurons. Transspinal stimulation produced short-latency excitatory postsynaptic potentials (EPSPs) followed by two distinct phases of inhibitory postsynaptic potentials (IPSPs) in most soleus motor neurons and only IPSPs in others. Transspinal stimulation generated double discharges at short interspike intervals in a few motor units. The short-latency EPSPs were likely mediated by muscle spindle group Ia and II afferents, and the IPSPs via excitation of group Ib afferents and recurrent collaterals of motor neurons leading to activation of diverse spinal inhibitory interneuronal circuits. Further studies are warranted to understand better how transspinal stimulation affects depolarization of α motor neurons over multiple spinal segments. This knowledge will be seminal for developing effective transspinal stimulation protocols in upper motor neuron lesions.NEW & NOTEWORTHY Transspinal stimulation produces distinct actions on soleus motor neurons: an early short-latency excitation followed by two inhibitions or only inhibition and doublets. These results show how transspinal stimulation affects depolarization of soleus α motor neurons in healthy humans.

Quantitative or qualitative biomolecular changes in blood serum composition induced by childhood obesity: A Fourier transform infrared examination.

Childhood obesity (CO) negatively affects one in three children and stands as the fourth most common risk factor of health and well-being. Clarifying the molecular and structural modifications that transpire during the development of obesity is crucial for understanding its progression and devising effective therapies. The study was indeed conducted as part of an ongoing CO treatment trial, where data were collected from children diagnosed with CO before the initiation of non-drug treatment interventions. Our primary aim was to analyze the biochemical changes associated with childhood obesity, specifically focusing on concentrations of lipids, lipoproteins, insulin, and glucose. By comparing these parameters between the CO group (n = 60) and a control group of healthy children (n = 43), we sought to elucidate the metabolic differences present in individuals with CO. Our biochemical analyses unveiled lower LDL (low-density lipoproteins) levels and higher HDL (high-density lipoproteins), cholesterol, triglycerides, insulin, and glucose levels in CO individuals compared to controls. To scrutinize these changes in more detail, we employed Fourier transform infrared (FTIR) spectroscopy on the serum samples. Our results indicated elevated levels of lipids and proteins in the serum of CO, compared to controls. Additionally, we noted structural changes in the vibrations of glucose, ß-sheet, and lipids in CO group. The FTIR technique, coupled with principal component analysis (PCA), demonstrated a marked differentiation between CO and controls, particularly in the FTIR region corresponding to amide and lipids. The Pearson test revealed a stronger correlation between biochemical data and FTIR spectra than between 2nd derivative FTIR spectra. Overall, our study provides valuable insights into the molecular and structural changes occurring in CO.

Single motor unit estimation of the cutaneous silent period in ALS.

OBJECTIVE: Recent evidence indicated that amyotrophic lateral sclerosis (ALS) also impairs spinal circuits, including those mediating cutaneous silent period (CSP). However, most studies utilised surface electromyography (sEMG), which needs more resolution to pinpoint changes at the single motoneuron level. We aimed to investigate CSP properties using single motor unit discharges in ALS. METHODS: In mild and severe ALS patients and controls, CSP was recorded in the first dorsal interosseus and analysed using the discharge rate method, which accurately shows the inhibitory postsynaptic potentials (IPSPs) profile. RESULTS: Our findings confirmed that the CSP latency was prolonged only in severe ALS patients. Moreover, the CSP duration was similar in each group, but late-stage ALS patients tend to have a longer CSP duration. The discharge rate method revealed a significantly longer duration (up to 150 ms) than the duration detected using sEMG. Strikingly, the motoneuron discharge rate - IPSP duration inverse relationship is lost in ALS patients, indicating a possible impairment in the motoneuron integrative properties. CONCLUSIONS: Our data support previous findings of prolonged latency, presented input-output modifications of motoneurons, and revealed the entire course of the CSP, representing a much stronger inhibitory event than previously thought. SIGNIFICANCE: Motoneuron integrative property modification assessed by CSP could be a new biomarker for ALS.

Chemical changes in childhood obesity blood as a marker of the disease. A Raman-based machine learning study.

