Different zeolite systems for colon cancer therapy: monitoring of ion release, cytotoxicity and drug release behavior.

Three types of oral administrated micronized zeolites [ZSM-5, zeolite A and Faujasite NaX (ZSM-5, ZA and ZX, respectively)] were prepared as anticancer 5-fluorouracil (5-Fu) delivery systems for colon cancer treatment. They were prepared by economically widespread and cheap natural resource, kaolin, at low temperatures, using microwave advanced tool. The obtained powders were characterized by XRD, SEM/EDX and BET; meanwhile, their degradation was investigated in two gastric fluids; FaSSGF (pH 1.6) and FeSSGF (pH 5), through concentration measurement of their solution disintegrated elemental constituents of Na+, Al3+ and Si4+ ions. Also, the processes of drug release and mechanism in both solutions were investigated. Moreover, the inhibition action of 5-Fu-free and 5-Fu-conjugated zeolites on colon cancer cells (CaCo-2) was estimated. The results showed that, the prepared zeolites possessed high surface areas of 526, 250, and 578 m2/g for ZSM-5, ZA and ZX, respectively. Although, zeolite structures seemed significantly stable, their frameworks seemed more likely reactive with time. The ions and drug release for zeolites occurred in successively two stages and found to be pH dependent, where the drug and zeolite ions were significantly of higher values in the more acidic media of the gastric solution (pH 1.6) than those of the mild acidic one (pH 5). The obtained activity indicated no cytotoxic affinity for all the prepared zeolite types. Accordingly, the synthesized zeolite frameworks are proposed to be of strong potential drug delivery vehicle for the treatment of gastrointestinal cancer.

Study of the dual effect of gamma irradiation and strontium substitution on bioactivity, cytotoxicity, and antimicrobial properties of 45S5 bioglass.

In this work, we studied simultaneous effect of gamma irradiation and SrO substitution for Na2 O on bioactivity, cytotoxicity and antimicrobial properties of 45S5 glass. Gamma irradiation was mainly introduced in this work as an effective sterilizing technique, improvement of bulk properties and surface modification of glass. Where, gamma irradiation is considered a modifier for glass network due to generation of defects resulted from this irradiation. Furthermore, SrO was introduced into the glass structure in place of Na2 O in order to reduce a probable toxic effect of Na2 O for surrounding tissue by decreasing its percentage. Where, Sr2+ is characterized by its antibacterial properties, as well as, it induces formation of bone tissue and inhibits its resorption. The cell viability was studied for selected samples using Vero cells. As well as, antimicrobial activity was evaluated against Bacillus subtilis, Staphylococcus pneumonia, and Escherichia coli and Pseudomonas aeruginosa bacteria. The results showed that substitution of Na2 O by SrO in glass composition decreased the glass dissolution in SBF. However, the glass dissolution increased after irradiation of such glass due to generation of nonbridgingoxygens (NBOs) throughout glass network by gamma irradiation, and this effect was more obvious for Sr-contained glass. On the other hand, two selected Sr-containing glasses (gamma irradiated at 0 and 25 kGy) showed a good ability to stimulate cell proliferation of normal fibroblast cells, as well as, they represented a potential ability to inhibit the growth of or kill bacteria, which is considered an important issue commonly found in a clinical situation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1646-1655, 2017.

Dissolution and drug release profiles of phosphate glasses doped with high valency oxides.

This paper investigates phosphate glasses incorporating vanadium and molybdenum oxides for effective management of dissolution and drug release. These glass formulations are found to reduce the rate of dissolution from the glass surfaces. The drug functional groups of vancomycin molecules loaded by immersion showed stronger hydrogen bonding with Vanadium doped glasses and consequently lower rate of drug release over 2 weeks indicating better surface attachment with the drug molecules and slow drug release profiles. This can be explained by the strong adherence of drug molecules to glass surfaces compared with the molybdenum containing glasses (PM5 and PM10). The strong attachment relates to hydrogen bonding between the amino-functional groups of vancomycin and the hydrated P-O-H groups in the glass network. In conclusion, the rate of dissolution of doped glasses and the rate of drug release can be administered to deliver the drug molecules over weeks.

