Decreased salivary beta-defensin 2 in children with asthma after treatment with corticosteroid inhaler.

PURPOSE: Asthma is the most common chronic disorder in childhood. Inhaled corticosteroid therapy is currently the most effective treatment for Asthma. The oral cavity complications related to this treatment may be in terms of the changes in the innate immune system of mouth. Salivary defensin has many immunomodulatory properties. The expression of beta-defensin 2 was measured before and after inhaled corticosteroid treatment in children with asthma to determine the potential impact of corticosteroids on defensin expression. METHODS: The present study was a cohort study conducted on the patients referred to Children's Medical Center for whom a diagnosis of Asthma was confirmed, and inhaled corticosteroid therapy was prescribed. Saliva was sampled once at the stage of diagnosis and before receiving any treatment. Another salivary sample was collected 4 weeks after receiving corticosteroids. ELISA was performed to assess beta-defensin 2. RESULTS: The beta-defensin 2 salivary level after inhaled corticosteroid therapy was significantly lower than before treatment. There is no significant difference in the salivary flow rate before and after treatment. CONCLUSIONS: Considering the limitations of the present study, the following conclusions can be made salivary beta-defensin 2 is decreased in children with asthma after treatment with a corticosteroid inhaler. Regular dental and oral soft tissue examinations in Asthmatic children under corticosteroid therapy could be suggested.

Combination therapy with TiO2 nanoparticles and cisplatin enhances chemotherapy response in murine melanoma models

Background Despite recent progressions in the treatment of melanoma, the response to conventional therapies and the long-term survival in melanoma patients still remain poor. Recently, the use of nanoparticles (NPs) has been highlighted for promoting the chemotherapeutic effects of cytotoxic drugs in melanoma. The aim of this study is to mechanistically evaluate the potential of titanium dioxide (TiO2) nanoparticles (NPs) for enhancing chemotherapy effects in in vitro and in vivo models of murine melanoma. Methods The F10 melanoma cells were exposed to different concentrations of TiO2 NPs and/or cisplatin, then cell growth, cell viability, and cell death were evaluated. In parallel, C57BL/6 syngeneic melanoma mice were treated by TiO2 NPs and/or cisplatin, and then drug responses, tumor size and mice’s organs were studied pathologically. Autophagy was examined by evaluating the formation of autophagosomes and gene expression levels of autophagy markers (ATG5 and ATG6) by fluorescent microscopy and qPCR, respectively. Results Nontoxic concentrations of TiO2 NPs (50 µg/ml) promote anti-proliferative and cytotoxic effects of cisplatin in F10 melanoma cells, which is mediated through the induction of autophagy and necrotic cell death. Whereas TiO2 NPs have no cytotoxic or metastatic effects in melanoma mice, its combination with cisplatin enhances drug responses (up to 50%), leading to higher inhibition of tumor growth compared with each monotherapy. Conclusion The combination of TiO2 NP with cisplatin enhances chemotherapy response in both in vitro and in vivo melanoma models. In addition, autophagy plays an essential role during sensitizing melanoma cells to chemotherapy (AU)

Decreased recurrence of symptoms in oral lichen planus with intralesional injection of hyaluronic acid and triamcinolone.

Oral lichen planus (OLP) is a chronic non-infectious, inflammatory, immunological disease. In contrast to skin lesions, which are often self-limiting, oral lesions rarely heal on their own and can be resistant to local and systemic treatments. In this clinical trial, hyaluronic acid (HA) was mixed with triamcinolone for intralesional injection to reduce side effects in the treatment of OLP. This randomized clinical trial with a split-mouth design was performed on 28 patients with OLP. The mouth was divided randomly into two sides: a test side, which received HA combined with triamcinolone, and a control side, which received triamcinolone alone. The rate of symptom recurrence was 74.1% on the control side and 11.1% on the test side (significant difference, P<0.01). Pain scores did not differ between the two groups when assessed after 2 weeks. The group treated with a combination of HA and triamcinolone experienced a significantly better resolution of lesions and symptoms. Considering the role of HA in tissue healing and in regulating inflammatory responses, as well as its antioxidant and hydration properties, it appears that HA could be effective in improving of OLP and decreasing the rate of symptom recurrence.

