Exosomes, and the potential for exosome-based interventions against COVID-19.

Since late 2019, the world has been devastated by the coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with more than 760 million people affected and ∼seven million deaths reported. Although effective treatments for COVID-19 are currently limited, there has been a strong focus on developing new therapeutic approaches to address the morbidity and mortality linked to this disease. An approach that is currently being investigated is the use of exosome-based therapies. Exosomes are small, extracellular vesicles that play a role in many clinical diseases, including viral infections, infected cells release exosomes that can transmit viral components, such as miRNAs and proteins, and can also include receptors for viruses that facilitate viral entry into recipient cells. SARS-CoV-2 has the ability to impact the formation, secretion, and release of exosomes, thereby potentially facilitating or intensifying the transmission of the virus among cells, tissues and individuals. Therefore, designing synthetic exosomes that carry immunomodulatory cargo and antiviral compounds are proposed to be a promising strategy for the treatment of COVID-19 and other viral diseases. Moreover, exosomes generated from mesenchymal stem cells (MSC) might be employed as cell-free therapeutic agents, as MSC-derived exosomes can diminish the cytokine storm and reverse the suppression of host anti-viral defences associated with COVID-19, and boost the repair of lung damage linked to mitochondrial activity. The present article discusses the significance and roles of exosomes in COVID-19, and explores potential future applications of exosomes in combating this disease. Despite the challenges posed by COVID-19, exosome-based therapies could represent a promising avenue for improving patient outcomes and reducing the impact of this disease.

Kaempferol alleviates bisphenol A reproductive toxicity in rats in a dose-dependent manner.

BACKGROUND: Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), are a major cause of male infertility by disrupting spermatogenesis. OBJECTIVE: Here, we examined the potential protective benefits of kaempferol (KMF), a flavonol known for its antioxidant properties, on BPA-induced reproductive toxicity in adult male rats. METHODS: Human skin fibroblast cells (HNFF-P18) underwent cell viability assays. Thirty-five male Wistar rats were assigned to four groups: 1) control, 2) BPA (10 mg/kg), 3,4) BPA, and different dosages of KMF (1 and 10 mg/kg). The study examined the rats' testosterone serum level, antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), oxidative markers malondialdehyde (MDA) and total antioxidant capacity (TAC), body weight, weight ratios of testis and prostate, and histopathological examinations. RESULTS: The study revealed that using KMF to treat rats exposed to BPA increased cell viability. Moreover, the rats' testosterone levels, which BPA reduced, showed a significant increase after KMF was included in the treatment regimen. Treatment with BPA led to oxidative stress and tissue damage, but simultaneous treatment with KMF restored the damaged tissue to its normal state. Histopathology studies on testis and prostate tissues showed that KMF had an ameliorative impact on BPA-induced tissue damage. CONCLUSIONS: The research suggests that KMF, a flavonol, could protect male rats from the harmful effects of BPA on reproductive health, highlighting its potential healing properties.

An Update on Betrixaban, The Challenging Anticoagulant Agent for Extended Venous Thromboembolism Prophylaxis.

ABSTRACT: Venous thromboembolism (VTE) is a prevalent yet preventable cause of death, particularly among hospitalized patients. Studies have shown that the risk of VTE remains high for up to 6 months after discharge, highlighting the need for extended thromboprophylaxis as a viable treatment approach. Despite the availability of several anticoagulant drugs such as vitamin K antagonists, heparinoids, rivaroxaban, apixaban, edoxaban, and dabigatran, none of them has received approval from the US Food and Drug Administration for long-term thromboprophylaxis. However, an emerging factor Xa inhibitor called betrixaban has shown promising results in Phase II and phase III trials, positioning itself as the first and only US Food and Drug Administration-approved anticoagulant for extended thromboprophylaxis in hospitalized patients after discharge. Betrixaban offers distinct pharmacological characteristics, including a long half-life, low renal excretion, and unique hepatic metabolism, making it an attractive option for various theoretical uses. Numerous articles have been published discussing the safety and efficacy of betrixaban, all of which have emphasized its usefulness and practicality. However, there has been limited discussion regarding its weaknesses and areas of ambiguity. Therefore, this article aimed to explore the challenges faced during the approval process of betrixaban and provide a comprehensive review of the literature on its advantages and disadvantages as a long-term prophylaxis approach for VTE. Furthermore, we aim to identify the ambiguous points that require further investigation in future studies.

