The localization and expression of gonadotropin inhibitory hormone in the hypothalamus of turkey hens during the prepubertal, pubertal and postpubertal phases.

Gonadotropin inhibitory hormone (GnIH), initially discovered in birds as a hypothalamic neuropeptide, inhibits the synthesis and release of gonadotropins by affecting GnRH neurons and gonadotropes. Therefore, it may be a key neuropeptide in reproduction in birds. The aim of the present study was to investigate the prepubertal, pubertal, and postpubertal localization of GnIH and changes in hypothalamic GnIH expression in British United Turkey hens. In prepubertal, pubertal, and postpubertal periods, the brains of turkey hens (n = 15) were removed after fixation. Sections (30 µm) were prepared from the entire hypothalamus and stained immunohistochemically against GnIH antibody. Gonadotropin inhibitory hormone-immunoreactive neurons were observed in the paraventricular nucleus. These neurons were significantly more abundant in the prepubertal turkeys than pubertal and postpubertal turkeys (P < 0.05). The results suggested that GnIH neurons have an important role in regulating the pubertal events in British United Turkey hens.

Fluctuations in Brillouin shifts and acoustic-phonon speeds in multiwavelength Brillouin Raman erbium-doped fiber laser generation.

Brillouin-shift (B-S) fluctuations in multiwavelength Brillouin Raman erbium-doped fiber laser generation are investigated to obtain a probability distribution of acoustic-phonon speeds in the crystal lattice of a dispersion-compensating fiber (DCF) in a linear cavity. Even though the available B-S line spacing can be at 0.076 and 0.08 nm when Raman pump (RP) power is zero or 76 mW, the other B-S possibilities are obvious, especially at RP power 257 mW. A crystal effective mass participating in the crystal vibration is obtained 8937, 8943, 8954, and 12,106 times the electron rest mass by fitting a general form of a Boltzmann density function and the resulting most probable speed of 5445 m/s at a fixed Brillouin pump power of 6.5 dBm and RP powers of 0, 76, 163, and 257 mW, respectively. Finally, an uncertainty in the crystal dimension is also estimated by Heisenberg's uncertainty principle.

Combined X-ray radiotherapy and laser photothermal therapy of melanoma cancer cells using dual-sensitization of platinum nanoparticles.

Metal nanostructures are promising agents sensitizing by laser light and X-ray in photothermal therapy (PTT) and radiotherapy (RT) of cancer that improve treatment strategies of cancer. Nanoscale platinum materials are favorable in nanomedicine applications. In this study, platinum nanoparticles (PtNPs) were synthesized and applied for cancer therapy upon 808-nm laser light and X-ray radiation, or their combination. Two power densities of laser (1.0 and 1.5 W cm-2) and three X-ray doses (2, 4 and 6 Gy) were selected for irradiation of B16/F10 cell line at 24 and 72 h-post treatment. The synthesized PtNPs had a spherical shape with a diameter of 12.2 ± 0.7 nm, and were cytocompatible up to 250 µg mL-1. A photothermal conversion activity in a concentration-dependent manner at 72 h-post treatment was observed. Also, PtNPs represented cytotoxicity upon X-ray radiation doses of 2, 4, and 6 Gy after 24 h, while, 72-h time passing led to deeper outcomes. Dual radiation of laser light and X-ray into PtNPs considerably improved the treatment via reactive oxygen species (ROS) production. PtNPs can act as a novel dual absorber of laser light and X-ray, a common sensitizer, for treatment of cancer. The results of this study can be considered after further clinical investigations for treatment of tumor models.

Enhanced melanoma cell-killing by combined phototherapy/radiotherapy using a mesoporous platinum nanostructure.

