Characterization and Evaluation of Nano-niosomes Encapsulating Docetaxel against Human Breast, Pancreatic, and Pulmonary Adenocarcinoma Cancer Cell Lines.

Background: Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity. Objective: In this study, nano-niosomes were introduced for improving therapeutic index of DXL. Material and Methods: In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments. Results: DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. Conclusion: Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.

Synchronized Chemotherapy/Photothermal Therapy/Sonodynamic Therapy of Human Triple-Negative and Estrogen Receptor-Positive Breast Cancer Cells Using a Doxorubicin-Gold Nanoclusters-Albumin Nanobioconjugate.

OBJECTIVE: Novel strategies for treating triple-negative breast cancer (TNBC) are ongoing because of the lack of standard-of-care treatment. Nanoframed materials with a protein pillar are considered a valuable tool for designing multigoals of energy-absorbing/medication cargo and are a bridge to cross-conventional treatment strategies. METHODS: Nanobioconjugates of gold nanoclusters-bovine serum albumin (AuNCs-BSA) and doxorubicin-AuNCs-BSA (Dox-AuNCs-BSA) were prepared and employed as a simultaneous double photosensitizer/sonosensitizer and triple chemotherapeutic/photosensitizer/sonosensitizer, respectively. RESULTS: The highly stable AuNCs-BSA and Dox-AuNCs-BSA have ζ potentials of -29 and -18 mV, respectively, and represent valuable photothermal and sonodynamic activities for the combination of photothermal therapy and sonodynamic therapy (PTT/SDT) and synchronized chemotherapy/photothermal therapy/sonodynamic therapy (CTX/PTT/SDT) of human TNBC cells, respectively. The efficiency of photothermal conversion of AuNCs-BSA was calculated to be a promising value of 32.9%. AuNCs-BSA and Dox-AuNCs-BSA were activated on either laser light irradiation or ultrasound exposure with the highest efficiency on the combination of both types of radiation. CTX/PTT/SDT of MCF-7 and MDA-MB-231 breast cancer cell lines by Dox-AuNCs-BSA were evaluated with the MTT cell proliferation assay and found to progress synergistically. CONCLUSION: Results of the MTT assay, detection of the generation of intracellular reactive oxygen species and occurrence of apoptosis in the cells confirmed that CTX/PTT/SDT by Dox-AuNCs-BSA was attained with lower needed doses of the drug and improved tumor cell ablation, which would result in the enhancement of therapeutic efficacy and overcoming of therapeutic resistance.

A Study of Sonodynamic Therapy of Melanoma C540 Cells in Vitro by Titania/Gold Nanoparticles.

Background: Sonodynamic Therapy (SDT), a safe and non-invasive strategy in tumor therapy, is in development using novel sono-sensitizers, activated by low-intensity ultrasound radiation. SDT mainly progresses through Reactive Oxygen Species (ROS) generation followed by cell annihilation. Objective: The current study aimed to investigate the effect of ultrasound therapy with titania/gold nanoparticles (NPs) on melanoma cancer. Material and Methods: In this experimental study, Titania/gold NPs (TGNPs) were synthesized, and their activity was investigated in sonodynamic therapy of a melanoma cancer cell line (C540). SDT was performed at 1.0 W cm-2 and 1.0 MHz for one minute. Results: The synthesized NPs that comprised gold NPs of <10 nm into titania NPs of <20 nm showed great stability and cytocompatibility. While TGNPs were biocompatible, a remarkable rate of cell ablation was observed upon ultrasound irradiation due to ROS generation. Conclusion: The SDT using TGNPs can be introduced as an alternative and low-cost treatment method for melanoma malignancy.

Nucleic acid-based electrochemical biosensor for detection of influenza B by gold nanoparticles.