Fabrication of an ultra-sensitive electrochemical DNA biosensor based on CT-DNA/NiFe2O4NPs/Au/CPE for detecting rizatriptan benzoate.

A novel and first electrochemical biosensor based on Deoxyribonucleic acid (DNA) as a biological component to measure an antimigraine drug, rizatriptan benzoate (RZB) for patients under treatment in biological samples was developed. A carbon paste electrode (CPE) was modified by calf thymus (CT) double-stranded (ds)-DNA, nickel ferrite magnetic nanoparticles (NiFe2O4NPs), and gold nanoparticles (AuNPs). The morphology of the CT-DNA/NiFe2O4NPs/AuNPs/CPE was characterized by Field emission scanning electron microscope (FESEM). The presence of NiFe2O4NPs and AuNPs was confirmed by energy-dispersive X-ray spectroscopy (EDS) image of the NiFe2O4NPs/AuNPs/CPE surface. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to determine the structure and electrochemical characteristics of the CT-DNA/NiFe2O4NPs/AuNPs/CPE. Differential pulse voltammetry (DPV) was used to investigate the electrochemical behavior of RZB. Chronoamperometry (CA) was applied to study the effect of CT-DNA immobilization time on the peak oxidation current of RZB accumulated on the surface of the CT-DNA/NiFe2O4NPs/AuNPs/CPE. The results showed that, under optimum conditions, the prepared electrode responded linearly to RZB concentrations between 0.01 and 2.0 µM, with a 0.0033 µM detection limit (LOD) and 0.01 µM limit of quantification (LOQ). The parameters influencing the biosensor performance (temperature, CT-DNA immobilization time, and RZB/CT-DNA accumulation time) were optimized. DPV showed the displacement of the peak potential towards positive values and the reduction of its current, indicating that the drug could intercalate between the guanine base pairs of CT-DNA. Our biosensor was successfully applied for RZB measurement in human urine, blood serum, plasma samples, and tablets. The presented biosensor was fast response, sensitive, selective, cost-effective, and easy-to-use for RZB determination in pharmaceutical formulations and biological samples.

Interaction of quercetin and 5-fluorouracil: cellular and pharmacokinetic study.

5-fluorouracil (5-FU) is a widely used chemotherapeutic agent, and its uncontrolled blood levels contribute to toxicity. Quercetin, as an important flavonoid, has many biological effects, including anti-tumor and anti-inflammatory features. The current study investigated the synergistic effect between 5-FU and quercetin using HT-29 cell line and fibroblast cells. Rats were assigned to two groups. The 5-FU/quercetin group received intraperitoneal quercetin (10 mg/kg) and the Tween was injected to the control group for 14 consecutive days. On the 15th day, both groups received 50 mg/kg of 5-FU. Upon the final injection, blood samples were obtained at different times. Pharmacokinetic parameters were evaluated using high-performance liquid chromatography (HPLC). The mean (±SD) of maximum plasma concentration (Cmax) of 5-FU in combination therapy group was 3.10 ± 0.18 µg/ml and the area under the curve (AUC) was 153.89 ± 21.36, which increased by 113% and 128% compared to control group, respectively. Quercetin increased anti-tumor activity of 5-FU and enhanced Cmax and AUC of 5-FU. These findings confirm the synergistic effects between quercetin and 5-FU at the usual doses in cancer treatment, which may lead to reduced toxicity.

The protective effects of quercetin nano-emulsion on intestinal mucositis induced by 5-fluorouracil in mice.

