The inhibitory effect of Acyclovir loaded nano-niosomes against herpes simplex virus type-1 in cell culture.

BACKGROUND: Wide distribution and low half-life of acyclovir has led to a high dose consumption of the drug. Recent studies have shown that encapsulation of acyclovir in nano-carriers can increase effectiveness and decrease its side effects. We investigated the inhibitory effect of acyclovir loaded nano-niosomes against herpes simplex virus type-1 (HSV-1) in cell culture. METHODS: In-vitro cytotoxicity study of empty niosomes (E-N), acyclovir loaded niosomes (ACV-N) and ACV as a free drug against HeLa cell line was performed by MTT assay and the viral titers was tested by TCID50 assay. RESULTS: The results indicated that a significant higher antiviral activity for acyclovir loaded nano-niosomes of about 3 times in comparison with free drug. CONCLUSION: The results of this study revealed ACV-N have a higher antiviral activity compared with free drug; it could be a suitable carrier for delivery of acyclovir in the treatment of HSV-1 infections.

Preclinical evaluation of holmium-166 labeled anti-VEGF-A(Bevacizumab).

Radiolabeled antiangiogenic monoclonal antibodies are potential agents for targeted therapy in specific types of malignancies. In this study, (166)Ho-DOTA-Bevacizumab was used in biodistribution studies using single-photon emission computed tomography (SPECT) to acquire dosimetric aspects of the radiolabeled antibody in mice. The liver toxicity of the radiolabeled antibody was also determined using serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase and alkaline phosphatase assay 2-7 days post-injection. The SPECT biodistribution demonstrated a similar pattern as the other radiolabeled anti-vascular endothelial growth factor A (VEGF-A) immunoconjugates. (166)Ho-DOTA-Bevacizumab was revealed as a potential compound for therapy/imaging of VEGF-A expression in oncology.

Effects of extremely low-frequency pulsed electromagnetic fields on morphological and biochemical properties of human breast carcinoma cells (T47D).

This study was carried out to investigate the effects of 100 and 217 Hz extremely low-frequency pulsed electromagnetic fields (ELF-PEMF) on cell proliferation, actin reorganization, and ROS generation in a human breast carcinoma cells (T47D). Cells were exposed for 24-72 h, at 100 and 217 Hz, 0.1 mT. The treatment induced a time dependent decrease in cell growth after 72 h and revealed an increase in fluorescence intensity in cytoplasm and actin aggregations around the nucleus as detected by fluorescence microscopy. The amount of actin in T47D cells increased after 48 h exposure to 100 Hz and 24 h to 217 Hz while no changes in nuclear morphology were detected. Exposing the cells to 217 Hz for 72 h caused a dramatically increase of intracellular ROS generation while with exposure to 100 Hz it remained nearly unchanged. These results suggest that exposure to ELF-PEMF (100, 217 Hz, 0.1 mT) are able inducing an increase of actin level, its migration toward nucleus but despite of these changes and dramatically increase in ROS generation the symptoms of apoptosis were not observed. Our results support the hypothesis that cell response to EMF may only be observed at certain window effects; such as frequency and intensity of EMF parameters.

Effects of Electromagnetic Stimulation on Gene Expression of Mesenchymal Stem Cells and Repair of Bone Lesions.

OBJECTIVE: Most people experience bone damage and bone disorders during their lifetimes. The use of autografts is a suitable way for injury recovery and healing. Mesenchymal stem cells (MSCs) are key players in tissue engineering and regenerative medicine. Their proliferation potential and multipotent differentiation ability enable MSCs to be considered as appropriate cells for therapy and clinical applications. Differentiation of stem cells depends on their microenvironment and biophysical stimulations. The aim of this study is to analyze the effects of an electromagnetic field on osteogenic differentiation of stem cells. MATERIALS AND METHODS: In this experimental animal study, we assessed the effects of the essential parameters of a pulsatile electromagnetic field on osteogenic differentiation. The main purpose was to identify an optimum electromagnetic field for osteogenesis induction. After isolating MSCs from male Wistar rats, passage-3 (P3) cells were exposed to an electromagnetic field that had an intensity of 0.2 millitesla (mT) and frequency of 15 Hz for 10 days. Flow cytometry analysis confirmed the mesenchymal identity of the isolated cells. Pulsatile electromagnetic field-stimulated cells were examined by immunocytochemistry and real-time polymerase chain reaction (PCR). RESULTS: Electromagnetic field stimulation alone motivated the expression of osteogenic genes. This stimulation was more effective when combined with osteogenic differentiation medium 6 hours per day for 10 days. For the in vivo study, an incision was made in the cranium of each animal, after which we implanted a collagen scaffold seeded with stimulated cells into the animals. Histological analysis revealed bone formation after 10 weeks of implantation. CONCLUSION: We have shown that the combined use of chemical factors and an electromagnetic field was more effective for inducing osteogenesis. These elements have synergistic effects and are beneficial for bone tissue engineering applications.

Determination of the Best Concentration of Streptozotocin to Create a Diabetic Brain Using Histological Techniques.

Alzheimer's disease (AD) is one of the most important disorders among neurodegenerative diseases which is characterized by neurofibrillary tangles and senile plagues. Intercerebroventricular (ICV) streptozotocin administration is a form of sAD which was applied to examine different factors following AD. Previous reports used different doses of streptozotocin (STZ) to create Alzheimer's model, but no standard dose has been introduced. Therefore, we decided to investigate the best concentration of STZ to induce a diabetic brain with lowest mortality rate and high severity of destruction. We treated rats with three different doses of STZ (STZ 1.5, 2.25, and 3 mg/kg, ICV). Spatial memory for treated rats was evaluated by Morris water maze (MWM). Locomotor activities of rats were assessed by open field test. Histological observation such as immunohistochemistry, immunofluorescence, and Nissl staining were performed on the brain especially in CA1, CA3, and DG regions of hippocampal neurons at residues P-ser396 and P-ser404. Our data suggest that although the percentage hyperphosphorylation of tau protein by injection of STZ 3 mg/kg was about 10 % more than STZ 2.25 mg/kg compared to the control group, we considered the latter doses due to no effect on motor activities and enhance the number of glial cells.

Effects of extremely-low-frequency pulsed electromagnetic fields on collagen synthesis in rat skin.

To investigate the effects of extremely-low-frequency PEMFs (pulsed electromagnetic fields) on the synthesis of epidermal collagen, six groups of animals each consisting of eight mature male rats were selected randomly: one group for the control and five for the test. Using a parallel set of Helmholtz coils, a uniform field intensity of 2 mT at different frequencies of 25, 50 and 100 Hz yielded the most effective frequency to be 25 Hz. Then, at this frequency, two different field intensities of 1 and 4 mT were applied. The treatment time of 2.5 h/day lasted for 8 days, keeping the same procedure for the control group, except with the field turned off. On the ninth day, the rats were killed and skin samples from the dorsal region were taken for collagen assessment by measuring hydroxyproline content using the Stegemann-Stalder [(1967) Clin. Chim. Acta 8, 267-273] method. The results indicated that a PEMF of 2 mT at 25 Hz increased the collagen synthesis (P < 0.05). The other intensities and frequency setting did not have any noticeable effect; however, at a frequency of 25 Hz at 4 mT, collagen increase was also noticed. It was concluded that at 25 Hz under a field setting of 2 mT for the duration of 8 days, stimulation of skin at 2.5 h/day would cause increase in collagen synthesis in rat skin.