Corneal Sensitivity in Bacterial Keratitis Patients with or without Diabetes Mellitus

The aim. To identify the features of corneal sensitivity of the sick and the fellow eye in bacterial keratitis patients with or without diabetes mellitus. Materials and methods. The analysis was performed on the basis of survey data of 62 type 1 diabetes patients with bacterial keratitis and 43 nondiabetic control patients with bacterial keratitis. The examination was performed at the first visit. In addition to standard ophthalmic examination, the patients underwent fluorescein test, OCT of the anterior segment of the eye, non-contact corneal aesthesiometry. Results and discussion. The average corneal sensitivity threshold in diabetic patients with bacterial keratitis at the first visit at all air flow temperatures exceeded the corresponding indicators in nondiabetic patients of the control group: by 33.5% at an air temperature of 5 °C, by 30.6% at 15 °C, by 28.8% at 20 °C, by 27% at 30 °C, and by 26.1% at 40 °C (p<0.05). The average corneal sensitivity threshold at a temperature of 20 °C in the fellow eye in diabetic patients with bacterial keratitis exceeded that in nondiabetic patients with bacterial keratitis of the control group by 32.9 % (p<0.05). Conclusions. Corneal sensitivity of the sick and fellow eye in patients with bacterial keratitis depends on the presence of diabetes mellitus. The average threshold of corneal sensitivity of the sick and fellow eye in diabetic patients with bacterial keratitis at the first visit exceeds the corresponding values in nondiabetic patients with bacterial keratitis. Keywords: diabetes mellitus, bacterial keratitis, corneal sensitivity.

Effect of ropivacaine on peripheral neuropathy in streptozocin diabetes-induced rats through TRPV1-CGRP pathway

Objective To determine the effect of ropivacaine on peripheral neuropathy in diabetic rats and its possible mechanism. Methods Forty-eight Sprague–Dawley rats were randomly divided into six groups: nondiabetic control group, nondiabetic group A (0.25% ropivacaine), nondiabetic group B (0.75% ropivacaine), diabetic control group (diabetic peripheral neuropathy (DPN) +artificial cerebrospinal fluid), diabetic group A (DPN+0.25% ropivacaine), and diabetic group B (DPN + 0.75% ropivacaine), with eight rats in each group. Within an hour of the last administration, the sciatic motor nerve conduction velocity (MNCV) of each group was measured, and the morphological changes of rat sciatic nerve were observed by HE, Weil’s staining and electron microscopy. The expression of transient receptor potential vanilloid (TRPV1) in the spinal cord dorsal horn of rats was analyzed by immunohistochemistry, and the expression of Calcitonin gene-related peptide (CGRP) protein in the spinal cord was analyzed by Western blot. Results Compared with the nondiabetic control group, elevated blood glucose, decreased weight and reduced average mechanical withdrawal threshold (MWT), additionally, the sciatic nerves showed significantly slowed conduction velocity (both P<0.001) and damaged pathological structure, the expression of TRPV1 and CGRP were decreased (both P<0.001) in the diabetic groups. Compared with the diabetic control group, down-regulation of TRPV1 and CGRP in spinal cord was significant for the diabetic groups A and B treated with 0.25 and 0.75% ropivacaine, the higher concentration of ropivacaine correlated with a greater change. Conclusion Ropivacaine can significantly block sciatic nerve conduction velocity in DPN rats in a concentration-dependent manner, which may be related to the expression of the TRPV1-CGRP pathway.

Invisible Color Variations of Facial Erythema: A Novel Early Marker for Diabetic Complications?

Aim. (1) To quantify the invisible variations of facial erythema that occur as the blood flows in and out of the face of diabetic patients, during the blood pulse wave using an innovative image processing method, on videos recorded with a conventional digital camera and (2) to determine whether this “unveiled” facial red coloration and its periodic variations present specific characteristics in diabetic patients different from those in control subjects. Methods. We video recorded the faces of 20 diabetic patients with peripheral neuropathy, retinopathy, and/or nephropathy and 10 nondiabetic control subjects, using a Canon EOS camera, for 240 s. Only one participant presented visible facial erythema. We applied novel image processing methods to make the facial redness and its variations visible and automatically detected and extracted the redness intensity of eight facial patches, from each frame. We compared average and standard deviations of redness in the two groups using t-tests. Results. Facial redness varies, imperceptibly and periodically, between redder and paler, following the heart pulsation. This variation is consistently and significantly larger in diabetic patients compared to controls (p value < 0.001). Conclusions. Our study and its results (i.e., larger variations of facial redness with the heartbeats in diabetic patients) are unprecedented. One limitation is the sample size. Confirmation in a larger study would ground the development of a noninvasive cost-effective automatic tool for early detection of diabetic complications, based on measuring invisible redness variations, by image processing of facial videos captured at home with the patient’s smartphone.

Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model–Part II: Microglia and Mitochondria

Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. This study tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions may depict abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks), left-brain hemispheres of the DBC and age-matched nondiabetic control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We observed an attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickened basement membranes, adherent red and white blood cells, neurovascular unit microbleeds and pathologic remodeling of protoplasmic astrocytes. In this second of a three-part series, we focus on the observational ultrastructural remodeling of microglia and mitochondria in relation to the NVU in leptin receptor deficient DBC models. This study identified novel ultrastructural core signature remodeling changes, which consisted of invasive activated microglia, microglial aberrant mitochondria with nuclear chromatin condensation and adhesion of white blood cells to an activated endothelium of the NVU. In conclusion, the results implicate activated microglia in NVU uncoupling and the resulting ischemic neuronal and synaptic damage, which may be related to impaired cognition and diabetic cognopathy.