The influenza virus is a pervasive pathogen that exhibits increased prevalence during colder seasons, resulting in a significant annual occurrence of infections. Notably, pharmaceutical interventions effective against influenza A strains often exhibit limited efficacy against influenza B variants. Against this backdrop, the need for innovative approaches to accurately and swiftly differentiate and detect influenza B becomes evident. Biosensors play a pivotal role in this detection process, offering rapid, specific, and sensitive identification of the virus, facilitating timely intervention and containment efforts. Oligonucleotide sequences targeting the conserved B/Victoria/2/87 influenza virus NP region were designed. Nasopharyngeal swabs were collected from patients suspected of influenza virus infection, and viral RNA was extracted. RNA quality was assessed through one-step PCR. cDNA synthesis was performed using random hexamers, and real-time PCR quantified the influenza genome. Gold nanoparticles were immobilized on a surface to immobilize the specific DNA probe, and electrochemical hybridization was electrochemically followed. The biosensor exhibited high selectivity and effective distinction of complementary sequences from mismatches and influenza virus cDNA genome. The biosensor successfully detected the influenza B virus genome in real samples. Non-influenza samples yielded no significant hybridization signals. The comparison between the results obtained from the biosensor and real-time PCR revealed full agreement of these methods. The biosensor utilized electrochemical detection of hybridization and proved effective in detecting the influenza B virus genome with high specificity, sensitivity, and selectivity. Comparative analysis with real-time PCR underscored the accuracy and potential applicability of the biosensor in rapid and specific virus detection. This innovative approach holds promise for future diagnostic and epidemiological applications in detecting influenza B virus and other pathogens.

Electrochemical Immunosensors Developed for Amyloid-Beta and Tau Proteins, Leading Biomarkers of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurological disease and a serious cause of dementia, which constitutes a threat to human health. The clinical evidence has found that extracellular amyloid-beta peptides (Aß), phosphorylated tau (p-tau), and intracellular tau proteins, which are derived from the amyloid precursor protein (APP), are the leading biomarkers for accurate and early diagnosis of AD due to their central role in disease pathology, their correlation with disease progression, their diagnostic value, and their implications for therapeutic interventions. Their detection and monitoring contribute significantly to understanding AD and advancing clinical care. Available diagnostic techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are mainly used to validate AD diagnosis. However, these methods are expensive, yield results that are difficult to interpret, and have common side effects such as headaches, nausea, and vomiting. Therefore, researchers have focused on developing cost-effective, portable, and point-of-care alternative diagnostic devices to detect specific biomarkers in cerebrospinal fluid (CSF) and other biofluids. In this review, we summarized the recent progress in developing electrochemical immunosensors for detecting AD biomarkers (Aß and p-tau protein) and their subtypes (AßO, Aß(1-40), Aß(1-42), t-tau, cleaved-tau (c-tau), p-tau181, p-tau231, p-tau381, and p-tau441). We also evaluated the key characteristics and electrochemical performance of developed immunosensing platforms, including signal interfaces, nanomaterials or other signal amplifiers, biofunctionalization methods, and even primary electrochemical sensing performances (i.e., sensitivity, linear detection range, the limit of detection (LOD), and clinical application).

Pulsed sonodynamic therapy of melanoma cancer cells using nanoparticles of and mesoporous platinum.

OBJECTIVE: Noble metal nanomaterials have been introduced as ideal sonosensitizers for sonodynamic therapy (SDT) of cancer. In this research, platinum nanoparticles (PtNPs) and mesoporous platinum (MPt) were first synthesized and then evaluated as novel sonosensitizers. METHODS: Ultrasound waves were radiated at two different power densities and two different pulse ratios to develop a pulsed radiation route for SDT of the malignant melanoma cell line C540 (B16/F10). Fluorescence emission was recorded as an indicator of intracellular reactive oxygen generation during the treatment. RESULTS: Platinum nanoparticles had an average diameter of 12 ± 7 nm and a zeta potential of -17.6 mV; also, MPt had a sponge-like and highly porous structure with a pore size <11 nm and a zeta potential of -39.5 mV. Both PtNPs and MPt, particularly the latter, enhanced the rate of inhibition of tumor cell growth on ultrasound radiation at an output power density of 1.0 W cm-2 and pulse ratio of 30% over 10 min without intensifying temperature. CONCLUSION: Use of the developed pulsed (rather than continuous) radiation in SDT and PtNPs or MPT, without hyperthermia, resulted in a new effective cancer treatment method based on the mechanisms of cavitation and/or ROS generation.

Fractionated Sonodynamic Therapy Using Gold@Poly(ortho-aminophenol) Nanoparticles and Multistep Low-Intensity Ultrasound Irradiation to Treat Melanoma Cancer: In Vitro and In Vivo Studies.