Effect of gamma irradiation on drug releasing from nano-bioactive glass.

In this work, we studied the effect of gamma irradiation on nano-bioactive glass (NBG) structure, bioactivity, drug loading efficiency, and drug release kinetic. Gamma irradiation was mainly introduced as a safe and cheap method to tailor the drug loading and release efficiencies. NBG was investigated before and after gamma irradiation with two doses 25 and 50 kGy. Vancomycin antibiotic was used as a drug model, and different kinetic models (first order, Higuchi, Hixson-Crowell, and Baker-Lonsdale models) were used to study the mechanism of drug release. It was found that G25 sample showed the lowest affinity for vancomycin adsorption, but it showed the highest release rate. Also, vancomycin was released from all samples by diffusion mechanism from spherically shaped carrier. On the other hand, the bioactivity of NBG was not altered by gamma irradiation; in contrary, newly formed apatite layers were more well-crystalline.

3,4,5-Trisubstituted Furan-2(5H)-one Derivatives: Efficient one-pot Synthesis and Evaluation of Cytotoxic Activity.

A series of 3,4,5-trisubstituted 2(5H)-furanone derivatives was synthesized through one-pot reaction of amines, aldehydes and diethyl acetylenedicarboxylate. Silica sulfuric acid efficiently catalyzes the 3-component reaction to afford the corresponding 2(5H)-furanones in high yields. The synthesized compounds were tested against HEPG2, MCF7 and CACO tumor cell lines. The cytotoxic activity for the tested compounds showed that: ethyl 2-(4-fluorophenyl)-5-oxo-4-(phenylamino)-2,5-dihydrofuran-3-carboxylate exhibited significant antitumor activity against HEPG2 and MCF7 cell lines (IC50 values 0.002 and 0.002 µM, respectively) more than reference drug (IC50 0.007, 0.005 µM).

Assessment of hepatic function, oxidant/antioxidant status, and histopathological changes in rats treated with atorvastatin: Effect of dose and acute intoxication with acetaminophen.

A major disadvantage that may occur in association with atorvastatin (ATV) therapy is elevation of serum transaminases. This study was designed to evaluate the effects of treatment of rats with various doses of ATV (2, 5, and 10 mg/kg/day) on liver function, oxidative stress, and histology and on the severity of acetaminophen (APAP) hepatotoxicity. ATV administration for 21 days resulted in a dose-dependent significant rise in serum activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. Only ATV at 10 mg/kg/day decreased reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity, increased malondialdehyde (MDA) levels, and elicited histopathological changes in the liver. In rats challenged with APAP (500 mg/kg), the livers showed centrilobular necrosis with evident oxidative stress and liver dysfunction after 24 h. Rats challenged with APAP after pretreatment with ATV 2 or 5 mg/kg/day showed significantly lower activities of serum enzymes, higher hepatic GSH levels and SOD activities, lower MDA levels and milder histopathological changes compared with rats challenged with APAP after pretreatment with ATV 10 mg/kg/day or without drug pretreatment. In conclusion, the effect of ATV on the liver is dose dependent. Our results showed that ATV, at the highest dose used, induced hepatic lipid peroxidation and injury, suggesting a role for oxidative stress in ATV-induced hepatotoxicity. However, lower doses of ATV attenuated APAP-induced hepatotoxicity via a mechanism related, at least in part, to a reduction of APAP-induced hepatic oxidative stress. These results are of practical interest as both drugs may be used concurrently in clinical practice.

Activation of natural killer cells by hepatitis C virus particles in vitro.

