Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid

BACKGROUND: Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. METHODS AND PRINCIPAL FINDINGS: RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. CONCLUSIONS: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption

Effect of atopic skin stressors on natural moisturizing factors and cytokines in healthy adult epidermis

Epidermal deficiency of filaggrin, and the derived natural moisturizing factors (NMF), is associated with increased risk of atopic dermatitis (AD). While filaggrin gene mutations cause filaggrin deficiency, there is limited insight in causative environmental factors. To explore the effect of selected exogenous skin stressors on NMF and skin cytokines levels in healthy adult epidermis. 40 healthy volunteers (18-49 years) were exposed to hard, soft, and chlorinated water, 0.5% SLS, house dust mite, cat allergen, staphylococcal enterotoxin B (SEB), cooling and histamine. Participants were tape-stripped and biophysiological measurements were performed. NMF was determined after 24 and 48 hours, while skin cytokines were measured after 24 hours for selected exposures. At 24 hours, a significant decrease in NMF was observed for soft (0.51±0.19) and hard water (0.61±0.32) compared to occlusion alone (0.71±0.18). Hard water led to increased levels of IL-4, IFN-ɣ and IL-10. Exposure to house dust mite and SEB led to a significant decrease in NMF after 24 hours (0.77 ±0.28 and 0.80±0.28, respectively) compared to occlusion alone (1.00±0.42). House dust mite led to an increase in IFN-ɣ, IL-2 and IL-4, as compared to the non-occluded control site. Based on experimental exposure to selected atopic skin stressors such as different water types, allergens and SEB, we conclude that NMF levels are decreased along with increased secretion of various skin cytokines in healthy individuals. Our data highlight environmental factors that might play a role in AD pathophysiology, but needs confirmation in AD patients. This article is protected by copyright. All rights reserve

Changes in filaggrin degradation products and corneocyte surface texture by season

Background During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly com- mon on weather-exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF). Objectives To investigate the effect of season on NMF levels and corneocyte surface texture in cheek and hand skin of healthy adults. Methods Eighty healthy volunteers (40 male and 40 female) were recruited: 40 aged 18 – 40 years and 40 aged ≥ 70 years. Cheek and dorsal hand skin was tape stripped in the winter and summer. Analysis for NMF and corneocyte surface tex- ture was done (Dermal Texture Index, DTI). Potential confounders were regis- tered and adjusted for. Results In cheek skin, NMF levels were reduced and DTI elevated during the winter compared with the summer. Older participants had higher NMF levels than younger participants. In the summer, DTI level was dependent on self-reported ultraviolet exposure. In hand skin, NMF levels were higher during the winter than in the sum- mer, and female participants had higher NMF levels than male participants. Conclusions Seasonal effects on NMF and DTI on the cheeks and hands were found, suggesting an influence of climatic factors at the biochemical and ultrastructural levels. Significant variations were also observed regarding age and sex, making it difficult to draw firm conclusions. Our study adds new pieces to the puzzle of seasonal differences in xerosis and dermatitis

Benzalkonium Chloride-Preserved Anti-Glaucomatous Eye Drops and Their Effect on Human Conjunctival Goblet Cells in vitro

Introduction: Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. Methods: Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol® (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. Results: All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; p = 0.93), 71% for DS (0.0075% BAK; p = 0.067), 70% for OP (0.01% BAK; p = 0.054), and 69% for LT (0.02% BAK; p = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (p = 0.217), 52% for DS (p = 0.011), 34% for OP (p = 0.017), and 31% for LT (p = 0.0007). Conclusion: LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding

Impact of benzalkonium chloride-preserved and preservative-free latanoprost eye drops on cultured human conjunctival goblet cells upon acute exposure and differences in physicochemical properties of the eye drops

Objective To investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties. Methods and analysis Primary GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using a lactate dehydrogenase assay. Mucin release was evaluated through mucin-specific immunostaining. pH value, osmolality, drop mass and surface tension for all LT eye drops were measured. Results After application with PF-LT for 30 min (min), the GC survival was maintained compared with control (p=0.9941), while all BAK-LT eye drops reduced survival with approximately 30% (p<0.02). Following application with PF-LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK-LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH value of the BAK-LT and PF-LT eye drops were 6.0–6.9 and 6.8, respectively. The osmolality was 258–288 mOsm/kg for the BAK-LT eye drops and 276 for PF-LT eye drops. The mean drop mass was 26–31 mg for the BAK-LT eye drops and 30 mg for PF-LT. The surface tension was lower for all BAK-LT eye drops (31.1–32.1 mN/m) compared with PF-LT (42 mN/m). Conclusion PF-LT compared with various branded and generic LT preparations containing BAK are less cytotoxic when applied to cultured GCs

Impact of glaucoma medications on the ocular surface and how ocular surface disease can influence glaucoma treatment

International audienc

Impact of glaucoma medications on the ocular surface and how ocular surface disease can influence glaucoma treatment

Glaucoma is a common disease with an increasing prevalence [1]. Ocular surface disease (OSD) is also common, and its prevalence is increasing [2,3], due in part to the adverse effects of topical glaucoma medications [4,5]. Given this glaucoma/OSD association, David A. Sullivan, MS, PhD (Boston, MA, USA) and Amy Gallant Sullivan (Paris, France) on behalf of the Tear Film & Ocular Surface Society (TFOS), and in collaboration with Miriam Kolko, MD, PhD (Copenhagen University Hospital & University of Copenhagen, Denmark), organized a one-day meeting which was held on Saturday, October 22, in Cernobbio, Italy. This meeting focused on the impact of glaucoma medications on the ocular surface, and how OSD can influence glaucoma treatment. The term "ocular surface" encompasses the surface (cornea and conjunctiva), tear film, and adnexa (lacrimal and meibomian glands). The speakers included internationally renowned glaucoma and OSD experts. The evidence-based proceedings of this meeting are presented in this TFOS Experts' Meeting report