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Background: Diabetic neuropathy is one of the most common microvascular complications associated with diabetes mellitus. Diabetic peripheral neuropathy (DPN) has been linked to hyperglycaemia and long duration of uncontrolled type 2 diabetes mellitus (T2DM) as measured by glycosylated haemoglobin (HbA1c). To our knowledge the estimated duration between diagnosis and developing DPN and the level of HbA1c have not yet been investigated in Sudanese patients with type 2 DM. Therefore, this study aims to investigate the relationship between the duration of diabetes and HbA1c with nerve conduction velocity (NCV) in patients with type 2 DM. Methods: This cross-sectional study recruited 63 male and female patients with T2DM who attended the diabetic outpatient clinic of Academy Charity Teaching Hospital (ACTH) and Alzaytouna Private Hospital for Nerve Conduction Velocity (NCV) and electromyography (EMG) tests. Nerve conduction was done by using ADInstruments PowerLab series 26. SPSS was used to analyse the data and p-value < 0.05 was considered significant. Results: The mean duration of DM was 14.7 (± SD 9.24) years and the mean age of participants was 57.71 (± SD 12.2) years. The most common symptom was numbness (50%). Pearson’s correlation test revealed a significant negative correlation between HbA1c and nerve conduction velocity (r = 0.4, p < 0.05) and negative significant correlation between the duration and the amplitude (r = 0.35, p < 0.05). Conclusion: There is a slowing of nerve conduction velocity in type 2 diabetic patients, which is accelerated by the poor glycaemic control (HbA1c). These findings support the need for tight glycaemic control to avoid drastic neuropathic complications of diabetes.

Background Diabetes mellitus (DM) is a metabolic disease which is complicated by occurrence of diabetic peripheral neuropathy (DPN). Vitamin D deficiency contributes to the etiology and progression of type 2 DM and development of micro-vascular complications so in this study we assessed vitamin D level in diabetic patients to evaluate the association between vitamin D level and occurrence of diabetic neuropathy and to assess if there is relationship with certain subtypes of diabetic neuropathy. This case–control study was conducted on 80 type 2 diabetic patients divided into four groups equally. (A): Diabetic patients with painful diabetic neuropathy. (B): Diabetic patients with painless diabetic neuropathy. (C): Diabetic patients with painless neuropathy, but have neuropathic ulcer. (D): Diabetic patients without neuropathy. All patients underwent clinical, neurological examination and nerve conduction study. Then CBC and vitamin D were estimated in the studied groups. Results Vitamin D level among the studied painful diabetic neuropathy group (A) ranged from 5.3 to 40.5 ng/dl with mean 17.4 ± 10.9. 70% of them had deficient vitamin D level. In the painless diabetic neuropathy group (B), vitamin D level ranged from 6.5 to 35.5 ng/dl with mean 18.9 ± 8.49. 60% of them had deficient vitamin D level, while only 5% of the diabetic patients without neuropathy had deficient vitamin D level. There is significant negative correlation between vitamin D level and score of neuropathy where the lower vitamin D level the higher neuropathy score. Conclusion Lower vitamin D levels were found in diabetic patients with neuropathy especially those with painful neuropathy.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. It often causes symmetrical paresthesia, loss of sensation, and hyperalgesia. Without early intervention, it might lead to diabetic foot ulceration, gangrene, and subsequent amputation in people with diabetes. DPN is an insidious disease and often underdiagnosed. This paper reviews the current national and international prevalence of DPN, screening methods for early DPN, including quantitative sensory measurement, neurological function scoring system, confocal microscopy, and high-frequency ultrasound, and summarizes the related research progress, clinical application, and development prospects of these methods in recent years.

Triple Negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2. TNBC accounts for 15-20% of all breast cancer cases but accounts for over 50% of mortality. We propose that Estrogen receptor-beta (ERβ) and IGF2 play a significant role in the pathogenesis of TNBCs, and could be important targets for future therapy. Tissue microarrays (TMAs) from over 250 TNBC patients' were analyzed for ERβ and IGF2 expression by immunohistochemistry. Expression was correlated with clinical outcomes. In addition, TNBC cell lines Caucasians (CA): MB-231/BT549 and African Americans (AAs): MB-468/HCC70/HCC1806 were used to investigate the effect of hormonal and growth factor regulation on cell proliferation. TMAs from AAs had higher expression of ERβ and IGF2 expression when compared to CA. ERβ and IGF2 were found to be upregulated in our TNBC cell lines when compared to other cell types. TNBC cells treated with ERβ agonist displayed significant increase in cell proliferation and migration when compared to controls. AA tissue samples from TNBC patients had higher expression of ERβ. African-American breast cancer TNBC tissue samples from TNBC patients have higher expression of ERβ. In addition, TNBC cell lines were also found to express high levels of ERβ. IGF2 increased transcription of ERβ in TNBC cells. Understanding the mechanisms of IGF2/ERβ axis in TNBC tumors could provide an opportunity to target this aggressive subtype of breast cancer.