Little is known about the ability of hepatitis C virus (HCV) to alter early innate immune responses in infected patients. Previous studies have shown that natural killer (NK) cells are functionally impaired after interaction of recombinant HCV glycoprotein E2 with the co-stimulatory CD81 molecule in vitro; however, the functional consequences of a prolonged contact of NK cells with HCV particles have remained unclear. We have examined the phenotypes of purified, interleukin-2-activated NK cells from healthy donors and HCV genotype 1b patients after culture for 5 days with HCV pseudoparticles (HCVpp) and serum samples containing HCV genotype 1b. NK cells from healthy donors and chronic HCV patients were found to up-regulate receptors associated with activation (NKp46, NKp44, NKp30, NKG2D), while NK receptors from the killer cell immunoglobulin-like receptor family (KIR/CD158), predominantly having an inhibitory function, were significantly down-modulated after culture in the presence of HCV particles compared with control cultures of NK cells. HCV-infected sera and HCVpp elicited significantly higher secretion of the NK effector lymphokines interferon-γ and tumour necrosis factor-α. Furthermore, HCV stimulated the cytotoxic potential of NK cells from normal donors and patients. The enhanced activation of NK cells after prolonged culture with HCVpp or HCV-containing sera for 5 days suggests that these innate effector cells may play an important role in viral control during early phases of HCV infection.

Evaluation of methods used to determine ochratoxin A in coffee beans.

A comparative study was conducted to evaluate four previously reported methods that proved to have a recovery greater than 80% for the determination of different levels of ochratoxin A (OTA) in green and roasted coffee beans and to select an accurate, sensitive, and less-expensive technique between the existing methods. The results indicated that the Association of Official Analytical Chemists (AOAC) official method for the extraction of OTA in green coffee and determination by high-performance liquid chromatography (HPLC) is recommended as an efficient method for the routine analyses of OTA in green and ground roasted coffee beans. This method proved to be an accurate, sensitive, and less-expensive method that employs routine materials and available equipment. Although the immunoaffinity column/HPLC procedure tested showed a significantly higher percentage than the AOAC recommended method, it is recommended for use in processed coffee beans where low concentrations of OTA may be expected to be detected.

Stability of ochratoxin A (OTA) during processing and decaffeination in commercial roasted coffee beans.

The fate of ochratoxin A (OTA) during the processing of artificially contaminated green coffee beans, the effect of decaffeination on the production of OTA in green and roasted coffee beans, and the effect of caffeine on the growth and OTA production by Aspergillus ochraceus were studied. The data indicated that the roasting, milling and decoction (brewing and Turkish coffee making) processes caused different percentage reductions in OTA. Decaffeinated samples showed a significantly higher concentration of OTA production than the caffeinated ones. A significantly higher percentage of OTA was reduced when the decaffeination process was performed before roasting treatment. Caffeine at 1.0 and 2.0% concentrations completely prevented OTA production and completely inhibited A. ochraceus growth in YES medium after 3-21 days.

Assessment of gentamicin-induced nephrotoxicity in rats treated with low doses of ibuprofen and diclofenac sodium.

1. The effects of two non-steroidal anti-inflammatory drugs, ibuprofen (20 mg day-1 kg-1) and diclofenac sodium (2.5 mg day-1 kg-1), on the severity of gentamicin-induced nephrotoxicity were evaluated in rats. 2. Administration of gentamicin (100 mg day-1 kg-1) for 5 days resulted in a significant increase in renal cortical total phospholipids accompanied by a significant decrease in cortical Na+, K(+)-ATPase activity. These changes were associated with a significant decrease in body weight and increases in kidney weight, serum creatinine and urea nitrogen. 3. In rats treated simultaneously with both gentamicin and either ibuprofen or diclofenac sodium for 5 days, all the measured parameters of renal dysfunction were similar in magnitude to those observed in rats treated with gentamicin alone. 4. In contrast, rats treated with either ibuprofen or diclofenac sodium for 27 days and injected concurrently with gentamicin during the last 5 days of the treatment period had significantly higher kidney weight, lower renal cortical Na+, K(+)-ATPase activity and higher cortical phospholipid content, serum creatinine and urea nitrogen than did rats treated with gentamicin alone. A 27-day treatment with ibuprofen or diclofenac sodium alone resulted in no change in renal function. 5. These results demonstrate that gentamicin nephrotoxicity was potentiated after the long (27 days) but not after the short (5 days) period of treatment with ibuprofen and diclofenac sodium. Thus, prolonged administration of non-steroidal anti-inflammatory drugs should be considered as a risk factor that may increase the nephrotoxic potential of gentamicin.

Experimental murine schistosomiasis: reduced hepatic morbidity after pre- and/or post-infection treatment with ibuprofen or diclofenac sodium.

