A review of the metabolism of 1,4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers.

BACKGROUND: Cosmetic procedures are growing ever more common, and the use of soft tissue fillers is increasing. Practicing physicians need to be aware of the biological behavior of these products in tissue to enable them to respond to any safety concerns that their patients raise. OBJECTIVES: To provide an overview of the metabolism of 1,4-butanediol diglycidyl ether (BDDE)-crosslinked hyaluronic acid (HA) dermal fillers and to examine the safety of the resulting byproducts. METHODS: A review of available evidence was conducted. RESULTS: After reaction with HA, the epoxide groups of BDDE are neutralized, and only trace amounts of unreacted BDDE remain in the product (<2 parts per million). When crosslinked HA, uncrosslinked HA, and unreacted BDDE degrade, they break down into harmless byproducts or into byproducts that are identical to substances already found in the skin. CONCLUSION: Clinical and biocompatibility data from longer than 15 years support the favorable clinical safety profile of BDDE-crosslinked HA and its degradation products. Given the strength of the empirical evidence, physicians should be confident in offering these products to their patients.

Reversible hepatocerebral degeneration-like syndrome due to portovenous shunts.

Ataxia and tremor are rare manifestations of hepatocerebral degeneration due to portovenous shunts. Ammonia is a neurotoxin that plays a significant role in the pathogenesis of hepatic encephalopathy. A 58-year old male patient was assessed with the complaints of gait disturbance, hand tremor, and impairment of speech. His neurological examination revealed dysarthric speech and ataxic gait. Bilateral kinetic tremor was noted, and deep tendon reflexes of the patient were hyperactive. Serum ammonia level was found to be 156.9 microg/dL. Cranial magnetic resonance (MR) imaging revealed increased signal intensity in bilateral globus pallidus on T1-weighted axial sections, and bilateral prominent hyperintense lesions in the middle cerebellar peduncles on T2-weighted axial sections. On his abdominal MR portography, multiple portohepatic venous collaterals were noted in the right and left lobes of liver parenchyma in 2D FIESTA axial MR sections. To our knowledge, we reported the first case of acquired hepatocerebral degeneration presenting with cerebral symptoms without any hepatic findings in which clinical improvement was noted, and hyperammonemia disappeared following medical treatment.

Inflammatory bowel disease and thrombosis.

Inflammatory Bowel Disease (IBD) is a group of chronic and relapsing inflammatory disorders of the gastrointestinalsystem. In these cases, findings are detected in extraintestinal systems also. There is a tendency for thrombotic eventsin IBD, as in the other inflammatory processes. The pathogenesis of this thrombotic tendency is multidimensional,including lack of natural anticoagulants, prothrombotic media induced via the inflammatory process, long-termsedentary life style, steroid use, surgery, and catheter placement. The aim of this review was to highlight the positiverelationship between IBD and thrombotic events, and the proper treatment of at-risk patients.

Beliefs About Medicines and Adherence to Treatment in Turkish Patients with Inflammatory Bowel Disease.

BACKGROUND: Although studies are investigating the perception and beliefs about treatment and adherence to treatment in different societies related to inflammatory bowel disease, there are no studies on this subject in Turkish people with different sociocultural structures. In our study, we aimed to evaluate the beliefs about treatment and its effect on adherence to treatment in the Turkish population with inflammatory bowel disease. METHODS: In the study, the "Medication Adherence Report Scale" and "Beliefs about Medicines Scale" scales were used to evaluate the treatment compliance and perception and beliefs about treatment. Characteristics that could affect treatment compliance were evaluated by statistical analysis. RESULTS: A total of 253 patients, 167 with ulcerative colitis and 86 with Crohn's disease, were included in the study. The non-adherence rate to the treatment was found as 41.9% in ulcerative colitis and 24.4% in Crohn's disease (P = .006). Intentional (29.3% in ulcerative colitis and 16.3% in Crohn's disease [P = .031] and unintentional non-adherence to treatment (28.1% in ulcerative colitis, 16.3% in Crohn's disease [P = .037] were significantly higher in ulcerative colitis than in Crohn's disease. Female gender (odds ratio = 2.59, P = .005), low education level (odds ratio = 4.8, P = .015), distal involvement in ulcerative colitis (P = .014), and thoughts about the disease would last too soon in Crohn's disease (odds ratio = 4.17, P = .049) were risk factors for non-adherence to treatment. CONCLUSION: The negative perception of treatment in inflammatory bowel disease affects adherence to the treatment. Considering some social factors that affect adherence to the treatment and taking measures to enhance the adherence to treatment will increase the success of treatment.

