Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects

OBJECTIVE—To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. RESEARCH DESIGN AND METHODS—A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7–36)amide/(7–37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7–36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS—Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7–36)amide/(7–37) at 30 and 60 min after the oral glucose load (63.8 ± 29.0 vs. 50.3 ± 15.6 pmol/l and 75.8 ± 35.4 vs. 46.9 ± 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1–0.5 μg/ml) significantly inhibited degradation of GLP-1(7–36)amide after a 30-min incubation at 37°C; similar results were obtained in a buffer solution containing DPP-IV. CONCLUSIONS—Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation

The Management of Dry Eye Disease: Proceedings of Italian Dry Eye Consensus Group Using the Delphi Method

Dry eye disease (DED) is a highly prevalent, chronic and progressive condition that affects 5–33% of the world’s adult population [1]. The 1995 definition of DED only considered patient-reported symptoms (ocular discomfort) and damage to the inter-palpebral ocular surface [2]. However, as it became apparent that this failed to reflect the complexity of the disease and its impact on visual function, inducing a risk of under-diagnosis, the 2007 International Dry Eye WorkShop (DEWS) redefined it as follows: “A multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” [3]. This introduced the concept that the ocular surface is a single system, added visual disturbances to the symptoms of ocular discomfort and drew attention to the key concepts of inflammation and tear hyperosmolarity. Subsequently, as it is not unusual in everyday clinical practice to encounter patients with moderate–severe symptoms who have no pathological signs on the ocular surface or, conversely, patients with severe signs who are asymptomatic because of decreased corneal sensitivity, DEWS II revised its definition to read “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles” [4] in order to indicate the occurrence of corneal nerves impairment, too. The symptoms characterizing the disease can severely affect the patients’ quality of life and everyday activities such as reading, driving or working on a computer [5–8] and are also associated with high levels of anxiety and depression [9]. Consequently, it is not only important to prescribe the appropriate treatment, but also to monitor its effects over time in order to ensure long-term relief and prevent disease chronicity [10,11]. Clinicians are clearly aware of the need to adopt a standardized approach to diagnose and treat DED that includes counselling, patient education and the establishment of a medical alliance to promote effective treatment [12,13]. The aim of this paper is to describe the process used by a group of Italian ophthalmologists (“Italian Dry Eye Consensus Group”) focused on DED for identifying four major statements related to the disease aimed at improving overall DED patient care [14]. Given the complexity of the disease and the different clinical contexts in which it may occur, the method used was based on real-life experience, as well as scientific data, and allowed the consideration of areas of still uncertain or unproven knowledge that may nevertheless help to guide everyday clinical practice and future research

The Pharmacogenetics of Cannabis in the Treatment of Chronic Pain

Background: The increase in the medical use of cannabis has revealed a number of beneficial effects, a variety of adverse side effects and great inter-individual variability. Association studies connecting consumption, addiction and side effects related to recreational cannabis use have led to the identification of several polymorphic genes that may play a role in the pharmacodynamics and pharmacokinetics of cannabis. Method: In total, 600 patients treated with cannabis were genotyped for several candidate polymorphic genes (single-nucleotide polymorphism; SNP), encoding receptors CNR1 and TRPV1; for the ABCB1 transporter; for biotransformation, bioactivation and biosynthesis; and CYP3A4, COMT and UGT2B7 conjugation. Results: Three polymorphic genes (ABCB1, TRPV1 and UGT2B7) were identified as being significantly associated with decline in pain after treatment with cannabis. Patients simultaneously carrying the most favourable allele combinations showed a greater reduction (polygenic effect) in pain compared to those with a less favourable combination. Considering genotype combinations, we could group patients into good responders, intermediate responders and poor or non-responders. Results suggest that genetic makeup is, at the moment, a significant predictive factor of the variability in response to cannabis. Conclusions: This study proves, for the first time, that certain polymorphic candidate genes may be associated with cannabis effects, both in terms of pain management and side effects, including therapy dropout. Significance: Our attention to pharmacogenetics began in 2008, with the publication of a first study on the association between genetic polymorphisms and morphine action in pain relief. The study we are presenting is the first observational study conducted on a large number of patients involving several polymorphic candidate genes. The data obtained suggest that genetic makeup can be a predictive factor in the response to cannabis therapy and that more extensive and planned studies are needed for the opening of new scenarios for the personalization of cannabis therapy

Antimicrobial Activity of a New Aloe vera Formulation for the Hygiene of the Periocular Area

Purpose: The aim of this study was to evaluate the antimicrobial activity of a novel preservative-free lid wipe formulation containing Aloe vera gel and hyaluronic acid that is commercialized for the hygiene of the periocular area. Methods:In vitro susceptibility testing of the solution contained in wipes against bacteria and fungi commonly colonizing the periocular area, both reference strains and multidrug-resistant (MDR) clinical isolates, was assessed following the CLSI M07-A9 and M27-A3 broth methods, respectively. The solution was 2-fold serially diluted in broth from 25 μL (25% v/v) to 0.012 μL (0.012% v/v) in microtiter plates. Plates were incubated and minimal inhibitory concentrations (MICs) were read visually. The antimicrobial effectiveness test was performed by inoculating the wipe solution with microbial suspensions at the initial concentration of 105–106 CFU/mL, as recommended by the international Pharmacopoeias. At different time intervals, samples were tested for microbial count. Results: The MIC value of the solution ranged from 25% to 12.5% for bacteria and was 6.25% for Candida albicans. The MIC for MDR isolates was 12.5%. By assessing antimicrobial effectiveness, we found that the solution meets the criteria reported by the European Pharmacopoeia and United States Pharmacopeia for its preservative effect. Conclusions: This study demonstrates that the novel wipes herein tested possess antimicrobial activity against bacteria and yeast commonly found in the periocular area, and against MDR clinical isolates. The microbial death curves obtained following deliberate contamination of the wipe solution revealed potent bactericidal and fungicidal activity of the formulation

The Management of Dry Eye Disease: Proceedings of Italian Dry Eye Consensus Group Using the Delphi Method

Dry eye disease (DED) is a highly prevalent, chronic and progressive condition that affects 5-33% of the world's adult population [...]