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1.  Three-dimensional quantification of facial symmetry in adolescents using laser surface scanning 
Laser scanning is a non-invasive method for three-dimensional assessment of facial morphology and symmetry. The aim of this study was to quantify facial symmetry in healthy adolescents and explore if there is any gender difference. Facial scans of 270 subjects, 123 males and 147 females (aged 15.3 ± 0.1 years, range 14.6–15.6), were randomly selected from the Avon Longitudinal Study of Parents and Children. Facial scans were processed and analysed using in-house developed subroutines for commercial software. The surface matching between the original face and its mirror image was measured for the whole face, upper, middle, and lower facial thirds. In addition, 3 angular and 14 linear parameters were measured. The percentage of symmetry of the whole face was significantly lower in males (53.49 ± 10.73 per cent) than in females (58.50 ± 10.27 per cent; P < 0.01). There was no statistically significant difference in the amount of symmetry among facial thirds within each gender (P > 0.05). Average values of linear parameters were less than 1 mm and did not differ significantly between genders (P > 0.05). One angular parameter showed slight lip line asymmetry in both genders. Faces of male 15-year-old adolescents were less symmetric than those of females, but the difference in the amount of symmetry, albeit statistically significant, may not be clinically relevant. Upper, middle, and lower thirds of the face did not differ in the amount of three-dimensional symmetry. Angular and linear parameters of facial symmetry did not show any gender difference.
PMCID: PMC3969526  PMID: 21795753
2.  Effects of ghrelin on protein expression of antioxidative enzymes and iNOS in the rat liver 
Archives of Medical Science : AMS  2014;10(4):806-816.
We investigated the effects of ghrelin on protein expression of the liver antioxidant enzymes superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), nuclear factor κB (NFκB) and inducible nitric oxide synthase (iNOS). Furthermore, we aimed to investigate whether extracellular regulated protein kinase (ERK1/2) and protein kinase B (Akt) are involved in ghrelin-regulated liver antioxidant enzymes and iNOS protein expression.
Material and methods
Male Wistar rats were treated with ghrelin (0.3 nmol/5 µl) injected into the lateral cerebral ventricle every 24 h for 5 days, and 2 h after the last treatment the animals were sacrificed and the liver excised. The Western blot method was used to determine expression of antioxidant enzymes, iNOS, phosphorylation of Akt, ERK1/2 and nuclear factor κB (NFκB) subunits 50 and 65.
There was significantly higher protein expression of CuZnSOD (p < 0.001), MnSOD (p < 0.001), CAT (p < 0.001), GPx, (p < 0.001), and GR (p < 0.01) in the liver isolated from ghrelin-treated animals compared with control animals. In contrast, ghrelin significantly (p < 0.01) reduced protein expression of iNOS. In addition, phosphorylation of NFκB subunits p65 and p50 was significantly (p < 0.001 for p65; p < 0.05 for p50) reduced by ghrelin when compared with controls. Phosphorylation of ERK1/2 and of Akt was significantly higher in ghrelin-treated than in control animals (p < 0.05 for ERK1/2; p < 0.01 for Akt).
The results show that activation of Akt and ERK1/2 is involved in ghrelin-mediated regulation of protein expression of antioxidant enzymes and iNOS in the rat liver.
PMCID: PMC4175782  PMID: 25276168
Akt; ERK1/2; superoxide dismutase; catalase; oxidative stress; nuclear factor κB
3.  A population-based cross-sectional study of the association between facial morphology and cardiometabolic risk factors in adolescence 
BMJ Open  2013;3(5):e002910.
To determine whether facial morphology is associated with fasting insulin, glucose and lipids independent of body mass index (BMI) in adolescents.
Population-based cross-sectional study.
Avon Longitudinal Study of Parents and Children (ALSPAC), South West of England.
From the ALSPAC database of 4747 three-dimensional facial laser scans, collected during a follow-up clinic at the age of 15, 2348 white British adolescents (1127 males and 1221 females) were selected on the basis of complete data on cardiometabolic parameters, BMI and Tanner's pubertal stage.
Main outcome measures
Fasting insulin, glucose and lipids (triglycerides, high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc)).
On the basis of the collection of 63 x, y and z coordinates of 21 anthropometric landmarks, 14 facial principal components (PCs) were identified. These components explained 82% of the variation in facial morphology and were used as exposure variables. With adjustment for age, gender and pubertal stage, seven PCs were associated with fasting insulin, none with glucose, three with triglycerides, three with HDLc and four with LDLc. After additional adjustment for BMI, four PCs remained associated with fasting insulin, one with triglycerides and two with LDLc. None of these associations withstood adjustment for multiple comparisons.
These initial hypotheses generating analyses provide no evidence that facial morphology is importantly related to cardiometabolic outcomes. Further examination might be warranted. Facial morphology assessment may have value in identifying other areas of disease risk.
PMCID: PMC3657674  PMID: 23793675
Epidemiology; Preventive Medicine; Statistics & Research Methods
4.  Fasting Induced Cytoplasmic Fto expression in Some Neurons of Rat Hypothalamus 
PLoS ONE  2013;8(5):e63694.
