Capece, B P; Castells, G; Pérez, F; Arboix, M; Cristòfol, C
Benzimidazole anthelmintic drugs are widely used in veterinary practice. Albendazole sulphoxide (ABZSO) is a benzimidazole drug with two enantiomers, as a consequence of a chiral centre in the sulphoxide group. The kinetics of these enantiomers were studied in male and female sheep. Plasma samples were obtained from the animals between 0.5 and 72 h after oral administration of 7.5 mg/kg of a racemic formulation of ABZSO (total-ABZSO). After a liquid-liquid extraction, the samples were analysed by HPLC to determine the concentrations of total-ABZSO and of the sulphone metabolite (ABZSO2). During the chromatographic analysis, the ABZSO peak was collected and reanalysed by an HPLC technique using a Chiral AGP column to quantify the enantiomeric proportion therein. After kinetic analysis, the AUCs obtained for the (+)-ABZSO were 5.8 and 4.0 times higher than those for the (-)-ABZSO in male and female animals, respectively. The mean residence times were 23.4 and 16.1 h for (+)-ABZSO and 22.2 and 17.4 h for (-)-ABZSO for male and female animals, respectively. The only significant difference between the sexes (p < 0.05) was in the Tmax of the (-)-ABZSO. Comparing both enantiomers within each sex, significant differences were found in all the kinetic parameters. Finally, no kinetic differences were found between sex for total-ABZSO or ABZSO2.
Capece, B P S; Navarro, M; Arcalis, T; Castells, G; Toribio, L; Perez, F; Carretero, A; Ruberte, J; Arboix, M; Cristòfol, C
Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found.
Virkel, G; Lifschitz, A; Soraci, A; Sansinanea, A; Lanusse, C
1. The enantioselective liver microsomal sulphoxidation of the benzimidazole anthelmintic, albendazole (ABZ), by cattle liver microsomes has been investigated. The influence of nutritional condition on this biotransformation process was also characterized. 2. ABZ was oxidized to its sulphoxide metabolite (ABZSO) in a NADPH concentration-dependent reaction and the (+) and (-) ABZSO enantiomers formed were identified. 3. Vmax (0.27 nmol ABZSO formed per min x mg(-1) microsomal protein) and Km (15.10 microM) for ABZ sulphoxidation by cattle liver microsomes were obtained. Different Vmax (0.11 and 0.16 nmol x min(-1) x mg(-1)) and Km (9.40 and 26.70 microM) characterized the enantioselective formation of (+) and (-) ABZSO antipodes, respectively. 4. Free fatty acid (FFA) concentrations and beta-hydroxybutyrate concentrations (beta-OHB) in serum and liver homogenates were significantly higher in feed-restricted (poor nutritional condition) compared with control animals in an optimal nutritional status. Serum protein concentrations and liver cytosolic glucose 6-phosphate dehydrogenase (G6PD) activity were significantly lower in the feed-restricted compared with control calf. 5. Animal nutritional condition affected the pattern of ABZ sulphoxidation. A higher Km for (total) ABZSO and (+) ABZSO production was observed in the calf subjected to a period of undernutrition. 6. A nutritionally induced impairment in the affinity of microsomal mixed-function oxidases responsible of ABZ oxidation may be responsible for the observed changes in the liver microsomal sulphoxidation of ABZ in the feed-restricted calf. Furthermore, undernutrition may affect primarily the FMO-mediated formation of (+) ABZSO. These in vitro observations agree with the changes observed in vivo following the administration of ABZ to the calf subjected to a dietary restriction.
Carlsson, Gunnar; Patring, Johan; Ullerås, Erik; Oskarsson, Agneta
Albendazole (ABZ) is used as an anthelmintic drug in humans and animals. ABZ has been shown to cause developmental toxicity in experimental animals, however it is not clear if this is caused by the parent compound or a metabolite. Zebrafish embryos were exposed from 1 to 144hpf (hours post fertilization) to investigate the developmental toxicity of ABZ, the first metabolite albendazole sulphoxide and the subsequent metabolites albendazole sulphone (ABZSO(2)) and albendazole-2-aminosulphone (ABZSO(2)NH(2)). The results showed that ABZ caused malformations of head and tail and embryonic lethality from 0.3μM. In contrast, the metabolites did not display developmental toxicity at any tested concentration. Dechorionation did not influence the developmental toxic potential of ABZ and ABZSO, indicating that bioavailability was not a limiting factor. Chemical analysis showed that at sublethal concentrations, most of ABZ was metabolized to ABZSO. The results demonstrate that in zebrafish embryos ABZ rather than ABZSO displays developmental toxicity.
Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A
Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is
Belaz, Kátia Roberta A; de O Cardoso, Josiane; da Silva, Carlos Alberto; Oliveira, Regina V
This work presents an in vitro investigation of the effect of protein restriction on the metabolism of albendazole (ABZ). This study was conducted using liver microsomal fractions obtained from Wistar rats. For the quantitative analysis, a multidimensional High Performance Liquid Chromatography (2D HPLC) method was fully validated for the determination of the ABZ metabolites: albendazole sulfoxide, albendazole sulfone and albendazole 2-aminesulfone. The target compounds were directly extracted using a C8-RAM-BSA column (5.0x0.46 cm i.d.) and analyzed on a chromatographic chiral column containing amylose tris(3,5-dimethylphenylcarbamate) (150x4.6 mm i.d.). The in vitro biotransformation results showed that the protein restriction influenced the oxidative metabolism of ABZ. The production of R-(+)-ABZ-SO (1309 nmol/L) and S-(-)-ABZ-SO (1456 nmol/L) was higher in the control animals than in the animals fed with a diet containing 6% protein, which produced 778.7 nmol/L and 709.5 nmol/L for R-(+) and S-(-)-ABZ-SO enantiomers, respectively. These results were statistically inspected by Student´s t test and the results showed a significant difference between the two means (p<0.05). Moreover, the production of ABZ-SO enantiomers was enantioselective where the S-(-)-ABZ-SO was formed in greater amounts than the R-(+)-ABZ-SO in control animals (p=0.0231). However, the enantioselectivity was not observed when the in vitro biotransformation of ABZ was conducted using the microsomal fractions obtained from protein restriction animals (p>0.05). Furthermore, animal nutritional condition could affect the pattern of ABZ sulphoxidation indicating that the protein nutrition affect primarily the formation of R-(+)-ABZSO and S-(-)-ABZ-SO enantiomers.