Improvement of Work Productivity and Quality of Life with Anti-Tumor Necrosis Factor Treatment Used in Crohn's Disease in Routine Clinical Practice in Turkey.

BACKGROUND: Patients with Crohn's disease experience major deterioration in work productivity and quality of life. We aimed to provide the long-term effects of anti-tumor necrosis factor agents on work productivity and activity impairment and quality of life in patients with Crohn's disease using the Inflammatory Bowel Disease Questionnaire and the Short-Form Health Survey-36. METHODS: Patients with Crohn's disease and initiated an anti-tumor necrosis factor treatment were included and followed up for 12 months in this observational study. RESULTS: A total of 106 patients were included in this study, and 64.2% of the patients were males. Mean [± standard deviation] age was 36.8 [± 10.9] years. At baseline, mostly perianal fistulas [65.7%] were observed [n = 23]. Intestinal stenosis was detected in 34.9% of the patients [n = 37], and most of the stenosis was located in the ileum [70.6%] followed by the colon [20.6%]. Extraintestinal symp- toms were observed in 24 patients [22.6%]. Most frequent extraintestinal symptom was arthritis with 71.4% [n = 15]. Mean time from first symptom to initiation of anti-tumor necrosis factor treatment was 6.3 [± 5.0] years. Improvements in work productivity and activ- ity impairment scores throughout 12 months were -24.1% [P = .003] for work time missed, -18.0% [P = .006] for impairment at work, -8.5% [P = .160] for overall work impairment, and -17.0% [P < .001] for daily activity impairment. Similarly, significant improvements [P < .001] were detected in all components of the Inflammatory Bowel Disease Questionnaire when compared to baseline. Statistically sig- nificant improvements [P < .05] were detected for all components of Short-Form Health Survey-36 except for mental health [P = .095]. CONCLUSION: Our study indicates the significant improvement in work productivity and activity impairment and quality of life of patients with Crohn's disease who receive long-term anti-tumor necrosis factor treatment.

Lift capabilities of hyaluronic acid fillers.

BACKGROUND: The lift capacity of a filler (ability to oppose deformation and flattening) relates to its suitability for correcting deeper wrinkles and folds, volumizing, and contouring. Lift capacity, considered as a function of both elastic modulus (G') and gel cohesivity, can be expected to differ among products owing to proprietary manufacturing processes. OBJECTIVES: To compare the lift capabilities of 24-mg/ml smooth, cohesive gel fillers (with ~6% and ~8% crosslinking) and a 20-mg/ml granular consistency gel filler (~2% crosslinking). METHODS: G' was measured using a parallel plate rheometer and the products were subjected to a small oscillatory strain. Cohesivity was measured using a linear compression test (quantitative) as well as a dye diffusion test (qualitative). RESULTS: The 24-mg/ml smooth, cohesive gel filler had a lower G' coupled with lower susceptibility to yield to a given strain versus the 20-mg/ml granular consistency gel filler. Both 24-mg/ml smooth, cohesive gel filler formulations demonstrated greater resistance to deformation in the linear compression test and lower rates of dye diffusion than the 20-mg/ml granular consistency gel filler. CONCLUSIONS: The 24-mg/ml smooth, cohesive HA gel fillers achieve a high lift capacity by combining higher cohesivity with lower relative G' versus the 20-mg/ml granular consistency gel filler.

Turkish IBD Organization's Position Statement on Inflammatory Bowel Disease Management Recommendations During COVID-19 Pandemic.