BACKGROUND: Intestinal mucositis is one of chemotherapeutics' most common adverse effects, such as 5-fluorouracil (5-FU). Quercetin (QRC), a naturally occurring flavonoid, has approved antioxidant and anti-inflammatory properties. Thus, in this article, the preventive and curative effects of emulsion and nano-emulsion formulations of QRC were investigated in a model of 5-FU-induced intestinal mucositis using biochemical, histopathological, and molecular approaches. METHOD: Thirty-six mice were divided into six different groups: Control (normal saline), 5-FU (a single dose of 5-FU 300 mg/kg), pre-treatment groups (pre-QRC, and pre-QRC-nano, receiving QRC 5 mg/kg emulsion and nano-emulsion before the induction of mucositis, respectively), and post-treatment groups (post-QRC, and post-QRC-nano, receiving QRC 5 mg/kg emulsion and nano-emulsion after the induction of mucositis, respectively). FINDING: The administration of quercetin emulsion and nano-emulsion could significantly alleviate the oxidant-antioxidant balance of mice serum samples and reverse the destructive histopathologic changes induced by 5-FU in the intestine tissue. Nevertheless, although the expression of both pro-inflammatory genes, NF-κB and HIF-1α, was decreased when quercetin was administered to mice, this reduction was not statistically significant. CONCLUSION: The administration of quercetin emulsion and nano-emulsion formulations could ameliorate the oxidative damage induced by chemotherapeutics, such as the 5-FU. Therefore, if confirmed in further studies, it could be used in clinical settings as a preventive and curative agent to decrease such catastrophic adverse events in chemotherapy patients.

Ameliorative effect of Alpinia officinarum Hance extract on nonylphenol-induced reproductive toxicity in male rats.

Nonylphenol (NP), an endocrine-disrupting chemical, interferes with reproductive function and induces oxidative stress in different organs, including the testis and prostate. Alpinia officinarum Hance (ALP), a plant species of the Zingiberaceae family, has proven antioxidant properties. This study aimed to evaluate the effect of the alcoholic extract of ALP treatment on NP-induced reproductive toxicity and oxidative stress in male rats using biochemical and histopathological biomarkers. Our experimental groups were defined as follows: oil treatment (control), NP 10 mg/kg, ALP 10 mg/kg (ALP HD), NP + ALP 5 mg/kg (NP + ALP LD) and NP + ALP 10 mg/kg (NP + ALP HD). NP administration caused significant cytotoxicity and a significant increase in oxidative stress prostate-specific antigen (PSA) levels accompanied by a significant reduction in testosterone levels. The relative weight of the testis of both NP + ALP LD and NP + ALP HD groups was significantly decreased compared to the control group. Histopathological evaluations revealed destructive effects in testis and prostate tissue samples. In conclusion, ALP administration improved cytotoxicity, oxidative stress, testosterone and PSA levels, and testis and prostate tissue destructive effects induced by the NP in male rats.

Design and synthesis of new imidazo[1,2-b]pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies.

A new series of imidazo[1,2-b]pyrazole derivatives 4a-o was designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed high inhibitory activity in the range of IC50 = 95.0 ± 0.5-372.8 ± 1.0 µM as compared to standard drug acarbose (IC50 = 750 ± 1.5 µM) and were also found to be non-cytotoxic. Among the synthesized compounds, the most potent compound was compound 4j with eightfold higher inhibitory activity compared to acarbose. Like acarbose, compound 4j inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most potent compounds 4j, 4f, 4o, and 4c were also conducted.

Simultaneous voltammetric determination of rizatriptan and acetaminophen using a carbon paste electrode modified with NiFe2O4 nanoparticles.

Nickel-ferrite nanoparticles (NiFe2O4) were synthesized by a hydrothermal method. They were used to modify a carbon paste electrode (CPE) and to prepare an electrochemical sensor for simultaneous determination of rizatriptan benzoate (RZB) and acetaminophen (AC). The structure and morphology of the bare CPE and modified CPE were studied using field emission scanning electron microscopy, while the structural characterization of NiFe2O4 was performed via X-ray diffraction. In the potential range 0.2-1.2 V, AC and RZB were detected at potentials of 0.5 V and 0.88 V (vs. Ag/AgCl saturated KCl 3 M), respectively. Both calibration plots are linear in the 1 to 90 µM concentration range. The limits of detection (at 3σ) of AC and RZB are 0.49 and 0.44 µM, respectively. The performance of the modified CPE was evaluated by quantifying the two drugs in spiked urine and in tablets. Graphical abstract The modified electrode consist of Nickel-ferrite and graphite by differential pulse voltammetry methods are schematically presented for simultaneous detection of acetaminophen (a painkiller drug) and rizatriptan benzoate (an antimigraine drug) in human urine and tablet samples.