Combination therapy with TiO2 nanoparticles and cisplatin enhances chemotherapy response in murine melanoma models.

BACKGROUND: Despite recent progressions in the treatment of melanoma, the response to conventional therapies and the long-term survival in melanoma patients still remain poor. Recently, the use of nanoparticles (NPs) has been highlighted for promoting the chemotherapeutic effects of cytotoxic drugs in melanoma. The aim of this study is to mechanistically evaluate the potential of titanium dioxide (TiO2) nanoparticles (NPs) for enhancing chemotherapy effects in in vitro and in vivo models of murine melanoma. METHODS: The F10 melanoma cells were exposed to different concentrations of TiO2 NPs and/or cisplatin, then cell growth, cell viability, and cell death were evaluated. In parallel, C57BL/6 syngeneic melanoma mice were treated by TiO2 NPs and/or cisplatin, and then drug responses, tumor size and mice's organs were studied pathologically. Autophagy was examined by evaluating the formation of autophagosomes and gene expression levels of autophagy markers (ATG5 and ATG6) by fluorescent microscopy and qPCR, respectively. RESULTS: Nontoxic concentrations of TiO2 NPs (50 µg/ml) promote anti-proliferative and cytotoxic effects of cisplatin in F10 melanoma cells, which is mediated through the induction of autophagy and necrotic cell death. Whereas TiO2 NPs have no cytotoxic or metastatic effects in melanoma mice, its combination with cisplatin enhances drug responses (up to 50%), leading to higher inhibition of tumor growth compared with each monotherapy. CONCLUSION: The combination of TiO2 NP with cisplatin enhances chemotherapy response in both in vitro and in vivo melanoma models. In addition, autophagy plays an essential role during sensitizing melanoma cells to chemotherapy.

The effects of exposure duration to optimal concentration of 2-phenoxyethanol on primary and secondary stress responses in kutum (Rutilus frisii kutum).

The goal of this study was to assess the anaesthetic induction and recovery time in kutum (Rutilus frisii kutum) after exposure to various concentrations (0.1, 0.3, 0.5, 0.7 and 0.9 ml/l) of 2-PE as an anaesthetic, as well as the effects of optimal concentration (0.7 ml/l) of 2-PE in relation to different exposure time (3, 10, 15 min) on some haematological and serum biochemical indices in this species. Moreover, the effects of 0.7 ml/l on blood parameters were assessed 24 h after the longest exposure. Significant increase was determined in Hb, MCH and MCHC after 10-min exposure to 2-PE (p < 0.05). Moreover, Hct, Hb and RBC levels increased significantly after 15 min-exposure to 2-PE (p < 0.05). There were no prominent changes in WBC and MCV. The plasma concentrations of glucose, cholesterol and cortisol increased significantly after 10- and 15-min exposure to 2-PE (p < 0.05) compared with the control group and all other exposure times. The activity of ALT and AST were significantly increased after 10- and 15-min exposure respectively (p < 0.05). In this study, it appears that anaesthetizing kutum with 2-PE at 0.7 ml/l for 3 min had no effect on the stress markers.

2D Computational Fluid Dynamic Modeling of Human Ventricle System Based on Fluid-Solid Interaction and Pulsatile Flow.

Many diseases are related to cerebrospinal fluid (CSF) hydrodynamics. Therefore, understanding the hydrodynamics of CSF flow and intracranial pressure is helpful for obtaining deeper knowledge of pathological processes and providing better treatments. Furthermore, engineering a reliable computational method is promising approach for fabricating in vitro models which is essential for inventing generic medicines. A Fluid-Solid Interaction (FSI)model was constructed to simulate CSF flow. An important problem in modeling the CSF flow is the diastolic back flow. In this article, using both rigid and flexible conditions for ventricular system allowed us to evaluate the effect of surrounding brain tissue. Our model assumed an elastic wall for the ventricles and a pulsatile CSF input as its boundary conditions. A comparison of the results and the experimental data was done. The flexible model gave better results because it could reproduce the diastolic back flow mentioned in clinical research studies. The previous rigid models have ignored the brain parenchyma interaction with CSF and so had not reported the back flow during the diastolic time. In this computational fluid dynamic (CFD) analysis, the CSF pressure and flow velocity in different areas were concordant with the experimental data.

