Anti-inflammatory activity of Punica granatum L. (Pomegranate) rind extracts applied topically to ex vivo skin

Coadministered pomegranate rind extract (PRE) and zinc (II) produces a potent virucidal activity against Herpes simplex virus (HSV); however, HSV infections are also associated with localised inflammation and pain. Here, the objective was to determine the anti-inflammatory activity and relative depth penetration of PRE, total pomegranate tannins (TPT) and zinc (II) in skin, ex vivo. PRE, TPT and ZnSO4 were dosed onto freshly excised ex vivo porcine skin mounted in Franz diffusion cells and analysed for COX-2, as a marker for modulation of the arachidonic acid inflammation pathway, by Western blotting and immunohistochemistry. Tape stripping was carried out to construct relative depth profiles. Topical application of PRE to ex vivo skin downregulated expression of COX-2, which was significant after just 6 h, and maintained for up to 24 h. This was achieved with intact stratum corneum, proving that punicalagin penetrated skin, further supported by the depth profiling data. When PRE and ZnSO4 were applied together, statistically equal downregulation of COX-2 was observed when compared to the application of PRE alone; no effect followed the application of ZnSO4 alone. TPT downregulated COX-2 less than PRE, indicating that tannins alone may not be entirely responsible for the anti-inflammatory activity of PRE. Punicalagin was found throughout the skin, in particular the lower regions, indicating appendageal delivery as a significant route to the viable epidermis. Topical application of TPT and PRE had significant anti-inflammatory effects in ex vivo skin, confirming that PRE penetrates the skin and modulates COX-2 regulation in the viable epidermis. Pomegranates have potential as a novel approach in ameliorating the inflammation and pain associated with a range of skin conditions, including cold sores and herpetic stromal keratitis

City of clones: Facsimiles and governance in Sao Paulo, Brazil

São Paulo is a megacity defined by formal and informal patterns of urbanization. Informally urbanized spaces are not absent of state intent, despite appearances. Grassroots-led social and spatial practices for survival, agency and self-governance contribute to the reproduction of urban political order in surprisingly unoriginal and routinely recognizable ways. This article argues that these unexceptional informal practices can be understood as ‘facsimiles’ of their formal institutional originals. Using the example of cloned cars the article shows that the facsimile and the original are the same in form and function. Facsimiles do not exist outside of political authority, but are a byproduct and a component of it. They are indistinguishable in their bureaucratic deployment, recognition and acceptance as part of social and spatial order. This is the author accepted manuscript. The final version is available from Sage via https://doi.org/10.1177/001139211665729

Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV

Background There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions. Materials and methods PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit. Results Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1) a value comparable to aciclovir (EC50 = 0.18 μg mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution. Conclusions The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores

In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection

Coadministration of pomegranate rind extract (PRE) and zinc (II) ions has recently been reported as a potential new topical treatment for Herpes simplex virus (HSV) infections. In the current work we examined the in vitro topical delivery of punicalagin (major phytochemical of PRE) and zinc from hydrogels across epithelial membranes that can become infected with HSV. Porcine epidermal, buccal and vaginal mucous membranes were excised and mounted in Franz diffusion cells and dosed with a simple hydrogel containing PRE and zinc sulphate (ZnSO4). The permeation of punicalagin and zinc were determined by HPLC and ICPMS respectively; punicalagin was also determined in the basal layers by reverse tape stripping. Receptor phases from the epidermal membrane experiment were also used to challenge HSV-1 in Vero host cells, and ex vivo porcine skin was used to probe COX-2 modulation. Punicalagin and zinc permeated each of the three test membranes, with significantly greater amounts of both delivered across the epidermal membrane. The amounts of punicalagin permeating the buccal and vaginal membranes were similar, although the amount of zinc permeating the vaginal membrane was comparatively very large – it is known that zinc interacts with vaginal mucosa. The punicalagin recovered by reverse tape stripping of the epidermal, buccal and vaginal membranes gave 0.47 ± 0.016, 0.45 ± 0.052 and 0.51 ± 0.048 nM cm− 2 respectively, and were statistically the same (p < 0.05). A 2.5 log reduction was achieved against HSV-1 using diffusion cell receptor phase, and COX-2 expression was reduced by 64% in ex vivo skin after 6 h. Overall, a hydrogel containing 1.25 mg mL− 1 PRE and 0.25 M ZnSO4 was able to topically deliver both the major bioactive compound within PRE and Zn (II) across all membranes and into the site specific region of Herpes simplex vesicular clusters, while maintaining potentiated virucidal and anti-inflammatory properties. This novel therapeutic system therefore has potential for the topical treatment of HSV infections

Fourth-Order Butterworth Active Bandpass Filter Design for Single-Sided Magnetic Particle Imaging Scanner

This paper describes the design and simulation of a fourth-order Butterworth active bandpass filter designed for single-sided magnetic particle imaging (MPI) scanner. Bandpass filters (BPF) are used in MPI scanner set-up to attenuate the harmonic distortions generated by the power amplifier before passing the purely sinusoidal signal to the excitation (Drive) coils. The BPF is designed based on the excitation frequency of 22.8 kHz, having Butterworth response, and realized using Sallen-Key topology by cascading one second-order highpass filter and one second-order lowpass filter, with values of the passive components calculated using the coefficient matching method. MATLAB and NI Multisim software are used to simulate the filter, and the results are compared. The magnitude response obtained using MATLAB have monotonic amplitude response in the pass and stopband, and maximally flat with small ripples in the passband than the NI Multisim implementation, while NI Multisimimplementation has better roll-off than MATLAB implementation