Chrysin Effect in Prevention of Acetaminophen-Induced Hepatotoxicity in Rat.

Acetaminophen is a commonly used analgesic drug that induces hepatotoxicity at high doses and produces the acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) through oxidase isoenzyme system. The antioxidant and anti-inflammatory activity of flavonoid chrysin has been reported in different studies. The present study was conducted to investigate the protective effect of chrysin on acute acetaminophen-induced hepatotoxicity. The cytotoxicity of chrysin on fibroblast cells was evaluated using MTT assay, and then, 54 rats were divided into nine groups of six, and acetaminophen (1500 mg/kg) was administered in all groups except for the control group, second and the seventh groups (40 mg/kg), and all groups were treated with chrysin for 14 days. Liver enzymes, inflammatory factors TNF-α and IL-2, and total antioxidant activity were measured in serum while liver tissue was histopathologically examined. Based on the MTT assay results, 31.25, 62.5, 125, 250, and 500 µg/mL chrysin had no adverse effects on healthy fibroblast cells (P < 0.05). Chrysin decreased the level of liver enzymes (ALT, AST, and ALP), which were previously increased after the use of acetaminophen (p < 0.05). The hepatoprotective effect and total antioxidant capacity increased in a dose-dependent manner and the effect of the highest concentration of chrysin was equal to the effect of silymarin (P < 0.05). TNF-α in groups 4 to 6 decreased in a dose-dependent manner (P = 0.04), and chrysin did not show any significant reducing effect on IL-2 compared to silymarin. Chrysin prevents the necrosis and injury of acute acetaminophen-induced hepatotoxicity by decreasing liver enzymes and TNF-α and increasing total antioxidant capacity and protecting the liver tissue.

Design and synthesis of new fused carbazole-imidazole derivatives as anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and in silico studies.

Twenty three fused carbazole-imidazoles 6a-w were designed, synthesized, and screened as new α-glucosidase inhibitors. All the synthesized fused carbazole-imidazoles 6a-w were found to be more active than acarbose (IC50 = 750.0 ±â€¯1.5 µM) against yeast α-glucosidase with IC50 values in the range of 74.0 ±â€¯0.7-298.3 ±â€¯0.9 µM. Kinetic study of the most potent compound 6v demonstrated that this compound is a competitive inhibitor for α-glucosidase (Ki value = 75 µM). Furthermore, the in silico studies of the most potent compounds 6v and 6o confirmed that these compounds interacted with the key residues in the active site of α-glucosidase.

miR-302/367-induced neurons reduce behavioral impairment in an experimental model of Alzheimer's disease.

In vivo reprogramming of reactive glial cells to neurons has opened a new horizon in regenerative medicine. Our previous study showed that astrocytes could be converted to neurons by the microRNA-302/367 (miR-302/367) cluster in adult brains. In this study, we investigated the possible contribution of miR-302/367-induced neurons in behavioral improvement and neural repair in an Alzheimer's disease (AD) animal model. The AD model was induced by an intracerebroventricular (i.c.v) injection of streptozotocin (STZ). GFP-only or miR-302/367+GFP expressing lentiviral particles were injected into the dentate gyrus of the hippocampus along with intraperitoneal (i.p) valproate (VPA) injection, 3weeks after the STZ administration. We assessed short-term and spatial memories by the Y-maze and Morris water maze (MWM) tasks, respectively. Electrophysiological activities of induced neuron-like cells were investigated using a whole-cell patch clamp technique, 6months after injection of miR-302/367. Behavioral analysis showed that the STZ injection significantly impaired short-term memory and increased escape latency parameter in the MWM task. Compared to STZ and STZ+VPA groups, miR-302/367 combined with VPA significantly improved the spontaneous alternation and spatial memory. Immunostaining against NeuN, as a mature neuronal marker, and its quantification indicated that co-labeled GFP and NeuN significantly increased in the miR-302/367+VPA group. Induced neurons were detected 6months after the miR-302/367 injection. The patch-clamp recording suggested that induced neurons could fire repetitive action potential like endogenous neurons. In conclusion, our results indicated that in vivo reprogramming of reactive astrocytes to neurons by the miR-302/367 cluster might be considered as a novel strategy to restore learning and memory in AD patients.