BACKGROUND: Metal nanomaterials have a significant potential as photosensitizer and radiosensitizer. The purpose of this study was to evaluate the cytotoxicity of a platinum mesoporous nanostructure (Pt MN) toward a melanoma cancer cell line upon combined laser radiation (808 nm, 1 and 1.5 W cm-2) and X-ray irradiation (6 MV, 2, 4, and 6 Gy). METHODS: Pt MN was synthesized by a simple procedure and characterized by field emission scanning and transmission electron microscopy. A mouse malignant melanoma cell line C540 (B16/F10) was treated with Pt MN, laser light and/or X-ray. RESULTS: Pt MN had a mesoporous structure with a sponge-resemble shape comprised of ensembles of very small adhered particles of <11 nm and about 5-nm pores. While Pt MN represented a low toxicity toward and considerable uptake into the cell line in a concentration range of 10-100 µg mL-1, laser light radiation alone was also not toxic, and X-ray irradiation alone induced a limited toxicity, Pt MN was toxic against the cells in a dose dependent manner upon laser light radiation, X-ray irradiation, or their combined exposure. The killing efficacy of Pt MN upon X-ray irradiation was more obvious at 72 h post-treatment. The combined exposure (laser radiation followed by X-ray irradiation) led to a deep cell killing and a very low melanoma cell viability (∼1%). Significant melanoma cancer cell killing of Pt MN was due to reactive oxygen species (ROS) production upon combined exposure of laser and X-ray, while cell killing upon laser light radiation was due to heat generation. CONCLUSION: Pt MN was introduced as a supreme laser/X-ray sensitizer for treatment of cancer with a high ability to produce ROS and a potent impact on decreasing cell viability.

The long-term oral administration of thyroxine: effects on blood hematological and biochemical features in broiler breeder hens.

Published data on the beneficial effect of short-term administration of thyroxine (T4) in broiler breeder hens to reduce the ascites incidence in their progeny chicks raises the question as to what extent might the long-term maternal administration of T4 affect the blood hematological and biochemical attributes in breeder hens. A total of 70 broiler breeder hens (47-wk-old) were randomly allotted to control or thyroxine treated (T4) groups. Pure T4 (0.3 mg/bird per day) was orally administered to T4 birds for 14 successive weeks, whereas the control group received the drinking water only. Blood samples were obtained from the brachial vein prior to the initiation of the trial as well as weeks 50, 53, 55, 57, 59, and 61 of age. Body weight was decreased but egg production was not affected by T4 treatment. Plasma concentration of T4, but not triiodothyronine (T3), was increased in T4-treated hens (P < 0.05). The total number of leukocytes and erythrocytes were also higher in T4 birds. A significant effect of time was observed for erythrocyte number and plasma cholesterol concentration (P < 0.05). The long-term administration of T4 did not affect the concentrations of serum calcium and plasma total protein, albumin, globulin, cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein, alanine amino transferase, and aspartate amino transferase (P > 0.05). However, serum concentrations of phosphorus, glucose, and alkaline phosphatase were higher in T4 hens as compared to their control counterparts. In spite of differences in circulatory concentrations of a number of traits between the experimental groups, the recorded values were within their reference ranges. Therefore, the administration of T4 for an extended period of time had no apparent adverse effect on the clinical profile in subjected hens, which may practically support the implementation of this preventative treatment as an approach to decrease the ascites incidence; however, a lower incidence rate in the progeny chicks produced from hens receiving T4 for long-term periods of time remains to be elucidated.

Sperm characteristics of Chukar partridge (Alectoris chukar) breeders as affected by the addition of calcitriol to the semen extender.