OBJECTIVE: Cancer treatment using ultrasound irradiation with low intensities along with a sonosensitizer has been found to have significant advantages, such as high penetration depth in tissues, non-invasive therapeutic character, minor side effects, good patient adherence and preferential tumor area treatment. In the present study, gold nanoparticles covered by poly(ortho-aminophenol) (Au@POAP NPs) were synthesized and characterized as a new sonosensitizer. METHODS: We investigated Au@POAP NPs efficacy on fractionated ultrasound irradiation for treatment of melanoma cancer in vitro as well as in vivo. DISCUSSION: In vitro examinations revealed that although Au@POAP NPs (with a mean size of 9.8 nm) alone represented concentration-dependent cytotoxicity against the B16/F10 cell line, multistep ultrasound irradiation (1 MHz frequency, 1.0 W/cm2 intensity, 60 s irradiation time) of the cells in the attendance of Au@POAP NPs led to efficient cell sonodynamic therapy (SDT) and death. Histological analyses revealed that in vivo fractionated SDT toward melanoma tumors of male balb/c mice led to no residual viable tumor cell after 10 d. CONCLUSION: A deep sonosensitizing effectiveness of Au@POAP NPs on fractionated low-intensity ultrasound irradiation was attained with the main mechanism of tumor cell eradication of promotion of apoptosis or necrosis through dramatically increased reactive oxygen species levels.

A ß-Amyloid(1-42) Biosensor Based on Molecularly Imprinted Poly-Pyrrole for Early Diagnosis of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a common form of dementia, characterized by production and deposition of ß-amyloid peptide in the brain. Thus, ß-amyloid peptide is a potentially promising biomarker used to diagnose and monitor the progression of AD. OBJECTIVE: The study aims to develop a biosensor based on a molecularly imprinted poly-pyrrole for detection of ß-amyloid. MATERIAL AND METHODS: In this experimental study, an imprinted poly-pyrrole was employed as an artificial receptor synthesized by electro-polymerization of pyrrole on screen-printed carbon electrodes in the presence of ß-amyloid. ß-amyloid acts as a molecular template within the polymer. The biosensor was evaluated by cyclic voltammetry using ferro/ferricyanide marker. The parameters influencing the biosensor performance, including electro-polymerization cycle umbers and ß-amyloid binding time were optimized to achieve the best biosensor sensitivity. RESULTS: The ß-amyloid binding affinity with the biosensor surface was evaluated by the Freundlich isotherm, and Freundlich constant and exponent were obtained as 0.22 ng mL-1 and 10.60, respectively. The biosensor demonstrated a detection limit of 1.2 pg mL-1. The biosensor was applied for ß-amyloid determination in artificial cerebrospinal fluid. CONCLUSION: The biosensor is applicable for early Alzheimer's disease detection.

Effects of labeling human mesenchymal stem cells with superparamagnetic zinc-nickel ferrite nanoparticles on cellular characteristics and adipogenesis/osteogenesis differentiation.

OBJECTIVE: An attractive cell source for stem cell-based therapy are WJ-MSCs. Hence, tracking WJ-MSCs using non-invasive imaging procedures (such as MRI) and contrast agents (Zn0.5Ni0.5Fe2O4, NFNPs) are required to evaluate cell distribution, migration, and differentiation. RESULTS: Results showed that the bare and dextrin-coated NFNPs were internalized inside the WJ-MSCs and had no effect on the cell viability, proliferation, apoptosis, karyotyping, and morphology of WJ-MSCs up to 125 µg/mL. Besides, treated WJ-MSCs were differentiated into osteo/adipocyte-like cells. The expression of RUNX 2, SPP 1 (P < 0.05), and OCN (P > 0.05) genes in the WJ-MSCs treated with dextrin-coated NFNPs was higher than the untreated WJ-MSCs; and the expression of CFD, LPL, and PPAR-γ genes was reduced in WJ-MSCs treated with both NFNPs in comparison with the untreated WJ-MSCs (P > 0.05). CONCLUSION: Overall, results showed that dextrin-coated NFNPs had no adverse effect on the cellular characteristics, proliferation, and differentiation of WJ-MSCs, and suggesting their potential clinical efficacy.

Development of a Composite of Polypyrrole-Coated Carbon Nanotubes as a Sonosensitizer for Treatment of Melanoma Cancer Under Multi-Step Ultrasound Irradiation.