Iranian propolis efficiently inhibits growth of oral streptococci and cancer cell lines.

BACKGROUND: Propolis is a natural bee product with a wide range of biological activities that are related to its chemical composition. The present study investigated the quantification of quercetin (Q) in Ardabil ethanol extract of propolis (AEEP), and then compared its anti-bacterial, anti- biofilm and cytotoxic effects on cancer and normal cell lines. METHOD: In the present study, the chemical composition of AEEP was determined through the high-performance liquid chromatography (HPLC). The AEEP and its main component, quercetin (Q), were evaluated in vitro against 57 oral streptococci by a broth micro-dilution method. The biofilm formation was assessed through the crystal violet staining and MTT assays. The impact of AEEP and Q anti-proliferative effect were evaluated on the fibroblast as normal and cancer cell lines (KB and A431). RESULTS: The Q concentration in the composition of AEEP was 6.9% of all its components. The findings indicated that the AEEP and Q were efficient against the cariogenic bacteria and were able to inhibit the S.mutans biofilm adherence at a sub-MIC concentration. Moreover, electron micrographs indicated the inhibition of biofilms compared to control biofilms. In addition, the AEEP and Q indicated a dose-dependent cytotoxic effect on A431 and KB cell lines. On the contrary, they had no cytotoxic effect on fibroblast cells. CONCLUSION: The results indicated that the synergistic impact of main components of AEEP was related to the inhibition of the cancer cell proliferation, cariogenic bacteria and oral biofilm formation. It may play a promising role in the complementary medicine and, it is suggested to be used as food additives.

Arbutin reduces cognitive deficit and oxidative stress in animal model of Alzheimer's disease.

Objectives: Recent evidences have shown the beneficial effects of natural products for treating of Alzheimer's disease (AD). Arbutin is derived from Pyrus biossieriana and exerts a wide range of pharmacological activities including anti-inflammatory and anti-oxidant effects. The present study was designed to examine the protective effects of arbutin on streptozotocin (STZ)-induced neurotoxicity in rats. Materials and methods: The spatial memory impairment was induced by intracerebroventricular (i.c.v) microinjection of STZ (3 mg/kg, 10 µL). Animals received the pretreatment of arbutin (50 mg/kg) for 21 days before STZ injection. The Morris Water maze (MWM) task was used to study the spatial learning and memory. The levels of oxidative stress markers including malondialdehyde (MDA), nitrite and carbonyl were measured in serum and hippocampus samples. In addition, antioxidant level was assessed by ferric reducing antioxidant power (FRAP) test. Results: The obtained result indicated that administration of STZ is led to memory impairment and increases the levels of oxidative stress markers in the hippocampus tissues. Conversely, arbutin improves spatial memory and reduces oxidative and nitrosative stress, as evidenced by a significant decrease in the amount of MDA and nitrite in the serum and hippocampus. In addition, an increase in FRAP levels of hippocampus was observed in arbutin receiving animals. The protein carbonyl content was not reduced in arbutin receiving animals. Conclusion: It could be concluded that arbutin protects the brain against STZ-induced memory impairment and oxidative damage in the hippocampus. The neuroprotective effect of arbutin might be mediated through its antioxidant and free radical scavenging effects.

Efficacy of Two Monoterpenoids, Carvacrol and Thymol, and Their Combinations against Eggs and Larvae of the West Nile Vector Culex pipiens.

