Assessing the carcinogenic and non-carcinogenic health risks of metals in the drinking water of Isfahan, Iran.

Metals are significant contributors to water pollution, posing serious threats to human health. This study aims to assess the carcinogenic and non-carcinogenic health risks associated with metals in Isfahan drinking water. Eighty water samples were randomly collected from the city's distribution network between January and March 2020-2021. Inductively coupled plasma Optical Emission Spectrometry was used to measure toxic metals, namely Pb, Cr, Cd, Ni, and As concentrations. Results revealed that the mean concentration of Ni (70.03 µg/L) exceeded the WHO reference value (70 µg/L), while the other metals were below the standard values. The average chronic daily intake order of toxic metals was Ni > Cr > Pb > As > Cd. Non-carcinogenic risk assessment through hazard quotient (HQ) and hazard index (HI) demonstrated that both THI for adults (HQingestion + HQdermal = 4.02E-03) and THI for children (HIingestion + HIdermal = 3.83E-03) were below the acceptable limit (less than 1). This indicated no non-carcinogenic risk to residents through water ingestion or dermal exposure. However, findings indicated that the ingestion route was the primary exposure pathway, with HQ values for ingestion exceeding HQ values for dermal adsorption. Carcinogenic risk assessment showed that the risk associated with As metal exceeded the acceptable limit (1 × 10-6). Therefore, implementing treatment improvement programs and appropriate control measures is essential to safeguard the health of Isfahan City residents.

Evaluation of Some Chemical Parameters of Hemodialysis Water: A Case Study in Iran.

Background: One of the most common diseases in the world is kidney failure, which can lead to the death of patients. Hemodialysis is a treatment for patients whose kidneys are failing. The water used to perform dialysis must be healthy, safe, and clean. This study aimed to investigate the concentration of heavy metals in hemodialysis water in one of the Hospitals in Iran and compare it with European Pharmacopeia (EPH) and Association for the Advancement of Medical Instrumentation (AAMI) standards. Methods: The present study is a descriptive-analytical study conducted on the inlet water of hemodialysis machines in hospital. The samples were collected for 3 months from June to September 2021, Which was examined in terms of free residual chlorine, electrical conductivity, pH, and calcium, magnesium, sodium, aluminum, zinc, copper, and lead concentration. Metals concentration in hemodialysis water was measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) technique. Results: The average value of parameters such as electrical conductivity, pH, residual free chlorine, sodium, calcium, magnesium, zinc, copper and lead in the hemodialysis water was less than the AAMI and EPH standards limits. There was a significant difference at the 95% confidence level with the standard limits, but the aluminum concentration was higher than the standard limits. Also, by examining the medical files of dialysis patients, the most observed problems were anemia and bone diseases, which are probably caused by exposure to high concentrations of aluminum in hemodialysis water. Conclusion: In present study the aluminum concentration is higher than the standard limits. Considering that the higher aluminum concentration can cause diseases such as anemia, bone diseases, nervous deterioration, and death in hemodialysis patients, therefore, it is recommended to continuously evaluate and monitor the quality of hemodialysis water and the performance of its treatment system.

Sulfonated calixarene modified Poly(methyl methacrylate) nanoparticles:A promising adsorbent for Removal of Vanadium Ions from aqueous media.

The poly (methyl methacrylate) (PMMA)-based nanoparticle was synthesized by surfactant-free emulsion polymerization method and then post modified with Calixarene using (3-Aminopropyl)triethoxysilane organo-silane as a linker after OH-treatment. The prepared structure was applied for efficient adsorption of Vanadium ions in the aqueous solution after characterization by FT-IR, SEM, TEM, DLS, and EDX. Additional investigations discovered that the prepared adsorbent has a good capacity to adsorb vanadium ions. The effect of key experimental factors was studied to find the optimal point of adsorbent efficiency including the initial concentration of analyte, sorbent dosage, pH of the solution, contact time, and type/quantity of the eluents. It was specified, the maximum adsorption capacity for the synthesized nanoparticles was obtained about 322 mg g-1. The adsorption mechanism was revealed that the model of Langmuir isotherm well-matched compared to the others due to the calculated equilibrium data. Besides, the kinetics of the adsorption process was fitted with pseudo-second-order. Eventually, the prepared adsorbent was successfully applied in vanadium adsorption from real water media.

