Derivatives of L-Ascorbic Acid in Emulgel: Development and Comprehensive Evaluation of the Topical Delivery System.

The dual controlled release of emulgels makes them efficient drug delivery systems of increasing interest. The framework of this study was to incorporate selected L-ascorbic acid derivatives into emulgels. From the formulated emulgels, the release profiles of actives were evaluated considering their different polarities and concentrations, and consequently their effectiveness on the skin via a long-term in vivo study that lasted for 30 days was determined. Skin effects were assessed by measuring the electrical capacitance of the stratum corneum (EC), trans-epidermal water loss (TEWL), melanin index (MI) and skin pH. In addition, the sensory and textural properties of emulgel formulations were compared with each other. The changes in the rate of the release of the L-ascorbic acid derivatives were monitored using the Franz diffusion cells. The obtained data were statistically significant, and indicated an increase in the degree of hydration of the skin and skin whitening potential, while no significant changes in TEWL and pH values were detected. The consistency, firmness and stickiness of the emulgels were estimated by volunteers applying the established sensory evaluation protocol. In addition, it was revealed that the difference in hydrophilic/lipophilic properties of L-ascorbic acid derivatives influenced their release profiles without changing their textural characteristics. Therefore, this study highlighted emulgels as L-ascorbic acid suitable carrier systems and one of the promising candidates as novel drug delivery systems.

The Relationship between Diabetes Mellitus and Pancreatic Cancer-Diabetes Mellitus as a Red Flag for Pancreatic Cancer.

The relationship between diabetes mellitus (DM) and pancreatic cancer is complex-DM is both a risk factor and early sign of pancreatic cancer. DM is a risk factor for pancreatic cancer because it increases insulin resistance, intrapancreatic concentrations of insulin, and the bioavailability of IGF, subsequently promoting ductal cell proliferation. Accordingly, treatment targeting the insulin/IGF pathway is the focus of many researchers. Antidiabetic drugs modify the risk for pancreatic cancer-metformin's antineoplastic effect being most notable and indicating potential clinical use in pancreatic cancer. New-onset DM can also be the first manifestation of pancreatic cancer. There are several theories for the pathogenesis of DM in pancreatic cancer, the most important being that DM is a paraneoplastic syndrome caused by diabetogenic factors. As a consequence of this intricate relationship, new-onset DM after the age of 50 is considered a red flag for pancreatic cancer, prompting the need for screening in this patient population. Multiple clinical studies are currently underway exploring this matter. A better understanding of the relationship between DM and pancreatic cancer could aid in developing novel screening and treatment strategies for pancreatic cancer. This could ultimately improve the prognosis and quality of life of patients with pancreatic cancer.

Conventional vs. Green Extraction Using Natural Deep Eutectic Solvents-Differences in the Composition of Soluble Unbound Phenolic Compounds and Antioxidant Activity.

The aim of this study was to investigate the effect of the use of green solvents, natural deep eutectic solvents (NaDES), in comparison with conventional solvents on the extraction of free unbound phenolic compounds and the antioxidant activity of extracts of dried bilberry fruit, bilberry leaves and green tea leaves. After preparation of the extracts via ultrasound-assisted extraction using NaDES and conventional solvents (water and ethanol), spectrophotometric determination of total phenolic and flavonoid content, HPLC analysis of extracted polyphenols and antioxidant determination using FRAP, DPPH and ABTS assays were conducted. The results showed that NaDES have a great potential as agents for the extraction of phenolic compounds with potent antioxidant activity; the highest values of phenolic content and antioxidant activity were detected in the samples obtained by extraction using the NaDES combination betaine + urea. The bilberry leaves exhibited the highest flavonoid content among all extracts and turned out to be more active than bilberry fruits, to which they are often just a by-product during processing. The most active extract of all was the betaine-urea green tea leaves extract. Further research into the most active NaDES extracts should be performed.

Cotton versus medical face mask influence on skin characteristics during COVID-19 pandemic: A short-term study.

BACKGROUND: In the still ongoing COVID-19 pandemic, one of the main prevention strategy remain to be the use of protective face masks. Changes in skin characteristics and dermatological problems related to wearing different types of masks have been observed. The aim of this study was to compare the short-term effects of cotton versus medical masks on skin biophysical parameters in general population. MATERIALS AND METHODS: Twenty-eight human volunteers were enrolled and divided in cotton mask and medical mask wearing groups. We measured four skin biophysical parameters: trans-epidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and erythema index (EI) before and 3 h after wearing masks on both uncovered and mask-wearing face area. RESULTS: TEWL increased after 3 h on exposed skin in cotton mask group and slightly decreased in medical mask group There was an increase in SCH after 3 h of wearing protective face masks in both groups. pH of the covered skin slightly decreased while EI increased after 3 h in both groups; changes were not statistically significant. Parameters did not change significantly on uncovered skin. CONCLUSION: There were no differences between the influence of cotton versus medical protective masks on the skin of healthy volunteers in our study. Both types of masks could be recommended for short-time protection in individuals with healthy skin during COVID-19 pandemic.