Sonodynamic therapy (SDT) has established a novel route for treating solid cancers. Low-intensity ultrasound irradiation accompanied by a sonosensitizer has revealed remarkable advantages for cancer therapy such as targeted uptake, access to deeper tumors, insignificant side effects and invasiveness, compared with other therapeutic methods. In this study, we scrutinized synthesis and characterization of a polypyrrole-coated multi-walled carbon nanotubes composite (PPy@MWCNTs). PPy@MWCNTs can absorb ultrasound irradiation by both of its components, and it was introduced as a new sonosensitizer. The composite was characterized by field emission scanning electron microscopy (FESEM), and its ability to temperature elevation was explored. FESEM images revealed that PPy@MWCNTs comprised nanotubes of 36.3 ± 5.1 nm in diameter with up to several micrometer in length. Ultrasound irradiation at 1 MHz and 1.0 W cm-2 for 60 s in four steps led to an efficient SDT in vitro (16.3 ± 2.8°C temperature increment for 250 µg mL-1 of PPy@MWCNTs), in C540 (B16/F10) cell line and a melanoma tumor model in male balb/c mice. In vitro examinations revealed that PPy@MWCNTs represented a concentration-dependent cytotoxicity on multi-step ultrasound irradiation (a cell viability of 8.9% for 250 µg mL-1 of PPy@MWCNTs). Histologic analyses and tumor volume decrement after 10 d revealed detrimental SDT effects of PPy@MWCNTs on tumors (75% necrosis and 50% decrement in tumor volume). Thermal effects and reactive oxygen species generation were the reasons of the working function of PPy@MWCNTs in SDT.

Photothermal inactivation of methicillin-resistant Staphylococcus aureus: anti-biofilm mediated by a polypyrrole-carbon nanocomposite.

Widespread resistance to antibiotics amongst pathogens has become a tremendous challenge of high morbidity and mortality rates which increases the needs to exploring novel methods of treatment. An efficient antimicrobial procedure to root out pathogenic bacteria is photothermal therapy. In this study, antimicrobial effects of a polypyrrole-carbon nanocomposite (PPy-C) upon laser irradiation in order to destroy the pathogenic gram-positive bacterium, methicillin-resistant Staphylococcus aureus (MRSA) were assessed. The bacterial cells were incubated with 500, 750 and 1000 µg ml-1 concentrations of PPy-C and irradiated with an 808-nm laser at a power density of 1.0 W cm-2. To indicate the biocompatibility and toxic effect of the nanocomposite without and with laser irradiation, the authors counted the number of CFUs and compared it to an untreated sample. Antibacterial mechanisms of PPy-C were assessed through temperature increment, reactive oxygen species production, and protein and DNA leakages. Photothermal heating assay showed that 26°C temperature increases in the presence of 1000 µg ml-1 PPy-C led to >98% killing of MRSA. Furthermore, 20 min radiation of near-infrared light to PPy-C in different concentrations indicated destruction and reduction in the MRSA biofilm formation. Therefore, PPy-C was introduced as a photothermal absorber with a bactericidal effect in MRSA.

A Cardiac Troponin T Biosensor Based on Aptamer Self-assembling on Gold.

In this study, a sensitive and accurate aptasensor was designed for early detection of myocardial infarction through the determination of troponin T (TnT). The successful immobilization of a specific aptamer sequence on the surface of gold that had a high affinity toward TnT was accomplished. TnT was electrochemically quantified. The results indicated that the aptasensor detected TnT in a range of 0.05-5 ng mL, and with a detection limit of 0.01 ng/mL. The performance of the aptasensor was investigated by analyzing 99 human serum samples. Both diagnostic specificity and sensitivity of the aptasensor were found to be 95%. The use of the designed aptamer-based biosensor could be an essential achievement in health policy, preventing deaths caused by myocardial infarction, and reducing patients with heart failure. The extensive use of this aptamer-based biosensor can also reduce costs, enhance speed, and improve accuracy in the diagnosis of TnT as an important myocardial infarction biomarker.

Preparation of meglumine antimonate loaded albumin nanoparticles and evaluation of its anti-leishmanial activity: an in vitro assay.

