Effect of prefabricated thermoformable foot orthoses on plantar surface temperature after running: A gender comparison

There is a lack of evidence about the effect of different type of foot orthoses on plantar surface temperature. Moreover, that effect could be different depending on gender due to anatomical and physiological differences between men and women. The aim of the study was to analyze the effect of a prefabricated thermoformable foot orthosis on plantar surface temperature after running and taking gender differences into account. Thirty recreational runners (15 males, mean (standard deviation): 28 (7) years, 69.7 (6.5) kg, 1.74 (0.05) cm and 22.9 (1.7) kg/m²; and 15 females: 35 (7) years, 55.2 (6.9) kg, 1.63 (0.06) cm and 20.6 (1.9) kg/m²) carried out a maximum incremental test as pre-test, and two running tests on a treadmill at the laboratory wearing previously randomized different foot orthoses (thermoformable and prefabricated generic). The plantar surface temperature of the dominant foot sole in ten regions of interest was assessed before and immediately after 30-min running at 75% of VO_2max. The use of thermoformable foot orthoses produced lower temperatures only in men after the run in medial heel (P = 0.033, ES = 0.7), which then disappeared in temperature variation (after – before) (P = 0.910). Regarding gender, women showed lower temperatures before the run in both orthosis conditions (P < 0.039, ES > 0.8), but no differences in temperatures after the run (P = 0.910) in comparison with men. Moreover, absolute temperatures after running were always greater than before the run (P < 0.001, ES > 5.0). In conclusion, the thermoformable foot orthoses do not modify plantar surface temperature after running in healthy runners of either gender, compared to prefabricated generic foot orthoses. Although women present lower baseline plantar temperatures than men, these differences disappear after exercise.     

Clodronate changes neurobiological effects of pulsed magnetic field on diabetic rats with peripheral neuropathy

Several studies have reported that pulsed magnetic fields (PMFs) can be a choice of therapy for diabetic peripheral neuropathy. However, the exact underlying mechanism of PMF is still not known. The purpose of this study was, therefore, to investigate the effects of clodronate encapsulated with liposome, a specific agent depleting macrophage, on PMF-treated streptozotocin-induced type I diabetic rats with peripheral neuropathy. Effects of PMF, liposome-encapsulated clodronate (LEC) or their combined treatments were investigated in diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels, serum insulin level, and body mass. In diabetic rats, PMF exhibited a decrease in the blood glucose levels but did not change the serum insulin level. Both mechanical thresholds and thermal latencies of diabetic rats enhanced throughout the PMF treatment. During the PMF treatment, the administration of LEC suppressed the PMF-induced decrease in blood glucose level, PMF-induced increase in mechanical threshold and thermal latencies in diabetic animals. In addition, PMF reduced the LEC-induced increase in insulin levels of diabetic rats. Findings demonstrated that although effects of both PMF alone and LEC alone on diabetic animals are mostly positive, LEC may remove the therapeutic efficacies of PMF in combined treatment.     

Statin use and peripheral sensory perception: A pilot study

Objectives. Peripheral sensory neuropathy is a neurological deficit resulting in decreased detection of sensation through the peripheral nervous system. Peripheral sensory neuropathy is commonly diagnosed with the use of a monofilament and either a tuning fork or neurothesiometer. Statins are a widely used medication and there has been some debate of association with their use and peripheral sensory neuropathy. This pilot study aimed to test the sensory perception of participants with long-term statin use and compare these results to their peers who were not taking statins.

Methods. Thirty participants were recruited and equally divided into a statin and non-statin group. Healthy participants were screened by their medical and medication history, Australian Type 2 Diabetes Risk assessment, and random blood glucose level. An assessor who was blinded to the participant group conducted sensory assessments using a 10?g monofilament and neurothesiometer.

Results. There was no difference in monofilament testing results between the groups. The statin group was less sensate at the styloid process (p?=?0.031) and medial malleolus (p?=?0.003) than the control group. Results at the hallux were not statistically significant (p?=?0.183).