Background: Insect vector control is facing the challenges of resistance development and environmental hazards caused by synthetic pesticides. This has led to a considerable market opportunity for botanical insecticides. In this scenario, our study investigated the potential of selected bioactive monoterpenoids, carvacrol and thymol, as safe and effective tools to control the West Nile vector Culex pipiens. Furthermore, the combined effect of thymol-carvacrol mixtures and their possible interactions were assessed. Methods: For determining larvicidal and ovicidal 50% lethal concentration (LC50), each monoterpenoid was tested at different concentrations (5-500 mg/L). Then, the fixed ratio method was used for evaluating their combinational efficacy. Results: Carvacrol was more toxic against larvae of Cx. pipiens, with a LC50 value of 14 mg/L, whereas thymol exhibited a LC50 value of 49 mg/L. Comparable trends of efficacy were observed when toxicity on Cx. pipiens eggs was investigated, with LC50 values of 7 and 13 mg/L for carvacrol and thymol, respectively. In combinational toxicity assays, the mixture thymol-carvacrol at 1:4 ratio achieved a synergistic effect against larvae of Cx. pipiens, whereas an additive effect was observed on eggs. Other ratios showed antagonistic effects. Conclusions: Overall, our findings pointed out that the 1:4 ratio of thymol-carvacrol blend can enhance the insecticidal efficacy on Cx. pipiens young instars and can be considered further as active ingredient for developing botanical insecticides to be used in mosquito control operations.

In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against Leishmania infantum.

BACKGROUND: One of the most important causative agents of visceral leishmaniasis (VL) is Leishmania infantum, which is mainly spread by Phlebotomus and Lutzomyia sandflies in the Old and New World, respectively. Novel and effective drugs to manage this neglected vector-borne disease are urgently required. In this study, we evaluated the toxicity of carvacrol, thymol and linalool, three common essential oil constituents, on amastigotes and promastigotes of L. infantum. Methods: in vitro experiments were performed by 24 h MTT assay. Carvacrol, thymol and linalool at concentrations ranging from 1.3 to 10 µg/mL were tested on promastigotes of L. infantum. For in vivo test, two groups of hamsters (Mesocricetus auratus) received 100 mg/kg of body weight/day of carvacrol and thymol as intraperitoneal injection on day 7 post-infection, followed by a 48 h later injection. The third group was treated with the glucantime as standard drug (500 mg/kg) and the last group (control) just received normal saline. On the 16th day, the number of parasites and histopathological changes in liver and spleen were investigated. RESULTS: 24 h MTT assay showed promising antileishmanial activity of thymol and carvacrol, with IC50 values of 7.2 (48 µM) and 9.8 µg/mL (65 µM), respectively. Linalool at all concentrations did not affect L. infantum promastigote viability. In vivo toxicity data of carvacrol and thymol showed that the former at 100 mg/kg was the safest and most effective treatment with little side effects on the liver. CONCLUSIONS: Overall, thymol and carvacrol are highly promising candidates for the development of effective and safe drugs in the fight against VL.

Quercetin conjugated with silica nanoparticles inhibits tumor growth in MCF-7 breast cancer cell lines.

BACKGROUND: Quercetin is a plant polyphenol from the flavonoid group that plays a fundamental role in controlling homeostasis due to its potent antioxidant properties. However, quercetin has extremely low water solubility, which is a major challenge in drug absorption. METHOD: In this study, we described a simple method for the synthesis of quercetin nanoparticles. The quercetin nanoparticles had an average diameter of 82 nm and prominent yellow emission under UV irradiation. Therefore, we used an in vitro model treated with quercetin and quercetin nanoparticles to investigate the effects of quercetin nanoparticles on MCF-7 breast cancer cell line. FINDING: MCF-7 cells were cultured with different concentrations (1-100 µM) of quercetin nanoparticles at the 24th, 48th and 72 nd hours, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In this study, we found that quercetin nanoparticles (1-100 µM) could significantly reduce cell vitality, growth rate and colony formation of MCF-7 cells. CONCLUSION: Quercetin nanoparticles can inhibit cell growth by blocking the cell cycle and promoting apoptosis in MCF-7 cells more than quercetin. As a result, quercetin nanoparticles may be useful therapy or prevention on breast cancer.

Stoss therapy using fortified biscuit for vitamin D-deficient children: a novel treatment.