The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2, has resulted in high mortality and morbidity worldwide and is still a growing problem. Inflammatory bowel disease (IBD) is a chronic inflammatory disease for which a substantial number of patients are treated with immunosuppressive medications, either occasionally or long-term. Despite the accumulating evidence, there is still a lack of knowledge about the impact of COVID-19 on IBD patients, especially those who are under immunosuppressive treatment. Moreover, following the emergence of several COVID vaccines, there are concerns regarding vaccine effectiveness and possible side effects in such patients. In this context, we tried to briefly summarize the accumulating evidence and recommendations for the management of IBD in the context of the COVID-19 pandemic.

Volumizing with a 20-mg/mL smooth, highly cohesive, viscous hyaluronic acid filler and its role in facial rejuvenation therapy.

BACKGROUND: The new 20 mg/mL hyaluronic acid (HA) dermal filler is a smooth, highly cohesive, viscous formulation developed to restore volume in aesthetic facial rejuvenation. OBJECTIVE Evaluate clinical experience with 20 mg/mL HA dermal filler to date and comment on its current and potential uses within the facial rejuvenation treatment paradigm. METHODS AND MATERIALS: In this paper, the authors review the unique physical and chemical properties of 20 mg/mL HA dermal filler as well as clinical experience with the product to date. RESULTS: Overall, the 20 mg/mL smooth, cohesive, viscous HA filler was especially effective in restoring volume in the malar region and chin. Volume loss resolved significantly in patients in clinical trials(1) and treatment effects were observed to be maintained from six to 18 months.(2) Physicians reported the agent was highly effective as well as easy to inject, sculpt and mold. The treatment was generally well tolerated and no instances of product migration from the injection site have been reported. Patient satisfaction was high, with the vast majority of trial participants acknowledging they would return for additional treatment and recommend the treatment to friends.(1,2) CONCLUSION: Initial experience shows the 20 mg/mL smooth, cohesive, viscous HA filler to be a useful addition to the facial rejuvenation armamentarium when used both alone and in combination with BTX-A.

Autonomic and diastolic dysfunction association with quality of life impairment in cirrhotic patients.

BACKGROUND AND STUDY AIMS: Cirrhosis is a multisystem disorder characterized by hyperdynamic circulation which can progress to multiple organ dysfunctions. Recent studies have demonstrated autonomic dysfunction and cirrhotic cardiomyopathy including diastolic dysfunction, systolic dysfunction with electrophysiologic abnormalities in patients with cirrhosis. Due to the long and complicated course of the disease, health related quality of life is affected. We aimed to evaluate the frequency of diastolic dysfunction and autonomic dysfunction in cirrhosis, and the effects on health-related quality of life. PATIENTS AND METHODS: Hundred cirrhotic patients were enrolled in the study. According to the Child-Pugh classification 35 patients were of Child A, 36 of Child B and 29 of Child C. The proportion of autonomic dysfunction was 52%, and diastolic dysfunction 51%. Autonomic dysfunction was diagnosed using bedside maneuvers and tests; diastolic dysfunction was diagnosed using the E/A ratio in echocardiographic findings. Health-related quality of life measurements was obtained from an SF-36 questionnaire. RESULTS: Patients with advanced Child-Pugh classifications were found to have significantly lower health-related quality of life values (p < 0.05). Likewise, health-related quality of life values were observed to be significantly lower in patients with autonomic dysfunction (p < 0.05). No significant difference was found in health related quality of life measurements between patients with and without diastolic dysfunction. CONCLUSION: Our study showed that autonomic dysfunction and diastolic dysfunction are found in patients with cirrhosis. Further studies are needed to assess the effects of autonomic dysfunction and diastolic dysfunction on health-related quality of life.

The relationship between virulence factors of Helicobacter pylori and severity of gastritis in infected patients.

The outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The best known genotypic virulence factors of H. pylori are cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA). The objective of this study was to assess the relationship between H. pylori cagA and vacA status and histopathological findings. Esophagogastrodoedonoscopy was performed in 80 dyspeptic patients. Antrum and corpus biopsies were obtained for isolation of H. pylori and for histopathological assessment. The polymerase chain reaction was used to detect cagA and vacA genes of H. pylori using specific primers. Biopsy samples were stained with hematoxylin and eosin, and histopathological findings were graded using the "updated Sydney system". H. pylori from 57 of the 80 patients was incubated. Of the 57 patients, 44 were cagA positive. In the corpus biopsy specimens there was a significant relationship between the density of H. pylori colonization (P = 0.02) and chronic inflammation (P = 0.02) and cagA-positive genotypes. In the antrum specimens there was a significant relationship between cagA positivity and neutrophil activity (P = 0.003) and glandular atrophy (P = 0.002), but not with H. pylori density, chronic inflammation, and intestinal metaplasia. The odds ratio of cagA-positive vs. cagA-negative strains for the presence of glandular atrophy, irrespective of grading and of gastric localization, was 4.62 (95% CI, 1.18-18.08, P = 0.041). No significant relationships were observed between vacA s1 and s2 genotypes and histopathological parameters. Corpus neutrophil infiltration was found to be more severe in the m1 group than in the m2 group (P = 0.004). Other histopathological features showed no difference between m1 and m2 genotypes. In conclusion H. pylori strains showing cagA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis.

Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats.

AIM: To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats. METHODS: Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method. RESULTS: Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 +/- 1.2, 33.8 +/- 2.9, 36.7 +/- 0.5 mug collagen/mg protein, respectively) compared to BDL (48.3 +/- 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% +/- 1.1%, 6.2% +/- 1.7%, 12.3% +/- 2.0%, respectively) compared to BDL (17.4% +/- 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 +/- 0.8 vs BDL: 3.1 +/- 0.7; P < 0.05). CONCLUSION: Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.

Effects of vitamins E and C supplementation on hepatic glutathione peroxidase activity and tissue injury associated with ethanol ingestion in malnourished rats.

BACKGROUND: Oxidative stress has been associated with tissue injury in alcoholic liver disease. Although this close association is well known, whether prevention of oxidative stress retards tissue injury has not been thoroughly investigated. OBJECTIVE: The aim of this study was to determine the effects of supplementation with vitamins E and C on antioxidant enzyme status and histologic changes in hepatic tissue in a rat model of alcoholic liver disease. METHODS: This 8-week, blinded, controlled study was conducted at the Department of Internal Medicine, Trakya University, Edirne, Turkey. Weanling albino female protein-deficient Wistar rats weighing ∼200 g were randomly assigned to 1 of 6 groups: (1) liquid diet+ethanol+vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet+ethanol+vitamin C 10 mg/kg PO (LDetvitC); (3) liquid diet+ethanol+vitamin E 15 mg/kg+vitamin C 10 mg/kg PO (LDetvitEC); (4) liquid diet+ethanol (LDet); (5) liquid diet+isocaloric sucrose (LDS); and (6) normal diet (control). The primary end point of the study was to determine whether antioxidant vitamin E/C combination therapy prevents development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After being euthanized at week 8, the rats were weighed, and their livers and spleens were weighed. Hepatic tissue specimens were histopathologically assessed according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide dismutase, and catalase activities were determined. Biochemical tissue collagen concentrations were measured to determine the presence of hepatic fibrosis. RESULTS: Seventy-two rats were included in the study (mean [SE] weight, 205 [21] g) (12 rats per group). Initially planned to last 48 weeks, the study was terminated at 8 weeks due to the death of 3 rats in each group (except the LDS group and control group). The relative liver weight was significantly lower in the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%] vs 4.8% [0.9%]; P<0.01). Mean (SE) hepatic tissue glutathione peroxidase activity was significantly reduced in the LDet-treated rats compared with controls (1.2 [0.2] vs 2.6 [0.3] U/mg protein; P<0.001). The groups that received supplementation with vitamin E, vitamin C, and vitamins E and C combined had significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5], 2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group (1.2 [0.2] U/mg protein) (all, P<0.001). No significant between-group differences in hepatic superoxide dismutase or catalase activities were found. Compared with controls (14.5 [1.9] µg collagen/mg protein), the mean (SE) histologic hepatic collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5 [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] µg collagen/mg protein in the LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P<0.01, P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Compared with the LDet group, the mean hepatic collagen concentration was significantly lower in the LDetvitE, LDetvitC, and LDetvitEC groups (P<0.01, P<0.05, and P<0.01, respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P<0.05). The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P<0.05). CONCLUSIONS: The results of this study in protein-deficient rats fed with a high-fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a combination of vitamins E and C was associated with decreased ethanol-induced hepatic glutathione peroxidase activity and hepatic fibrosis, and that supplementation with vitamins E and C might have attenuated the development of hepatomegaly and hepatic necroinflammation, whereas this result was not found in the group given a liquid diet and ethanol in this 8-week study. (Curr Ther Res Clin Exp. 2006;67:118-137) Copyright © 2006 Excerpta Medica, Inc.