The in-vitro study of novel phospholipid micelles loaded with amphotericin B on plasmodium falciparum protozoan.

Malaria is one of the most challenging parasitic infectious diseases in tropical and subtropical regions all over the world. The increasing drug resistance of plasmodium falciparum even makes the treatment procedure of malaria challenging and more problematic. Therefore, it is essential to develop new antimalarial drugs for effective treatments. In this study, the encapsulated amphotericin B (Constantinides et al.) in DSPC/DSPE-PEG2000 micelles was investigated as an antimalarial drug against P. falciparum 3D7 strain. The mean particle size, morphological and microstructural properties of drug-free and drug-loaded micelles prepared with amphotericin B were determined through DLS, FESEM, and TEM analysis. The synthesized phospholipid micelles containing AmB drug with a mean diameter of 115 nm and a polydispersity index of 0.331. The TEM and SEM studies indicate the uniform and homogeneous morphology of the micelles. Drug encapsulation efficiency is 88.3%. The slow release of the micellar system shows the maximum drug release of 75.67% within 24 h. This in vitro study was conducted on P. falciparum 3D7 to investigate the interactions between AmB micelles and P. falciparum parasites using different drug ratios. According to the findings, the IC50 of free AmB is 4.834 µg/ml, while the nano-diameter AmB has a significantly lower IC50 of 2.394 µg/ml. The results of this study suggest that the drug-loaded phospholipid micelles have significantly higher bioactivity and greater plasmodial properties compared to the direct application of AmB against P. falciparum. Moreover, according to the results of this study, the encapsulated AmB drugs are promising nanostructures for malaria treatment. Therefore the nanoencapsulation AmB showed promising application for malaria treatment.

Monitoring of urinary arsenic (As) and lead (Pb) among a sample of pregnant Iranian women.

PURPOSE: Heavy metals, as significant toxic environmental contaminants, can cause serious adverse health outcomes on the human body even in trace concentrations. There is limited evidence on heavy metal concentrations existing in the body fluids of pregnant women. This study aims to evaluate the urinary levels of arsenic (As) and lead (Pb), as two main toxic heavy metals, among pregnant women and their lifestyle determinants. METHODS: The study was performed in 2019-2020 in Isfahan, Iran. A number of 140 urine samples of pregnant women who were in their first pregnancy trimester were examined. Inductively coupled plasma optical emission spectrometry (ICP-OES) was applied to analyze the urinary concentrations of As and Pb. Socio-demographic data including age, pre-pregnancy body mass index (BMI), education status, and family income, as well as the use of cleaning products (cosmetic and household cleaning products), and lifestyle habits (food intake, smoking, and physical activity) were collected using a validated questionnaire. RESULTS: The mean concentration of As and Pb were 8.14 ± 10.8 and 9.6 ± 7.1 µg/g creatinine, respectively. The mean urinary concentration of Pb indicated significant differences in the levels of cosmetic usage, second-hand smoking exposure, and the use of Copper, Aluminum, Teflon, Steel, and Enameled utensils for cooking (p-value < 0.05). Furthermore, the mean of urinary Pb concentrations at high levels of physical activity and scratched utensils using was significantly different from the other categories (p-value = 0.02). No significant differences were found between As and Pb concentration with other socio-demographic factors. CONCLUSION: The lifestyle determinants and cosmetic products use are important predictors of urinary heavy metals in pregnant women, rather than sociodemographic characteristics. Additional research is necessary to determine long-term adverse birth outcomes of exposure to these heavy metals.

Prenatal exposure to chromium (Cr) and nickel (Ni) in a sample of Iranian pregnant women: urinary levels and associated socio-demographic and lifestyle factors.