Enhanced Skin Performance of Emulgel vs. Cream as Systems for Topical Delivery of Herbal Actives (Immortelle Extract and Hemp Oil).

Immortelle, as rich source of chlorogenic acid and the phloroglucinol alpha-pyrone compound arzanol, possesses anti-inflammatory and antioxidant properties, affects cell regeneration, and has positive effect on many skin conditions. Hemp oil, characterized by a favorable omega-6 to omega-3 ratio, as well as an abundance of essential fatty acids and vitamin E, participates in immunoregulation and also act as an anti-inflammatory. In the present study, we examined the effect on the skin of creams and emulgels with immortelle extract and hemp oil, by comparing them to placebo samples and a non-treated control. A long-term in vivo study of biophysical skin characteristics, which lasted for 30 days, was conducted on 25 healthy human volunteers. Measured parameters were electrical capacitance of the stratum corneum, trans-epidermal water loss (TEWL), and skin pH and erythema index. Further, a sensory study was carried out in which the panelists had to choose descriptive terms for sensory attributes in questionnaire. The results showed that application of all preparations led to increase of skin hydration and TEWL reduction, while the skin was not irritated, and its normal pH was not disrupted. This study also showed importance of the carrier. Not only were emulgels described by panelists as preparations with better sensory properties, there was a significant difference between the skin hydration effect of emulgel with immortelle extract and hemp oil compared to the placebo emulgel, which was not the case with creams. Such findings indicated enhanced delivery of herbal active substances from emulgel compared to the cream.

CARDIOMETABOLIC RISK AMONG MONTENEGRIN URBAN CHILDREN IN RELATION TO OBESITY AND GENDER.

Considering previously reported discrepant results in the literature, we aimed to investigate the impact of gender and overweight/obesity on cardiometabolic risk (CMR) among Montenegrin urban children. The cross-sectional study included random sample of 201 schoolchildren aged 7-12 years (64% of boys) from Podgorica. Children's nutritional status was determined according to the International Obesity Task Force criteria. CMR was assessed using a sum of z values of the following five indicators: glucose, total cholesterol, inverted value of high-density lipoprotein cholesterol, triglycerides, and hypertension. Higher CMR was found among both overweight and obese boys compared to normal weight boys (p<0.001). The effect size of the difference in CMR between overweight and obese girls and normal weight counterparts was less prominent (p<0.05). Logistic regression analysis revealed that body mass index was independent predictor of high CMR [odds ratio (OR)=1.06; 95% confidence interval (CI)=1.02-1.10); p=0.002]. On the contrary, we found no impact of socioeconomic status, physical activity or sedentary time on CMR in the examined cohort of schoolchildren. In conclusion, both overweight and obesity even among young population are related to higher CMR and this effect is more prominent among boys as compared to girls.

Old Plant, New Possibilities: Wild Bilberry (Vaccinium myrtillus L., Ericaceae) in Topical Skin Preparation.

Bilberry represents a valuable source of antioxidant substances responsible for its application for the treatment of different conditions (such as inflammation, cardiovascular disease, cancer, diabetes, and different age-related diseases) associated with increased oxidative stress. As oxidative stress might cause skin impairments, we aim to evaluate a topical preparation containing bilberry leaves extract and bilberry seeds oil, obtained as a byproduct of the food industry. To obtain the extracts, the conventional maceration technique for leaves, and supercritical carbon dioxide extraction for seeds were employed. The chemical profile of both actives was achieved by HPLC and GC methods, revealing the presence of phenolic acids (chlorogenic being the most abundant), flavonoids (isoquercetin in the highest amount), and resveratrol in leaves extract, while in seeds oil the essential ω-3 and ω-6 fatty acids were determined in favorable ratio, almost being 1. Antioxidant potential of the wild bilberry extract and seed oil was evaluated using in vitro DPPH and FRAP assays. Finally, effects of the oil-in-water creams with mentioned wild bilberry isolates on the skin were investigated in an in vivo study conducted on healthy human volunteers, revealing the significant beneficial effects when topically applied.

Relationship between insulin-like growth factor-1, insulin resistance and metabolic profile with pre-obesity and obesity in children.

