The effect of formulations and experimental conditions on in vitro human skin permeation-Data from updated EDETOX database

In vitro methods are commonly used in order to estimate the extent of systemic absorption of chemicals through skin. Due to the wide variability of experimental procedures, types of skin and data analytical methods, the resulting permeation measures varies significantly between laboratories and individuals. Inter-laboratory and inter-individual variations with the in vitro measures of skin permeation lead to unreliable extrapolations to in vivo situations. This investigation aimed at a comprehensive assessment of the available data and development of validated models for in vitro skin flux of chemicals under various experimental and vehicle conditions. Following an exhaustive literature review, the human skin flux data were collated and combined with those from EDETOX database resulting in a dataset of a total of 536 flux reports. Quantitative structure-activity relationship techniques combined with data mining tools were used to develop models incorporating the effects of permeant molecular structure, properties of the vehicle, and the experimental conditions including the membrane thickness, finite/infinite exposure, skin pre-hydration and occlusion. The work resulted in statistically valid models for estimation of the skin flux from varying experimental conditions, including relevant real-world mixture exposure scenarios. The models indicated that the most prominent factors influencing flux values were the donor concentration, lipophilicity, size and polarity of the penetrant, and the melting and boiling points of the vehicle, with skin occlusion playing significant role in a non-linear way. The models will aid assessment of the utility of dermal absorption data collected under different conditions with broad implications on transdermal delivery research.     

Dietary Intake Assessment of Pre-Packed Graviera Cheese in Greece and Nutritional Characterization Using the Nutri-Score Front of Pack Label Scheme

Gravieras are ‘gruyere’ type hard cheeses with a variety of different products and the second highest consumption in Greece. In this study, we present a dietary intake assessment and a nutritional characterization of pre-packed graviera products sold in the Greek market using Nutri-Score Front of Pack Label (FoPL). The nutrient contents of 92 pre-packed graviera products were combined with daily individual consumption data extracted from the Hellenic National Nutrition Health Survey (n = 93), attempting to evaluate the contribution of graviera’s consumption to the Greek diet. The analysis of nutrients’ intake as a Reference Intake (RI) percentage ranked saturated fat first on the nutrients’ intake list, with RI percentage ranging from 36.1 to 109.2% for the 95th percentile of consumption. The respective % RI for energy, total fat, carbohydrates, sugars, proteins and salt ranged from 12.7–20.7%, 21.6–50.4%, 0–3.1%, 0–6.1%, 37–57.1% and 6.3–42%. Nutri-Score classified 1% of the products to C—light orange class, 62% to D—orange and 37% to E—dark orange, while no products were classified to A—dark green or B—green classes. The comparison between the Nutri-Score classification and the nutrients’ intake assessment, also separately conducted within the classes, showed a higher salt intake after the consumption of products classified as D—orange and E—dark orange.     

HPV detection rate in saliva may depend on the immune system efficiency

BACKGROUND: Human papilloma virus (HPV) has been established as a major etiological factor of anogenital cancer. In addition, HPV has also been implicated in oral carcinogenesis but its detection rates appear to be highly variable, depending on the patient population tested, the molecular methodology used, as well as the type of oral specimen investigated. For example, saliva is an oral fluid that may play a role in HPV transmission, although the detection rates of the virus are lower than tissue. Recent evidence has indicated that HPV-related pathology is increased in the oral cavity of human immunodeficiency virus (HIV)-positive individuals. In order to investigate whether the presence of different HPV types in saliva depends on immune system efficiency, oral fluid samples of patients with oral cancer and without any known immune deficiency were compared with those of HIV-positive individuals. PATIENTS AND METHODS: Saliva samples were collected from 68 patients with oral squamous cell carcinoma and 34 HIV seropositive individuals. HPV DNA sequences were detected by L1 concensus polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) analysis and DNA sequencing for HPV typing. RESULTS: HPV DNA was detected in 7/68 (10.3%) of the oral cancer patients and in 12/34 (35.3%) of the HIV-positive individuals, a highly significant difference (p = 0.006; odds ratio 4.753; 95% confidence interval 1.698-13.271). Among HPV-positive samples, the prevalence of HPV types associated with high oncogenic risk was similar in oral cancer and HIV-positive cases (71.4% and 66.7%, respectively). In both groups, the most common HPV type was high-risk 16 (50% and 42.8%, respectively). CONCLUSION: Although a similar pattern of HPV high-risk types was detected in oral cancer and HIV-positive cases, the quantitative detection of HPV in saliva significantly depended on immune system efficiency. Furthermore, the significantly increased detection rates of HPV in saliva of HIV-positive individuals may be associated with high risk for development of HPV-related oral lesions, including malignancy.     

Epidemiology and management of cryptococcal meningitis: developments and challenges

The significance of cryptococcal infection as a cause of human disease has dramatically evolved in recent years. The objective of this study was to outline the worldwide significance of cryptococcosis and review developments in the management of cryptococcal meningitis. Cryptococcus neoformans var. grubii remains an important cause of disease, particularly in hosts with acquired immunosuppression. Cryptococcus gattii, on the other hand, infects hosts with seemingly normal immune systems and a recent dramatic outbreak in a new ecologic environment highlights the emerging clinical significance of this fungal pathogen. The introduction of new antifungal agents and the adoption of strategies for controlling elevated intracranial pressure in cryptococcal meningitis have added to our therapeutic options. However, the mortality from this infection remains unacceptably high and we are faced with the specific challenges in the management of this disease.     