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene-gene interactions in Crohn's disease and ulcerative colitis in a Turkish population.

BACKGROUND/AIMS: Inflammatory bowel diseases are chronic, relapsing, inflammatory conditions. They have a genetic backround resulting in patient susceptibility. The aim of our study is to investigate the involvement of IL23R, JAK2, and STAT3 polymorphisms in inflammatory bowel diseases in a Turkish population. MATERIALS AND METHODS: Polymorphisms in IL23R (rs11209026), JAK2 (rs10758669), and STAT3 (rs3816769, rs2293152, rs744166, rs957970, rs8074524) were genotyped in 69 Crohn's disease patients, 157 ulcerative colitis patients, and 89 healthy controls. RESULTS: The presence of (C) in rs10758669, (T) and (TT) in rs957970, and (TT) in rs744166 were found to increase the susceptibility to Crohn's disease (p=0.049, p=0.016, p=0.010, p=0.035, respectively), while rs2293152 (GC), rs744166 (CT), and rs957970 (CT) provide protection against Crohn's disease (p=0.007, p=0.043, p=0.043, respectively). While rs2293152 (GC) was protective, rs2293152 (CC) increased the susceptibility to ulcerative colitis (p=0.009, p=0.001). All the polymorphisms were associated with age-at-diagnosis, except rs11209026. Furthermore, rs2293152 was associated with an extension in ulcerative colitis, while rs10758669, rs3816769, rs744166, rs2293152, and rs957970 were associated with the subphenotype in Crohn's disease. The presence of rs10758669 (AC) was protective against perianal Crohn's disease (p=0.016). Additionally, rs10758669 and rs2293152 in Crohn's disease and rs8074524, rs3816769, and rs10758669 in ulcerative colitis were associated with the requirement of immunsuppression. Finally, rs8074524 and rs10758669 in Crohn's disease and rs11209026 in ulcerative colitis were associated with disease-related operation. CONCLUSION: This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohn's disease in a Turkish population. It was demonstrated that these polymorphisms may be effective in the etiology of inflammatory bowel disease in this Turkish population.

Cerebral sinus thrombosis in patients with inflammatory bowel disease: a case report.

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the gastrointestinal tract. The pathophysiology of IBD is probably the result of the complex interaction of genetic susceptibility and environmental influences. There is a well-known risk of thrombosis in patients with IBD. We present the case of a 53-year-old man with ulcerative colitis, who spontaneously developed intracranial sinus thrombosis that was treated with low molecular weight heparin. Literature was searched to assess the frequency and characteristics of cerebral sinus thrombosis in IBD and the role of certain etiopathological factors in such thrombotic patients.

Prothrombotic gene mutations and Crohn's disease; is there any association?