OBJECTIVES: Childhood obesity is a serious medical condition with alarmingly high rates worldwide. There is controversy regarding the relationship between insulin-like growth factor-1 (IGF-1) and pediatric obesity. We investigated the relationship between IGF-1, insulin resistance and metabolic profile with childhood pre-obesity/obesity. METHODS: The study involved 201 children aged 7-15 years, divided in three groups according to their nutritional status (International Obesity Task Force criteria): normal-weight (n=84), pre-obese (n=82), obese (n=35). Laboratory IGF-1, insulin, fasting blood glucose (FBG), lipid profile, alanine-aminotransferase (ALT), uric acid (UA), anthropometric and body composition parameters were analyzed. Body mass index and IGF-1 standard deviation score (SDS), waist-to-height ratio (WtHR) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score were calculated. RESULTS: Pre-obese/obese children had significantly higher IGF-1 SDS, FBG, insulin, HOMA-IR, UA, ALT, triglycerides, and lower high-density lipoprotein cholesterol (HDL-c); obese group had higher WtHR and low-density lipoprotein cholesterol (LDL-c) compared to controls (p<0.05). In obese group, IGF-1 SDS was positively correlated with fat free/muscle mass, total body water (p<0.05) and negatively correlated with LDL-c (p<0.05). In pre-obese/obese HOMA-IR and insulin were positively correlated with age, total body fat (TBF) (p<0.05) and negatively correlated with HDL-c (pre-obese) (p<0.05). Multivariate ordinal logistic regression analyses showed that IGF-1 SDS (OR=1.94; 95%CI: 1.21-3.11), TBF (OR=1.37; 95%CI: 1.21-1.54) were predictors of nutritional status (p<0.001). FBG (OR=42.39; 95%CI: 2.31-77.2) and UA (OR=1.03; 95%CI: 1.01-1.05) were predictors of IR (p<0.001). CONCLUSIONS: IGF-1 SDS and TBF were predictors of nutritional status. Further studies are required to clarify the role of IGF-1 in pathophysiology of obesity and its comorbidities.

Maternal education, health profession and cigarette smoking are decisive factors for self-medication in children by parents.

Self-medication of children by their parents (SMCP) is an important public health issue as the effects and potential risks may be unpredictable. The objective of this first national Montenegrin study was to assess the prevalence of and factors influencing SMCP among schoolchildren. Data were obtained from a national representative sample of 4496 schoolchildren aged 7-13 years (50.4 % boys). Parents/caregivers completed a questionnaire concerning their demographic characteristics, socio-economic and cultural status, as well as the self-medication (SM) of their children. The association between SMCP and parents' socio-economic, demographic or cultural status was assessed by logistic regression analyses. The prevalence rate of SMCP was 24.6 %. Univariate logistic regression showed that maternal socio-demographic characteristics (educational level, employment status, health care profession and smoking habits) were relevant for SMCP. In a multiple logistic regression the independent effect /adjusted odds ratio (AOR) (95 % CI)/of maternal factors on SMCP remained for: education /2.23 (1.18-4.24)/, university-level vs. no education; profession /1.50 (1.07-3.00)/, health profession vs. non-health profession; and smoking habit /1.22 (1.04-1.42)/smokers vs. non-smokers. SMCP may be expected for every fourth child in Montenegro. Specific maternal factors that independently raise the probability of SMCP are higher education, health profession and smoking.

Association between inflammation, oxidative stress, vitamin D, copper and zinc with pre-obesity and obesity in school children from the city of Podgorica, Montenegro.

Background Childhood obesity is a serious health condition with increasing rates worldwide. The aim of this study was to investigate the association between inflammation, oxidative stress, vitamin D, copper and zinc in pre-obese and obese children compared to controls. Methods The study involved 202 children aged 7-15 years (63.9% boys), randomly chosen from 10 elementary schools in Podgorica, Montenegro. Participants were divided into three groups according to their nutritional status (International Obesity Task Force [IOTF] criteria): normal-weight (42.1%), pre-obese (40.6%) and obese (17.3%). Serum biochemical analyses were performed (C-reactive protein [CRP], retinol-binding protein [RBP], total antioxidant status [TAS], total vitamin D [VD], copper and zinc). Results Serum TAS and CRP concentrations were higher in pre-obese and obese children compared to controls (p < 0.001). Serum VD concentrations were lower in pre-obese and obese children compared to their normal-weight peers (p = 0.027 and p = 0.054, respectively). Copper, zinc and RBP concentrations did not differ significantly among the groups (p > 0.05). In pre-obese and obese children, a positive correlation was found between CRP and copper (r = 0.305, p = 0.011 and r = 0.440, p = 0.013, respectively), and TAS and RBP (r = 0.528, p < 0.001 and r = 0.434, p = 0.015, respectively). Standard regression analyses showed that CRP and TAS increase (p < 0.001) whereas VD decreases (p = 0.011) with the body mass index (BMI). Conclusions We show that pre-obesity and obesity in childhood are positively associated with oxidative stress and inflammation, and inversely associated with VD status. Copper and zinc concentrations were not associated with excess fat in children.