Argüello-García, Raúl; Cruz-Soto, Maricela; González-Trejo, Rolando; Paz-Maldonado, Luz María T.; Bazán-Tejeda, M. Luisa; Mendoza-Hernández, Guillermo; Ortega-Pierres, Guadalupe
Albendazole (ABZ) is a therapeutic benzimidazole used to treat giardiasis that targets β-tubulin. However, the molecular bases of ABZ resistance in Giardia duodenalis are not understood because β-tubulin in ABZ-resistant clones lacks mutations explaining drug resistance. In previous work we compared ABZ-resistant (1.35, 8, and 250 μM) and ABZ-susceptible clones by proteomic analysis and eight proteins involved in energy metabolism, cytoskeleton dynamics, and antioxidant response were found as differentially expressed among the clones. Since ABZ is converted into sulphoxide (ABZ-SO) and sulphone (ABZ-SOO) metabolites we measured the levels of these metabolites, the antioxidant enzymes and free thiols in the susceptible and resistant clones. Production of reactive oxygen species (ROS) and levels of ABZ-SO/ABZ-SOO induced by ABZ were determined by fluorescein diacetate-based fluorescence and liquid chromatography respectively. The mRNA and protein levels of antioxidant enzymes (NADH oxidase, peroxiredoxin 1a, superoxide dismutase and flavodiiron protein) in these clones were determined by RT-PCR and proteomic analysis. The intracellular sulfhydryl (R-SH) pool was quantified using dinitrobenzoic acid. The results showed that ABZ induced ROS accumulation in the ABZ-susceptible Giardia cultures but not in the resistant ones whilst the accumulation of ABZ-SO and ABZ-SOO was lower in all ABZ-resistant cultures. Consistent with these findings, all the antioxidant enzymes detected and analyzed were upregulated in ABZ-resistant clones. Likewise the R-SH pool increased concomitantly to the degree of ABZ-resistance. These results indicate an association between accumulation of ABZ metabolites and a pro-oxidant effect of ABZ in Giardia-susceptible clones. Furthermore the antioxidant response involving ROS-metabolizing enzymes and intracellular free thiols in ABZ-resistant parasites suggest that this response may contribute to overcome the pro-oxidant cytotoxicity of ABZ. PMID
Argüello-García, Raúl; Cruz-Soto, Maricela; González-Trejo, Rolando; Paz-Maldonado, Luz María T; Bazán-Tejeda, M Luisa; Mendoza-Hernández, Guillermo; Ortega-Pierres, Guadalupe
Albendazole (ABZ) is a therapeutic benzimidazole used to treat giardiasis that targets β-tubulin. However, the molecular bases of ABZ resistance in Giardia duodenalis are not understood because β-tubulin in ABZ-resistant clones lacks mutations explaining drug resistance. In previous work we compared ABZ-resistant (1.35, 8, and 250 μM) and ABZ-susceptible clones by proteomic analysis and eight proteins involved in energy metabolism, cytoskeleton dynamics, and antioxidant response were found as differentially expressed among the clones. Since ABZ is converted into sulphoxide (ABZ-SO) and sulphone (ABZ-SOO) metabolites we measured the levels of these metabolites, the antioxidant enzymes and free thiols in the susceptible and resistant clones. Production of reactive oxygen species (ROS) and levels of ABZ-SO/ABZ-SOO induced by ABZ were determined by fluorescein diacetate-based fluorescence and liquid chromatography respectively. The mRNA and protein levels of antioxidant enzymes (NADH oxidase, peroxiredoxin 1a, superoxide dismutase and flavodiiron protein) in these clones were determined by RT-PCR and proteomic analysis. The intracellular sulfhydryl (R-SH) pool was quantified using dinitrobenzoic acid. The results showed that ABZ induced ROS accumulation in the ABZ-susceptible Giardia cultures but not in the resistant ones whilst the accumulation of ABZ-SO and ABZ-SOO was lower in all ABZ-resistant cultures. Consistent with these findings, all the antioxidant enzymes detected and analyzed were upregulated in ABZ-resistant clones. Likewise the R-SH pool increased concomitantly to the degree of ABZ-resistance. These results indicate an association between accumulation of ABZ metabolites and a pro-oxidant effect of ABZ in Giardia-susceptible clones. Furthermore the antioxidant response involving ROS-metabolizing enzymes and intracellular free thiols in ABZ-resistant parasites suggest that this response may contribute to overcome the pro-oxidant cytotoxicity of ABZ.
Cristòfol, C; Navarro, M; Franquelo, C; Valladares, J E; Arboix, M
Sex differences in the disposition of albendazole metabolites in sheep after oral administration of 20 mg/kg of netobimin have been studied. Some kinetic parameters of both metabolites show statistical differences between sexes; the sulphoxide and sulphone t1/2beta and MRT were lower in male animals than in females. Peak concentrations and AUC of sulphone metabolites were higher in males suggesting a greater oxidation rate compared with females. Urine excretion of albendazole metabolites, sulphoxide, sulphone, and amino sulphone appeared to be greater in female sheep than in males, mainly the sulphoxide metabolite. These differences between sexes can be caused by male sexual hormones, because testosterone and progesterone can induce or inhibit the microsomal Cytochrome P450 metabolism. Plasma protein-binding of albendazole sulphoxide and albendazole sulphone has been studied between male and female sheep, also their binding to sheep albumin and globulins. Both albendazole metabolites readily bind to sheep albumin and globulins. Male animals show a significantly lower binding of albendazole metabolites than females. These differences could be responsible for the non-esterified fatty acids (NEFA) present in the plasma. Males have significantly higher plasma levels of NEFA than females and which may compete with albumin for binding to albendazole metabolites.