BACKGROUND/AIMS: Patients with inflammatory bowel disease have an increased tendency for thromboembolism. In this study we aimed to determine the frequency of FV gene and Prothrombin G20210A gene mutations in a group of patients with Crohn's Disease (CD) and estimate its correlation with disease activity and clinical subtype. METHODOLOGY: Forty-four CD patients and 43 healthy controls were included in the study. Twenty-three of the patients had inflammatory CD, while 11 had fibrostenotic and 10 had fistulizing CD. Only one patient had a history of deep vein thrombosis. Polymorphism Light Cycler FV Leiden mutation detection kit and Light Cycler prothrombin (G20210A) mutation detection kit were used for the detection of mutations in DNA samples. RESULTS: Forty of the CD patients had normal factor V genotype, three (6.8%) patients showed a heterozygous, and one (2.3%) patient homozygous pattern. Two (4.7%) of the 43 controls showed heterozygous factor V mutation and 41 had normal FV genotype. Two (4.6%) CD patients had heterozygous prothrombin G20210A mutation, and there was only one (2.3%) homozygous mutation in the control group. There was no significant difference between controls and CD patients neither for factor V mutation (p > 0.05) nor for prothrombin G20210A mutations (p > 0.05). No correlation was found between disease activity and both gene mutations (p > 0.05), as well as between disease subtype and gene mutations (p > 0.05). CONCLUSIONS: The prevalence of prothrombin G20210A gene and factor V Leiden gene mutations were found to be statistically insignificant among CD patients and control group.

Tyrosine kinase-2 gene polymorphisms are associated with ulcerative colitis and Crohn's disease in Turkish Population.

BACKGROUND AND OBJECTIVE: Inflammatory bowel disease is a group of chronic inflammatory conditions affecting gastrointestinal tract. Lots of genes have been identified resulting in susceptibility to inflammatory bowel disease. Any polymorphism leading to functional modifications in tyrosine kinase-2 may precipitate excessive immune response in the intestinal mucosa. The aim of our study is to investigate the involvement of tyrosine kinase-2 polymorphisms in the patients with inflammatory bowel disease in Turkish population. METHODS: Four single nucleotide polymorphisms in tyrosine kinase-2 (rs280523, rs2304256, rs280519 and rs280496) were genotyped in 60 Crohn's disease, 151 ulcerative colitis patients and 89 unrelated healthy controls. These polymorphisms were detected by real-time polymerase chain reaction. RESULTS: The presence of genotype (CC) in rs2304256 and (AA) in rs280519 were found to increase the susceptibility to ulcerative colitis (P=0.024, 0.025, respectively). rs2304256 (CA) and rs280519 (AG) have provided protection against ulcerative colitis (P=0.021, 0.012, respectively). rs280519 (AG) was protective against Crohn's disease (P=0.045). rs2304256 (CC) increased the susceptibility to inflammatory Crohn's disease (P=0.014). The presence of rs2304256 (A) increased the susceptibility to perianal Crohn's disease (P=0.03). Both rs280519 and rs2304256 polymorphisms were associated with the requirement of corticosteroid and immunosuppressive therapy in ulcerative colitis. CONCLUSION: This study is the first demonstration of the single marker association of tyrosine kinase-2 polymorphisms with ulcerative colitis and Crohn's disease in Turkish population. They may be effective in the etiology of inflammatory bowel disease in our population. Disparity between our study and others may be related to ethnic differences.

On the origin of size-dependent tortuosity for permeation of hydrophilic solutes across the stratum corneum.

Due to their low skin permeabilities, transdermal transport of hydrophilic solutes is poorly understood. In this study, we sought to determine the dependence of solute tortuosity on solute size and stratum corneum (SC) porosity. With porous pathway model, transdermal transport of hydrophilic solutes through the SC was modeled as diffusion through imperfections/defects that occur between/within the lipid lamellar organization of the SC. In order to seek an analytical solution, we assumed that the pores in the SC were cylindrical and organized in a cubical pattern. The proposed theoretical model describing the dependence of solute tortuosity on solute size and SC porosity is in agreement with prior experimentally derived tortuosity values.

Incorporation of lipophilic pathways into the porous pathway model for describing skin permeabilization during low-frequency sonophoresis.

Application of low-frequency sonophoresis (LFS) has been shown to increase skin permeability, thereby facilitating delivery of hydrophilic solutes. We have previously shown that the modified porous pathway model provides an adequate theoretical description of transdermal delivery of hydrophilic solutes through pores in the presence and absence of ultrasound. However, small hydrophilic solutes (M(w)<400 Da) that exhibit a moderate partition coefficient, K(o/w) (0.1