The Role of Recombinant Fibroblast Growth Factor 1 in Enhancing the Angiogenesis in Random Cutaneous Flaps in Animal Model of Rat.

BACKGROUND: Randomized skin flaps have been used as a basic treatment modality for covering skin defects for a long time but they have always been in the risk of an inherent ischemia. Fibroblast growth factor 1 is a known angiogenic factor in in vitro studies which has shown conflicting results in in vivo investigation. We aimed to determine the effect of recombinant fibroblast growth factor on the angiogenesis rate of random cutaneous flap in animal model of rats. METHODS: This experimental study was conducted on 24 adult male rats randomized to 2 groups. In the first group FGF1 was injected subdermally in equally divided doses and distances of random flap surface in days 1, 3 and 5. In second group, normal saline was injected as control. Flap surgery was done on day 21 after first injection. The extent of necrosis and angiogenesis (mean vessel density) were assessed in day 14 after surgery. RESULTS: The mean percentage of clinically apparent necrosis was 35.2% (±10.5) in intervention (FGF1) group and 38.1% (±8.7) in control (normal saline), respectively. Mean vessel density was 86.20±5.6/mm2 in control group and 90.17±5.5/mm2 in intervention group, which showed no statistically significant difference. CONCLUSION: Mean vessel density and mean percentage of clinically apparent necrosis area were similar in 2 groups of rats with random cutaneous flaps receiving FGF1 or normal saline.

Trigger Thumb in Twins: Case Report.

Although trigger finger is common, pediatric trigger thumb is uncommon. In trigger thumb the finger is held in flexed position. The etiology of trigger finger is unknown and can occur isolated without any relation to other syndromes, however there are some evidences that suggest genetic etiology. We reported 2.5 year old twins both having bilateral trigger thumb. Grandfather of the twins had the disease. Although trigger thumb and finger have the same presentation, they can involve different anatomical structures. Bent or straightening of thumb or finger would produce painful popping and clicking and the affected finger or thumb can get stuck in bent and extended position. Based on physical examination and symptoms trigger finger are classified into four stages and each has its own treatment. There are evidences that support congenital hypothesis in pediatric trigger thumb such as bilateral presentation in identical twins, first degree familiar association and etc. Before the 1st year of life, 30% of trigger thumb will get resolved and it is better to postpone the surgery until 2 year of age. A1 pulley release has a good result in pediatric trigger thumb treatment.

Comparison of the Never Repair with Fibrin Glue and Perineural Micro-Suture in Rat Model.

BACKGROUND: Many different methods for nerve repair have been introduced. Nerve repair with micro-suture is the gold standard one; however, the use of fibrin glue is a promising method. This study compared the never repair with fibrin glue and perineural micro-suture in rat model. METHODS: Ten 3-4 month old male rats, weighting between 250-300 grams were divided into two groups. Left sciatic nerves of the rats were transected and repaired with fibrin glue (TissucolR) in one group (A) and direct peri-neural micro-suture in another group (B). The time of nerve repair was compared between the two groups after 8 weeks. A biopsy from was taken from anastomosis site and the histopathological assessment was undertaken for axonal growth rate after anastomosis and compared between the two groups. RESULTS: The time of repair in group A was significantly lower than group B. Axonal growth rate was pretty similar between the two groups, and the difference was not significant. The mean (SD) time for repair of nerves with micro-sutures was 7.1 (1.5) minutes and the mean (SD) for repair of nerves with fibrin glue was 2.5 (0.5) minutes and the difference was significant. The number of calcification such as psammoma bodies was significantly higher in fibrin glue group. CONCLUSION: Nerve repair with fibrin glue was shown to be simpler and more time saving. The number of axons after the repair was not different in the two groups. We showed that fibrin glue may have more tissue reactions compared with micro-sutures.

Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size : Structure-activity relationships of non-digestible oligosaccharides.

PURPOSE: The direct effects of galacto-oligosaccharides (GOS), including Vivinal® GOS syrup (VGOS) and purified Vivinal® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure-activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin. METHODS: Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA. RESULTS: In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release. CONCLUSIONS: This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

The intestinal barrier as an emerging target in the toxicological assessment of mycotoxins.

Mycotoxins, the secondary metabolites of fungal species, are the most frequently occurring natural food contaminants in human and animal diets. Risk assessment of mycotoxins focused as yet on their mutagenic, genotoxic and potential carcinogenic effects. Recently, there is an increasing awareness of the adverse effects of various mycotoxins on vulnerable structures in the intestines. In particular, an impairment of the barrier function of the epithelial lining cells and the sealing tight junction proteins has been noted, as this could result in an increased translocation of luminal antigens and pathogens and an excessive activation of the immune system. The current review aims to provide a summary of the available evidence regarding direct effects of various mycotoxins on the intestinal epithelial barrier. Available data, based on different cellular and animal studies, show that food-associated exposure to certain mycotoxins, especially trichothecenes and patulin, affects the intestinal barrier integrity and can result in an increased translocation of harmful stressors. It is therefore hypothesized that human exposure to certain mycotoxins, particularly deoxynivalenol, as the major trichothecene, may play an important role in etiology of various chronic intestinal inflammatory diseases, such as inflammatory bowel disease, and in the prevalence of food allergies, particularly in children.