Dorsal root ganglion stimulation (DRG-S) is a form of neuromodulation that can target specific dermatomes to obtain better coverage of the distal extremity. Previously proposed mechanisms of action for DRG-S focused on the dorsal root ganglion (DRG) itself, without consideration of orthodromic effects in the dorsal horn and antidromic effects on the nerve root and sympathetic chain. Diabetic peripheral neuropathy (DPN) is an axonal neuropathy that affects around half of all patients with diabetes mellitus, causing severe pain and sensory impairment in the distal extremities. We present a case of a patient with DPN in both feet, in addition to low back pain, who underwent a DRG-S trial with right T12 and S1 leads. The trial was performed unilaterally for seven days, allowing the patient to compare the treated versus the untreated (left) side. Pain, disability, general health status, and quality of life measures improved significantly. In addition to the significant pain relief in the low back and feet, the patient had near resolution of other DPN-related symptoms, including numbness, bluish discoloration, and allodynia of both feet. He also demonstrated functional and psychological benefits with only a single-sided lead. Overall, the placement of unilateral T12 and S1 DRG-S leads resulted in symmetric improvement of DPN symptoms. A possible mechanism of action is antidromic propagation of action potential signaling into the sympathetic chain to a central ganglion and then to the contralateral sympathetic chain. Given the DRG's ability to directly affect afferent sympathetic fibers with low-frequency stimulation, DRG-S may be an effective neuromodulatory treatment for DPN.

Diabetic peripheral neuropathy (DPN) is a complication of diabetes connected with morbidity and mortality. DPN presents deterioration of peripheral nerves with pain, feebleness, and loss of sensation. Particular medications might display their remedial potential by controlling neuroinflammation. Palmitoylethanolamide (PEA) is an autacoid local injury antagonist distinguished for its neuroprotective, analgesic, and anti-inflammatory properties in numerous experimental models of neuroinflammation. Based on these findings, the goal of this work was to better test the neuroprotective effects of a formulation of micronized PEA (PEA-m) and the probable mechanism of action in a mouse model of DPN induced by streptozotocin (STZ) injection. Diabetic and control animals received PEA-m (10 mg/kg) by oral gavage daily starting 2 wk from STZ injection. After 16 wk, the animals were euthanized, and blood, urine, spinal cord, and sciatic nerve tissues were collected. Our results demonstrated that after diabetes induction, PEA-m was able to reduce mechanical, thermal hyperalgesia, and motor alterations as well as reduce mast cell activation and nerve growth factor expression. In addition, PEA-m decreased neural histologic damage, oxidative and nitrosative stress, cytokine release, angiogenesis, and apoptosis. Moreover, spinal microglia activation (IBA-1), phospho-P38 MAPK, and nuclear factor NF-κB inflammatory pathways were also inhibited. The protective effects of PEA-m could be correlated at least in part to peroxisome proliferator-activated receptor-α activation. In summary, we demonstrated that PEA-m represents a new therapeutic strategy for neuroinflammation pain associated with mixed neuropathies.-Impellizzeri, D., Peritore, A. F., Cordaro, M., Gugliandolo, E., Siracusa, R., Crupi, R., D'Amico, R., Fusco, R., Evangelista, M., Cuzzocrea, S., Di Paola, R. The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice.