Cutaneous leishmaniasis is still a health problem worldwide, especially in tropical and subtropical areas. Currently, pentavalent antimony compounds are used to treat leishmaniasis. These compounds cause various side effects in the body. Therefore, there is a need to discover new drugs with less toxicity and more therapeutic effects. In this study, we encapsulated the meglumine antimonate into the albumin as a drug carrier and evaluated the anti-leishmanial effect of the prepared nanoparticles. The precipitation method was used for this purpose by applying different concentrations of glutaraldehyde and N-(3-Dimethylaminopropyl)-N-ethyl carbodiimide hydro chloride Ethyl (DEC) and then, field emission test was performed using Scanning Electron Microscopy for evaluating the morphology and size particles. The cytotoxicity and inhibitory of drugs were evaluated on J774 macrophages and Leishmania major promastigotes, respectively. Nanodrugs prepared using glutaraldehyde (10 µl/ml) and DEC (13 mg/ml) had the smallest and largest size, respectively. The highest anti-leishmanial activity was observed in the drugs prepared with glutaraldehyde (10 µl/ml). Also this nanodrug had the lowest cytotoxicity against macrophages. Given that meglumine antimonate loaded albumin nanoparticles prepared with glutaraldehyde (10 µg/ml), can improve the anti-leishmanial effects of this old drug, it can be a good option as a drug delivery system.

A signal-on built in-marker electrochemical aptasensor for human prostate-specific antigen based on a hairbrush-like gold nanostructure.

A green electrodeposition method was firstly employed for the synthesis of round hairbrush-like gold nanostructure in the presence of cadaverine as a size and shape directing additive. The nanostructure which comprised of arrays of nanospindles was then applied as a transducer to fabricate a signal-on built in-marker electrochemical aptasensor for the detection of human prostate-specific antigen (PSA). The aptasensor detected PSA with a linear concentration range of 0.125 to 128 ng mL-1 and a limit of detection of 50 pg mL-1. The aptasensor was then successfully applied to detect PSA in the blood serum samples of healthy and patient persons.

Inhibitory Effects of Some Carbohydrates on Nano-Globular Aggregation of both Normal and Glycated Albumin.

BACKGROUND: Protein aggregation is one of the important, common and troubling problems in biotechnology, pharmaceutical industries and amyloid-re-lated disorders. METHODS: In the present study, the inhibitory effects of some carbohydrates (alginate, ß-cyclodextrin and trehalose) on the formation of nano-globular aggregates from normal (HSA) and glycated (GHSA) human serum albumin were studied; when the formation of aggregates was induced by the simultaneous heating and addition of dithiotheritol. For the investigations, the biophysical methods of UV-vis spectrophotometry, circular dichroism spectroscopy, transmission electron microscopy and tensiometry were employed. RESULTS: The effect of inhibitory mechanism of these inhibitors on the aggregation of HSA and GHSA was expressed and compared together. CONCLUSION: The results showed that the nucleus formation step of the aggregation process of HSA and GHSA was different in the presence of alginate (compared to ß-cyclodextrin and trehalose). The inhibition efficiencies of the carbohydrates on the aggregate formation of HSA and GHSA were different, arising from the differences in the hydrophobicities of HSA and GHSA, and also, the differences between HSA- and GHSA-carbohydrate interactions.

Effect of Magnetic Fluid Hyperthermia on Implanted Melanoma in Mouse Models.

BACKGROUND: Nowadays, magnetic nanoparticles (MNPs) have received much attention because of their enormous potentials in many fields such as magnetic fluid hyperthermia (MFH). The goal of hyperthermia is to increase the temperature of malignant cells to destroy them without any lethal effect on normal tissues. To investigate the effectiveness of cancer therapy by magnetic fluid hyperthermia, Fe0.5Zn0.5Fe2O4 nanoparticles (FNPs) were used to undergo external magnetic field (f=515 kHz, H=100 G) in mice bearing implanted tumor. METHODS: FNPs were synthesized via precipitation and characterized using transmission electron microscopy (TEM), vibrating sample magnetometer, and Fourier transform infrared. For in vivo study, the mice bearing implanted tumor were divided into four groups (two mice per group), namely, control group, AMF group, MNPs group, and MNPs&AMF group. After 24 hours, the mice were sacrificed and each tumor specimen was prepared for histological analyses. The necrotic surface area was estimated by using graticule (Olympus, Japan) on tumor slides. RESULTS: The mean diameter of FNPs was estimated around 9 nm by TEM image and M versus H curve indicates that this particle is among superparamagnetic materials. According to histological analyses, no significant difference in necrosis extent was observed among the four groups. CONCLUSION: FNPs are biocompatible and have a good size for biomedical applications. However, for MFH approach, larger diameters especially in the range of ferromagnetic particles due to hysteresis loss can induce efficient heat in the target region.

Zepto-molar electrochemical detection of Brucella genome based on gold nanoribbons covered by gold nanoblooms.