Arachidonic-acid metabolites appear to participate in skin penetration by and transformation of schistosome cercariae and in the pathogenesis of schistosomiasis. With this in mind, mice were treated with one of two cyclooxygenase inhibitors before and/or after infection with Schistosoma mansoni. The effects of the treatment on liver morbidity and the parasitic infection were then evaluated, using infected, untreated and uninfected, treated mice as controls. Treatment with ibuprofen (20 mg/kg.day) or diclofenac sodium (2.5 mg/kg.day) for 7 days before infection led to significantly lower liver weights, worm loads and hepatic hydroxyproline contents than in the untreated mice. If treatment with either drug was continued after infection, for 28 days, there was an additional significant decrease in hepatic gamma-glutamyl transpeptidase activity. All these parameters except liver weight were similarly affected when treatment with either drug was begun on the day of infection and continued for 28 days. There was no significant change in liver weight or worm load when treatment was delayed until day 28 post-infection but faecal egg counts were reduced in the treated groups. In additional experiments, using a smaller dose of diclofenac sodium (1.25 mg/kg.day), all the measured parameters of infection were significantly decreased when the treatment was initiated 7 days before infection and continued until day 28 post-infection. The results indicate that the treatment of S. mansoni-infected mice with ibuprofen or diclofenac sodium was effective in reducing the severity of infection and in attenuating hepatic fibrosis, particularly when the treatment was started early in relation to the time of infection.

Hepatic glutathione and lipid peroxidation in rats treated with theophylline. Effect of dose and combination with caffeine and acetaminophen.

As theophylline, caffeine and acetaminophen (APAP) are commonly found in combination in prescription and non-prescription drugs, the present study was designed to evaluate changes of hepatic glutathione (GSH) and lipid peroxidation in rats treated concurrently with these widely used drugs. In rats treated with different doses of theophylline, a dose-related depletion of hepatic GSH was observed (r = -0.88, P < 0.001). After a dose of 100 mg/kg of caffeine given alone and in combination with 50 mg/kg of theophylline, hepatic GSH levels were decreased by 22.5% (P > 0.05) and 35.5% (P < 0.01) of the control value, respectively. Also, the challenge with 500 mg/kg of APAP significantly depleted hepatic GSH in rats pretreated with either saline or the combination of both theophylline and caffeine (50 and 100 mg/kg, respectively), P < 0.001. In the latter group, hepatic GSH levels were approximately 47% of the corresponding values in rats that received APAP (P < 0.02). Such severe depletion of hepatic GSH, in rats that received the three drugs, was associated with a significant rise in the extent of lipid peroxidation (P < 0.05). The other experimental groups treated with one or two drugs did not exhibit similar changes. These results suggest that the concomitant administration of theophylline, caffeine and APAP may enhance the susceptibility of the liver cells to the toxic effect of APAP by severely depleting hepatic GSH with subsequent induction of lipid peroxidation.

Elevation of serum triacylglycerol concentration in association with hepatic microsomal enzyme induction after treatment with phenylbutazone and diclofenac sodium in rats.

1. The relationship between serum triacylglycerol concentration and hepatic microsomal enzyme activity was examined in rats. 2. Two groups of rats were injected with diclofenac sodium at doses of 2.5 and 5 mg day-1 kg-1. A third group was injected with phenylbutazone at a dose of 20 mg day-1 kg-1. The treatment was continued for 15 days and the rats were killed 24 h after the last dose. 3. In all drug-treated rats, the serum triacylglycerol concentration and the hepatic microsomal activities of aminopyrine N-demethylase and aniline hydroxylase were significantly increased as compared with the corresponding values in control rats. The correlations between the serum triacylglycerol concentrations and the activities of the two enzymes, as indices of the hepatic microsomal activity, were highly significant. 4. These results indicate that the possibility of hypertriglyceridaemia as an adverse effect of the induction of the hepatic microsomal enzymes after the administration of phenylbutazone and diclofenac sodium should be considered.

Verapamil increases the nephrotoxic potential of gentamicin in rats.