This study was carried out to determine the effect of supplementing the semen extender with calcitriol on in vitro sperm characteristics in Chukar partridges. A total of 60 male Chukar partridges were habituated for semen collection by abdominal massage. Pooled ejaculates from several males were extended (1 to 5 v/v ratio) in the Sexton's diluent containing 0, 24, 48, 96, or 192 µg calcitriol/mL. These concentrations represented 0-, 2-, 4-, 8-, and 16-fold levels of the mean seminal calcitriol concentration, respectively. A total of 12 subsamples from each treatment group were kept at 4 to 5°C or 19 to 24°C for 4, 24, or 48 h. The percentages of motile sperm, live sperm, abnormal sperm, incidence of hypoosmotic swelling (HOS), and thiobarbituric acid reactive species (TBARS) concentrations were determined. The data were analyzed by the xtmixed procedure of STATA software. The percentages of motile sperm, live sperm, abnormal sperm, and seminal TBARS were affected by calcitriol (P < 0.05). There was no effect of treatments on HOS (P > 0.05). There was an interaction effect between calcitriol, storage time, and storage temperature on sperm motility, sperm viability, and seminal TBARS. Supplementation of the diluent with 96 µg calcitriol/mL resulted in the highest sperm motility at 4°C. Also, the same treatment group recorded the highest sperm viability and lowest seminal TBARS at 19 to 24°C. Supplementing the diluent with calcitriol had beneficial effects on spermatozoa; however, the fertility rate of spermatozoa extended in calcitriol-supplemented diluent needs to be determined before the procedure can be recommended for use in artificial insemination programs.

A numerical-experimental study on thermal evaluation of orthodontic tooth movement during initial phase of treatment.

The most desired target of orthodontic treatment is tooth movement as a result of application of efficient force system. In this study, effect of tooth loading is studied on temperature profile around the tooth at early stages of treatment. The basis of temperature variation is increase of cell number and activities in periodontium as a result of compression and tension of this layer. Highest cellular activities occur in the beginning of loading procedure and aim to reduce mechanical stress in the periodontium which finally ends up with orthodontic tooth movement during couple of years. To find out the correlation between temperature variation and the applied force, in vivo experiments are conducted on ten rats and temperature is measured in specific time periods. It is observed that temperature is higher in direction of the net force about 0.3℃. Next, numerical finite element analysis is carried out on the rat tooth model. Mechanical stress results show that regions with compressive stress have rather high temperature in the experiments. Mechanical stress on periodontium-bone interface is multiplied by a coefficient to simulate cellular activities on this boundary as a heat source and thermal analysis is carried out to obtain temperature profile. The thermo-mechanical coefficient is identified for each rat by imposing the experimental temperatures on numerical outputs. For assessment of a treatment efficiency and deduction of the applied force, temperatures could be measured experimentally and compared with the corresponding numerical analysis temperature result obtained by employing the thermo-mechanical coefficient found earlier for each rat.

MRS Shimming: An Important Point Which Should not be Ignored.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) is a well-known device for analyzing the biological fluids metabolically. Obtaining accurate and reliable information via MRS needs a homogeneous magnetic field in order to provide well-defined peaks and uniform water suppression. There are lots of reasons which can disturb the magnetic field homogeneity which can be corrected by a process known as shimming. This study is intended to recall the importance of shimming and also the significant role of quality control (QC) in achieving an accurate quantification. MATERIAL AND METHOD: An acrylic cylindrical quality control phantom was designed as an analog of brain MRS test phantoms in order to control the accuracy of the obtained signal of a 1.5 T Siemens MRI system which belonged to one of Shiraz hospitals. The signal of NAA, Cho, Cr, the combination of these metabolites and also the distilled water, which was used in this study, was evaluated using separate phantoms. A QC test was performed using Siemens QC phantom and a standard test phantom. RESULTS: The spectrum of our home- made phantom had a significant difference with the expected spectrum. The results of checking the spectrum of metabolites separately also confirmed that there was a systemic problem that affects all the signals originated from all metabolites and even the pure distilled water. The MRS system could not pass QC tests, and peak broadening was common in all spectra. The complex spectrum of standard test phantom was not produced successfully by the MRS system. DISCUSSION: By a simple check of the water peak characteristics, lots of information can be obtained, one of which is the status of shimming that has a considerable effect on the accuracy of the spectrum. Thus, performing an automatic or manual shimming is not a criterion of the spectrum accuracy, and performing a periodic quality control using a test phantom by a specialist is necessary. CONCLUSION: Briefly, the quality control of MRS and all the other clinical device must be taken seriously. Sometimes QC can be the boundary of a right or a wrong decision for the patient.