A Novel Algorithm for Human Fall Detection using Height, Velocity and Position of the Subject from Depth Maps

Human fall detection systems play an important role in our daily life, because falls are the main obstacle for elderly people to live independently and it is also a major health concern due to aging population. Different approaches are used to develop human fall detection systems for elderly and people with special needs. The three basic approaches include some sort of wearable devices, ambient based devices or non-invasive vision-based devices using live cameras. Most of such systems are either based on wearable or ambient sensor which is very often rejected by users due to the high false alarm and difficulties in carrying them during their daily life activities. This paper proposes a fall detection system based on the height, velocity and position of the subject using depth information from Microsoft Kinect sensor. Classification of human fall from other activities of daily life is accomplished using height and velocity of the subject extracted from the depth information. Finally position of the subject is identified for fall confirmation. From the experimental results, the proposed system was able to achieve an average accuracy of 94.81% with sensitivity of 100% and specificity of 93.33%

Formation of the Stomatal Outer Cuticular Ledge Requires a Guard Cell Wall Proline-Rich Protein

Stomata are formed by a pair of guard cells which have thickened, elastic cell walls to withstand the large increases in turgor pressure that have to be generated to open the pore that they surround. We have characterised FOCL1, a guard cell-expressed, secreted protein with homology to hydroxyproline-rich cell wall proteins. FOCL1-GFP localises to the guard cell outer cuticular ledge and plants lacking FOCL1 produce stomata without a cuticular ledge. Instead the majority of stomatal pores are entirely covered-over by a continuous fusion of the cuticle, and consequently plants have decreased levels of transpiration and display drought tolerance. The focl1 guard cells are larger and less able to reduce the aperture of their stomatal pore in response to closure signals suggesting that the flexibility of guard cell walls is impaired. FOCL1 is also expressed in lateral root initials where it aids lateral root emergence. We propose that FOCL1 acts in these highly specialised cells of the stomata and root to impart cell wall strength at high turgor and/or to facilitate interactions between the cell wall and the cuticle

The effect of a high-egg diet on cardiovascular risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) study-a 3-mo randomized controlled trial

BACKGROUND: Previously published research that examined the effects of high egg consumption in people with type 2 diabetes (T2D) produced conflicting results leading to recommendations to limit egg intake. However, people with T2D may benefit from egg consumption because eggs are a nutritious and convenient way of improving protein and micronutrient contents of the diet, which have importance for satiety and weight management. OBJECTIVE: In this randomized controlled study, we aimed to determine whether a high-egg diet (2 eggs/d for 6 d/wk) compared with a low-egg diet (<2 eggs/wk) affected circulating lipid profiles, in particular high-density lipoprotein (HDL) cholesterol, in overweight or obese people with prediabetes or T2D. DESIGN: A total of 140 participants were randomly assigned to one of the 2 diets as part of a 3-mo weight maintenance study. Participants attended the clinic monthly and were instructed on the specific types of foods and quantities to be consumed. RESULTS: There was no significant difference in the change in HDL cholesterol from screening to 3 mo between groups; the mean difference (95% CI) between high- and low-egg groups was +0.02 mmol/L (-0.03, 0.08 mmol/L; P = 0.38). No between-group differences were shown for total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glycemic control. Both groups were matched for protein intake, but the high-egg group reported less hunger and greater satiety postbreakfast. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intakes significantly increased from baseline in both groups. CONCLUSIONS: High egg consumption did not have an adverse effect on the lipid profile of people with T2D in the context of increased MUFA and PUFA consumption. This study suggests that a high-egg diet can be included safely as part of the dietary management of T2D, and it may provide greater satiety. This trial was registered at the Australia New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12612001266853

Intestinal model of Inflammation in primary cells

The gastrointestinal tract contains an enormous mucosal surface, which is continuously exposed to antigens hence making it susceptible to an inflammatory response. Such response targets potential pathogens by direct activation of the mucosal immune cells, however, in newborns the continuous inflammation attacks the intestine which leads to induction of necrotising enterocolitis. The present study aims at developing an “in-vitro” intestinal model of inflammation to assist in understanding the complex interplay of pro-inflammatory mediators during the immune response in neonates. Segments (1.5cm length) from the ileum were obtained from SD rat neonates (1-4 days old) and exposed to 0.25% trypsin/EDTA for 30min. Following trituration and subsequent centrifugation for 5min at 450xg, cells were suspended in DMEM-Hepes supplemented with 10% FCS, 2.5% Penicillin/Streptomycin, 2.5% L-Glutamine, and 0.2% Amphotericin B. Cell suspension were transferred to culture flaks and incubated at 37°C. Once confluent, the cell preparation media was replaced by FCS-free media, and treated with 0, 10, 50, and 100'g/ml of LPS. IL-8 and nitric oxide (NO) response were subsequently measured. In separate studies cell proliferation, cell viability, and cell adhesion were analysed. Additionally, the phenotypic properties of the intestinal muscle cells were also investigated via immunocytochemistry. Initial studies demonstrated that LPS treatments induced a significant increase in the release of IL-8 and NO compared to controls. The effect of LPS treatments on cell dynamics demonstrated small changes in cell viability and adhesion, whereas an increase in cell proliferation was observed. Immunocytochemistry studies indicated that LPS treatment caused a decrease in the expression of actin fibers with impaired distribution compared to controls. In the present model key aspects of intestinal inflammation were replicated “in-vitro” including the activation of pro-inflammatory mediators, the loss in enteric innervations and subsequent tissue hyperplasia. Thus, this model may be used as a tool to investigate the anti-inflammatory properties of candidate drugs targeting functional GI diseases