Obesity in children is a global problem, leading to different medical conditions that may contribute to metabolic syndrome and increase the risk of diabetes, dyslipidemia, hypertension, and cardiovascular diseases in future health. Metabolic disorders are the results of the body's chemical process. The changes in the chemical compositions could be determined by Raman spectroscopy. Therefore, in this study, we measured blood collected from children with obesity to show chemical changes caused by obesity disease. Moreover, we will also show characteristic Raman peaks/regions, which could be used as a marker of obesity, not other metabolic syndromes. Children with obesity had higher glucose levels, proteins, and lipids than the control ones. Furthermore, it was noticed that the ratio between CO and C-H is 0.23 in control patients and 0.31 in children with obesity, as well as the ratio between amide II and amide I was 0.72 in control and 1.15 in obesity, which suggests an imbalance in these two fractions in childhood obesity. PCA with discrimination analyses showed that the accuracy, selectivity, and specificity of Raman spectroscopy in differentiation between childhood obesity and healthy children was between 93% and 100%. There is an increased risk of metabolic changes in childhood obesity with higher glucose levels, lipids, and proteins in children with obesity. Also, there were differences in the ratio between proteins and lipids functional groups and glucose, amide II, and amide I vibrations as a marker of obesity. The results of the study offer valuable insights into potential alterations in protein structure and lipid composition in children with obesity, emphasizing the importance of considering metabolic changes beyond traditional anthropometric, measurements.

Application of Fourier transform infrared spectroscopy to detect biochemical changes in blood serum of obese patients.

Obesity is frequently a significant risk factor for multiple obesity-associated diseases that have been increasing in prevalence worldwide. Anthropometric data such as body mass index, fat, and fat mass values are assessed for obesity. Therefore, we aimed to propose two Fourier transform infrared (FT-IR) spectral regions, 800-1800 cm-1 and 2700-3000 cm-1 , as sensitive potential band assignments for obesity-related biochemical changes. A total of 134 obese (n = 89) and controls (n = 45) biochemical characteristics and clinical parameters indicative of obesity were evaluated. The FT-IR spectra of dried blood serum were measured. Anthropometric data of the obese have the highest body mass index, %fat, and fat mass values compared to the healthy group (p < 0.01). Also, the triglyceride and high-density lipoprotein cholesterol levels were higher than in healthy subjects (p < 0.01). Principal component analysis (PCA) technique successfully distinguished obese and control groups in the fingerprint, accounting for 98.5% and 99.9% of the total variability (800-1800 cm-1 ) and lipids (2700-3000 cm-1 ) regions presented as 2D and 3D score plots. The loading results indicated that peaks corresponding to phosphonate groups, glucose, amide I, and lipid groups were shifted in the obese group, indicating their potential as biomarkers of obesity. This study suggests that FTIR analysis based on PCA can provide a detailed and reliable method for the analysis of blood serum in obese patients.

The relationship between childhood obesity with inflammatory mediators.

OBJECTIVE: To determine the association of various obesity markers with systemic immune-inflammatory index. METHODS: The cross-sectional study was conducted at Marmara University, Istanbul, Turkey, from January 2018 to October 2018 and comprised children aged 6-16 years admitted to the outpatient clinic due to obesity. The patients were evaluated for height, weight, body mass index (BMI), fat percentage (F%), fat mass (FM) and fat-free mass (FFM). Waist circumference was measured and neutrophil, platelet and lymphocyte counts and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated on the basis of haemogram. Data was analysed using Number Cruncher Statistical System 2007. RESULTS: Of the 335 subjects, 203(60.6%) were girls and 132(39.4%) were boys. Univariate analysis of girls showed the effects of BMI, F%, FM, FFM and WC on NLR. FM remained a significant and independent risk factor for NLR (p<0.01). The effects of BMI, F%, FFM and WC were not significant in multivariate model (p>0.05). Univariate analysis of girls also showed the effects of BMI, F%, FM, FFM and WC measurements on SII. F% remained a significant and independent risk factor on SII (p<0.01). The effects of BMI, fat mass, FFM and WC were not significant in multivariate model (p>0.05). CONCLUSION: In this study, the increase of SII, NLR and thrombocyte in terms of weight, BMI, fat percentage and fat mass supports the increase of inflammation due to the increase of fat in obesity. In terms of comorbidities in obesity, SII and NLR suggest that there may be inflammatory biomarkers which can be used in follow-up.

Jendrassik maneuver effect on spinal and brainstem reflexes.

The effect of Jendrassik Maneuver (JM) has been extensively studied on monosynaptic reflexes in numerous muscles below the level at which the maneuver was performed. Here we hypothesize that the effect of JM could be observed also on other reflexes, indicating a widespread influence of performing a motor act such as the JM. We examined polysynaptic reflexes caudal (i.e., the withdrawal reflex of the lower extremities) and rostral (i.e., the blink reflex to supraorbital nerve stimulation) to the level of JM contraction. We have assessed soleus tendon (T) reflex; withdrawal reflex in tibialis anterior and soleus muscle; blink reflex (BR), blink reflex excitability recovery curve (BR-ER) and prepulse inhibition of the blink reflex. Our results showed that (1) T-reflex amplitude increased during JM and decreased just after and 15 min after JM; (2) no change in the withdrawal reflex; (3) R2 area of BR reduced significantly just after or 15 min after JM; (4) Prepulse inhibition in BR reduced significantly during JM; (5) no change in BR-ER. Our results indicate that JM leads to generalized effects on neural excitability at both caudal and rostral levels. Furthermore, JM has a selective effect on excitability of reflex circuitries.