The effect of verapamil on the nephrotoxic potential of gentamicin was examined in rats. Rats were injected with one of the two or both drugs for 6 days and sacrificed 48 h after the last injection. In verapamil-treated rats (5 mg/kg/day), no histological or biochemical evidence of renal injury was detected. In all gentamicin-treated rats (100 mg/kg/day), a significant increase in kidney weight was observed (p less than 0.001). The renal histopathologic lesions were more extensive in rats treated simultaneously with both gentamicin and verapamil. These rats exhibited a decline in body weight earlier (from day 4) than rats injected with gentamicin alone (from day 6). Serum urea nitrogen and creatinine in the latter group of rats were 24.9 +/- 3.7 and 1.1 +/- 0.1 versus 47.4 +/- 8.6 and 1.6 +/- 0.2 mg/dl, respectively, in rats treated with the combined therapy (p less than 0.05). These results indicate that verapamil increases the severity of gentamicin nephrotoxicity. This interaction should be considered as a factor that can potentially increase the nephrotoxic risk associated with gentamicin administration.

Vibration pattern of different endosonic instruments.

The history of using ultrasound in dentistry goes back to 1952. The first report on the use of ultrasound as an adjunct to mechanical debridement was given by Richman in 1957. It's popularity started with the work of Martin then many clinical evaluations were reported mainly discussing the efficiency of ultrasonics in root canal preparation.

Evaluation of a synthetic peptide-based assay and a rapid dot-blot recombinant test for detection of antibodies to HIV-1 and HIV-2.

Our objective was to evaluate two new serologic assays for detecting HIV-1 and HIV-2 positive and negative sera. A total of 154 human sera from African countries were tested using a synthetic peptide-based passive hemagglutination assay (PHA) and a rapid dot-blot recombinant test (Test-Pack), both of which are marketed as HIV-1/HIV-2 combination assays. Results indicated that the PHA identified all HIV-1 and HIV-2 positive sera, although some were only weakly reactive. It produced one false positive reaction. The Test-Pack correctly detected all positive and negative sera, although several negative sera produced extremely weak reactions. Both tests detected two HIV-2 positive sera which were non-reactive by HIV-1 screening assays.

Rare mid-line congenital anomalies of the face.

Three rare cases of congenital anomalies (mid-line nasal proboscis, subintegumental mid-line cleft lip and congenital palatoglossal synechia) are presented with their management. The embryological considerations of these cases are discussed.

Hormonal receptors in juvenile nasopharyngeal angiofibroma.

Specific thermostable androgen receptors were detected in the tissues of nasopharyngeal angiofibroma. The receptors seemed to be specific with high affinity toward DHT more than testosterone. No abnormalities in serum levels of DHT, testosterone, and estradiol-17 beta could be detected in the patients studied. A concept of pathogenesis of the tumor in relation to that reported in literature recently is interpreted in the text.

Acute hepatic damage in rats impairs metharbital metabolism.

Metharbital metabolism was impaired in rats after acute hepatic damage induced by carbon tetrachloride. Compared to control rats, hepatic damage prolonged the metharbital sleeping time and reduced the slopes of log metharbital plasma concentration-time curves. Renal contributions to metharbital elimination from plasma were negligible since only about 6% of the metharbital administered was eliminated unchanged in urine. In rats with hepatic damage, metharbital clearance from plasma and elimination of its demethylated metabolite, barbital, in urine decreased with increasing severity of damage. These results indicate that the kinetics of both metharbital and its metabolite reflect sensitively hepatic drug-metabolizing capacity. Measuring urinary elimination of barbital, following metharbital administration, may serve as a convenient laboratory test to evaluate the hepatic drug-metabolizing capacity.

Aminopyrine breath test and zonal hepatic damage in rats.

Acute hepatic damage in centrilobular or periportal areas was induced in two groups of rats by intraperitoneal injections of bromobenzene or allyl alcohol, respectively. The effect of this zonal damage on the demethylation of 14C-aminopyrine was evaluated by measuring the elimination of 14CO2 in breath following intravenous administration of a tracer dose of the labeled compound. In rats with centrilobular hepatic damage 14CO2 elimination in breath was significantly decreased compared to controls. In rats with periportal hepatic damage, elimination of 14CO2 in breath was unchanged. These results suggest functional heterogeneity of hepatocytes in vivo with respect to drug-metabolizing capacity.