Fat mass and obesity associated protein (Fto) is a nucleic acid demethylase, with a preference for thymine or uracil, according to the recent structural data. This fact suggests that methylated single-stranded RNA, rather than DNA, may be the primary Fto substrate. Fto is abundantly expressed in all hypothalamic sites governing feeding behavior. Considering that selective modulation of Fto levels in the hypothalamus can influence food intake, we set out to investigate the effect of 48 h fasting on the Fto expression in lateral hypothalamic area, paraventricular, ventromedial and arcuate nucleus, the regulatory centres of energy homeostasis. We have demonstrated that 48 h fasting causes not only an increase in the overall hypothalamic levels of both Fto mRNA and protein, but also alters Fto intracellular distribution. This switch happens in some neurons of paraventricular and ventromedial nucleus, as well as lateral hypothalamic area, resulting in the majority of the enzyme being localized outside the cell nuclei. Interestingly, the change in the Fto intracellular localization was not observed in neurons of arcuate nucleus, suggesting that fasting did not universally affect Fto in all of the hypothalmic sites involved in energy homeostasis regulation. Both Fto mRNA and catechol-O-methyltransferaze mRNA were upregulated in the identical time-dependent manner in fasting animals. This fact, combined with the knowledge of the Fto substrate preference, may provide further insight into monoamine metabolism in the state of disturbed energy homeostasis.
PMCID: PMC3646013  PMID: 23671692
5.  Regulation of Inducible Nitric Oxide Synthase (iNOS) and its Potential Role in Insulin Resistance, Diabetes and Heart Failure 
Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. NO is a reactive oxygen species as well as a reactive nitrogen species. It is a free radical which mediates several biological effects. It is clear that the generation and actions of NO under physiological and pathophysiological conditions are regulated and extend to almost every cell type and function within the circulation. In mammals 3 distinct isoforms of NOS have been identified: neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The important isoform in the regulation of insulin resistance (IR) is iNOS. Understanding the molecular mechanisms regulating the iNOS pathway in normal and hyperglycemic conditions would help to explain some of vascular abnormalities observed in type 2 diabetes mellitus (T2DM). Previous studies have reported increased myocardial iNOS activity and expression in heart failure (HF). This review considers the recent animal studies which focus on the understanding of regulation of iNOS activity/expression and the role of iNOS agonists as potential therapeutic agents in treatment of IR, T2DM and HF.
PMCID: PMC3141344  PMID: 21792376
Inducible nitric oxide synthase; insulin resistance; diabetes; heart failure.
6.  Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain 
The Journal of Endocrinology  2009;202(1):87-97.
Chronic stress and impaired glucocorticoid receptor (GR) feedback are important factors for the compromised hypothalamic–pituitary–adrenal (HPA) axis activity. We investigated the effects of chronic 21 day isolation of Wistar rats on the extrinsic negative feedback part of HPA axis: hippocampus (HIPPO) and prefrontal cortex (PFC). In addition to serum corticosterone (CORT), we followed GR subcellular localization, GR phosphorylation at serine 232 and serine 246, expression of GR regulated genes: GR, CRF and brain-derived neurotropic factor (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that phosphorylate GR. These parameters were also determined in animals subjected to acute 30 min immobilization, which was taken as ‘normal’ adaptive response to stress. In isolated animals, we found decreased CORT, whereas in animals exposed to acute immobilization, CORT was markedly increased. Even though the GR was predominantly localized in the nucleus of HIPPO and PFC in acute, but not in chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated under both acute and chronic stresses. Thus, the transcriptional activity of GR under chronic isolation did not seem to be exclusively dependent on high serum CORT levels nor on the subcellular location of the GR protein. Rather, it resulted from the increased Cdk5 activation and phosphorylation of the nuclear GR at serine 232 and the decreased JNK activity reflected in decreased phosphorylation of the nuclear GR at serine 246. Our study suggests that this nuclear isoform of hippocampal and cortical GR may be related to hypocorticism i.e. HPA axis hypoactivity under chronic isolation stress.
PMCID: PMC2695659  PMID: 19406955
7.  Amphiphilic star-like macromolecules as novel carriers for topical delivery of nonsteroidal anti-inflammatory drugs 
AAPS PharmSci  2003;5(4):1-12.
The objective of this study was to evaluate amphiphilic star-like macromolecules (ASMs) as a topical drug delivery system. Indomethacin, piroxicam, and ketoprofen were individually encapsulated into the ASMs using coprecipitation. The effects of the ASMs on percutaneous permeation of nonsteroidal anti-inflammatory drugs (NSAIDs) across full thickness, hairless mouse skin were evaluated in vitro using modified Franz diffusion cells. In addition, solubility and in vitro release experiments were performed to characterize ASMs behavior in aqueous media. Poly(ethylene glycol) (PEG) and Pluronic P-85 were used as polymer controls to compare the role of PEG and amphiphilic behavior in the ASMs. In vitro release experiments indicated that ASMs can delay drug release (P⋖05), whereas solubility measurements showed that ASMs can increase NSAIDs aqueous solubility (P⋖05). Percutaneous permeation studies revealed that ASMs decreased both flux and Q24 of drugs compared with the control (P⋖10). Skin pretreatment studies with ASM-containing solution before drug application demonstrated that pretreatment similarly influenced NSAID percutaneous permeation. In conclusion, ASMs likely slow drug permeation through 2 mechanisms, delayed drug diffusion from its core and skin dehydration by its shell. Thus, ASMs may be useful for delayed dermal delivery or prevention of compound permeation through the skin (eg, sunscreens, N,N-diethyl-m-toluamide [DEET]) from aqueous formulations.
PMCID: PMC2750988  PMID: 15198514
topical drug delivery; NSAIDs; polymeric micelle; permeation; drug release

Results 1-7 (7)