Hospital Aim To examine whether a novel MUNE method so called MScanFit MUNE (MScan) can detect early motor involvement in diabetic polyneuropathy (DPN). Methods In this study, 100 patients with diabetes mellitus type II will be prospectively included as a part of International Diabetic Neuropathy Consortium (IDNC) project. Preliminary results of 24 patients (18 males, 6 females, mean age: 63, range: (44–74) will be presented here. Nerve conduction studies (NCS) of three motor (median, peroneal, tibial) and three sensory (bilateral sural and median) nerves and MScan in abductor pollicis brevis (APB) muscle were done in all patients.NCS results were compared to laboratory controls. MScan results were compared to 20 age-matched healthy subjects. Results From NCSs, DPN was classified by Dyck’s criteria. Six of 24 patients (25%) had DPN while 18 patients had normal NCS. None of the 24 patients had decreased CMAP amplitude of median nerve. MScan was abnormal in eight of 24 patients (33%). Of these eight, two patients had DPN and six had normal NCS. Discussion Normal MScan in patients with DPN may be due to length dependent feature of DPN, thereby unaffected upper extremities as these patients had slight sensory neuropathy. However, MScan could detect abnormality in nerves with normal CMAP amplitude and normal NCS. Conclusion MScan may improve electrodiagnosis of DPN by detection of early motor involvement and motor unit loss. Significance MScan is a promising novel method which may be useful in quantifying motor unit loss in different neuromuscular disorders including DPN.

The ovarian hormone 17β-estradiol is known to regulate the release, expression and immunoreactivity of arginine-vasopressin (AVP) in the supraoptic and paraventricular hypothalamic nuclei of rodents. Previous studies have shown that estrogen receptor α is involved in the effects of chronic estradiol administration on arginine-vasopressin immunoreactivity in the female rat hypothalamus. In this study we have examined the effect of an acute administration of estradiol or specific agonists for estrogen receptors α, β and G protein-coupled estrogen receptor 1 on the immunoreactivity of arginine-vasopressin in the hypothalamus of adult ovariectomized female rats. Acute estradiol administration resulted in a significant decrease in the number of arginine-vasopressin immunoreactive neurons in the supraoptic and paraventricular nuclei after 24 h. The effects of the specific estrogen receptors agonists suggest that the action of estradiol on arginine-vasopressin immunoreactivity is mediated in the supraoptic nucleus by G protein-coupled estrogen receptor 1 and in the paraventricular nucleus by both estrogen receptor β and G protein-coupled estrogen receptor 1. Thus, in contrast to previous studies on the effect of chronic estrogenic treatments, the present findings suggest that estrogen receptor β and G protein-coupled estrogen receptor 1 mediate the acute effects of estradiol on arginine-vasopressin immunoreactivity in the hypothalamus of ovariectomized rats., PC, HP, DG, NL and LMGS acknowledge support from Ministerio de Economıa y Competitividad, Spain (PSI2014-57362-P), Agencia Estatal de Investigación, Spain (BFU2017-82754-R), Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain and Fondos FEDER. GCP and MM have been supported by University of Torino and Cavalieri-Ottolenghi Foundation, Orbassano, Italy. The study was also supported by Ministero dell’Istruzione, dell’Università e della Ricerca – MIUR project “Dipartimenti di Eccellenza 2018–2022” to Dept. of Neuroscience “Rita Levi Montalcini”. MM fellowship was supported by a generous donation of Prof. G.C. Bergui.

Diabetic polyneuropathy (DPN) is the most common microvascular complication in diabetes mellitus (DM). The nerve fibers injury was caused by the interaction between metabolic and vascular factor. Prolonged hyperglycemia will induce several mechanisms, such as sorbitol pathway, hypoxia, oxidative stress, and increased of advanced glycation end products (AGE). Those mechanisms will trigger the production of vascular endothelial growth factor (VEGF). The production of VEGF in neovascularization was followed by the changes in microvascular structure that were marked by the enhancement of arteriol basal membrane, vein distention, arteriovenous shunting, intimal hyperplasia and hypertrophy, and endothelial fenestration. The VEGF production was a response to the hyperglycemia that was considered related to endotheliopathy and increased vascular permeability. Therefore, VEGF was acknowledged to contribute to hypoxia and acts as a potential proinflammatory substance. Nevertheless, VEGF also was considered to have a neuroprotective activity by its capability to trigger remyelination and neurogenesis. Based on this evidence, VEGF was assumed to have 2 different roles (dual effect) which are first by acting in the pathogenesis of DPN by induced hypoxia, increased vascular permeability, and caused inflammation, and second acts as a protective agent by induced nerve regeneration. This review is aimed to describe the proposed role of VEGF in the pathogenesis of DPN as well as some genetic studies regarding VEGF gene and its association with DPN.