The association between follicle stimulating hormone and glutathione peroxidase activity is dependent on abdominal obesity in postmenopausal women.

PURPOSE: Menopause is frequently associated with an increase in visceral fat, thus modifying redox status by promoting oxidative damage and decreasing antioxidant defense systems. It is known that at higher concentrations estradiol has some antioxidant properties, while its decline in postmenopause is associated with pro-oxidant effects. However, the role of follicle stimulating hormone (FSH) in antioxidant defense in postmenopausal women is still not well elucidated. Therefore, we aimed to evaluate the potential complex association between visceral obesity, FSH and enzymatic antioxidant defense as measured by glutathione peroxidase (GPx) in postmenopausal women. METHODS: A total of 150 postmenopausal women (mean age 56.6 ± 4.8 years), among them 50 normal weight and 100 overweight/obese, were included. GPx activity, FSH, luteinizing hormone, estradiol, total testosterone, cardiometabolic and anthropometric parameters, were determined. RESULTS: With increasing tertiles of serum FSH levels, significant increase in GPx activity (P = 0.005) was found. Also, the highest number of overweight/obese subjects were in the group with the lowest FSH values (χ 2 = 14.9, P < 0.001). After multiple linear regression analysis, the relationship between GPx and FSH disappeared, whereas only higher waist circumference (ß = -0.218, P = 0.045) predicted lower FSH level (adjusted R 2 = 0.227). CONCLUSION: Higher GPx activity is associated with higher FSH level, but abdominal obesity may be the underlying determinant of this relationship.

The Association Between Retinol-Binding Protein 4 and Cardiovascular Risk Score is Mediated by Waist Circumference in Overweight/Obese Adolescent Girls

Retinol-binding protein 4 (RBP4) is an emerging risk factor for atherosclerotic disease in adults. However, to our knowledge, there are no studies examining the relationship between RBP4 and cardiovascular risk in young population. Therefore, we aimed to estimate this potential relationship in overweight/obese adolescent girls. Seventy overweight/obese adolescent girls, mean age 17.6±1.20 years, were included. Anthropometric and biochemical parameters were measured. Cardiovascular risk score (CVRS) was calculated by adding points for each risk factor (e.g., sex, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, smoking, blood pressure and fasting glycemia). According to the risk status, we divided adolescent girls into low, medium and high risk groups (-2≤ CVRS ≤1, 2≤ CVRS ≤4 and CVRS ≥5, respectively). We found significantly higher RBP4 in the high risk group as compared with low risk group (p<0.001). However, multiple linear regression analysis showed waist circumference (beta=0.257, p=0.031) to be the only independent predictor of higher cardiovascular risk (adjusted R(2)=0.342, p<0.001). In conclusion, RBP4 may be associated with higher cardiovascular risk in overweight/obese adolescent girls, but this association is mediated by abdominal obesity.

RECENT INCIDENCE OF TYPE 1 DIABETES MELLITUS IN MONTENEGRO: A SHIFT TOWARD YOUNGER AGE AT DISEASE ONSET.

In the last several decades, a great number of studies have pointed to a dramatic increase of type 1 diabetes mellitus (T1DM) incidence in the whole world, especially in younger age groups. Therefore, the aim of the study was to assess changes in the age distribution at onset of T1DM in Montenegro children aged < 15 years during a 15-year period (1997-2011) and analyze the seasonal pattern. Primary case ascertainment was from diabetes register, secondary and tertiary independent data sources were hospital case records and register of children receiving free test stripes in pharmacy. Standardized incidence rates were calculated using the Poisson regression. Case ascertainment was 100% complete using the capture-recapture method. The mean age-standardized incidence was 18.6/100,000 (95% CI: 13.0-24.1) from 2007 to 2011 compared with 13.4/100,000 95% CI, 11.5-15.5) from 1997 to 2006. The incidence of T1DM increased predominantly in younger age groups. Relative increase of incidence per 5-year period was largest in boys aged 0-4 and 5-9 years: 64.7% (95% CI: 20.6-10.7; p = 0.004) and 52.8% (95% CI: 16.9-88.8; p = 0.004), respectively. Seasonality in monthly case counts of T1DM was apparent. The greatest number of cases were diagnosed during autumn and winter months. In conclusion, the onset of T1DM was found to occur at an ever younger age in Montenegro children. Our results indicated a seasonal pattern of the disease onset.