Conclusion. This result is suggestive of a potential association between long-term statin use and a decrease in peripheral sensory perception. This may be because of peripheral sensory neuropathy. Limitations such as consideration of participant height, participant numbers, and inability to analyze results against statin groups are reported. As statins are a life-saving medication, careful consideration should be applied to these results and further research be conducted to determine if these results are applicable to larger populations.     

Beneficial effects of n-hexane bark extract of Onosma echioides L. on diabetic peripheral neuropathy

Onosma echioides Linn (Boraginaceae) is the most frequently used curative herb widely used for kidney obstruction, sciatic pain, and gout. The present study was designed to investigate the therapeutic effects of n-hexane bark extract of O. echioides (OE) L. root in vivo against Streptozotocin-induced diabetic neuropathy in SD rats. For in vivo activity, the experiment was categorized into five different groups (n = 5). Group-I was considered as nondiabetic/normal control (NC) treated with 0.5% carboxymethyl cellulose (CMC), Group II as diabetic control, Group-III, IV, and V served as diabetic treated with OE 50, OE 100, and pregabalin at a dose of 50, 100, and 10 mg/kg body weight, orally, respectively. Body weight, blood glucose, oral glucose tolerance test, behavioral studies (motor coordination test, thermal hyperalgesia, cold allodynia, locomotor activity, oxidative biomarkers (thio barbituric acid reactive substances [TBARS], superoxide dismutase [SOD], glutathione [GSH], and catalase), and histopathology of the sciatic nerve were performed. Treatment with OE showed a dose-dependent increase in neuroprotective activity by improving the myelination and decreasing the axonal swelling of nerve fibers. The verdicts of behavioral activities showed a remarkable effect on animals after the treatment of extract and standard drug pregabalin. In conclusion, our findings supported the traditional application of OE and explored its importance in the management of diabetic neuropathy. Additional clinical experiments may provide novel therapeutic drugs for diabetes and its complications.     

肠道微生物群在糖尿病肾病防治中的研究进展

糖尿病肾病(diabetic kidney disease, DKD)是由糖尿病引起的严重的代谢性疾病,在高糖情况下,引起肾脏慢性炎症和氧化应激,破坏肾脏生理结构并导致肾脏间质纤维化。大量研究表明,肠道微生物群能够影响机体代谢和健康。本文通过梳理肠道微生物群与DKD相关性的最新研究成果,以期阐明肠道微生物群在DKD的发生和防治过程中的作用。首先,阐明了肠道屏障和肠道微生物群代谢物与DKD的联系;其次,总结近几年抗DKD研究中的作用机制;最后,对补充益生元、益生菌和粪便移植在DKD治疗中的可行性进行了讨论。通过梳理相关内容,本文可为DKD的防治提供一定的理论参考与数据支持。     

Liraglutide ameliorated peripheral neuropathy in diabetic rats: Involvement of oxidative stress,inflammation and extracellular matrix remodeling

Diabetic peripheral neuropathy is one of the most common microvascular complications that occurs with both type 1 and type 2 diabetes mellitus. It has a significant negative impact on patients’ quality of life; as it starts with loss of limbs’ sensation and may lead to lower limb amputation. This study aimed at investigating the effect of liraglutide on peripheral neuropathy in diabetic rats. Experimental diabetes was induced by single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were allocated into five groups. Two groups were given saline or liraglutide (0.8 mg/kg, s.c.). Three diabetic groups were either untreated or treated with liraglutide (0.8 mg/kg, s.c.) or pregabalin (10 mg/kg, i.p.). After 2 weeks of treatment, behavioral, biochemical, histopathological, and immunohistochemical investigations were performed. Treatment with liraglutide‐restored animals’ body weight, normalized blood glucose, decreased glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of both tail flick and hind paw cold allodynia tests and reversed histopathological alterations. Treatment with liraglutide also normalized malondialdehyde, matrix metalloproteinase‐2 and ‐9 contents in sciatic nerve. Likewise, it decreased sciatic nerve nitric oxide and interleukin‐6 contents, DNA fragmentation and expression of cyclooxygenase‐2. Meanwhile, it increased superoxide dismutase and interleukin‐10 contents in sciatic nerve. These findings indicate the neuroprotective effect of liraglutide against diabetic peripheral neuropathy probably via modulating oxidative stress, inflammation, and extracellular matrix remodeling.