Effects of Vitamin D on Endometriosis-Related Pain: A Double-Blind Clinical Trial.

BACKGROUND Endometriosis is a disabling disease of reproductive-age women. Dysmenorrhea, dyspareunia, and pelvic pain are the main symptoms of endometriosis. Its etiology is not clear. Endometriosis may have various causes, including vitamin D deficiency, but its effect is controversial. MATERIAL AND METHODS In this double-blind clinical trial, we enrolled patients with endometriosis diagnosed and treated by laparoscopy, with scores of at least 3 for of dysmenorrhea and/or pelvic pain at 8 weeks after surgical treatment. They were randomly prescribed vitamin D (50 000 IU weekly for 12 weeks) or placebo. Severity of pain in the 2 groups (placebo and treatment) was compared by VAS test at 24 weeks after surgical treatment. RESULTS There were 19 patients in the vitamin D group and 20 in the placebo group. Baseline characteristics in the 2 groups were similar. Following the treatment with vitamin D or placebo, we did not find significant differences in severity of pelvic pain (p=0.24) and dysmenorrhea (p=0.45) between the 2 groups. Mean pelvic pain at 24 weeks after laparoscopy in the vitamin D group was 0.84±1.74 and in placebo group it was 0.68±1.70 (p=0.513). Mean dysmenorrhea was 2.10±2.33 in the vitamin D group and 2.73±2.84 in the placebo group (p=0.45). CONCLUSIONS After ablative surgery for endometriosis, vitamin D treatment did not have a significant effect in reducing dysmenorrhea and/or pelvic pain.

Deoxynivalenol and Its Modified Forms: Are There Major Differences?

Considering the diverse toxic effects of the Fusarium toxin deoxynivalenol (DON), its common occurrence in wheat-based products, and its stability during processing, DON constitutes an increasing health concern for humans and animals. In addition to the parent compound DON, human and animal exposure encompasses the acetylated fungal metabolites 3-acetyl-deoxynivalenol (3ADON) and 15-acetyl-deoxynivalenol (15ADON) as well as the plant-derived DON-glucoside (DON3G) and the bacterial product de-epoxy-DON (DOM-1). In the current study we used the well-established Caco-2 cell model to compare the effects of these naturally occurring forms of DON on cell viability and markers of barrier integrity, as well as on the release of the pro-inflammatory chemokine chemokine CXC motif ligand (CXCL8). Results show that 3ADON is less potent in inducing adverse effects on barrier integrity when compared to DON, whereas 15ADON appears to be slightly more potent than DON. In contrast, DON3G and DOM-1 exerted no measurable adverse effects on the intestinal barrier. It was also demonstrated that galacto-oligosaccharides (GOS) are able to protect epithelial cells against DON and its acetylated forms, which suggests that GOS are beneficial food additives in the protection of vulnerable segments of the human population against adverse effects of DON and its derivatives.

Folic acid supplementation reduces plasma homocysteine in postmenopausal women.

Plasma homocysteine, which is increased after menopause, can be a risk factor for cardiovascular disease and osteoporosis. The purpose of the present study was to determine the effect of folic acid supplementation on plasma homocysteine in postmenopausal women. The study was performed as a randomized placebo controlled trial on 48 healthy postmenopausal women (aged 50-70 years) and plasma homocysteine of all women was measured. In the case group, folic acid, and in the control group, placebo was prescribed. The second plasma homocysteine was measured 16-17 weeks later and was compared in the two groups. There was no significant difference between the two groups according to age, BMI, parity, duration of menopause and the first plasma homocysteine level. Plasma homocysteine level was significantly lower in the case group than control group 16 weeks after folic acid administration (10.33 ± 3.51 µmol/l vs 13.21 ± 3.11 µmol/l, p=0.004). There was no significant correlation between plasma homocysteine level and BMI and parity. However, there was a weak-moderate positive correlation between plasma homocysteine and age (p<0.05, r=0.33), and there was a significant but weak correlation between plasma homocysteine and duration of menopause (p=0.05, r=0.28).

Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions.

BACKGROUND: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease--actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). METHODS: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. RESULTS: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (2.33 µg/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 µg/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. CONCLUSION: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. GENERAL SIGNIFICANCE: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy.

Dendritic cells inversely regulate airway inflammation in cigarette smoke-exposed mice.