Heavy metals have been well documented to pose detrimental health effects. The current study aimed to measure the concentration of chromium (Cr) and nickel (Ni) in urinary samples of Iranian pregnant females and determine their potential correlations with different lifestyle variables. The study was conducted in 2019-2020 in Isfahan, Iran, and the urine samples were collected from 140 pregnant women. The concentrations of Cr and Ni in the urinary samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Data on socio-demographic characteristics, use of cleaning products, and lifestyle profiles was collected by validated questionnaires. Cr and Ni were detected in 100% of urinary samples with the mean concentration of 4.1±3.4 and 7.5±4.8 µg/g creatinine, respectively. Significant associations were found between the mean concentration of Cr and Ni with using cooking utensils made of copper, aluminum, Teflon, steel, and enameled, as well as with cosmetic use, and second-hand smoking exposure during pregnancy. The results also showed that the mean urinary Ni and Cr concentrations were significantly different among individuals who consumed seafood and canned food (p-value <0.05). Furthermore, the mean of urinary Cr and Ni concentrations at high levels of physical activity and scratched utensils used was significantly different from the other categories (p-value <0.05). According to our findings, the lifestyle determinants and cosmetic products had superiority to socio-demographic characteristics in predicting urinary heavy metals in Iranian pregnant women.

Effect of Castor Oil on Bioprocess Parameters of Erythromycin Fermentation by Saccharopolyspora Erythraea.

Background: Increased economic competitiveness in the biopharmaceutical industry requires continuous improvement of bioprocesses. In this regard compositions of fermentation media have an important role in bioprocesses. Objectives: The modification of the culture medium has proven effective in enhancing the yield and productivity of fermentation processes. The objective was to investigate the influence of castor oil as the main carbon source for Saccharopolyspora erythraea, on the yield of antibiotic fermentative production. Material and Methods: The titer of erythromycin was evaluated in Saccharopolyspora erythraea cultures, containing various concentrations of castor oil, in comparison to the control culture containing rapeseed oil. Results: The results showed an enhancement in erythromycin production when 50 g.L-1and 40 g.L-1of castor oil were added to the fermentation culture instead of rapeseed oil, respectively. The highest amount of production was obtained on the eleventh day of fermentation time in all media. Conclusion: Erythromycin production in the control medium was relatively less than that of the treatments, indicating that S. erythraea consumed castor oil as a rich alternative carbon source. The results show that castor oil was more suitable as a carbon source for erythromycin production than a medium containing rapeseed oil.

The Effect of Phase Transition Temperature on Therapeutic Efficacy of Liposomal Bortezomib.

AIMS: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor. BACKGROUND: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment. OBJECTIVE: Evaluating anti-tumor activity of bortezomib liposomal formulations. METHODS: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models. RESULT: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice. CONCLUSION: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.

Preparation and characterization of nanoliposomal bortezomib formulations and evaluation of their anti-cancer efficacy in mice bearing C26 colon carcinoma and B16F0 melanoma.

Three Bortezomib (BTZ) liposomal formulations including of HSPC/Cholesterol/DSPE-mPEG2000 (F1), HSPC/DSPG/Cholesterol (F2), and HSPC/DSPG/Cholesterol/DSPE-mPEG2000 (F3) were prepared and characterized. Results demonstrated that the size of formulations ranged 72-92 nm. The DSPE-mPEG2000 containing formulations (F1 and F3) had higher BTZ encapsulation compared to F2 formulation. The size of the liposomal formulations increased slightly when stored at 4 °C for 6 months; the zeta potential of formulations remained constant. There were no significant differences in the release properties BTZ from liposomal formulations in pH 7.0; however, in acidic pH of 5.5 the release of BTZ from F1 and F3 was higher than F2. Three formulations cytotoxicity studies demonstrated IC50 values more than free BTZ on all cell lines examined. Evaluation of antitumor activity in mice bearing C26 colon carcinoma and B16F0 melanoma tumors showed that all the designed liposomal formulations have higher efficacy compared to free BTZ. In tumor models, F2 was more effective than the F1 and F3. Our findings indicated that F2 considerably increased the therapeutic efficacy of BTZ, which promises new formulation with the potential use in clinic and merits further investigation.