Canevari, J; Ceballos, L; Sanabria, R; Romero, J; Olaechea, F; Ortiz, P; Cabrera, M; Gayo, V; Fairweather, I; Lanusse, C; Alvarez, L
The main goal of the current work was to develop and validate an in vitro fluke egg hatch test, as a method for the detection of albendazole (ABZ) resistance in the liver fluke, Fasciola hepatica. Fluke eggs (200/ml, n= 5) from six different isolates were used in the current experimental work. They were obtained from different geographical locations and named Cullompton (UK), CEDIVE (Chascomus, Argentina), INTA-Bariloche (Bariloche, Argentina), Rubino (Uruguay), Cajamarca (Perú) and Río Chico (Catamarca, Argentina). The fluke eggs were incubated (25 °C) for a 12-h period in the presence of either ABZ or its sulphoxide metabolite (ABZ.SO) (5, 0.5 or 0.05 nmol/ml). Untreated eggs were incubated as a control. Incubated eggs (with or without drug present) were kept in darkness at 25 °C for 15 days. Afterwards, the trematode eggs were exposed to daylight over a 2-h period. Hatched and unhatched eggs were evaluated using an optical microscope, and the ovicidal activity was assessed for each fluke isolate. A very low ovicidal activity ( ≤ 13.4%) was observed in the ABZ-resistant CEDIVE isolate for both ABZ and ABZ.SO. Conversely, in the INTA-Bariloche and Río Chico isolates, which are suspected to be susceptible to ABZ, ovicidal activities ≥ 70.3% were observed after incubation with ABZ at the lowest concentration tested (0.05 nmol/ml). This finding correlates with that previously described for the ABZ-susceptible Cullompton. Finally, the Cajamarca and Rubino isolates behaved as ABZ resistant, since no ovicidal activity was observed after eggs were incubated with ABZ at 0.5 nmol/ml. Considering the specific results obtained for each isolate under assessment, the egg hatch test described here may be a suitable method for detection of ABZ resistance in F. hepatica.
Virkel, G; Lifschitz, A; Sallovitz, J; Pis, A; Lanusse, C
The enantioselective sulfoxidation of the prochiral anthelmintic compounds albendazole (ABZ) and fenbendazole (FBZ) was investigated in liver, lung and small intestinal microsomes obtained from healthy sheep and cattle. The microsomal fractions were incubated with a 40 microM concentration of either ABZ or FBZ. Inhibition of the flavin-containing monooxygenase (FMO) system was carried out by preincubation with 100 microM methimazole (MTZ) either with or without heat pretreatment (2 min at 50 degrees C). ABZ and FBZ were metabolized to the (+) and (-) enantiomers of their sulfoxide metabolites, named albendazole sulfoxide (ABZSO) and oxfendazole (OFZ), respectively. ABZ sulfoxidation rates were higher (p < 0.001) than those observed for FBZ. The FMO-mediated liver sulfoxidation of ABZ was enantioselective (100%) toward the (+) ABZSO production in both species. Liver sulfoxidation of FBZ by FMO was also enantioselective toward (+) OFZ (sheep = 65%; cattle = 79%). Cytochrome P450 was found to be mainly involved in the production of (-) ABZSO in the liver. MTZ did not affect the sulfoxidation of ABZ by lung microsomes, which may indicate that FMO is not involved in the production of ABZSO in this tissue. A significant (p < 0.05) inhibition of (-) ABZSO production by liver microsomes was observed after ABZ incubation in the presence of erythromycin (cattle = 21%) and ketoconazole (sheep = 36%). Both CYP3A substrates induced a reduction in the production of (-) ABZSO (sheep = 67-78%, cattle = 50-78%) by lung microsomes. Overall, the results reported here contribute to the identification of the metabolic pathways involved in the biotransformation of benzimidazole anthelmintics extensively used for parasite control in ruminants.
Cotting, J; Zeugin, T; Steiger, U; Reichen, J
The pharmacokinetics of albendazole and its main metabolite, albendazole sulphoxide, have been examined after giving a single oral dose of 200 mg albendazole to 19 patients with either Echinococcus multilocularis or E. granulosus, 5 of whom had significant extrahepatic obstruction due to the underlying disease. The AUC of albendazole sulphoxide was increased in the latter patients (mean 122 mumols.h.l-1 compared to 17 mumols.h.l-1 in the non-obstructed group). Obstructed patients had delayed absorption, ka averaging 0.39 compared to 1.41 h-1 in non-obstructed patients. The corresponding elimination rate constant, ke was also prolonged, averaging 0.041 and 0.13 h-1 in the two groups, respectively. Four patients were restudied after complete or partial resolution of the cholestasis. The pharmacokinetic parameters in them had returned towards values comparable to those in the non-obstructed patients.
Gokbulut, C; Bilgili, A; Hanedan, B; McKellar, Q A
The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.
Walker, Michael; Gray, Kirstin; Hopley, Christopher; Mussell, Christopher; Clifford, Louise; Meinerikandathevan, Jayanie; Firpo, Leonardo; Topping, Joanna; Santacruz, Daniel
Albendazole, one of the benzimidazole anthelmintics, is used in ruminants and has maximum residue limits in muscle, fat and other tissue owing to reported teratogenicity. Albendazole is extensively metabolised in domestic animals and humans with rapid conversion to a sulphoxide and subsequently sulphone and amino sulphone metabolites. Sulphoxide metabolites are responsible for the systemic biological activity of benzimidazole drugs. Herein we report a case of disputed results for albendazole in a consignment sampled at import in which the Official Analyst certified against the consignment for excess albendazole. A laboratory acting for the importer reported data below the MRL, including a finding of the parent drug which is not included in the residue definition. The Government Chemist has a statutory duty as a route of technical appeal in the UK Official Food Control system and the case was referred for referee analysis. We report our findings based on a LC-MS/MS method, which confirmed the official findings, did not reveal the presence of the parent drug but identified hot spots of albendazole marker residues in the consignment. We discuss the need for recommendations on official sampling at import and interpretation of results.