     

基于网络药理学和分子对接探索桑白皮治疗糖尿病周围神经病变的潜在机制

本研究运用网络药理学和分子对接方法对中药桑白皮治疗糖尿病周围神经病变(DPN)的活性成分、潜在作用靶点和信号通路进行研究,探索桑白皮治疗DPN的可能作用机制。首先从中药系统药理学数据库(TCMSP)筛选出桑白皮的活性成分及靶点基因。通过GeneCards数据库及OMIM数据库筛选出DPN的疾病靶点基因,并用Cytoscape软件构建"药物-有效成分-靶基因-疾病"中药调控网络图。将有效成分靶标与疾病靶标上传到STRING数据库,构建蛋白互作网络图(PPI),并使用R语言对得到的PPI进行核心基因的筛选。运用R语言对关键靶点进行GO富集分析和KEGG通路富集分析。其次从活性成分及靶点基因中根据degree值筛选出前3个关键成分,并将该网络中的基因靶点以degree值高低进行排序,选择前3个核心靶点,然后从RCSB数据库下载相关蛋白的结构,使用Pymol软件去除溶剂分子与配体,使用AutoDock软件进行分子对接。最后通过酶联免疫吸附实验和荧光光谱实验验证网络药理学富集分析的结果。最终预测到31个桑白皮活性成分,312个活性成分相关靶点,120个桑白皮-糖尿病周围神经病变共同有效靶点。活性...     

Clinical application of fresh fibroblast allografts for the treatment of diabetic foot ulcers: a pilot study

Diabetic foot ulcers often pose a difficult problem for health care professionals because of the defects associated with fibroblast functioning. Although there has been much interest recently in the use of topical growth factors for the treatment of diabetic foot ulcers, the effects are generally not very dramatic. Cryopreserved fibroblast implants, which are able to adjust to a wound's environment and provide the desired growth factors and other substances that may be lacking in a chronic wound, represent an exciting development and a major advance. These products may well provide growth factors in the right concentration and in the right sequence, something that has proved difficult to achieve with the topical application of recombinant growth factors. However, cell activities are impaired by cryopreservation. The purpose of this study was to assess the effects of fresh human allogeneic fibroblast grafting for the treatment of diabetic foot ulcers. Eight patients with diabetic foot ulcers ranging from 6 to 17 weeks in duration were treated. The size of the wounds ranged from 2.0 to 6.0 cm2, with three patients exhibiting exposed bones. A history of diabetic foot ulcers was present in five patients. Human dermal fibroblasts from healthy teenagers were cultured in Dulbecco's modified Eagle medium/Ham's F-12 supplemented with 10% autologous serum. The cultured cells were applied over the wounds immediately after debridement; fibrin was used as a cell carrier. A dressing was then applied with Tegaderm and kept moist until healing was complete. The progress and time for complete wound closure and patient satisfaction were assessed, with follow-up time ranging from 6 to 18 months. Complete wound healing occurred in all patients. Eleven to 21 days were needed for complete reepithelization of the wound, and no clinical or laboratory abnormalities were noted. Patient satisfaction was also very positive. In this study, the use of fresh human fibroblast allografts was found to be a safe and effective treatment for diabetic foot ulcers.     

Abundance of triacylglycerols in ganglia and their depletion in diabetic mice: implications for the role of altered triacylglycerols in diabetic neuropathy

Herein, we report the first study on the mass distribution and molecular species composition of abundant triacylglycerols (TAG) in ganglia. This study demonstrates five novel findings. First, unanticipated high levels of TAG were present in all examined ganglia from multiple species (e.g. mouse, rat and rabbit). Second, ganglial TAG mass content is location-dependent. Third, the TAG mass levels in ganglia are species-specific. Fourth, dorsal root ganglial TAG mass levels in streptozotocin-induced diabetic mice are dramatically depleted relative to those found in untreated control mice. Fifth, mouse ganglial TAG mass levels decrease with age although molecular species composition is not changed. Collectively, these results indicate that TAG is an important component of ganglia and may potentially contribute to pathological alterations in peripheral neuronal function in diabetic neuropathy.     