Prevalence of and contributing factors for overweight and obesity among Montenegrin schoolchildren.

BACKGROUND: Newly emerging Western style economic systems provide new opportunities to study the prevalence and predictors of childhood obesity. We also provide for the first time a national study of childhood obesity using all three international anthropometric criteria. METHODS: The sample included 4097 Montenegrin children, 2076 boys (50.7%) and 2021 girls. Anthropometric measurements were performed in school. The questionnaire for parents included questions on 24 potential contributing factors for childhood obesity. Nutritional status was assessed according to World Health Organization, US Center for Disease Prevention and Control and International Obesity Task Force (IOTF) criteria. RESULTS: Overall percentage of Montenegrin children who are overweight or obese (IOTF) is 22.9% of which 5.3% are obese (7.0% boys vs. 3.5% girls). We found 10 factors to be independently associated with child obesity. Positive relations [odds ratio (95% confidence interval)] were found with maternal obesity [2.05 (1.68-2.51)], paternal obesity [1.67 (1.32-2.10)], paternal employment [1.40 (1.12-1.74)], maternal smoking [1.32 (1.08-1.61)], obesity at birth [1.33 (1.04-1.70)] and computer game playing [per hour--1.11 (1.00-1.24)]. Negative relations were found with female gender [0.64 (0.53-0.78)], the number of siblings [0.88 (0.78-0.98)], birth order [0.73 (0.64-0.83)] and age [0.92 (0.88-0.98)]. CONCLUSION: One out of four Montenegrin children is overweight, with two times more frequent obesity among boys compared with girls. Some previously salient predictors did not appear salient in this sample. To enable worldwide comparability, we propose the use of all three childhood obesity criteria in national studies.

Blood pressure among rural Montenegrin children in relation to poverty and gender.

BACKGROUND: Health inequalities may begin during childhood. The aim of this study was to investigate the main effect of poverty and its interactive effect with gender on children's blood pressure. METHODS: The study was performed in two elementary schools from a rural region near Podgorica, the capital of Montenegro. A questionnaire including questions on family monthly income, children's physical activity and the consumption of junk food was self-administered by parents of 434 children (223 boys and 211 girls) aged 6-13 years. Children's poverty level was assessed using the recommendations from the National Study on Poverty in Montenegro. Children's body weight and height were measured and body mass index-for-gender-and-age percentile was calculated. An oscillometric monitor was used for measurement of children's resting blood pressure in school. RESULTS: A two-factorial analysis of variance with body mass index percentile, physical activity and junk food as covariates showed an interaction of gender and poverty on children's blood pressure, pointing to synergy between poverty and female gender, with statistical significance for raised diastolic pressure (F = 5.462; P = 0.021). Neither physical activity nor the consumption of junk food explained the interactive effect of poverty and gender on blood pressure. CONCLUSION: We show that poverty is linked to elevated blood pressure for girls but not boys, and this effect is statistically significant for diastolic pressure. The results are discussed in the light of gender differences in stress and coping that are endemic to poverty.

Evaluation of pharmacotherapy of obstructive airway diseases in the Montenegrin outpatient care: comparison with two Scandinavian countries.

BACKGROUND: This study is aimed at evaluating the pharmacotherapy of obstructive airway diseases (OAD) in the Montenegrin outpatient care (MOC) in 2010. METHODS: Data on the reimbursed drugs which were prescribed during the reference period were obtained from the National Database that was established within the Health Insurance Fund of Montenegro in 2004. We have applied the standard pharmacoepidemiologic methodology with the defined daily dose (DDD) along with the Anatomical Therapeutic Chemical (ATC) classification of drugs. Clinical entities of OAD were classified according to the International Classification of Diseases (ICD-Revision X). RESULTS: Prescribing and the subsequent use of drugs for OAD (ATC code R03) in 2010 was 18.18 DDD/1000inhabitants/day, much lower than in some developed countries. Fenoterol/ipratropium and salmeterol/fluticasone fixed combinations had the highest utilisation level, accounting for more than 50% of all OAD drugs. About 90% of OAD drugs were prescribed for COPD and asthma. CONCLUSIONS: Obtained results indicate that there are still large differences in OAD drug utilisation in MOC when compared with developed countries, but also some improvement in pharmacological approach to the pharmacotherapy of OAD in comparison to the earlier period.