Collier, G S; Pratt, J M; De Wet, C R; Tshabalala, C F
The nature of the complexes and equilibria shown by solutions of protohaemin in dimethyl sulphoxide/water mixtures and in the presence of acid and base were studied by u.v.-visible spectrophotometry. In neutral solutions containing from 40 to 100% dimethyl sulphoxide, haemin is present as a monomeric complex in which the Cl-ion is not coordinated. Only a single pH-dependent equilibrium pK12 is observed over the range 40-80% dimethylsulphoxide, corresponding to formation of the mu-oxo dimer. As the dimethyl sulphoxide content is lowered below 35%, so the single equilibrium (pK12) is replaced by two equilibria (pK1 and pK2); with solutions of 5 microM-haemin, pK1 decreases (from pK12 7.55 in 65% dimethyl sulphoxide to pK1 approx. 1.5 in 0.01% dimethyl sulphoxide), whereas pK2 hardly changes (from pK12 7.55 in 65% to pK2 approx. 7.5 in 0.01%). PMID:486081
Waring, R H; Harris, R M; Steventon, G B; Mitchell, S C
A nearly complete recovery of radioactivity was achieved over 14 days following the oral administration of [35S]-S-methyl-L-cysteine sulphoxide and [35S]-S-carboxymethyl-L-cysteine sulphoxide to four healthy male volunteers. The urine was the major pathway of excretion of radioactivity (c. 96% in 0-14 days; c. 59% in 0-24 hours), with the faecal route being relatively unimportant (c. 1.7% in 0-3 days). Inorganic sulphate was an important degradation product, incorporating a substantial proportion of radioactive sulphur derived from these molecules (c. 40% in 0-14 days; c. 20% in 0-24 hours). Subtle differences were noted in the pattern of radioactive sulphate excretion following administration of the two cysteine-sulphoxide compounds, suggesting that their sulphur-containing moieties may enter different catabolic routes.
Materazzo, Sabrina; Carradori, Simone; Ferretti, Rosella; Gallinella, Bruno; Secci, Daniela; Cirilli, Roberto
Four commercially available immobilized amylose-derived CSPs (Chiralpak IA-3, Chiralpak ID-3, Chiralpak IE-3 and Chiralpak IF-3) were used in the HPLC analysis of the chiral sulfoxides albendazole (ABZ-SO) and fenbendazole (FBZ-SO) and their in vivo sulfide precursor (ABZ and FBZ) and sulfone metabolite (ABZ-SO2 and FBZ-SO2) under organic-aqueous mode. U-shape retention maps, established by varying the water content in the acetonitrile- and ethanol-water mobile phases, were indicative of two retention mechanisms operating on the same CSP. The dual retention behavior of polysaccharide-based CSPs was exploited to design greener enantioselective and chemoselective separations in a short time frame. The enantiomers of ABZ-SO and FBZ-SO were baseline resolved with water-rich mobile phases (with the main component usually being 50-65% water in acetonitrile) on the IF-3 CSP and ethanol-water 100:5 mixture on the IA-3 and IE-3 CSPs. A simultaneous separation of ABZ (or FBZ), enantiomers of the corresponding sulfoxide and sulfone was achieved on the IA-3 using ethanol-water 100:60 (acetonitrile-water 100:100 for FBZ) as a mobile phase.
Takayanagui, O M; Bonato, P S; Dreossi, S A C; Lanchote, V L
Aims Albendazole (ABZ) is effective in the treatment of neurocysticercosis. ABZ undergoes extensive metabolism to (+) and (−)-albendazole sulphoxide (ASOX), which are further metabolized to albendazole sulphone (ASON). We have investigated the distribution of (+)-ASOX (−)-ASOX, and ASON in cerebrospinal fluid (CSF) of patients with neurocysticercosis. Methods Twelve patients with a diagnosis of active brain parenchymal neurocysticercosis treated with albendazole for 8 days (15 mg kg−1 day−1) were investigated. On day 8, serial blood samples were collected during the dose interval (0–12 h) and one CSF sample was taken from each patient by lumbar puncture at different time points up to 12 h after the last albendazole dose. Albendazole metabolites were determined in CSF and plasma samples by h.p.l.c. using a Chiralpak AD column and fluorescence detection. Population curves for CSF albendazole metabolite concentration vs time were constructed. Results The mean plasma/CSF ratios were 2.6 (95% CI: 1.9, 3.3) for (+)-ASOX and 2.7 (95% CI: 1.8, 3.7) for (−)-ASOX, with the two-tailed P value of 0.9873 being non-significant. These data indicate that the transport of ASOX through the blood–brain barrier is not enantioselective, but rather depends on passive diffusion. The present results suggest the accumulation of the (+)-ASOX metabolite in the CSF of patients with neurocysticercosis. The CSF AUC(+)/AUC(−) ratio was 3.4 for patients receiving albendazole every 12 h. The elimination half-life of both ASOX enantiomers in CSF was 2.5 h. ASOX was the predominant metabolite in the CSF compared with ASON; the CSF AUCASOX/AUCASON ratio was approximately 20 and the elimination half-life of ASON in CSF was 2.6 h. Conclusions We have demonstrated accumulation of the (+)-ASOX metabolite in CSF, which was about three times greater than the (−) antipode. ASOX concentrations were approximately 20 times higher than those observed for the ASON metabolite. PMID:12207631
Brockmöller, J; Staffeldt, B; Roots, I
A quantitative study has been made of the metabolism of S-carboxymethyl-L-cysteine (CMC) and its sulphoxides in volunteers by HPLC. Precolumn derivatization was applied prior to gradient reversed phase HPLC separation and fluorescence detection. For CMC and its metabolites containing a primary amino group the reagent 9-fluorenylmethylchloroformate was used. The other metabolites of CMC were derivatized at their carboxylic group with 1-pyrenyldiazomethane to give stable fluorescent products. Urine samples were collected for 8 h after oral administration of 1.125 g CMC to 33 healthy volunteers. Elimination of CMC in urine as sulphoxides did not account for more than 1% of the dose in any of the volunteers. Thus, CMC-sulphoxide metabolites are not quantitatively important. Recovery of the original substance in 8-hour urines ranged from 10 to 30% and a further 2 to 20% was recovered as the metabolite thiodiglycolic acid. Oral doses of 0.19, 1.125, and 2.25 g CMC in a second group of 12 healthy volunteers did not reveal dose dependence of the urinary excretion of the sulphoxides or of thiodiglycolic acid. Serum concentration-time-curves of CMC, (S)- and (R)-CMC sulphoxide were measured in a group of 9 healthy volunteers. The CMC sulphoxides in serum reached 1.5% of the parent substance after 4 hours. The ratio of CMC to its sulphoxide metabolites was similar in serum and urine. Pharmacogenetic polymorphism of sulphoxidation was not confirmed by the specific HPLC methods used.