Performance evaluation of waste stabilization ponds on removal of Listeria spp.: a case study of Isfahan, Iran.

The aim of the present study was to assess performance of waste stabilization ponds (WSPs) on the removal of Listeria spp. in Isfahan, Iran. A total of 104 samples were taken from eight sampling locations from influent and effluent of a wastewater treatment plant (WWTP). Sewage samples were analyzed for the presence of Listeria spp. using selective enrichment protocol. Listeria isolates were also identified by biochemical and polymerase chain reaction (PCR) amplification. Listeria spp. was enumerated by a three tube most probable number (MPN) for total coliform counts (TC), fecal coliform counts (FC), total suspended solids (TSS), and total dissolved solids (TDS). In total, 54/104 (51.92%), 49/104 (47.11%), 36/104 (34.61%), and 27/104 (25.95%) samples were positive for Listeria spp., L. monocytogenes, L. innocua, and L. seeligeri, respectively. The mean MPN/100 mL enumeration of L. monocytogenes for influent, anaerobic, facultative ponds 1, 2, 3, 4 and maturation ponds 1 and 2 were 21.54, 10.61, 8, 5.77, 4, 2.54, 1.38, and 0.46, respectively. The removal percentage of Listeria spp. in the anaerobic, facultative, and maturation ponds were 44.71, 76.5, and 81.4%, respectively. Results showed that the WSPs were able to decrease the Listeria spp. levels significantly, although unable to remove them completely.

Determination of Bortezomib in API Samples Using HPLC: Assessment of Enantiomeric and Diastereomeric Impurities.

A new, normal phase high performance liquid chromatography (NP-HPLC) method was developed for separation of Bortezomib (BZB) enantiomers and quantitative determination of (1S,2R)-enantiomer of BZB in active pharmaceutical ingredient (API) samples. The developed method was validated based on International Conference on Harmonisation (ICH) guidelines and it was proved to be accurate, precise and robust. The obtained resolution (RS) between the enantiomers was more than 2. The calibration curve for (1S,2R)-enantiomer was found to be linear in the concentration range of 0.24-5.36 mg/L with regression coefficient (R2) of 0.9998. Additionally, the limit of detection (LOD) and limit of quantification (LOQ) were 0.052 and 0.16 mg/L, respectively. Also, in this study, a precise, sensitive and robust gradient reversed-phase HPLC (RP-HPLC) method was developed and validated for determination of BZB in API samples. The detector response was linear over the concentration range of 0.26-1110.5 mg/L. The values of R2, LOD and LOQ were 0.9999, 0.084 and 0.25 mg/L, respectively. For both NP-HPLC and RP-HPLC methods, all of the RSD (%) values obtained in the precision study were <1.0%. System suitability parameters in terms of tailing factor (TF), number of theoretical plates (N) and RS were TF < 2.0, N > 2,000 and RS > 2.0. The performance of two common integration methods of valley to valley and drop perpendicular for drawing the baseline between two adjacent peaks were investigated for the determination of diastereomeric impurity (Imp-D) in the BZB-API samples. The results showed that the valley to valley method outperform the drop perpendicular method for calculation of Imp-D peak areas. Therefore, valley to valley method was chosen for peak integration.

In vitro effect of imatinib mesylate loaded on polybutylcyanoacrylate nanoparticles on leukemia cell line K562.

The study aimed to prepare imatinib mesylate-loaded polybutylcyanoacrylate (PBCA) nanoparticles and evaluate their efficacy on leukemia cell line K562. The formulation was prepared by miniemulsion polymerization technique. Nanoparticles were characterized by dynamic light scattering (DLS), spectrophotometry, Fourier transform infrared spectroscopy (FTIR), dialysis membrane, and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) techniques. Nanoscale particles with high encapsulation efficiency (86%) and physical entrapment of drug were observed. In addition, nanoparticles showed suitable drug retention capability and potentiate the cytotoxicity effects of imatinib mesylate. Findings of study suggested PBCA nanoparticles are promising carrier for imatinib mesylate delivery to leukemia cell line K562.