Interactions of copper with glycated proteins: Possible involvement in the etiology of diabetic neuropathy

Humans and animals with diabetes frequently develop peripheral vascular dysfunction and peripheral neuropathies. There is accumulating evidence that impaired peripheral nerve function may derive from diminished endoneural blood flow. The decrements in nerve blood flow may, in turn, be due to diminished endothelium-dependent vasodilation. Although a number of possible causes of this defective vasodilation have been suggested, none has been definitely proven. Regardless of the precise cause, the impaired vasodilatory activity may reflect diminished availability of endothelium-derived relaxing factor (EDRF), variously thought to be nitric oxide or thiol adducts of nitric oxide. Other investigators have reported that administration of transition metal chelators to diabetic rats corrects EDRF-mediated arterial relaxation and restores both neural blood flow and nerve conduction velocity, suggesting the involvement of transition metals. Our investigations center about the hypothesis that glycated proteins bind transition metals such as copper and iron, and that such 'glycochelates' accumulate within the vasculature in diabetes and catalytically inactivate EDRF. In partial support of this hypothesis: (1) Glycated albumin binds 3-fold greater amounts of both copper and iron. (2) Copper bound to glycated albumin remains redox active (e.g. capable of supporting the oxidation of ascorbic acid). (3) Copper and copper-containing glycochelates cause the rapid decomposition of one putative form of EDRF, nitrosocysteine. (4) The amount of exchangeable (i.e. chelatable) copper in the plasma of diabetic rats is approximately twice that in normal rat plasma. (5) Similarly, tail tendons of diabetic animals have about twice as much bound copper as do tendons of normal rats. (6) Implants bearing adsorbed glycated albumin placed in the peritonea of normal mice for 48 h accumulate 5 times as much bound copper as do implants coated with control albumin. Overall, these observations support – but do not conclusively prove – the hypothesis that transition metals such as copper, bound to glycated proteins, may blunt normal EDRF-dependent relaxation of diabetic arteries and provide a rationale for the use of transition metal chelators in the therapy of diabetic vasculopathy and neuropathy.     

Efficacy and safety of pregabalin 600 mg/d for treating painful diabetic peripheral neuropathy: A double-blind placebo-controlled trial

Background  

Recent consensus guidelines recommend pregabalin as a first-tier treatment for painful diabetic peripheral neuropathy (DPN). We evaluated the efficacy of pregabalin 600 mg/d (300 mg dosed BID) versus placebo for relieving DPN-associated neuropathic pain, and assessed its safety using objective measures of nerve conduction (NC).     

Evaluating the effect of health education program on outcomes of type I diabetic patients: A randomized controlled study

Background; findings from the meta-analysis have shown that patients present improvements in glycaemic control, and in the prevention and control of the acute and chronic complications, when they receive effective treatment, self-management support and regular monitoring. The present study aimed to evaluate the effect of implementing a health education program on outcomes of type I diabetic patients. Quasi-experimental study design was used to fulfill the aim of the study. The study was conducted in the outpatient diabetic clinic at Asyut University Hospital; 60 adult male and female patients who attended the outpatient diabetic clinic were included. Two tools were used in this study; structured interviewing questionnaire with three parts; part one: demographic patient variables, part two: patient's medical data and part three: patient's knowledge regarding diabetes, the second tool is evaluation of type I diabetic patients' outcomes (pre/post). Results revealed that the highest percentage of the studied samples were in the age group 18 to less than 30 years, 90.0% of the study group and 83.4% of the control group were having a family history of diabetes, a statistically significant difference was found in the study group patients pre and post application of the program regarding insulin injection and glycemic control. Conclusion: this study demonstrated the effectiveness of health education program implementation on the outcomes of type I diabetic patients in terms of improved knowledge and practicing exercise, teeth care, feet care and on glycemic control.     