Craig, A. W.; Jackson, H.; James, R. M. V.
The work described was undertaken after the observation that the diuresis induced by several derivatives of ethyleneimine could be correlated with their content of ethyleneimine. The preparation of 35S-labelled di(aziridin-1-yl) sulphoxide (diethyleneiminosulphoxide) is described together with its metabolism in rat, mouse, rabbit and dog. The drug was completely metabolized in all species and, with the exception of the dog, most of the activity was excreted in the urine within 3 days. The main radioactive metabolite in all species was sulphate. In vitro studies demonstrated that the compound was slowly broken down to sulphite and free ethyleneimine; this hydrolysis was greatly accelerated in the presence of phosphate. PMID:14110758
Kesavulu, Muppuru Muni; Ramasubramanian, Sundaramoorthy; Suguna, Kaza . E-mail: email@example.com
The structure of porcine pepsin crystallized in the presence of dimethyl sulphoxide has been analysed by X-ray crystallography to obtain insights into the structural events that occur at the onset of chemical denaturation of proteins. The results show that one dimethyl sulphoxide molecule occupies a site on the surface of pepsin interacting with two of its residues. An increase in the average temperature factor of pepsin in the presence of dimethyl sulphoxide has been observed indicating protein destabilization induced by the denaturant. Significant increase in the temperature factor and weakening of the electron density have been observed for the catalytic water molecule located between the active aspartates. The conformation of pepsin remains unchanged in the crystal structure. However, the enzyme assay and circular dichroism studies indicate that dimethyl sulphoxide causes a slight change in the secondary structure and complete loss of activity of pepsin in solution.
de Kaminsky, R G
The results are presented of albendazole trials on human taeniasis infections in Honduras, involving 56 of 68 individuals (2% of the inhabitants) found to be infected during surveys conducted in 15 rural communities. Of the 3 methods used for diagnosis of infection, the Kato cellophane thick smear showed 80% reliability, a combination of Kato and 'Scotch' tape perianal swab 88%, and clinical history of proglottid expulsion less than 50%. Individuals were treated with a dose of 400 mg of albendazole per day for 3 d, followed for 5 d to verify tapeworm expulsion, and evaluated again at 60 and 90 d to assess drug efficacy. All 56 treated individuals remained stool-negative after 60 and 90 d; a partial strobila or segments were recovered from 21 of them (37.5%). Of these, Taenia saginata was identified from 4, and T. solium from 15; 2 specimens could not be specifically identified. Based on negative stool examinations and clinical history after 60 and 90 d, albendazole seems to be a well tolerated, very effective drug for treating infections with Taenia spp. However, confirmation of these results is needed due to the difficulty of making a reliable diagnosis of such infections.
Lima, Renata Monteiro; Ferreira, Maria Augusta Drago; de Jesus Ponte Carvalho, Teresa Maria; Dumêt Fernandes, Bruno José; Takayanagui, Osvaldo Massaiti; Garcia, Hector Hugo; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia
AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0–48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P≤ 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml−1 h), (−)-ASOX by 358% (0.14 vs. 0.50 µg ml−1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml−1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (–)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (–)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml−1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (–)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination. PMID:21395645
Emery, P; Panayi, G S; Huston, G; Welsh, K I; Mitchell, S C; Shah, R R; Idle, J R; Smith, R L; Waring, R H
Sulphoxidation of carbocysteine, a drug structurally similar to D-penicillamine, displays a skewed distribution within a population. In 66 patients with rheumatoid arthritis (RA) a significant association between impaired sulphoxidation and toxicity (p less than 0.001) was found; HLA-DR3, although associated with toxicity (p less than 0.05), appeared to be an independent risk factor of most importance in the group with extensive sulphoxidation. The relative risk of toxicity in a patient possessing either DR3 or impaired sulphoxidation was 25. The prevalence of poor sulphoxidizers within this group of RA patients was increased compared to that in a previous population study and requires further investigation. Our findings explain a number of the toxic phenomena associated with D-penicillamine administration in RA.
Aggarwal, P; Wali, J P
Ten patients with pulmonary hydatid disease diagnosed on the basis of a chest radiograph and a positive response to the indirect haemagglutination test for hydatid disease were treated with albendazole 10 mg/kg/day for eight weeks. None of the 10 patients showed any radiological or serological improvement with this treatment regimen. Albendazole in these doses appears to have little role in the treatment of pulmonary hydatid disease. PMID:1926033
... to treat neurocysticercosis (infection caused by the pork tapeworm in the muscles, brain, and eyes that may ... cystic hydatid disease (infection caused by the dog tapeworm in the liver, lung, and lining of the ...
Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo
In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…
Hughes, G J; de Jong, C; Fischer, R W; Winterhalter, K H; Wilson, K J
Native rat haemoglobins were found to bind simetryn sulphoxide to an extent 40-fold greater than human haemoglobin. This specific behaviour was studied by using only high-pressure ('performance') liquid chromatography for the preparative separation of globin chains and the isolation of peptides resulting from chemical and enzymic degradation. High recoveries (greater than 80%) of peptides throughout the procedures in combination with microsequence techniques, allow a definitive assignment of the residue undergoing modification. The haemoglobin beta-chain cystine-125 residue, with a stoichiometry of one per tetramer of rat haemoglobin, was found to be modified. Stereochemical implications of this finding are discussed. Simetryn sulphoxide would appear to be useful as a specific reagent for the mapping of exposed thiol residues in proteins. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:7337714
Mitchell, S C; Waring, R H; Haley, C S; Idle, J R; Smith, R L
Interindividual variation in the sulphoxidation of S-carboxymethyl-L-cysteine (750 mg p.o.) was investigated in 200 healthy volunteers. Nearly a 100-fold difference was observed between individuals with respect to the amount of sulphoxide metabolites detected in their 0-8 h urine (0.6 to 59.1% recovery). Such a difference was shown to be reproducible over several months in 40 subjects who spanned the entire range of capacities. Cumulative plots and maximum likelihood analysis of the distribution indicated that a bimodal model was most probable. Analysis of pedigree data obtained from 12 families suggested a genetic effect with overlying environmental influences. Images Figure 4 PMID:6487492
Watson, R G; Olomu, A; Clements, D; Waring, R H; Mitchell, S; Elias, E
On the basis of previous experimental studies we postulated that individuals who were phenotypically good hydroxylators but poor sulphoxidisers would be susceptible to chlorpromazine jaundice. Sulphoxidation capacity was assessed in 12 subjects with a history of chlorpromazine jaundice, using S-carboxymethyl-L-cysteine as an in vivo probe. Following an oral dose of 750 mg, unchanged compound and sulphoxide metabolites were measured in urine. All 12 subjects (100%) were shown to be poor sulphoxidisers compared to 22% of normal controls (P less than 0.001) and 23.8% of liver disease controls (P less than 0.001). No subjects with a history of chlorpromazine jaundice had an impaired hydroxylation capacity as assessed by recovery of 4-hydroxydebrisoquine in urine following oral debrisoquine. The results support the hypothesis and demonstrate an inherent metabolic basis of susceptibility to chlorpromazine jaundice.
Fritsch, Reinhard M; Keusgen, Michael
Methiin was present in all investigated samples. In the genus Allium, methiin-dominated species (rarely used by man) were common, but the occurrence of the other cysteine sulphoxides was variable and was largely correlated with use as spices or vegetables. Two major chemical types (named according to the species where they occur) could be distinguished, and at least two more may be recognized. Isoalliin dominates in the widely used "onion-type", which includes chive (A. schoenoprasum) and top onion (A.xproliferum). Pearl onion and leek (A. ampeloprasum) have higher relative amounts of methiin and propiin, respectively. Alliin dominates in the widely used "garlic-type", which includes wild leek (A. obliquum) and sand leek (A. scorodoprasum). Alliin and isoalliin rarely co-dominate, being only found in the cultivated Chinese leek (A. tuberosum). A triple mix of almost equal amounts of methiin, alliin and isoalliin is present in ramson (A. ursinum). General trends in the three evolutionary lines of the genus Allium were apparent. In the first lineage, high amounts of methiin were more frequent, and propiin, although being a minor component in all three evolutionary lines, was present in the highest amounts. Most of the species in the second line showed only traces of cysteine sulphoxides. In the third line, the "onion-type" dominates, the "garlic type" is characteristic for subgenus Allium, and co-dominating alliin and isoalliin also occur. Generally, the total cysteine sulphoxide amount increased, and the complexity of cysteine sulphoxide patterns decreased in the transition from the first to the third evolutionary line.
González-Hernández, Iliana; Ruiz-Olmedo, María Isabel; Cárdenas, Graciela; Jung-Cook, Helgi
The development and validation of an LC-MS/MS method for the simultaneous determination of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in human plasma are described. Samples of 200 μL were extracted with ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic separation was performed using a C(18) column with methanol-formic acid 20 mmol/L (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both analytes the method was precise (RSD < 12%) and accurate (RE <7%) with high recovery (>90%). The method was successfully applied to determine the plasma and cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in patients with subarachnoidal neurocysticercosis who received albendazole at 30 mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and reliable protocol for determining albendazole sulfoxide and albendazole sulfone concentrations in plasma and cerebrospinal fluid samples and is applicable to therapeutic monitoring.
... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....
... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....
... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....
Yılmaz-Topa, Özge; Tuygun, Nilden; Akça, Halise; Polat, Emine; Karacan, Can Demir
Drug-induced dystonic reactions are a common presentation to the Pediatric Emergency Department frequently with antiemetics, antidepressants, dopamineblocking agents and antipyschotics. We report a case of generalized form of dystonia after taking albendazole and cetirizine. There is only one case with albendazole induced and two cases with cetirizine induced dystonia in the literature.
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole...
Maji, S; Kumar, Satendra; Sankaran, K
Ligand sensitized fluorescence of europium ion using thenoyltrifluoroacetone (TTA) as a sensitizing ligand and dimethyl sulphoxide (DMSO) as a solvent is studied for the first time. TTA ligand enhances the fluorescence of Eu(3+) by a factor of 40000 in DMSO. Linearity is obtained for a concentration range of 0.076-7.6ng/mL of Eu(3+) with a detection limit of 7.6pg/mL. The quenching of Eu(3+)-TTA fluorescence by uranium matrix was studied in different solvents and found to be less in DMSO. Consequently, estimation of Eu(3+) in a large excess of uranium becomes a possibility without the need to separate uranium from the solution, which has been demonstrated in this paper. Satisfactory results are obtained when Eu(3+) is present at a concentration of 0.6μg/g in uranium.