Gold nanoribbons covered by gold nanoblooms were sonoelectrodeposited on a polycrystalline gold surface at -1800 mV (vs. AgCl) with the assistance of ultrasound and co-occurrence of the hydrogen evolution reaction. The nanostructure, as a transducer, was utilized to immobilize a Brucella-specific probe and fabrication of a genosensor, and the process of immobilization and hybridization was detected by electrochemical methods, using methylene blue as a redox marker. The proposed method for detection of the complementary sequence, sequences with base-mismatched (one-, two- and three-base mismatches), and the sequence of non-complementary sequence was assayed. The fabricated genosensor was evaluated for the assay of the bacteria in the cultured and human samples without polymerase chain reactions (PCR). The genosensor could detect the complementary sequence with a calibration sensitivity of 0.40 µA dm(3) mol(-1), a linear concentration range of 10 zmol dm(-3) to 10 pmol dm(-3), and a detection limit of 1.71 zmol dm(-3).

Efficacy of calcium- and fluoride-containing materials for the remineralization of primary teeth with early enamel lesion.

The aim of the study was to determine the efficacy of different products containing fluoride, calcium and phosphate for enamel remineralization in eroded primary teeth. A total of 90 sound primary canine teeth were randomly divided into 5 groups of 18 teeth each: 1) control (polished enamel), 2) 5% DuraShield sodium fluoride varnish, 3) 500 ppm fluoridated toothpaste, 4) casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) cream, and 5) Clinpro White varnish containing functionalized tri-calcium phosphate (fTCP). Enamel microhardness (EMH) was measured in all samples before and after demineralization and after 28 days of remineralization. Also 8 samples in groups 2 to 5 and four samples of sound and demineralized enamel were examined with atomic force microscopy (AFM). All data were analyzed with one-way ANOVA (p<0.05). Mean microhardness of demineralized enamel was significantly lower than in enamel at baseline (p<0.001). Remineralization significantly increased microharness in groups 2 to 5 compared to the control group (p<0.001). Percent EMH after remineralization with CPP-ACP was significantly higher than after fTCP (p=0.029), toothpaste (p< 0.001) or fluoride varnish (p<0.001); however, there was no significant difference between toothpaste and fluoride varnish (p=0.062). Microhardness increased more after fTCP treatment than after treatment with sodium fluoride varnish (p<0.001) or fluoridated toothpaste (p=0.045). AFM images showed that enamel roughness decreased most after treatment with fTCP, followed by CPP-ACP, toothpaste and fluoride varnish. The efficacy of CPP-ACP cream for remineralizing eroded enamel was greater than fluoride toothpaste, fluoride varnish or fTCP varnish.

Lactic acidosis treatment by nanomole level of spermidine in an animal model.

Lactic acidosis occurs in a number of clinical conditions, e.g. in surgeries, orthotopic liver transplant, and anesthetic agent administration, which has deleterious effects on the patient's survival. The most rational therapy for these patients, the sodium bicarbonate administration, cannot prevent those accompanying deficiencies and may actually be harmful. In addition, tromethamine adjusts the blood pH, it does not affect the lactate accumulation. Therefore, discovery of a therapeutic agent is still a major unsolved problem. In this study, the rats were divided into different groups and lactic acidosis type B was induced in them. Then, the effect of different injection doses of spermidine (0-20nmol) on lactic acidosis was analyzed by measuring the lactate level and pH in the rat blood samples. The results showed that spermidine effectively and simultaneously inhibited the lactate and pyruvate accumulations, and also adjusted the pH of bloodstream. On the other hand, it has been shown (Damuni et al., 1984; Rahmatullah and Roche, 1988) that spermidine increases the activity of phosphatase, leading to prevention of lactate accumulation. The results indicate that administration of only nanomole level of spermidine may be the best treatment in the liver transplant and other patients suffering from lactic acidosis type B.

Deferiprone: structural and functional modulating agent of hemoglobin fructation.

Diabetic complication arises from the presence of advanced glycation end products in different sites of the body. Great attention should be paid to recognizing anti-glycation compounds. Here, deferiprone as an oral iron chelator drug administrated in treatment of ß-thalassemic patients was selected to find its effect on the fructation of hemoglobin (Hb). Our results indicated that deferiprone could prevent the AGE and carbonyl formation via inhibition of structural changes in the structure of Hb during the fructation process. Moreover, deferiprone can preserve peroxidase and esterase activities of fructated Hb similar to native Hb. Therefore, deferiprone can be introduced as an anti-glycation drug to prevent the AGE formation.