A reliability study on the cumulative averaging method for estimating effective stimulus time in vibration studies

Finding the reflex circuitry responsible for high-frequency vibration-induced muscle contraction takes work. The main challenge is to determine the effective stimulus time (EST) point at which continuous (sinusoidal) stimulation (i.e., vibration) triggers the reflex response. A novel “cumulated averaging method” has been previously proposed for estimating the EST point. In the current study, we aimed to test the reliability of the cumulated average method. We used five different whole-body vibration (WBV) frequencies in two experiments. The consistency between the EST points estimated from the first and second experiments was analysed with the intraclass correlation (ICC) and technical error of measurement (TEM). The ICC coefficient with 95% CI for the EST point estimation was 0.988 (0.950–0.997). The relative TEM was 1.3%. We concluded that the cumulated average method is highly reliable in estimating the effective stimulus time point for high-frequency continuous sinusoidal signals.     

Mechanism of reducing knee adduction moment by shortening of the knee lever arm via medio-lateral manipulation of foot center of pressure: A pilot study

Prominent conservative treatment options for medial-compartment knee osteoarthritis include footwear that reduces knee adduction moment (KAM) correlated with detrimental loads in the medial compartment of the knee, thus providing clinical benefit. The proposed mechanism by which they reduce KAM is a lateral shift in foot center of pressure (COP) and a consequent shortening of the knee lever arm (KLA), thereby reducing KAM, which can be simply calculated as KLA multiplied by the frontal plane ground reaction force (FP-GRF). The present study investigated this mechanism for a unique biomechanical device capable of shifting COP by means of moveable convex elements attached to the shoe. Fourteen healthy young male subjects underwent gait analysis in two COP configurations of the device for comparison: (1) laterally and (2) medially deviated. Average midstance KLA and KAM were decreased by 8.2% and 8.7%, respectively, in the lateral COP compared to medial. Ground reaction force parameters, frontal plane knee angle (FP-KA), and spine lateral flexion angle (SLF) did not differ between COP configurations. No study parameters differed for terminal stance. Linear mixed effects models showed that COP and FP-GRF components, but not FP-KA and SLF, were significant predictors of KLA. In addition, KLA and FP-GRF were significant predictors of KAM; although, FP-GRF did not change significantly with medio-lateral COP shift, while KLA did. This suggests that the mechanism by which the study device reduces KAM is primarily through shortening of KLA brought on by a lateral shift in COP.     

Autologous stem cells for the treatment of post-mastectomy lymphedema: a pilot study

BACKGROUND AIMS. Lymphedema is a common complication with breast cancer treatment that does not have a definite cure. Our objective was to determine the efficacy of autologous stem cells (ASC) in the treatment of lymphedema secondary to mastectomy and axillary lymphadenectomy in comparison with traditional decongestive treatment with compression sleeves. METHODS. A prospective study including 20 women with lymphedema secondary to breast cancer surgery with axillary lymphadenectomy was conducted. Women were assigned at random to one of two groups. One group of 10 women was injected with ASC in the affected arm, whereas the other 10 women comprised the control group and received traditional compression sleeve therapy (CST). The follow-up for both groups was 12 weeks. Pain, sensitivity and mobility were assessed before and after therapy. RESULTS. There was improvement in the volume of lymphedema in both groups, with no significant difference. In the ASC group there was an overall volume reduction during the follow-up, whereas in the CST group lymphedema recurred after the compression sleeve was removed. CONCLUSIONS. Our findings suggest that ASC injection for patients with lymphedema can be an effective treatment. It reduces arm volume and associated co-morbidities of pain and decreased sensitivity. Traditional CST was also effective for lymphedema reduction, but it was dependent on continuous use of the treatment.     

Miltefosine for the treatment of cutaneous leishmaniasis—A pilot study from Ethiopia

BackgroundCutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.Methodology and principal findingsIn an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.Conclusions/SignificanceBased on miltefosine’s good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04004754","term_id":"NCT04004754"}}NCT04004754.