Persistence of Efficacy of 0.1% Cyclosporin A Cationic Emulsion in Subjects with Severe Keratitis Due to Dry Eye Disease: A Nonrandomized,Open-label Extension of the SANSIKA Study

Purpose

Results from a 6-month double-masked and a 6-month open-label study (SANSIKA) established the efficacy and safety of once-daily 0.1% cyclosporin A cationic emulsion (CsA CE) in severe keratitis due to dry eye disease (DED). This article presents results from the Post-SANSIKA study, a 24-month extension of SANSIKA assessing the sustained efficacy of CsA CE after treatment discontinuation.

Deconvoluting the dual hypoglycemic effect of wedelolactone isolated from Wedelia calendulacea: investigation via experimental validation and molecular docking

Wedelia calendulacea has a long history of use in the Indian Ayurvedic System of Medicine for the treatment, prevention, and cure of a diverse range of human diseases such as diabetes obesity, and other metabolic diseases. A wide range of chemical constituents, such as triterpenoid saponin, kauren diterpene, and coumestans, has been isolated from the plant. Conversely, no published literature is available in relation to the isolation of wedelolactone (WEL) for its anti-diabetic effect. The aim of the present study was to isolate the bioactive phyto-constituent from Wedelia calendulacea and to scrutinize the antidiabetic effect with its possible mechanism of action. The structure of the isolated compound was elucidated by different spectroscopy techniques. Proteins, such as dipeptidyl peptidase-4 (DPPIV), glucose transporter 1 (GLUT1), and peroxisome proliferator-activated receptors-γ (PPARγ), were also subjected to in silico docking. Later, this isolated compound was scrutinized against α-glucosidase and α-amylase enzyme activity along with an oral glucose tolerance test (OGTT) for estimation of glucose utilization. Streptozotocin (STZ) was used for the induction of type II diabetes mellitus (DM) in Wistar rats. The rats were divided into different groups and received the WEL (5, 10, and 20 mg kg⁻¹, b.w.) and glibenclamide (2.5 mg kg⁻¹, b.w.) for 28 days. The blood glucose level (BGL), plasma insulin, and body weight were determined at regular time intervals. The serum lipid profile hypolipidemic effect for the different antioxidant markers and hepatic tissue markers were scrutinized along with an inflammatory mediator to deduce the possible mechanism. With the help of spectroscopy techniques, the isolated compound was identified as wedelolactone. In the docking study, WEL showed docking scores of −6.17, −9.43, and −7.66 against DPP4, GLUTI, and PRARY, respectively. WEL showed the inhibition of α-glucosidase (80.65%) and α-amylase (93.83%) and suggested an effect on postprandial hyperglycemia. In the OGTT, WEL significantly (P < 0.001) downregulated the BGL, a marker for better utilization of drugs. In the diabetes model, WEL reduced the BGL and enhanced the plasma insulin and body weight. It also significantly (P < 0.001) modulated the lipid profile; this suggested an anti-hyperlipidemia effect. WEL significantly (P < 0.001) distorted the hepatic tissue, acting as an antioxidant marker in a dose-dependent manner. WEL significantly (P < 0.001) downregulated the C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) level. On the basis of the available results, we can conclude that WEL can be an alternative drug for the treatment of type II DM either by inhibiting the production of inflammatory mediator or by the downregulation of oxidative stress.

Wedelia calendulacea has a long history of use in the Indian Ayurvedic System of Medicine for the treatment, prevention, and cure of a diverse range of human diseases such as diabetes obesity, and other metabolic diseases.     

Does hyaluronan affect inflammatory cytokines in knee osteoarthritis?

Our aim was to investigate the effects of hyaluronan on inflammatory cytokines in the synovial fluid of patients with knee osteoarthritis. The study was single blind, placebo-controlled, and randomized. We administered hyaluronan to 22 patients in the study group and placebo to 19 in the control group. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines. Both HA and placebo caused a significant decrease in interleukin (IL)-6 levels (P=0.0001 and P=0.04, respectively). But it was more significant in the study group. However, IL-8 and tumor necrosis factor alpha (TNF-) levels did not change in either group (P>0.05). The amount of effusion decreased significantly in the study group (P=0.001) but not in the control group (P=0.133). It can be concluded that hyaluronan considerably decreased IL-6 levels, which correlated with clinical improvement, but had no effect on IL-8 and TNF- levels in synovial fluid. However, larger studies with longer follow-up periods are needed to explain the effect of hyaluronan on cytokines.     