Posture modulates the sensitivity of the H-reflex.

The effect of body posture on the human soleus H-reflex via electrical stimulation of the tibial nerve at the popliteal fossa was studied. All parameters that may influence the reflex were controlled stringently. H-reflexes were elicited in three different body postures while keeping the level of background muscle activation to a minimum. The H-reflex curve relative to the M-wave curve did not change significantly in any of the body postures. However, the maximal H-reflex amplitude significantly increased in the prone position compared with the sitting (p = 0.02) and standing positions (p = 0.01). The background level of electrical activity of the soleus muscle did not significantly change during varying body postures. Together, these findings indicate that the effectiveness of the spindle primary afferent synapse on the soleus motor neuron pool changes significantly in prone position as compared to sitting and standing positions. Given that we have controlled the confounding factors excluding the head position relative to the gravity and the receptors that may be differentially activated at varying body postures such as the proprioceptors, it is concluded that the tonic activity from these receptors may presynaptically interfere with the effectiveness of the spindle primary afferent synapses on the soleus motor neurons.

Effect of Resveratrol on Leptin and Sirtuin 2 Expression in the Kidneys in Streptozotocin-induced Diabetic Rats.

OBJECTIVE: To investigate the effect of resveratrol (RSV) on the histopathology and leptin and sirtuin 2 expression levels of the kidneys in streptozotocin (STZ)-induced diabetic rats. STUDY DESIGN: The study was carried out with 33 young, healthy, female Wistar Albino rats. STZ was given (50 mg/kg, intraperitoneal, single dose) to the rats to induce and constitute a diabetes model. After 1 month of STZ, resveratrol (10 mg/kg) was given for 15 days. Then the kidneys were evaluated histopathologically and the leptin and sirtuin 2 expressions were analyzed immunohistochemically. RESULTS: High glucose and fewer weight levels were seen in the STZ-induced diabetes mellitus group. The glucose levels in the RSV-administered diabetic group showed a tendency to decrease but not significantly. Decreased signs of histopathologic kidney damage was seen in the RSV-administered diabetic group, and an increased expression of leptin was seen in the diabetic kidney tissues. There were no significant differences of sirtuin 2 expression levels among the groups. CONCLUSION: It was observed that resveratrol caused changes in the diabetic kidney histology and leptin expression level. Resveratrol may be effective, with its antioxidant and antidiabetic effects, in the prevention of kidney damage caused by long-term hyperglycemia.

Protective effects of citicoline on TNBS-induced experimental colitis in rats.

The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism.

Protective effects of leflunomide on intestinal ischemia-reperfusion injury: leflunomide against intestinal ischemia-reperfusion.

AIM: The aim of this study was to investigate the possible protective effects of leflunomide, which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats. MATERIALS AND METHODS: Forty female Wistar albino rats were divided into six groups: control (n = 5), drug control (n = 7), sham operated (n = 7), IR alone (n = 7), IR plus vehicle (IR + vehicle, n = 7) and IR plus 20 mg/kg leflunomide (IR + Leflunomide, n = 7). While rats were pretreated intragastrically with leflunomide (20 mg/kg) and vehicle in three doses prior to the experiment, respectively, in the IR + Leflunomide and IR + vehicle groups, no additional application was done in the IR alone group. Intestines were exteriorized, and the superior mesenteric artery was occluded for 45 min ischemia, and then the clamp was removed for 120 min reperfusion. After the experiment, the intestines were removed for biochemical and histological examinations. Additionally, blood samples were taken for measurements of antioxidant parameters. RESULTS: The intestinal IR significantly increased the MDA level and MPO activity; however, treatment with leflunomide reversed those findings (P < 0.05). The CAT activity of the IR + Leflunomide group was significantly higher than in the IR groups (P < 0.05). The SOD activity was increased in the intestinal IR group, and leflunomide treatment reversed that, too (P <0.05). The light microscopic findings showed that IR caused mucosal necrosis and leflunomide treatment reduced the morphological alterations associated with IR (P < 0.05). CONCLUSION: Intestinal IR injury may be reversed by the anti-inflammatory and antioxidant actions of leflunomide.

Protective effects of caffeic acid phenethyl ester on intestinal ischemia-reperfusion injury.

