Improvement of Metabolic and Histological Changes of Adiposity in Rats by Synthetic Oleoyl Chalcones.

We previously reported that synthetic oleoyl chalcones had a favorable effect to alleviate metabolic consequences of obesity in male SD rats. In this work, we prepared and characterized by spectroscopic tools, a set of six oleoyl chalcones (5a-c, 10 and 11a,b). The comparative effects of the previously prepared oleoyl chalcones and their new synthetic analogs on metabolic and histological changes in obese male SD rats were studied. It was found that the oleoyl chalcones IIIa and IV were the best in improving many metabolic parameters, e. g., FBG, FI, ISI, TG, and total cholesterol. They cured systemic inflammation, through inhibition of the TNF-α and induction of adiponectin production. Moreover, chalcones IIIa and IV alleviated the oxidative stress accompanying obesity through the induction of the antioxidant enzymes GPX, SOD and CAT besides, GSH. Interestingly, chalcones IIIa and IV exerted hepatoprotective potency and ameliorated the manifestations of NAFLD via inhibition of apoptosis and induction of autophagy of hepatic cells. In conclusion, the oleoyl chalcones IIIa and IV were the most effective candidates among the series of synthetic chalcones in correcting body weight and the consequent metabolic and histological changes in adiposity.

Relationship between skin temperature monitoring with Smart Socks and plantar pressure distribution: a pilot study.

OBJECTIVE: Increased skin temperature at the plantar aspect of the foot can predict foot ulceration. However its relation to plantar pressure overload is unknown. The aim of this study was to assess the ability of 'smart socks', monitoring plantar temperature under real-life conditions, to predict plantar pressure distribution. METHOD: The 'smart socks' have seven thermal sensors woven into the fabric of the sock to measure the temperature beneath the foot in real-life conditions. The upper part of the sock is connected to a central unit through which changes in the sensor resistance is converted into temperature changes. Participants were instructed to wear the socks for three continuous hours. Plantar pressure was measured by the MatScan plantar-pressure measurement system (Tekscan Inc., US). RESULTS: The study included 25 healthy volunteers (11 males, 14 females, mean age was 41.1 years (standard deviation (SD): 17.6) years, a mean body mass index of 29.4 kg/m2 (SD: 6.95). Temperature changes at sensor (S) five significantly correlated with metatarsal (M) 2 pressure time integral (PTI) (r=0.519, p=0.008), M3 PTI (r=0.435, p=0.03), M4 PTI (r=0.452, p=0.023). Changes at S5 also significantly correlated with peak pressure at M2 (r=0.66, p=0.000), M3 (r=0.52, p=0.01), and M4 (r=0.60, p=0.002). Temperature changes at S6 were significantly correlated with changes at S1, S2, S3, S4, S5, and S7. CONCLUSION: Temperature changes at the plantar aspect of the foot measured by the smart socks are correlated with plantar pressure distribution. Furthermore, two sensors at positions S5 and S6 were sufficient to predict plantar pressure changes.

Plasma levels of Asymmetric Di Methyl Arginine and endothelial dysfunction in diabetic subjects with neuropathic foot ulcer.

OBJECTIVE: Asymmetric dimethyl arginine (ADMA) is an amino acid that acts as an endogenous competitive inhibitor of Nitric oxide synthase, leading to endothelial dysfunction (ED). The aim of this study was to evaluate the relationship between plasma ADMA (p-ADMA) level and ED in diabetic subjects with neuropathic foot ulcer (NFU), and the possible predictors of p-ADMA level. MATERIALS AND METHODS: 80 diabetic subjects of matched age, sex and BMI were included; 40 with NFU (G1), 20 with peripheral nerve dysfunction (PND) (G2) and 20 without PND (G3), plus 20 matched healthy subjects (G4). Flow-mediated-dilatation (FMD) of brachial artery and Carotid-intima-media-thickness (CIMT) were measured to evaluate ED and subclinical atherosclerosis, respectively. RESULTS: G1&2 had a significantly lower FMD than G3&4 [-5.09 (-22.5 to 22.92), 4.67 (-15 to 23.91) vs. 15.74 (8.33-36.59) and 20.1 (10.0-46.15)%, respectively] (p < 0.001), and higher CIMT [0.9 (0.6-1.5), 0.9 (0.6-1.3) vs. 0.6 (0.5-0.8) and 0.7 (0.5-0.9) cm, respectively] (p < 0.001, r = 0.237, p = 0.034, r = 0.330, p = 0.003, respectively), with no significant correlation with FMD (r = -0.176, p = 0.118). FMD was inversely and strongly related to CIMT (r = -0.520, p < 0.001). p-ADMA levels were significantly higher in uncontrolled hypertensive patients in comparison to controlled and normotensive subjects [717 (286-3611) vs. 648 (335-874) and 686 (526-857) ng/L, respectively] (p = 0.026). Metformin users and hypertensive subjects on ACEIs or ARBs had the lowest p-ADMA levels than the non-users (p < 0.001, p = 0.007, respectively). CONCLUSION: The remarkable ED in diabetic subjects with NFU is unlikely to be due to alteration in p-ADMA. Further studies are needed in order to conclude a causal association between p-ADMA and ED in this group of patients.