Risk factors for Age-related Macular Degeneration in a Greek population: The Thessaloniki Eye Study

Purpose: To assess the association of potential risk factors with early and late age-related macular degeneration (AMD) in the Thessaloniki Eye Study (TES) population

Design: Population-based, cross-sectional study of subjects over age of 60 living in Thessaloniki, Greece

Methods: Subjects without any AMD features and subjects with early and late AMD (neovascular AMD or geographic atrophy) were identified in the TES cohort using standardized procedures and masked grading of stereo color fundus photos. Demographic, lifestyle, systemic and other ophthalmic covariates were also collected during a detailed examination process. Their association with AMD was investigated using univariate and multivariate adjusted logistic regression models.

Results: Among the 2108 participants with gradable photos, the grading process identified 1204 subjects with no AMD, 848 subjects with early AMD, and 56 subjects with late AMD (24 with geographic atrophy and 32 with neovascular AMD). In multivariate analysis, compared to no AMD, late AMD was positively associated with older age (OR:1.16; 95%CI:1.10–1.22 per year of age), current smoking (smoking vs. never smoking, OR:2.34; 95%CI:1.12–4.90), prior cataract surgery (cataract surgery vs. no cataract surgery OR:2.06; 95%CI:0.96–4.40), marital status (divorced/separated vs. married, OR:3.10; 95%CI:1.08–8.93) and with 60% lower odds when sleeping in the afternoon (yes vs. no, OR:0.40; 95%CI:0.22–0.72). Early AMD was positively associated with older age (OR: 1.03; 95%CI:1.01–1.05 per year of age) and negatively with higher pulse pressure (OR:0.99; 95%CI:0.98–0.99 per mmHg).

Conclusions: In TES, apart for well-known risk factors for AMD like age, smoking, and cataract surgery, two novel behavioral risk factors for prevalent late AMD were suggested. Sleeping in the afternoon was associated with 60% decreased odds for late AMD and 67% decreased odds for neovascular AMD. Being divorced/separated compared to married was associated with 3-fold higher odds for late AMD. Large longitudinal population-based studies will be necessary to further establish the potential late AMD risk effects of these two novel factors, to demonstrate potential implications of underlying pathogenetic mechanisms, and to explore preventive measures and therapeutic targets.     

Characterization of “γ-Eye”: a Low-Cost Benchtop Mouse-Sized Gamma Camera for Dynamic and Static Imaging Studies

Purpose

Several preclinical imaging systems are commercially available, but their purchase and maintenance costs make them unaffordable for the majority of small- and medium-sized groups. Taking into account the needs of average users, we developed “γ-eye”, a mouse-sized, benchtop γ-camera suitable for in vivo scintigraphic imaging.

Procedures

The γ-eye is based on two position-sensitive photomultiplier tubes, coupled to a CsI(Na) pixelated scintillator and a low-energy lead collimator with parallel hexagonal holes.

Results

The spatial resolution of the system is 2 mm at 0 mm. The energy resolution is 26 % at 140 keV and the maximum recorded sensitivity 210 cps/MBq. The system was evaluated in a proof-of-concept animal study, using three different clinical Tc-99m-labeled radiopharmaceuticals. Phantom and animal studies demonstrate its ability to provide semiquantitative results even for short scans.

Conclusions

Systems’ performance, dimensions, and cost make γ-eye a unique solution for efficient whole-body mouse nuclear imaging.

     

Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia

BACKGROUND: The role of various proteases in the pathogenesis of Alzheimer's disease is well documented. Recently, many members of the human tissue kallikrein family, a group of 15 secreted serine proteases, were found to be highly expressed in the central nervous system (CNS). Some of these enzymes can be measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies. METHODS: We quantified various kallikreins in CSF of 20 patients with Alzheimer's disease (AD), 16 patients with frontotemporal dementia (FTD), and 15 controls. We then correlated the levels of various kallikreins with presence of AD or FTD. Among all kallikreins measured, detectable levels in CSF were identified for kallikreins hK6, hK7, and hK10. Other tested kallikreins (hK5, hK8, hK11, and hK13) were unmeasurable. The most notable differences between kallikrein levels in CSF and the three groups of subjects were seen between controls and FTD patients for hK6 (decrease in FTD; P = 0.017), controls and FTD patients for hK7 (decrease in FTD; P < 0.001), and controls and AD patients for hK7 (decrease in AD; P = 0.019). In addition, significant differences were seen between FTD patients or control subjects and patients with AD patients for hK10 (increase in AD; P < 0.02). Approximately half of the AD patients had CSF hK10 levels that were higher than all patients with FTD except one and all control subjects except two. Various kallikrein concentrations in CSF were correlated, the strongest correlation seen between hK6 and hK7 (r(s) = 0.58). We also observed a statistically significant association between decreasing hK7 concentration in CSF and possession of one or two ApoE4 alleles (P = 0.014). CONCLUSIONS: We demonstrate for the first time significant alterations of hK6, hK7, and hK10 concentration in CSF of patients with AD and FTD. Notably, all three kallikreins (hK6, hK7, and hK10) are decreased in CSF of FTD patients and hK10 is increased in CSF of AD patients, in comparison to control subjects. The possible connection between these enzymes and the pathogenesis and progression of AD and FTD needs to be further investigated.