Noninvasive Real-Time Characterization of Renal Clearance Kinetics in Diabetic Mice after Receiving Danshensu Treatment

Danshensu (DSS) is an active ingredient extracted from the root of the Danshen that could ameliorate oxidative stress via upregulation of heme oxygenase- (HO-) 1. Little is known about the treatment effects of DSS on kidney function in diabetic mice. Therefore, the primary aim of the present study was to characterize the renal clearance kinetics of IRdye800CW in db/db mice after DSS treatment. The secondary aim was to measure several biomarkers of renal function and oxidative stress (urinary F2-isoprostane, HO-1 in kidney and serum bilirubin). Fourteen db/db diabetic mice were randomly assigned into two groups and received either DSS treatment (DM + DSS) or vehicle treatment (DM). A third group that comprised of db/+ nondiabetic mice (non-DM control) received no DSS treatment and served as the nondiabetic control. At the end of a 3-week intervention period, serum and urinary biomarkers of renal function and oxidative stress were assessed and the renal clearance of IRdye800CW dye in all mice was determined noninvasively using Multispectral Optoacoustic Tomography. The major finding from this study suggested that DSS treatment in db/db mice improved renal clearance. Increased expression of HO-1 after DSS treatment also suggested that DSS might represent a potential therapeutic avenue for clinical intervention in diabetic nephropathy.

Down Syndrome-Associated Diabetes Is Not Due To a Congenital Deficiency in β Cells

Aims/Hypothesis: We sought to establish whether the increased incidence of diabetes associated with Down syndrome was due to a congenital deficit in β cells. Methods: The pancreas was obtained at autopsy from nondiabetic subjects with Down syndrome (n = 29) and age-matched nondiabetic control subjects without Down syndrome (n = 28). The pancreas sections were evaluated for the fractional β-cell area. Results: No difference was found in the fractional β-cell area between the subjects with Down syndrome and the control subjects. Conclusions/Interpretations: The increased incidence and prevalence of diabetes in individuals with Down syndrome is not due to an underlying congenital deficiency of β cells.

Antihyperglycemic, Antidiabetic, and Antioxidant Effects of Garcinia pedunculata in Rats

The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract of Garcinia pedunculata (GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions.

The Relation between Periodontopathogenic Bacterial Levels and Resistin in the Saliva of Obese Type 2 Diabetic Patients

This study aims to investigate the relation between resistin and periodontopathogenic bacterial levels in the saliva of obese adults compared to healthy control and to examine whether salivary resistin can serve as a biomarker of type 2 diabetes in obese patients. A total of 78 saliva samples were collected from patients attending to the University Dental Hospital, Sharjah, UAE. The patients were divided into three equal groups: obese diabetics, obese nondiabetics, and nonobese nondiabetic control. Salivary resistin was measured using ELISA. The levels of bacterial species associated with periodontitis (Treponema denticola, Porphyromonas gingivalis, Tannerella forsythia, and Actinobacillus actinomycetemcomitans) and gingivitis (Fusobacterium spp.) were measured using real-time PCR. Both salivary resistin and periodontopathogenic bacteria including Fusobacterium spp., P. gingivalis, and T. forsythia were detected in significantly higher quantities in the obese patients (diabetics and nondiabetics) than nonobese nondiabetic control. Resistin concentrations were significantly correlated with BMI; however, its level was not correlated with the blood glucose. In this study, high salivary resistin was associated with obesity, which is a major predisposing factor for type 2 diabetes and also a risk factor for oral diseases. The high levels of salivary periodontopathogenic bacteria could upregulate the local release of salivary resistin in obese people.

Scaffolding protein IQGAP1: an insulin-dependent link between caveolae and the cytoskeleton in primary human adipocytes?

The ubiquitously expressed IQ motif-containing GTPase activating protein-1 (IQGAP1) is a scaffolding protein implicated in an array of cellular functions, in particular by binding to cytoskeletal elements and signaling proteins. A role of IQGAP1 in adipocytes has not been reported. We therefore investigated the cellular IQGAP1 interactome in primary human adipocytes. Immunoprecipitation and quantitative mass spectrometry identified caveolae and caveolae-associated proteins as the major IQGAP1 interactors alongside cytoskeletal proteins. We confirmed co-localization of IQGAP1 with the defining caveolar marker protein caveolin-1 by confocal microscopy and proximity ligation assay. Most interestingly, insulin enhanced the number of IQGAP1 interactions with caveolin-1 by five-fold. Moreover, we found a significantly reduced abundance of IQGAP1 in adipocytes from patients with type 2 diabetes compared with cells from nondiabetic control subjects. Both the abundance of IQGAP1 protein and mRNA were reduced, indicating a transcriptional defect in diabetes. Our findings suggest a novel role of IQGAP1 in insulin-regulated interaction between caveolae and cytoskeletal elements of the adipocyte, and that this is quelled in the diabetic state.