The recruitment and activation of inflammatory cells into the respiratory system is considered a crucial feature in the pathophysiology of chronic obstructive pulmonary disease (COPD). Because dendritic cells (DCs) have a pivotal role in the onset and regulation of immune responses, we investigated the effect of modulating DC subsets on airway inflammation by acute cigarette smoke (CS) exposure. CS-exposed mice (5 days) were treated with fms-like tyrosine kinase 3 ligand (Flt3L) and 120g8 antibody to increase total DC numbers and deplete plasmacytoid DCs (pDCs), respectively. Flt3L treatment decreased the number of inflammatory cells in the bronchoalveolar lavage (BALF) of the smoke-exposed mice and increased these in lung tissue. DC modulation reduced IL-17 and increased IL-10 levels, which may be responsible for the suppression of the BALF cells. Furthermore, depletion of pDCs led to increased infiltration of alveolar macrophages while restricting the presence of CD103(+) DCs. This study suggests that DC subsets may differentially and compartment-dependent influence the inflammation induced by CS. pDC may play a role in preventing the pathogenesis of CS by inhibiting the alveolar macrophage migration to lung and increasing CD103(+) DCs at inflammatory sites to avoid extensive lung tissue damage.

Differences in Susceptibility to Heat Stress along the Chicken Intestine and the Protective Effects of Galacto-Oligosaccharides.

High ambient temperatures negatively affect the human well-being as well as animal welfare and production. The gastrointestinal tract is predominantly responsive to heat stress. The currently available information about the multifaceted response to heat stress within different parts of the intestine is limited, especially in avian species. Hence, this study aims to evaluate the heat stress-induced sequence of events in the intestines of chickens. Furthermore, the gut health-promoting effect of dietary galacto-oligosaccharides (GOS) was investigated in these heat stress-exposed chickens. Chickens were fed a control diet or diet supplemented with 1% or 2.5% GOS (6 days) prior to and during a temperature challenge for 5 days (38-39°C, 8h per day). The parameters measured in different parts of the intestines included the genes (qPCR) HSF1, HSF3, HSP70, HSP90, E-cadherin, claudin-1, claudin-5, ZO-1, occludin, TLR-2, TLR-4, IL-6, IL-8, HO-1, HIF-1α) and their associated proteins HSP70, HSP90 and pan-cadherin (western blots). In addition, IL-6 and IL-8 plasma concentrations were measured by ELISA. In the jejunum, HSF3, HSP70, HSP90, E-cadherin, claudin-5, ZO-1, TLR-4, IL-6 and IL-8 mRNA expression and HSP70 protein expression were increased after heat stress exposure and a more pronounced increase in gene expression was observed in ileum after heat stress exposure, and in addition HSF1, claudin-1 and HIF-1α mRNA levels were upregulated. Furthermore, the IL-8 plasma levels were decreased in chickens exposed to heat stress. Interestingly, the heat stress-related effects in the jejunum were prevented in chickens fed a GOS diet, while dietary GOS did not alter these effects in ileum. In conclusion, our results demonstrate the differences in susceptibility to heat stress along the intestine, where the most obvious modification in gene expression is observed in ileum, while dietary GOS only prevent the heat stress-related changes in jejunum.

Galacto-oligosaccharides Protect the Intestinal Barrier by Maintaining the Tight Junction Network and Modulating the Inflammatory Responses after a Challenge with the Mycotoxin Deoxynivalenol in Human Caco-2 Cell Monolayers and B6C3F1 Mice.

BACKGROUND: The integrity of the epithelial layer in the gastrointestinal tract protects organisms from exposure to luminal antigens, which are considered the primary cause of chronic intestinal inflammation and allergic responses. The common wheat-associated fungal toxin deoxynivalenol acts as a specific disruptor of the intestinal tight junction network and hence might contribute to the pathogenesis of inflammatory bowel diseases. OBJECTIVE: The aim of the current study was to assess whether defined galacto-oligosaccharides (GOSs) can prevent deoxynivalenol-induced epithelial dysfunction. METHODS: Human epithelial intestinal Caco-2 cells, pretreated with different concentrations of GOSs (0.5%, 1%, and 2%) for 24 h, were stimulated with 4.2-µM deoxynivalenol (24 h), and 6/7-wk-old male B6C3F1 mice were fed a diet supplemented with 1% GOSs for 2 wk before being orally exposed to deoxynivalenol (25 mg/kg body weight, 6 h). Barrier integrity was determined by measuring transepithelial electrical resistance (TEER) and intestinal permeability to marker molecules. A calcium switch assay was conducted to study the assembly of epithelial tight junction proteins. Alterations in tight junction and cytokine expression were assessed by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, or ELISA, and their localization was visualized by immunofluorescence microscopy. Sections of the proximal and distal small intestine were stained with hematoxylin/eosin for histomorphometric analysis. RESULTS: The in vitro data showed that medium supplemented with 2% GOSs improved tight junction assembly reaching an acceleration of 85% after 6 h (P < 0.05). In turn, GOSs prevented the deoxynivalenol-induced loss of epithelial barrier function as measured by TEER (114% of control), and paracellular flux of Lucifer yellow (82.7% of prechallenge values, P < 0.05). Moreover, GOSs stabilized the expression and cellular distribution of claudin3 and suppressed by >50% the deoxynivalenol-induced synthesis and release of interleukin-8 [IL8/chemokine CXC motif ligand (CXCL8)] (P < 0.05). In mice, GOSs prevented the deoxynivalenol-induced mRNA overexpression of claudin3 (P = 0.022) and CXCL8 homolog keratinocyte hemoattractant (Kc) (Cxcl1) (P = 0.06) as well as the deoxynivalenol-induced morphologic defects. CONCLUSIONS: The results demonstrate that GOSs stimulate the tight junction assembly and in turn mitigate the deleterious effects of deoxynivalenol on the intestinal barrier of Caco-2 cells and on villus architecture of B6C3F1 mice.