Development and validation of a HPTLC method for analysis of Sunitinib malate

ABSTRACT A simple high performance thin layer chromatography (HPTLC) has been developed and validated for determination of sunitinib malate and possible impurities. The samples were applied in forms of bands on an aluminum TLC plate pre-coated with silica gel and were separated using dichloromethane: methanol: toluene: ammonia solution as the mobile phase. Sunitinib malate was thoroughly separated from impurities including E-isomer, sunitinib N-oxide and impurity B with a retention factor (RF) of 0.35±0.02. Quantitative analysis of sunitinib was carried out using a mobile phase consisting of dichloromethane:methanol:ammonia solution, RF value was 0.53±0.02 for Z isomer. Detection was performed densitometrically in absorbance mode at 430 nm. This method was found to produce sharp, symmetrical, and well resolved peaks. Linear relationship with the coefficients of determination > 0.99 was achieved over the concentration range of 27.34 to 437.5 ng/spot. This method provides robust, replicable and accurate results with acceptable sensitivity.

New Oral Formulation and in Vitro Evaluation of Docetaxel-Loaded Nanomicelles.

Intravenous administration of Taxotere® (a commercial form of docetaxel, DTX) leads to many problems such as hypersensitivity, hemolysis, cutaneous allergy, and patient refusal due to its prolonged injection. The oral absorption of DTX is very low due to its hydrophobic nature. The purpose of this study was to prepare and carry out an in vitro evaluation of DTX-loaded nanomicelles for oral administration in order to increase the oral delivery of DTX. Studied formulations were prepared with the two surfactants Tween 20 and Tween 80 and were characterized for their particle size, zeta potential, stability, encapsulation efficiency, stability studies in gastric fluid and intestinal fluid, toxicity studies in C26 colon carcinoma cell line, and cellular uptake. The prepared nanomicelles with particle size of around 14 nm and encapsulation efficiency of 99% were stable in gastric fluid and intestinal fluid for at least 6 h and IC50 decreased significantly after 72 h exposure compared to that of Taxotere®. Nanomicelles increased the water solubility of DTX more than 1500 times (10 mg/mL in nanomicelles compared to 6 µg/mL in water). Results of this study reveal that the new formulation of DTX could be used for the oral delivery of DTX and merits further investigation.

Poly (I:C)-DOTAP cationic nanoliposome containing multi-epitope HER2-derived peptide promotes vaccine-elicited anti-tumor immunity in a murine model.

In the current study we aimed at developing a vaccine delivery/adjuvant system to enhance anti-tumor immunity against the natural multi-epitope HER2/Neu-derived P5 peptide. Polyriboinosinic: polyribocytidylic acid [Poly (I:C)] is a strong immunoadjuvant able to enhance specific antitumor immunity induced by peptide-based vaccines. Nevertheless, delivering the peptide and adjuvant intracellularly into their target site remains a challenging issue. We hypothesized this barrier could be overcome through the use of a cationic nanoliposome carrier system which can carry and protect the antigen and adjuvant in the extracellular environment and augment the induction of antitumor immunity. P5 was encapsulated in cationic nanoliposomes composed of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-Cholesterol either alone or complexed with Poly (I:C). Immunocompetent BALB/c mice were immunized with the formulations 3 times in two-week intervals and the efficiency and type of immune response were then evaluated both in vitro and in vivo. The groups immunized with Lip-P5+PIC (DOTAP-Cholestrol-P5+Poly (I:C)) and Lip+PIC (DOTAP-Cholestrol+Poly (I:C)) enhanced the release of Interferon (IFN)-γ in comparison with other groups. Flow cytometry analysis revealed that Lip-P5+PIC formulation induced the highest level of IFN-γ in CD8(+) lymphocytes. Lip-P5+PIC, Lip+PIC and Lip-P5 (DOTAP-Cholestrol-P5) provided some extent of protection in terms of tumor regression in TUBO tumor mice model during the first 65days post tumor challenge but at the end only the tumors of mice immunized with Lip-P5+PIC were significantly smaller than all other groups. Furthermore, tumors of mice receiving Lip-P5+PIC grew at a significantly slower rate throughout the observation period. Our results showed that the combination of Poly (I:C) and DOTAP with the tumor antigen and without applying additional T-helper epitope induced strong antitumor responses. The observations presented here are of great interest for future vaccine studies.

Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80.

Amphotericin B (AmB) and Nystatin (Nys) are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, using a coarse-grained (CG) molecular dynamics (MD) simulation approach, we investigated the interaction of AmB and Nys with Polysorbate 80 (P80) to gain insight into the behavior of these polyene antibiotics (PAs) in nanomicellar solution and derive potential implications for their formulation development. While the encapsulation process was predominantly governed by hydrophobic forces, the dynamics, hydration, localization, orientation, and solvation of PAs in the micelle were largely controlled by hydrophilic interactions. Simulation results rationalized the experimentally observed capability of P80 in solubilizing PAs by indicating (i) the dominant kinetics of drugs encapsulation over self-association; (ii) significantly lower hydration of the drugs at encapsulated state compared with aggregated state; (iii) monomeric solubilization of the drugs; (iv) contribution of drug-micelle interactions to the solubilization; (v) suppressed diffusivity of the encapsulated drugs; (vi) high loading capacity of the micelle; and (vii) the structural robustness of the micelle against drug loading. Supported from the experimental data, our simulations determined the preferred location of PAs to be the core-shell interface at the relatively shallow depth of 75% of micelle radius. Deeper penetration of PAs was impeded by the synergistic effects of (i) limited diffusion of water; and (ii) perpendicular orientation of these drug molecules with respect to the micelle radius. PAs were solvated almost exclusively in the aqueous poly-oxyethylene (POE) medium due to the distance-related lack of interaction with the core, explaining the documented insensitivity of Nys solubilization to drug-core compatibility in detergent micelles. Based on the obtained results, the dearth of water at interior sites of micelle and the large lateral occupation space of PAs lead to shallow insertion, broad radial distribution, and lack of core interactions of the amphiphilic drugs. Hence, controlled promotion of micelle permeability and optimization of chain crowding in palisade layer may help to achieve more efficient solubilization of the PAs.

A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS Diminution in Mice.

Licofelone is a COX/5-LOX inhibitor, which recently was approved as an effective treatment for osteoarthritis. Beside its analgesic and anti-inflammatory effects, some reports show neuro-protective properties for this agent in central nervous system. Several lines of evidence declare the involvement of COX or LOX isoenzymes in epileptic disorders. To set the foundation for future research into the neurobiology of licofelone as a potential therapeutic agent, we studied the effect of licofelone in an animal model of epilepsy. Although different neurotransmitters and neuro-modulators like nitric oxide were introduced as suggested targets of licofelone, the underlying mechanisms of central effects of this drug are not still fully understood. We have utilized pentylenetetrazole-induced clonic seizure model to investigate the behavioral consequences of licofelone administration and its possible mechanisms in seizure susceptibility. Licofelone revealed anticonvulsant properties at the dose of 10 mg/kg (i.p) or higher in mice. Pre-treatment with NO (nitric oxide) donor, L-arginine, reversed this anticonvulsant effects dose dependently. L-NAME, as a non-selective nitric oxide synthase (NOS) inhibitor, potentiated the anticonvulsant effects of licofelone. A neuronal NOS inhibitor, 7-NI did not affect seizure threshold alone or in combination with licofelone. Using non-effective doses of selective inhibitors of inducible NOS, aminoguanidine or 1400W, significantly increased the seizure threshold when were accompanied by licofelone in low doses. These data support the involvement of NO as an important role player in the central neuro-protective properties of licofelone. Furthermore, it implies that down regulation of iNOS seems crucial for anticonvulsant properties of this COX/5-LOX inhibitor in seizure susceptibility.