A distinct autosomal recessive ocular anomaly in Chaharborj, Islamic Republic of Iran.

In Chaharborj, a village in north-eastern ofthe Islamic Republic of Iran, a high prevalence of congenital blindness (1.1%) has been reported. The clinical findings have not been fully described. We therefore assessed the clinical aspects of this condition in a case series of 20 congenitally blind patients and 24 of their parents. All patients had been blind since birth. There was anterior segment dysgenesis and retinal non-attachment in all patients. There were no systemic anomalies. Histopathologically, there was iridocorneal adhesion, normal angle structure and retinal dysplasia. No significant difference was found in the frequency of different HLA class I alleles compared with the general population. The anomaly causing congenital blindness in these patients has components of both anterior and posterior segment dysgenesis. It appears to be a distinct entity with an autosomal recessive pattern of inheritance.

A distinct autosomal recessive ocular anomaly in Chaharborj, Islamic Republic of Iran

In Chaharborj, a village in north-eastern of the Islamic Republic of Iran, a high prevalence of congenital blindness [1.1%] has been reported. The clinical findings have not been fully described. We therefore assessed the clinical aspects of this condition in a case series of 20 congenially blind patients and 24 of their parents. All patients had been blind since birth. There was anterior segment dysgenesis and retinal non-attachment in all patients. There were no systemic anomalies. Histopathologically, there was iridocorneal adhesion, normal angle structure and retinal dysplasia. No significant difference was found in the frequency of different HLA class I alleles compared with the general population. The anomaly causing congenital blindness in these patients has components of both anterior and posterior segment dysgenesis. It appears to be a distinct entity with an autosomal recessive pattern of inheritance

Carbenoxolone induces apoptosis and inhibits survivin and survivin-ΔEx3 genes expression in human leukemia K562 cells.

BACKGROUND AND THE PURPOSE OF THE STUDY: Leukemia is a malignant disorder of the blood progenitor/stem cells which is characterized by abnormal proliferation of white blood cells. Although anti-cancer drugs induce apoptosis in cancerous cells, drug resistance is the significant problem mainly due to over-expression of inhibitors of apoptosis proteins (IAPs) such as survivin. In this content, it has been reported that an anti-inflammatory drug, Carbenoxolone (CBX), could induce apoptosis and growth inhibition in several types of cancerous cells. In the present study, effects of CBX on apoptosis and level of the expression of survivin gene and its ΔEx3 splicing variant have were evaluated in K562 cells. METHODS: K562 cells were cultured and treated with different concentrations of CBX (50-300 µM) at different time intervals (12-48 hrs). Trypan blue exclusion test was used to evaluate cell viability. Fluorescent microscopy (Acridine Orange/Ethidium Bromide double staining) and DNA fragmentation assay were used to study apoptosis. The expression level of survivin and its ΔEx3 splice variant were studied by RT-PCR. RESULTS AND MAJOR CONCLUSION: It was found that both growth inhibition and apoptosis occurred in K562 cells. In addition, down-regulation of survivin and survin-ΔEx3 were observed, after 2-4 hrs treatment with 150 µM of CBX. However, the expression level of survivin and its ΔEx3 splice variant increased in subsequent time (6-12 hrs) nearly to the level of control cells. From the results of this study, it may be concluded that CBX can be considered as a candidate for further studies in CML treatment, especially in the case of drug-resistant leukemia cells.

Core shell methyl methacrylate chitosan nanoparticles: In vitro mucoadhesion and complement activation.

BACKGROUND AND THE PURPOSE OF THE STUDY: Studies show that chitosan nanoparticles increase mucoadhesivity and penetration of large molecules across mucosal surface. The aim of the present study was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system. METHODS: Methyl methacrylate nanoparticles were coated with thiolated chitosan using a radical polymerization method. Thiolation was carried out using glutathione (GSH) to improve mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion studies were carried out by calculating the amount of mucin adsorbed on nanoparticles in a specific period of time. Complement consumption was assessed in human serum (HS) by measurement of the hemolytic capacity of the complement system after contact with nanoparticles. RESULTS: The FT-IR and (1)HNMR spectra both confirmed the synthesis and showed the conjugation of thiolated chitosan to methyl methacrylate (MMA) homopolymer. Nanoparticles were spherical having a mean diameter within the range of about 334-650 nm and their positive zeta potential values indicated the presence of the cationic polysaccharide at the nanoparticle surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and complement activation. However there was not dose dependent correlation between these phenomenons and the absence of thiolated chitosan led to particles with larger size, and without ability to activate complement process. MAJOR CONCLUSION: It can be concluded that nanoparticles could be used for the mucosal delivery of peptides and proteins. Results show that the thiolated chitosan had higher mucoadhesion and complement activation than unmodified chitosan.