Type 2 diabetes mellitus (T2DM) is more prevalent in aging populations. Older adults with diabetes have higher rates of macro and micro vascular complications. Our study assessed whether age is an independent factor for both large and small nerve dysfunctions in Chinese patients with T2DM. This cross-sectional study involved a total of 950 patients with type 2 diabetes (mean age: 60.01±12.30 years). Diabetic peripheral neuropathy (DPN) was assessed according to clinical symptoms and physical examinations by using neuropathy symptom score (NSS), the neuropathy disability score (NDS), Michigan Neuropathy Screening Instrument (MNSI score), vibration perception threshold (VPT) and SUDOSCAN test. By using independent logistic regression model, we showed that age was an independent risk factor of DPN (odds ratio [OR] = 1.036, 95% confidence interval [CI] 1.018-1.054, P< 0.01). T2DM patients over 71 years had a higher risk of DPN determined by using NSS/NDS (OR= 2.087; 95% CI 1.112-3.918; P

Mesembryanthemum edule is an edible medicinal halophyte traditionally used to treat several human diseases. In this study, particular importance was attached to the influence of environmental conditions on phenolic composition and antioxidant activities of two M. edule provenances from contrasting climatic regions (Djerba and Monastir sampled from arid and superior semi-arid bioclimatic stages, respectively). Shoot phenolic content was evaluated using colorimetric method and its composition was identified by HPLC analysis with or without thiolysis. Antioxidant activities were assessed by five in vitro antioxidant systems. Results showed that the two M. edule provenances were significantly different according to their antioxidant activity as well as their polyphenol profiles. Indeed, plants from Djerba (lack of rainfall and long light hour periods) exhibited stronger antioxidant activity together with higher phenolic content. For instance, Djerba provenance shoots showed much lower IC 50 (4.8 μg ml −1 ) and EC 50 (80 μg ml − 1 ) values for DPPH and Fe-reducing tests, respectively. In addition, the superiority of this provenance (Djerba) was more marked as compared to positive controls (BHT, BHA, and VitC). HPLC identification revealed also an important difference between the two provenances on major flavonoid components. This difference was confirmed by the mean degrees of tannin polymerization (DP n ) which was higher in Djerba plants. These data suggest that M. edule adaptation to environmental stresses proceeds through induced particular phenol quality and DP n for the improvement of their antioxidant capacities to protect plant tissues against oxidative stress.

To evaluate the extent to which each estrogen receptor (ER) subtype contributes to the stimulation or to the inhibition of mammary tumor growth, we evaluated the effects of specific agonists in MC4-L2 cells, which are stimulated by 17β-estradiol (E 2), and in mammary carcinomas of the MPA mouse breast cancer model, which are inhibited by E 2. Both express ERα and ERβ. In MC4-L2 cells, 4,4,4-(4-propyl-(1H)-pyrazole-1,3,5- Triyl)trisphenol (PPT; ERα agonist) and (4-hydroxy-phenyl)-propionitrile (DPN; ERβ agonist) stimulated cell proliferation, whereas the opposite occurred in C4-HI primary cultures. The inhibitory effect was associated with a decrease in ERa and cyclin D1 expression and an increase in progesterone receptor (PR) expression as well as in the Bax/Bcl-xl ratio. In vivo, mice carrying C4-HI or 32-2-HI tumors were treated with E 2, PPT or DPN (3 mg/kg/day) or with vehicle. PPT and DPN inhibited tumor size, as did E 2, during the first 72 h. After a few days, DPN-Treated tumors started to grow again, while PPT-Treated tumors remained quiescent for a longer period of time. A pronounced decrease in the mitotic index and an increase in the apoptotic index was associated with tumor regresion. All treated tumors showed: (a) an increase in integrin α6 and Bax expression, (b) an increased stromal laminin redistribution, and (c) a decrease in ERα, Bcl-xl and Bcl-2 expression (P

Low birth weight is correlated with low adiposity at birth, a phenotype that influences neonatal survival and later adiposity. A better understanding of events affecting the fetal adipose tissue development and its functionality around birth is thus needed. This study was undertaken to examine the impact of spontaneous intra-uterine growth restriction (IUGR) on circulating concentrations of hormones and nutrients together with the developmental expression patterns of various genes in subcutaneous adipose tissue of pig fetus during the last third of pregnancy and just after birth. At 71 and 112 days post-conception and 2 days postnatal, pairs of same-sex piglets were chosen within litters to have either a medium (MBW) or a low (LBW) weight (n=6 pairs at each stage). The results indicate that IUGR counteracts the temporal fall of DLK1 gene expression in developing adipose tissue across gestation. It also attenuates the time-dependent increase in expression levels of many genes promoting adipocyte differentiation (PPARG, CEBPA) and lipogenesis (LPL, SREBF1, FASN, FABP4). Opposite responses to IUGR were observed for the IGF system, so that IGF1 mRNA levels were lower (P