Initial stage of atomic layer deposition of 2D-MoS2 on a SiO2 surface: a DFT study.

In this study, we investigate the reactions involving Atomic Layer Deposition (ALD) of 2D-MoS2 from the heteroleptic precursor Mo(NMe2)2(NtBu)2 and H2S as the co-reagent on a SiO2(0001) surface by means of density functional theory (DFT). All dominant reaction pathways from the early stage of adsorption of each ALD reagent to the formation of bulk-like Mo and S at the surface are identified. In the metal pulse, proton transfer from terminal OH groups on the SiO2 to the physisorbed metal precursor increases the Lewis acidity of Mo and Lewis basicity of O, which gives rise to the chemical adsorption of the metal precursor. Proton transfer from the surface to the dimethylamido ligands leads to the formation and desorption of dimethylamine. In contrast, the formation and desorption of tert-butylamine is not energetically favorable. The tert-butylimido ligand can only be partially protonated in the metal pulse. In the sulphur pulse, co-adsorption and dissociation of H2S molecules give rise to the formation and desorption of tert-butylamine. Through the calculated activation energies, the cooperation between H2S molecules ('cooperative' mechanism) is shown to have a profound influence on the formation and desorption of tert-butylamine, which are crucial steps in the initial ALD deposition of 2D-MoS2 on SiO2. The cyclic ALD reactions give rise to the formation of a buffer layer which might have important consequences for the electrical and optical properties on the 2D layer formed in the subsequent homodeposition.

Intrapericardial neurofibromatosis with coronary involvement: A case report.

Neurocutaneous syndromes are heterogenous diseases that are diagnosed in the presence of skin and central nervous system disorders. Neurofibromatosis (NF) is one of these disorders, with autosomal dominant inheritance, that causes tumors that grow on nerves as well as other abnormalities such as skin changes and bone deformities. The most common form of NF is type I. A 6-year-old Iranian boy with neurofibromatosis was referred to the pediatric cardiology clinic due to a soft holosystolic murmur discovered on routine examination. The echocardiographic findings included a large intrapericardial, encapsulated echodense homogenous mass located in the posterior part of the pericardium, attached to the posterior aspect of the left atrium and left ventricle. The mass measured about 6.3×6.5×5.5cm and exerted a compressive effect on the left-side chambers, with mild mitral regurgitation and mild pericardial effusion. Magnetic resonance imaging confirmed these findings showing encasement of the left circumflex artery, while the open biopsy through a midsternotomy procedure showed a mildly cellular mesenchymal tumor composed of spindle cells suggestive of neurofibroma. Further resection of the mass was not performed because of the risk of coronary injury and the stable situation of the patient. Visceral involvement of neurofibroma is uncommon and rarely involves the heart. As shown in this case, besides the chance for involving the pericardium, despite its benign nature, this tumor sometimes shows unusual involvement of structures such as the coronary arteries.

Effect of age-dependent bone electron density on the calculated dose distribution from kilovoltage and megavoltage photon and electron radiotherapy in paediatric MRI-only treatment planning.