A rapid hydrolysis method and DABS-Cl derivatization for complete amino acid analysis of octreotide acetate by reversed phase HPLC.

Octreotide as a synthetic cyclic octapeptide is a somatostatin analog with longer half-life and more selectivity for inhibition of the growth hormone. The acetate salt of octreotide is currently used for medical treatment of somatostatin-related disorders such as endocrine and carcinoid tumors, acromegaly, and gigantism. Octreotide contains both cysteine and tryptophan residues which make the hydrolysis part of its amino acid analysis procedure very challenging. The current paper introduces a fast and additive-free method which preserves tryptophan and cysteine residues during the hydrolysis. Using only 6 M HCl, this hydrolysis process is completed in 30 min at 150 °C. This fast hydrolysis method followed by pre-column derivatization of the released amino acids with 4-N,N-dimethylaminoazobenzene-4'-sulfonyl chloride (DABS-Cl) which takes only 20 min, makes it possible to do the complete amino acid analysis of an octreotide sample in a few hours. The highly stable-colored DABS-Cl derivatives can be detected in 436 nm in a reversed phase chromatographic system, which eliminates spectral interferences to a great extent. The amino acid analysis of octreotide acetate including hydrolysis, derivatization, and reversed phase HPLC determination was validated according to International Conference of Harmonization (ICH) guidelines.

Enhanced oxygen transfer rate and bioprocess yield by using magnetite nanoparticles in fermentation media of erythromycin.

BACKGROUND: Magnetite nanoparticles have widespread biomedical applications. In the aerobic bioprocesses, oxygen is a limiting factor for the microbial metabolic rate; hence a high availability of oxygen in the medium is crucial for high fermentation productivity. This study aimed to examine the effect of using magnetite nanoparticles on oxygen transfer rate in erythromycin fermentation culture. METHODS: Magnetite nanoparticles were synthetized through co-precipitation method. After observing the enhanced oxygen transfer rate in deionized water enriched with magnetite nanoparticles, these nanoparticles were used in the media of by Saccharopolyspora erythraea growth to explore their impact on erythromycin fermentation titer. Treatments comprised different concentrations of magnetite nanoparticles, (0, 0.005, 0.02 v/v). RESULTS: In the medium containing 0.02 v/v magnetite nanoparticles, KLa was determined to be 1.89 time higher than that in magnetite nanoparticle-free broth. An improved 2.25 time higher erythromycin titer was obtained in presence of 0.02 v/v nanoparticles. CONCLUSIONS: Our results, demonstrate the potential of magnetite nanoparticles for enhancing the productivity of aerobic pharmaceutical bioprocesses.

An inhibitory enzyme electrode for hydrogen sulfide detection.

An enzymatic biosensing system has been developed to study the capability of ascorbate oxidase (AOx), EC (1.10.3.3), in hydrogen sulfide (H2S) detection, based on the inhibition of AOx activity. The immobilization parameters including glutaraldehyde (GA) concentration and pH were optimized using experimental design. The optimized values of GA concentration and pH were found to be 12.5% (w/w) and 7, respectively, where the enzymatic reaction reached the steady-state level within 55 s. A linear relationship was observed between the decrease in the oxygen concentration and H2S concentration, where H2S concentration is in the range of 1-15 mg/L. Moreover, to investigate the selectivity of the biosensor, a certain H2S concentration (9 mg/L) was used against different ions. The results indicated that Fe(3+) and SO4(-2) ions had no significant (11% error) effect on the H2S detection. The operational stability of the biosensing system was determined in terms of response to H2S concentration, at optimal working conditions. The enzyme electrode could retain 73% of its original sensitivity after this period, which has made it possible for the system to measure H2S with concentrations as low as 0.5 mg/L.