Ceballos, Laura; Elissondo, Celina; Sánchez Bruni, Sergio; Denegri, Guillermo; Lanusse, Carlos; Alvarez, Luis
The need to identify improved therapy against cystic echinococcosis (CE) has motivated pharmacology-based research. The comparative pharmacological performances of the benzimidazole compounds flubendazole (FLBZ) and albendazole (ABZ) were addressed here. The goals of the work were as follows: (i) to evaluate the ex vivo activities of FLBZ, ABZ, and their respective metabolites against Echinococcus granulosus protoscoleces, (ii) to compare the plasma and cyst disposition kinetics for the two drugs in infected mice, and (iii) to compare the clinical efficacies of FLBZ and ABZ against CE in mice. For the ex vivo study, E. granulosus protoscoleces were incubated with FLBZ, reduced FLBZ (R-FLBZ), ABZ, and ABZ-sulfoxide (ABZSO) (10 nmol/ml). Protoscolex viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). For the pharmacokinetic study, BALB/c mice with CE were allocated to two different groups and orally treated with either FLBZ or ABZ (5 mg/kg of body weight), both formulated as a cyclodextrin-based solution. Blood and cyst samples were taken up to 12 h posttreatment and analyzed by high-performance liquid chromatography (HPLC). For the efficacy study, CE-infected BALB/c mice were divided into three groups: the unmedicated control group and the FLBZ- and ABZ-treated groups. Oral treatments were performed twice a day during 25 days. After treatment, all animals were killed and the weight of the cysts was recorded. Loss of protoscolex viability was observed after drug incubation. FLBZ was detected in plasma (area under the concentration-versus-time curve [AUC] = 1.8 μg·h/ml) and cysts (AUC = 0.3 μg·h/g) collected from treated infected animals. Conversely, ABZSO was the only active molecule measured in plasma (AUC = 4.4 μg·h/ml) and cysts (AUC = 1.5 μg·h/g) after ABZ treatment. FLBZ induced a 90% reduction in cyst weight in comparison to those collected from untreated control mice (P < 0.05). However, no differences
Moroni, Samanta; Moscatelli, Guillermo; Bournissen, Facundo García; González, Nicolás; Ballering, Griselda; Freilij, Héctor; Salgueiro, Fabián; Altcheh, Jaime
Introduction Cystic echinococcosis is endemic in Argentina. The standard pharmacological treatment for the disease is albendazole, but surgery is a common alternative. Even though primary infection occurs mainly in the pediatric population, the optimal therapeutic option in pediatrics is not clearly defined and few pediatric cohorts with cystic echinococcosis treated with albendazole have been described to date. Objective To describe therapeutic response to albendazole in a cohort of pediatric patients with abdominal cystic echinococcosis. Population and Methods Patients (0–18 years old) with abdominal cystic echinococcosis who were treated with albendazole between January 1998 and August 2013. Diagnosis of abdominal cystic echinococcosis was made by ultrasound. All patients received albendazole, 10–15 mg/kg/day. Epidemiological data, symptoms, number, location and outcome of the cysts, serology and treatment received were analyzed. The parameter used to assess treatment response was cyst changes evaluated by ultrasound follow up using the WHO-IWGE classification. Results A total of 28 patients (with 46 abdominal cysts) were included in the cohort. Mean age at enrolment was 9.4 years and mean duration of follow-up, 23.8 months. All patients resided in rural areas and had had contact with dogs. The asymptomatic form of the disease was the most common presentation. All patients received albendazole (mean duration: 142.5 days), with low incidence of adverse events. Albendazole had a positive effect on most of the cysts. Surgery was performed in 13 patients. Conclusion Treatment with albendazole for uncomplicated cystic echinococcosis cysts is safe and effective, and can potentially reduce the need for surgical intervention. PMID:27589236
Nangia, Ashwini; Desiraju, Gautam R.
The thiazolidine ring of the penam skeleton exists in two distinct conformations wherein the 3α-CO 2H group is in the axial or equatorial orientation. Crystal structure data have been retrieved from the Cambridge Structural Database (CSD) on 49 penams. These include 30 penicillins, 10 sulphoxides and 9 sulphones. Of the penicillins, 24 are in the axial conformation and 6 are in the equatorial conformation. The 19 sulphoxides and sulphones are exclusively in the equatorial conformation. It is suggested that the axial conformation in penicillins is stabilised by intramolecular NH⋯S and CH⋯O hydrogen bonds, jointly worth about 3 kcal/mol. Calculations show that the sulphoxides and sulphones do not adopt the axial conformation because of a repulsive C⋯O interaction between the gem-dimethyl group in the C2 position and the sulphoxide/sulphone O-atom. The pharmocophore groups of the penicillin antibiotics and the sulphoxides/sulphones lie in distinct, well-defined regions and this suggests that the biologically active conformation is the one with the axially oriented 3α-CO 2H group.
Restrepo, Juan C
We report a case of a 47-year-old male, who was referred to the clinical hepatology services at Pablo Tobón Uribe Hospital for evaluation of a jaundice syndrome. After undergoing several exams, we diagnosed hepatic hydatidosis and the patient was treated with albendazole; however, after five months of uninterrupted treatment the patient again consulted and his liver test showed marked hepatocellular damage. This time, the patient was diagnosed with drug-induced liver injury due to albendazole, based on information from the clinical record, history of drug consumption, clinical and laboratory tests improved after discontinuing the medication and after discarding other possible causes; this diagnosis was supported by the CIOMS/RUCAM scale, which showed a "likely" correlation between hepatocellular damage and drug toxicity etiology. PMID:24892458
Zavoikin, V D; Tumolskaya, N I; Mazmanyan, M V; Zelya, O P; Tikhonova, D V
The paper gives the results of treatment with micronized albendazole (Gelmodol-BM, World Medicine, UK) in 87 patients of the Department of Medical Parasitology and Tropical Diseases, Clinical and Diagnostic Center, Clinical Center, I.M.Sechenov First Moscow State Medical University. Thirty-two patients with echinococcosis 8 with alveococcosis (including 4 inoperable patients), 10 with ascariasis, 10 with toxocariasis, 15 with enterobiasis, and 12 people diagnosed with larva migrans were treated in 2013-2014. The drug's routine doses and dosage regimens were used. Albendazole (Gelmodol, World Medicine, UK) showed a high efficacy with good tolerability, which is highly competitive with that of the drugs manufactured by IPCA Laboratories Ltd., India (such as nemozole). Both medicaments above-mentioned may be successfully used in the treatment of many helminthisms.