The Effect of Intra-CA1 Agmatine Microinjection on Water Maze Learning and Memory in Rat.

BACKGROUND: Reports on agmatine are controversial showing that it may improve memory, it can deteriorate memory and some did not notice any interference with learning and memory. In the present study, the effect of directly intra-CA1 agmatine microinjection on water maze learning and memory has been assessed. METHODS: The cannuls were implanted in hippocampal CA1 regions of rats in a sterotaxic frame after general anesthesia. After one week recovery period, the animals were assessed in the reference memory version of water maze. Agmatine (1, 10, 100 or 200 µg/0.5 µl) or saline were infused 20 minutes before or immediately after training. RESULTS: Agmatine-treated rats did not show any significant difference neither in water maze acquisition nor in consolidation task in comparison with control and sham groups. CONCLUSION: Agmatine does not affect water maze learning and memory.

Involvement of nitric oxide in insulin induced memory improvement.

Although brain was considered as an insulin-insensitive organ, recently it has appeared that insulin has some interesting effects on some brain regions like hippocampus. It has been known that intra-hippocampally administered insulin can improve learning and memory. Knowing that insulin can stimulate nitric oxide (NO) synthesis via eNOS activation and also that NO synthase (NOS) inhibitors can affect learning and memory, the aim of this study was to assess if NO is involved in insulin induced memory improvement. Wistar male rats were intra-CA1 cannulated and the effect of post-training and pre-probe trial intra-hippocampal administration of N-nitro-L-arginine methyl ester (L-NAME) (5, 10, 30 microg), insulin+L-NAME+/-L-arginine were assessed in a single-day testing version of Morris water maze (MWM) task. Our results show that, l-NAME can prevent insulin induced memory improvement. This drug had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous nitric oxide has a role in spatial learning and memory improvement caused by insulin.

An evaluation of a combined spline based and rate of energy dissipation based segmentation of medical blood flow images.

Domain characteristics provide some constraints for accurate segmentation of special domain (e.g. flow) images. These constraints usually obtain a type of region based segmentation and in combination with the intensity based segmentation methods obtain overcoming results. When a boundary based segmentation method is considering to be aligned with these region based methods, some special efforts are necessary to make them compatible. Here we address a method to combine two boundary and regional based segmentation methods. In this regard boundary based segmentation is changed to be compatible with a regional based energy dissipation constraint in a sample flow domain. A quadratic spline function is used for boundary based segmentation of flow domain. The regional equivalent factor of this method is provided using the Gauss theorem. The numerical implementation of this method is provided with construction of boundary elements on the spline boundary segments. The rate of energy dissipation at blood elements is applied as the regional segmentation factor. It calculated from the velocity data of the flow Image. An overcoming segmentation factor is provided by mixing both methods. For implementation of this method a simulated Phase- Contrast Magnetic Resonance Image (PC-MRI) of Couette flow system is considered.

Flow simulation of a diaphragm-type ventricular assist device with structural interactions.

A numerical simulation of the fluid and structure interactions was performed for a diaphragm-type Ventricular Assist Device (VAD). The simulation was included two incompressible fluids and three elastic solid regions. The detailed information of both fluid and solid dynamic are crucial to evaluate the performance of the device. Localization of potential points prone to hemolysis and thrombus formation and disturbed flow with creation of recirculation zones are vary important. Here, the HeartSaver VAD was modeled as a two dimensional chambers with an inlet and an outlet elastic valves, an elastic sac-shape membrane, driving fluid and blood. A pulsatile velocity condition was applied at the inlet of the driving fluid chamber. As the results, the flow characteristics affecting the blood cells including velocity, pressure, wall shear stress and the elastic valves operation were presented in details.