OBJECTIVE: MRI-only treatment planning (TP) can be advantageous in paediatric radiotherapy. However, electron density extraction is necessary for dose calculation. Normally, after bone segmentation, a bulk density is assigned. However, the variation of bone bulk density in patients makes the creation of pseudo CTs challenging. This study aims to assess the effects of bone density variations in children on radiation attenuation and dose calculation for MRI-only TP. METHODS: Bone contents of <15-year-old children were calculated, and substituted in the Oak Ridge National Laboratory paediatric phantoms. The percentage depth dose and beam profile of 150 kVp and 6 MV photon and 6 MeV electron beams were then calculated using Xcom, MCNPX (Monte Carlo N-particle version X) and ORLN phantoms. RESULTS: Using 150 kVp X-rays, the difference in attenuation coefficient was almost 5% between an 11-year-old child and a newborn, and ~8% between an adult and a newborn. With megavoltage radiation, the differences were smaller but still important. For an 18 MV photon beam, the difference of radiation attenuation between an 11-year-old child and a newborn was 4% and ~7.4% between an adult and a newborn. For 6 MeV electrons, dose differences were observed up to the 2 cm depth. The percentage depth dose difference between 1 and 10-year-olds was 18.5%, and between 10 and 15-year-olds was 24%. CONCLUSION: The results suggest that for MRI-only TP of photon- or electron-beam radiotherapy, the bone densities of each age group should be defined separately for accurate dose calculation. Advances in knowledge: This study highlights the need for more age-specific determination of bone electron density for accurate dose calculations in paediatric MRI-only radiotherapy TP.

A novel approach for early evaluation of orthodontic process by a numerical thermomechanical analysis.

The main objective of this paper is to propose a novel method that provides an opportunity to evaluate an orthodontic process at early phase of the treatment. This was accomplished by finding out a correlation between the applied orthodontic force and thermal variations in the tooth structure. To this end, geometry of the human tooth surrounded by the connective soft tissue called the periodontal ligament and the bone was constructed by employing dental CT scan images of a specific case. The periodontal ligament was modeled by finite strain viscoelastic model through a nonlinear stress-strain relation (hyperelasticity) and nonlinear stress-time relation (viscoelasticity). The tooth structure was loaded by a lateral force with 15 different quantities applied to 20 different locations, along the midedge of the tooth crown. The resultant compressive stress in the periodontal ligament was considered as the cause of elevated cell activity that was modeled by a transient heat flux in the thermal analysis. The heat flux value was estimated by conducting an experiment on a pair of rats. The numerical results showed that by applying an orthodontic force to the tooth structure, a significant temperature rise was observed. By measuring the temperature rise, the orthodontic process can be evaluated.

Synergistic Effects of NDRG2 Overexpression and Radiotherapy on Cell Death of Human Prostate LNCaP Cells.

BACKGROUND: Radiation therapy is among the most conventional cancer therapeutic modalities with effective local tumor control. However, due to the development of radio-resistance, tumor recurrence and metastasis often occur following radiation therapy. In recent years, combination of radiotherapy and gene therapy has been suggested to overcome this problem. The aim of the current study was to explore the potential synergistic effects of N-Myc Downstream-Regulated Gene 2 (NDRG2) overexpression, a newly identified candidate tumor suppressor gene, with radiotherapy against proliferation of prostate LNCaP cell line. MATERIALS AND METHODS: In this study, LNCaP cells were exposed to X-ray radiation in the presence or absence of NDRG2 overexpression using plasmid PSES- pAdenoVator-PSA-NDRG2-IRES-GFP. The effects of NDRG2 overexpression, X-ray radiation or combination of both on the cell proliferation and apoptosis of LNCaP cells were then analyzed using MTT assay and flow cytometery, respectively. RESULTS: Results of MTT assay showed that NDRG2 overexpression and X-ray radiation had a synergistic effect against proliferation of LNCaP cells. Moreover, NDRG2 overexpression increased apoptotic effect of X-ray radiation in LNCaP cells synergistically. CONCLUSION: Our findings suggested that NDRG2 overexpression in combination with radiotherapy may be an effective therapeutic option against prostate cancer.

Adaptive Response Induced by Pre-Exposure to 915 MHz Radiofrequency: A Possible Role for Antioxidant Enzyme Activity.