BACKGROUND: To evaluate the efficacy of stoss therapy using fortified biscuit for vitamin D-deficient children. METHODS: A total of 108 children aged 30-72 months with vitamin D deficiency were studied in a randomized single-blind clinical trial. The deficient children were assigned to three groups, namely, vitamin D-fortified biscuit (BG), capsule vitamin D (CG), and ampoule vitamin D (AG). Capsules and biscuits containing 50,000 IU of cholecalciferol were consumed twice per week for 3 consecutive weeks. Ampoules with 300,000 IU of cholecalciferol were injected intramuscularly in a single dose. Three weeks after treatment, serum 25(OH)D concentrations were measured, and the three groups were compared. RESULTS: Each method of treatment could increase the mean serum 25(OH)D concentration to optimal level. Serum 25(OH)D concentrations ≥100 ng/mL were observed in six children, including four from AG and two from CG (P = 0.09). The comparison of the mean serum 25(OH)D concentrations after treatment showed between ampoule and capsule (P = 0.3) and capsule and biscuit (P = 0.62) were insignificant; however, the ampoule and biscuit groups differed significantly (P = 0.012). CONCLUSION: Stoss therapy using fortified biscuit may be an effective way to improve compliance in children who cannot take capsules without adverse effects and may also be recommended for prevention purposes.

Low dose administration of Bisphenol A induces liver toxicity in adult rats.

BACKGROUND: Bisphenol A (BPA) is one of the most widely used chemicals, often used in epoxy resins, health products and colors. This study aims to investigate the effect of various doses of BPA on hepatotoxicity in rats. METHOD: This experimental study was conducted using 20 male adult Wistar rats older than 2 months weighing 150-200 g. (5, 25 and 125 µg/kg) BPA was administered by gavage for 35 consecutive days. The animals were weighed at the beginning and the end of the experiment. The level of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were determined using colorimetric method. The liver tissue was kept in the freezer at -80 °C for histological studies. FINDING: The body weight of rats receiving BPA decreased significantly compared to control group and this weight loss was more evident at doses of 25 and 125 µg/kg (p < 0.001). Results of the study demonstrated that the level of ALP and AST decreases significantly (p < 0.001 and p < 0.05, respectively), while the level of ALT did not change. The results that BPA significantly decreased Beta-2 protein and increased Gama protein serum levels in rats (p < 0.01). CONCLUSION: Results of this study demonstrated that BPA increase gamma globulin protein levels and decreases the level of alkaline phosphatase, aspartate aminotransferase and serum protein ß2 and causes weight loss in rats after treatment. This research also demonstrated that the toxic effect of BPA on liver is induced by oxidative stress.

The effect of lamotrigine on learning in mice using the passive avoidance model.

INTRODUCTION: Lamotrigine (LTG) is an antiepileptic drug that inhibits the release of glutamate by blocking sodium channels. The present study was conducted to evaluate the effect of LTG in different stages of memory using a passive avoidance learning task in mice. METHODS: Male albino mice in the weight range 20-25g were used. They were divided into four groups (control group and three groups receiving various doses of LTG). LTG was given in three doses of 10, 25, and 50mg/kg as intraperitoneal (IP) injections. The doses of LTG were used in three injection groups: before acquisition, after consolidation, and before retrieval at 24h. The retention latency times in each group were recorded using a step-through passive avoidance task 24h and one week after consolidation. RESULTS: Retention latency in the group receiving a high dose of LTG (25mg/kg) after one week was significantly increased in comparison to the group receiving a low dose of LTG (10mg/kg) (267±49.96 vs. 198.87±57.22, P=0.015). With injection of LTG after consolidation, the retention latency times were increased in all doses after a one-week retrieval compared to the control (P=0.023). Kaplan-Mayer surveillance analysis also showed significant differences in the latencies of the LTG-receiving group after 24h and one week's retrieval (P=0.041). Administration of LTG before retrieval at 24h showed a significant difference in retention latency time, which was increased for two doses of LTG (10 and 50mg/kg) after one week (203.5±63.67 vs. 270.25±19.78, P=0.024). CONCLUSION: LTG at higher doses may facilitate the learning process in mice and appears to improve memory function at different stages.