AIM: Intestinal ischemia reperfusion (IR) causes tissue injury in two ways, starting a pro-inflammatory cascade and oxidative stress. The aim of this study was to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE), which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats. MATERIALS AND METHODS: Forty male Wistar-Albino rats were divided into five groups: Sham, IR, IR plus ethanol (vehicle), IR plus 10 mg/kg (IR + 10CAPE), and 30 mg/kg CAPE (IR + 30CAPE) at the 30-min ischemic period. Intestines were exteriorized and the superior mesenteric artery was occluded for 45-min ischemia and then the clamp was removed for 120-min reperfusion. After the experiment, the intestines were removed for biochemical and light microscopic examinations. Additionally, blood samples were taken for plasma TNF-alpha measurement. RESULTS: The TBARS levels of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). Both CAPE treatments decreased TBARS levels in comparison with the IR group (P < 0.05). In both CAPE-treated groups, while the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were increased compared to all other groups, which was similarly the case for the CAT activity compared to the Sham and IR + Ethanol groups (P < 0.05). There were no significant differences between GSH levels of all study groups. The TNF-alpha levels of the IR and IR + Ethanol groups were non-significantly increased compared to the Sham group (P > 0.05). The TNF-alpha levels of 10 and 30 mg/kg CAPE groups were non-significantly decreased compared to the IR group (P > 0.05). The tissue MPO activities of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). The MPO activities of the IR + 10CAPE and IR + 30CAPE groups were not significantly different from the Sham group (P > 0.05). There was necrosis of mucosa in the IR and IR + Ethanol groups in light microscopic evaluations. Those changes were significantly reversed by 30 mg/kg CAPE treatment. CONCLUSION: The intestinal IR injury may be reversed by anti-inflammatory and antioxidant actions of the CAPE. However, 30 mg/kg CAPE treatment may be more efficient in preventing intestinal IR injury in rats.

The effects of caffeic acid phenethyl ester (CAPE) on TNBS-induced colitis in ovariectomized rats.

AIM: The aim of this investigation was to examine the effects of caffeic acid phenethyl ester (CAPE) on the development of colitis and antioxidant parameters in bilateral ovariectomized rats subjected to trinitrobenzene sulfonic acid (TNBS)-induced colitis. MATERIALS AND METHODS: Twenty-one Wistar Albino ovariectomized female rats were divided into four subgroups (n = 5 or 6) (colitis control, vehicle control, CAPE 10 and 30 mg/kg, respectively). Colitis was induced using an enema of TNBS and ethanol, following which CAPE was administrated for 3 days to induce colitis and effect of CAPE was subsequently evaluated. RESULTS: Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and the vehicle-treated groups, whereas treatment with CAPE 10 and 30 mg/kg, respectively, caused a significant reduction in colon injury compared to that observed in rats of the TNBS-colitis and vehicle-treated groups. The histologies of both treatment groups were not significantly different. In terms of the biochemical analyses, myeloperoxidase levels in rats from the CAPE 10 and 30 mg/kg groups were significantly different from that of the colitis control rats; however, the levels of malondialdehyde (MDA), catalase and reduced glutathione (GSH) were only significantly different from the levels found colitis control rats in rats administered 10 mg/kg. The levels of MDA, GSH and SOD in rats given CAPE were also significantly different from those of rats in the vehicle control group. These results were consistent with histological findings. CONCLUSION: CAPE may have a positive effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of CAPE may occur through antiinflammatory and antioxidant mechanisms.

Effects of tamoxifen on myocardial ischemia-reperfusion injury model in ovariectomized rats.

The purpose of this study is to examine the antiarrhythmic and antioxidant effects of tamoxifen, one of the selective estrogen modulators, in ovariectomized rats subjected to myocardial ischemia-reperfusion (I/R) injury. A month after ovariectomy, rats were divided into four groups: (I) ovariectomized controls without any treatment, (II) ovariectomized rats treated with vehicle dimethylsulfoxide (DMSO), (III)-(IV) ovariectomized rats treated with tamoxifen 1 or 10 mg/kg,sc daily for 14 days. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. The blood pressure (BP), heart rate (HR), electrocardiography (ECG) was recorded before and during the ischemia-reperfusion period. The blood levels of malondialdehyde (MDA), creatine kinase (CK), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and catalase (CAT) were measured after the rats were killed. Tamoxifen reduced the incidence of ventricular tachycardia (VT) on ischemia and reperfusion as well as the incidence and duration of reversible ventricular fibrillation (VF) on reperfusion. I/R injury caused a significant fall in GSH, GSH-Px as well as an increase in MDA and CK levels in the control group when compared to tamoxifen treated groups. The changes in levels of CAT and GR were however, not significant. In conclusion, our findings suggest that tamoxifen has cardioprotective effects against I/R injury in rats, likely its antioxidant properties.