BACKGROUND: Over the past few years, the rapid use of high frequency electromagnetic fields like mobile phones has raised global concerns about the negative health effects of its use. Adaptive response is the ability of a cell or tissue to better resist stress damage by prior exposure to a lesser amount of stress. This study aimed to assess whether radiofrequency radiation can induce adaptive response by changing the antioxidant balance. MATERIALS AND METHODS: In order to assess RF-induced adaptive response in tissues, we evaluated the level of GSH and the activity of GR in liver. 50 rats were divided into 5 groups. Three groups were pre-exposed to 915 MHz RF radiation, 4 hours per day for one week at different powers, as low, medium and high. 24 hours after the last exposure to radiation, they were exposed to 4 Gy sublethal dose of gamma radiation and then sacrificed after 5 hours. Their livers were removed, washed and were kept at -80o C until used. RESULTS: Our finding showed that pre-exposure to 915 MHz radiofrequency radiation with specific power could induce adaptive response in liver by inducing changes in the activity and level of antioxidant enzymes. CONCLUSION: It can be concluded that pre-exposure to microwave radiation could increase the level of GSH and the activity of GR enzyme, although these increases were seen just in low power group, and the GR activity was indicated in medium power group. This increase protects tissue from oxidative damage induced by sublethal dose of gamma radiation.

Revision of orthovoltage chest wall treatment using Monte Carlo simulations.

PURPOSE: Given the high local control rates observed in breast cancer patients undergoing chest wall irradiation by kilovoltage x-rays, we aimed to revisit this treatment modality by accurate calculation of dose distributions using Monte Carlo simulation. METHODS AND MATERIAL: The machine components were simulated using the MCNPX code. This model was used to assess the dose distribution of chest wall kilovoltage treatment in different chest wall thicknesses and larger contour or fat patients in standard and mid sternum treatment plans. Assessments were performed at 50 and 100 cm focus surface distance (FSD) and different irradiation angles. In order to evaluate different plans, indices like homogeneity index, conformity index, the average dose of heart, lung, left anterior descending artery (LAD) and percentage target coverage (PTC) were used. Finally, the results were compared with the indices provided by electron therapy which is a more routine treatment of chest wall. RESULT: These indices in a medium chest wall thickness in standard treatment plan at 50 cm FSD and 15 degrees tube angle was as follows: homogeneity index 2.57, conformity index 7.31, average target dose 27.43 Gy, average dose of heart, lung and LAD, 1.03, 2.08 and 1.60 Gy respectively and PTC 11.19%. Assessments revealed that dose homogeneity in planning target volume (PTV) and conformity between the high dose region and PTV was poor. To improve the treatment indices, the reference point was transferred from the chest wall skin surface to the center of PTV. The indices changed as follows: conformity index 7.31, average target dose 60.19 Gy, the average dose of heart, lung and LAD, 3.57, 6.38 and 5.05 Gy respectively and PTC 55.24%. Coverage index of electron therapy was 89% while it was 22.74% in the old orthovoltage method and also the average dose of the target was about 50 Gy but in the given method it was almost 30 Gy. CONCLUSION: The results of the treatment study show that the optimized standard and mid sternum treatment for different chest wall thicknesses is with 50 cm FSD and zero (vertical) tube angle, while in large contour patients, it is with 100 cm FSD and zero tube angle. Finally, chest wall kilovoltage and electron therapies were compared, which revealed that electron therapy produces a better dose distribution than kilovoltage therapy.

The genetic background influences the cellular and humoral immune responses to vaccines.