Oral Alpha Lipoic Acid Treatment for Symptomatic Diabetic Peripheral Neuropathy: A Randomized Double-Blinded Placebo-Controlled Study.

BACKGROUND: Alpha-lipoic acid (ALA) was used in the treatment of diabetic peripheral neuropathy (DPN) using different routes, doses and treatment durations. The aim of this work is to assess the efficacy of oral 600mg ALA twice daily over 6 months in the treatment of patients with DPN. METHODS: This is a prospective, single-center, double-blinded, placebo-controlled study conducted at the outpatient clinic of Mansoura Specialized Hospital, Mansoura University. A total of 200 patients with DPN were randomly assigned to add on treatment with either oral 600mg twice daily ALA (n=100) or placebo (n=100) for 6 months. Treatment outcome was assessed using vibration perception threshold (VPT), neurological symptom score (NSS), neurological disability score (NDS), and visual analog scale (VAS) for pain at baseline and at each visit (1, 3 and 6 months) after the start of treatment. RESULTS: Comparison between the study groups regarding the baseline data revealed no statistically significant differences. with respect to the outcome parameters, no significant differences were found between the studied groups at baseline. However, in subsequent visits, ALA-treated patients had significantly better results regarding almost all the outcome parameters (NSS, NDS, VAS, VPT). Mild nausea was reported in 6 patients. None of the studied patients discontinued treatment. CONCLUSION: Oral 600mg ALA twice-daily treatment for DPN over 6 months is effective, safe and tolerable.

Pressure distribution under the contralateral limb in Charcot arthropathy with different walking speeds.

BACKGROUND: The total contact cast has been recognized as the "gold standard" for treatment of Charcot neuro-osteoarthropathy (CN). However, removable cast walkers (RCWs) became an alternative option especially after resolution of the acute stage. RCWs with an elevated sole construction often induce leg length discrepancy (LLD) that could significantly affects plantar pressure (PP) distribution in diabetic patients with neuropathy. AIM: To study the additional effect of walking speed on PP abnormalities induced by LLD. METHOD: The study included 16 patients with diabetes (59±8.8years; 8 men and 8 women), with unilateral CN offloaded by RCW. In-shoe PP distribution was measured using F-scan (Tekscan Inc.), whilst patients walked at their normal speed (53±4 steps/min), versus short slow steps (24±3/min) under the two walking conditions: (1) neglected LLD, and (2) corrected LLD. RESULTS: The greatest reduction in PP was seen during reduction of walking speed, with corrected LLD, followed by corrected LLD with normal walking speed, followed by neglected LLD with slowing of walking speed. The highest PP was found when the patient remain on their normal walking speed and LLD was neglected. CONCLUSION: The contralateral foot of CN offloaded with RCW, is subjected to high pressure loads beneath the hallux, 1st, 2nd, 3rd, and 5th metatarsal heads. As such, care should be taken not only to avoid minor LLD, but to also advise the patient to practice short slow steps while walking, so that pressure overload on contralateral limb and its possible contribution to the development of bilateral Charcot, could be minimized.

Novel antibiotics for the management of diabetic foot infections.

Foot infections are a major cause of morbidity in diabetic patients. Staphylococcus aureus is the most important pathogen in mild infections; moderate to severe infections are frequently polymicrobial. Multidrug resistance is an increasing problem in isolates from diabetic feet. Worldwide, up to 30% of patients with diabetic foot infection (DFI) are colonised with methicillin-resistant S. aureus (MRSA), whilst extended-spectrum beta-lactamase-producing Gram-negative bacteria are also common in some countries. This emergence of drug resistance has coincided with the launch or imminent availability of many new antibiotics. Most of these were developed to target multidrug-resistant Gram-positive bacteria, although some have a spectrum of activity that includes Gram-negative bacteria and anaerobes. There is a variable amount of experience with these agents in treating skin and skin-structure infections (SSSIs), especially for DFI. However, at least some have a spectrum of activity and/or pharmacological properties that suggest that they may be of value in managing DFIs. The aim of this paper is to review evidence for the efficacy of new antibiotics in the management of SSSIs, including any data relating specifically to the diabetic foot, and to consider where they might fit into the therapeutic armory against DFI.