Vascularized axillary lymph node transfer: A novel model in the rat

Vascularized lymph node transfer (VLNT) is a promising microvascular free flap technique for the surgical treatment of lymphedema. To date, few experimental animal models for VLNT have been described and the viability of lymph nodes after the transfer tested. We aimed to evaluate the feasibility of axillary VLNT in the rat. Lymph node containing flaps were harvested from the axillary region in 10 Lewis rats based on the axillary vessels. Flaps were transferred to the ipsilateral groin and end‐to‐side microanastomosis was performed to the femoral vessels using 10‐0 sutures. Indocyanine green (ICG) angiography was used to confirm flap perfusion. On postoperative day 7, flaps were elevated to assess their structure and vessel patency. Hematoxylin and eosin staining was used to confirm the presence and survival of lymph nodes. All animals tolerated the procedure well. Immediate post‐procedure ICG angiography confirmed flap perfusion. No signs of ischemia or necrosis were observed in donor extremities. At postoperative day 7, all flaps remained viable with patent vascular pedicles. Gross examination and histology confirmed the presence of 3.6 ± 0.5 lymph nodes in each flap without any signs of necrosis. This study showed that the transfer of axillary lymph nodes based on the axillary vessels is feasible. The flap can be used without the need for donor animals and it contains a consistent number of lymph nodes. This reliable VLNT can be further utilized in studies involving lymphedema, transplantation, and induction of immunologic tolerance. © 2015 Wiley Periodicals, Inc. Microsurgery 35:662–667, 2015.     

Hounsfield Units: A new indicator showing maxillary resistance in rapid maxillary expansion cases?

Objective:To determine if density measurements of several maxillary regions in Hounsfield Units (HU) and outcomes of rapid maxillary expansion (RME) are correlated. Is correlation powerful enough to give us direct information about maxillary resistance to RME?Materials and Methods:Twenty-two computed tomographic (CT) scans (14 years) are used in this archive study. Two CT records were collected, one before RME (T₁) and one after 3 months of retention period (T₂). Maxillary measurements were made using dental and skeletal landmarks in first molar and first premolar slides to measure the effects of RME. Density of midpalatal suture (MPSD) and segments of maxillary bone is measured in HU at T₁. Correlation analysis was conducted between density measurements and maxillary variables. Regression analysis was then performed for variables that showed positive correlation.Results:There was no correlation between density and skeletal measurements. Intermolar angle (ImA) in molar slice showed statistically significant correlation with density measurements. The ImA variable showed the highest correlation with MPSD in frontal section (r  =  0.669, P < .01).Conclusions:There is correlation of 32.1–43.3% between density measurements and ImA increase. Our density measurements explain a certain percentage of ImA increase, but density is not the only and definitive indicator of changes after RME.     

Power wheelchair driving challenges in the community: a users’ perspective

Purpose: There is limited information on the difficulties individuals experience in manoeuvring their power wheelchairs during daily activities. The aim of this study was to describe the nature and context of power wheelchair driving challenges from the perspective of the user. Methods: A qualitative design using semi-structured interviews with power wheelchair users. Qualitative content analysis was used to identify themes. Results: Twelve experienced power wheelchair users were interviewed. Findings revealed that power wheelchair driving difficulties were related to the accomplishment of activities of daily living, and the influence of environmental context. Four key themes emerged: (1) difficulties accessing and using public buildings-facilities, (2) outdoor mobility, (3) problems in performing specific wheelchair mobility tasks/manoeuvres and (4) barriers and circumstances that are temporary, unforeseen or specific to a particular context. Conclusion: This qualitative study furthers our understanding of the driving difficulties powered wheelchair (PW) users experience during daily activities. This knowledge will assist clinicians and researchers in two areas: in choosing assessment measures that are ecologically valid for power wheelchair users; and, in identifying and refining the content of training programs specific to the use of power wheelchairs.

• Implications for Rehabilitation

• A better understanding of the everyday challenges individuals experience in driving their power wheelchair will assist clinicians and researchers in:

• Choosing assessment measures and identifying training programs for this population.

• Refining the content of power wheelchair training programs.