The assessment of Toll-like receptor (TLR) agonists as candidate adjuvants for induction of effective T helper type 1 (Th1) immunity continues to rely on the use of mice. However, the genetic variation among inbred mice may influence the efficacy of adjuvants and bias a study's conclusions. Here, we evaluated the differences in cellular and humoral responses of genetically non-identical mouse strains immunized with ovalbumin (OVA) plus alum, TLR-3, TLR-4, TLR-7/8 or TLR-9 agonists. We found that all the tested TLR agonists recruited dendritic cells (DCs) and natural killer (NK) cells significantly into the lymph nodes, promoted DC-NK cross-talk and enhanced the cellular responses in B6 strain. In contrast, TLR-3 and TLR-7/8 were the only two agonists that showed the cellular adjuvanticity in the BALB/c strain. Compared with other TLR agonists, TLR-3 and TLR-7/8 were demonstrated to be the most effective adjuvants to generate interferon (IFN)-γ-producing effector NK, CD4, and CD8 T cells in B6 and BALB/c strains, respectively. We also found that compared with alum, all adjuvants induced the recruitment of B cells and production of OVA-specific immunoglobulin (Ig)G2a more effectively in both strains. In addition, the B6 strain recruited more B cells, but surprisingly produced significantly lower amounts of OVA-specific IgG2a in response to all adjuvants. However, consistent with the frequency of IFN-γ-producing effector cells observed in individual strains following immunizations, we detected more OVA-specific IgG2a in serum of B6 and BALB/c strains in response to TLR-3 and TLR-7/8, respectively. Our data suggest that genetic background should be taken into consideration when evaluating the activities of TLR agonists for the development of prophylactic and therapeutic vaccines.

Fast and accurate Monte Carlo modeling of a kilovoltage X-ray therapy unit using a photon-source approximation for treatment planning in complex media.

To accurately recompute dose distributions in chest-wall radiotherapy with 120 kVp kilovoltage X-rays, an MCNP4C Monte Carlo model is presented using a fast method that obviates the need to fully model the tube components. To validate the model, half-value layer (HVL), percentage depth doses (PDDs) and beam profiles were measured. Dose measurements were performed for a more complex situation using thermoluminescence dosimeters (TLDs) placed within a Rando phantom. The measured and computed first and second HVLs were 3.8, 10.3 mm Al and 3.8, 10.6 mm Al, respectively. The differences between measured and calculated PDDs and beam profiles in water were within 2 mm/2% for all data points. In the Rando phantom, differences for majority of data points were within 2%. The proposed model offered an approximately 9500-fold reduced run time compared to the conventional full simulation. The acceptable agreement, based on international criteria, between the simulations and the measurements validates the accuracy of the model for its use in treatment planning and radiobiological modeling studies of superficial therapies including chest-wall irradiation using kilovoltage beam.

A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins.

INTRODUCTION: Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. MATERIALS AND METHODS: Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. RESULTS: Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). CONCLUSION: Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

Nicotine exposure alters the mRNA expression of Notch ligands in dendritic cells and their response to Th1-/Th2-promoting stimuli.

Dendritic cells (DCs) utilize polarizing signals to instruct the differentiation of T helper (Th) cells into Th1 and Th2 effector cells: antigen-specific 'signal 1', costimulatory 'signal 2' and polarizing cytokines 'signal 3'. Accumulating evidence suggests the involvement of an additional signal, the Notch signalling pathway. We reported that in response to Th1-promoting stimuli, both mouse and human DCs generated in the presence of the immune modulator nicotine (nicDCs) fail to support the development of effector memory Th1 cells. However, in response to Th2-promoting stimuli, these nicDCs preferentially support the differentiation of antigen-specific IL-4-producing Th2 effector cells. Here, we show that when compared to their control counterparts, immature mouse and human nicDCs display higher levels of the Notch ligands D1, D4 and J2 mRNA expression. In response to Th1- and Th2-promoting stimuli, mouse nicDCs display higher levels of the Notch ligands D1, D4 and J2, while human nicDCs show higher levels of D1, D4 and J1 mRNA expression. Furthermore, both stimulated mouse and human nicDCs express higher CD86 to CD80 ratio and produce lower amount of IL-12. Collectively, our data suggest that these changes in addition to an increase in Jagged expression correlate with the ability of nicDCs to modulate the Th1/Th2 balance in favour of Th2 generation.