Frequency of molar pregnancies in health care centers of tehran, iran.

BACKGROUND: Hydatidiform mole is an important obstetric problem which can result in harmful and serious outcomes. In this study, an attempt was made to determine the proportion of hydatidiform mole in prenatal clinics of Iran University of Medical Sciences (IUMS) to find the precise frequency of this disease. METHODS: Between January 2012 and January 2013, all women who immediately after positive pregnancy test or after retarded menstruation came to prenatal clinics in health care centers of IUMS were included in the study. The women were followed until 8-10 weeks of pregnancy and at this time abdominal sonography was used for confirmation or exclusion of molar pregnancy. RESULTS: In this descriptive study between January 2012 and January 2013, 8614 pregnant women with mentioned criteria were included and 61 cases of hydatidiform mole were diagnosed (0.7% or 7 per 1000 pregnancy). Ten cases (16.4%) were patients with partial moles. There was no significant difference in blood types in molar and non-molar pregnancies, but molar group differed significantly from non-molar group in terms of history of molar pregnancy, abortion, OCP use and ovulation induction. DISCUSSION: Proportion of hydatidiform mole in this study was more than the reported European and American statistics.

Intraosseous benign lesions of the jaws: a radiographic study.

BACKGROUND: Benign maxillo-mandibular tumors and cysts, which are relatively common findings on radiographs, namely the ubiquitous panoramic view, have to be dealt with by dentists on a daily basis. OBJECTIVES: The aim of this study is to evaluate the panoramic radiographic findings pertaining to benign and tumoral lesions in the maxilla and mandible. PATIENTS AND METHODS: Applying a case series method, panoramic images of 61 patients with cysts, benign tumors and tumor-like lesions in the jaws who were referred to Hamedan dental school between 2009 and 2011 were evaluated by two radiologists. They were both blind to histopathological results as well as the objectives of our study. Lesions were assessed based on their location, periphery, internal structure and impaction on the surrounding structures. Then the obtained data were analyzed using descriptive tables. RESULTS: Cysts were mostly more common in men despite the equal propensity of both genders to benign tumors. In contrast, women showed a higher frequency of tumor-like lesions. The most common site of involvement was the posterior mandible, with peri-apical tooth lesions as the most prevalent dental association. Radiographically, what we most encountered was unilocular radiolucency pertaining to cysts and benign tumors; nevertheless, tumor-like lesions tended to present with a well-defined radiopacity. CONCLUSIONS: Despite its known shortcomings, like every other diagnostic tool, panoramic radiography can contribute to the early detection of maxillary/mandibular lesions that in turn enable the dentist to devise an appropriate treatment plan.

Effect of Letrozole on endometriosis-related pelvic pain.

BACKGROUND: To determine the role of Letrozole, an aromatase inhibitor, in the treatment of endometriotic pain. METHODS: In this prospective, randomized, controlled clinical trial in minimally invasive surgery research center, 51 women with pelvic endometriosis and endometriotic pain (dyspareunia, dysmenorrhea, pelvic pain) score of 5 or more (for at least one of these endometriotic pain), after laparoscopic diagnosis and conservative laparoscopic surgery were treated with either Letrozole plus OCP (n=25) or only OCP (n=26) for 4 months continuously. RESULTS: Using VAS test, the score of dyspareunia, dysmenorrhea and pelvic pain 4 months after the laparoscopic surgery declined significantly in both groups but the difference between results of the two groups was not significant. CONCLUSION: Both treatment modalities showed comparable effectiveness in the treatment of pains related to endometriosis and in comparison with OCP, Letrozole did not affect the outcome.