Intra CA1 insulin microinjection improves memory consolidation and retrieval.

Although the brain was considered as an insulin-insensitive organ, recent studies have shown that insulin receptors exist in the brain and insulin modulates some of the brain tasks. Insulin and its receptor are found in specific areas of CNS with a variety of region-specific functions different from its direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. The improving effect of insulin on spatial memory acquisition has been shown. In the present study, the effect of insulin microinjection into the CA1 region of rat hippocampus on spatial memory consolidation and retrieval has been investigated. Insulin in 12 MU (but not in 0.5 and 6 MU) improved both memory retrieval and consolidation.

Insulin protects against stress-induced impairments in water maze performance.

The presence of insulin receptor in the hippocampus suggests that this organ is a target for insulin. However, unlike the classic peripheral insulin target tissues such as adipocyte, muscle and liver, where the primary function of insulin is to regulate glucose homeostasis, insulin in the central nervous system (CNS) exhibits more diverse actions, most of which have not been clearly understood. A direct role of hippocampal insulin receptor signaling in improving cognitive functions, including learning and memory, and the association of insulin receptor deterioration with brain degenerative dementia (e.g., Alzheimer's disease) have attracted increasing interest. Additionally it has been shown that insulin can be a neuroprotective agent against memory loss induced by ischemia, lesions and some pharmacological agents. In the present study we evaluate the hypothesis that the bilateral intra CA1 insulin injection can protects against stress-induced memory deficit. Chronic restraint stress (2h per day x 7 days) significantly impaired spatial performance in Morris water maze and elevated serum corticosterone level. Intrahippocampal insulin microinjection was done 15-20 min before every stress episode. Insulin in low dose (0.5 MU) had no significant effect on memory deficit induced by stress. But in higher doses (6 and 12 MU) insulin protects animals against the deleterious effect of stress. Insulin alone daily injection had no effect on water maze performance. These results suggest that spatial learning and memory is compromised during chronic stress and insulin may protect against this effect.

The effect of intrahippocampal insulin microinjection on spatial learning and memory.

Insulin is best known for its action on peripheral target tissues such as the adipocyte, muscle and liver to regulate glucose homeostasis. Insulin and its receptor are found in specific area of CNS with a variety of region-specific functions different from its direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. Previous studies about the effect of insulin on memory are controversial. In the present study, the effect of insulin microinjection into CA1 region of rat hippocampus on water maze performance has been investigated. Insulin had a discrepant effect dose dependently. The spatial learning and memory were impaired with lower dose of insulin, had not changed with intermediate doses, while they improved with higher doses. These results suggest that insulin may have a dose-dependent effect on spatial learning and memory.

In vivo evaluation of the effects of continuous exercise on skeletal muscle triglycerides in trained humans.

Magnetic resonance spectroscopy (1H MRS) and imaging (MRI) were used to investigate the effects of a bout of moderate prolonged exercise on intra (IMCL)- and extramyocellular lipid (EMCL) utilization in the soleus, tibialis anterior, and gastrocnemius muscles of five trained human subjects. MRI and 1H MRS measurements were obtained before and after a 90 min run on a calibrated treadmill at a velocity corresponding to 64 +/- 1.5% of each subjects' maximal rate of oxygen consumption. There were significant decreases in IMCL following exercise in the tibialis (pre: 22.37 +/- 4.33 vs. post: 15.16 +/- 3.25 mmol/kg dry wt; P < 0.01) and soleus (pre: 36.93 +/- 1.45 vs. post: 29.85 +/- 2.44 mmol/kg dry wt; P < 0.01) muscles. There was also a decrease in the gastrocnemius muscle, although this did not reach the level of significance (pre: 33.78 +/- 5.35 vs. post: 28.48 +/- 5.44 mmol/kg dry weight; P < 0.10). No significant changes were observed in EMCL or subcutaneous fat. In conclusion, this study showed that IMCL were significantly utilized in the tibialis and soleus muscles of aerobically endurance-trained humans. The absence of significant utilization of IMCL in the gastrocnemius may reflect differences in fiber type and/or intensity of contraction for each muscle group.