Ríos, David; Restrepo, Juan C
We report a case of a 47-year-old male, who was referred to the clinical hepatology services at Pablo Tobón Uribe Hospital for evaluation of a jaundice syndrome. After undergoing several exams, we diagnosed hepatic hydatidosis and the patient was treated with albendazole; however, after five months of uninterrupted treatment the patient again consulted and his liver test showed marked hepatocellular damage. This time, the patient was diagnosed with drug-induced liver injury due to albendazole, based on information from the clinical record, history of drug consumption, clinical and laboratory tests improved after discontinuing the medication and after discarding other possible causes; this diagnosis was supported by the CIOMS/RUCAM scale, which showed a "likely" correlation between hepatocellular damage and drug toxicity etiology.
Douri, Thaer; Shawaf, A Z
Crusted scabies is a severe variant of scabies caused by the ectoparasite Sarcoptes scabiei. It is characterized by high mite burden, extensive hyperkeratotic scaling, crusted lesions, variable pruritus, generalized lymphadenopathy, erythroderma, and eosinophilia, in some cases. There is an increased incidence of crusted scabies, particularly among patients with HIV infection. We describe a 22-year-old Syrian immunocompetent female who had hyperkeratotic psoriasiform plaques and hyperkeratosis without itching. She was treated with oral albendazole and topical crotamiton with salicylic acid 5 percent.
Introduction Drug-related hepatotoxicity is a common medical problem with implications for health systems. It constitutes a cause of acute liver failure and, in many cases, is responsible for the rejection of new pharmacological agents during efficacy and safety studies. Risk factors, as well as pathogenesis of drug-induced liver injury, are poorly understood. The diagnosis of drug-induced liver injury is challenging; it is difficult to define the cause of drug hepatotoxicity due to the heterogeneity of the clinical presentation and the absence of established criteria for accurate and reproducible identification of drug-associated liver toxicity. Case presentation We report the case of a 25-year-old Hispanic woman admitted to our Clinical Hepatology Unit with symptoms of acute hepatitis of unknown etiology. She was diagnosed with albendazole-induced granulomatous hepatitis after ruling out other possible causes, based on laboratory studies, liver biopsy, medical history, detailed drug history, and spontaneous improvement of her liver biochemical profile after medication withdrawal. This diagnosis was supported by the Council for International Organizations of Medical Sciences-Roussel Uclaf Causality Assessment Method, which showed a likely correlation between hepatocellular damage and drug toxicity as the etiology. Conclusions Our patient’s suspected diagnosis was albendazole-induced granulomatous hepatitis with confirmatory histologic pattern. This case deserves particular attention due to the wide use of albendazole in our country (Colombia) and the prevalent medical issue of drug-related hepatotoxicity. PMID:23889970
Zeugin, T; Zysset, T; Cotting, J
A sensitive and specific reversed-phase high-performance liquid chromatography (HPLC) method is described for the quantitative determination of albendazole sulfoxide (ASOX); since albendazole sulfone (ASON) appears only in small amounts and albendazole (ABZ) normally does not appear in human plasma, only a qualitative determination of ASON and ABZ was made in human plasma. Plasma samples were extracted three times using ethylacetate and petroleum benzine; this yielded optically clear samples which after evaporation were dissolved in the HPLC solvent and injected onto an RP-C18 column, with ultraviolet detection at 290 nm. The detection limit of the main metabolite ASOX was 50 nM and that of ASON was 100 nM. The intraday coefficient of variation for ASOX was 3.3% at a concentration of 2.2 microM, and the interday coefficients of variation were 14.5, 7.3, and 9.1% at ASOX concentrations of 0.5, 2.5, and 5.0 microM, respectively. Calibration was linear in a concentration range of 0.05-12 microM for ASOX and 0.1-8 microM for ASON, respectively. Pharmacokinetic data of a patient with echinococcosis are presented.
Beehler, B.A.; Tuggle, B.N.
Albendazole is a broad-spectrum anthelmintic of the benzimidazole group which has been tested in several rodents and domestic animals. Albendazole has been used effectively to treat trematodes in sheep, cattle, dogs, and cats. The use of this anthelmintic in exotic small mammals has not been reported to the authors' knowledge.
Steiger, U; Cotting, J; Reichen, J
We prospectively studied the effect of albendazole on microsomal reserve and on first-pass activation to albendazole sulfoxide in patients with hydatid disease. An aminopyrine breath test was performed in 12 patients while they were receiving albendazole treatment and while they were not. Excretion of 14CO2 in breath averaged 0.70%.kg.mmol-1 +/- 0.20%.kg.mmol-1 without treatment and 0.54%.kg.mmol-1 +/- 0.14%.kg.mmol-1 with treatment (p less than 0.005). Plasma levels of albendazole sulfoxide were measured 4 hours after the morning dose during the first and second half of the 4-week treatment cycles. In nine of the 12 patients albendazole sulfoxide levels decreased during the second half of the cycle by an average of 0.84 +/- 0.76 mumol/L (p less than 0.02). Transaminase levels increased in 10 of the 12 patients during long-term albendazole treatment, and major side effects, including hepatotoxicity, neutropenia, and alopecia, were observed in three patients. We conclude that albendazole partially inhibits microsomal enzyme function but induces its own metabolism. Hepatotoxicity and other possible severe side effects necessitate close therapeutic monitoring of patients who are given albendazole.
Chattah, Ana K; Pfund, Laura Y; Zoppi, Ariana; Longhi, Marcela R; Garnero, Claudia
Novel complexes of two different solid forms of Albendazol and β-cyclodextrin were investigated in an attempt to obtain promising candidates for the preparation of alternative matrices used in pharmaceutical oral formulations. The interaction between each form of Albendazol and β-cyclodextrin was studied in solution and solid state, in order to investigate their effect on the solubility and dissolution rate of Albendazol solid forms. The solid supramolecular systems were characterized using a variety of techniques including natural-abundance (13)C cross-polarization magic-angle-spinning nuclear magnetic resonance, powder X-ray diffraction, Fourier transform-infrared spectroscopy and scanning electron microscopy. The results obtained showed the highest increment of solubility and dissolution rate, in simulated gastric fluid, for the Albendazole II:β-cyclodextrin systems. Thus, these new complexes constitute an interesting alternative for improving the oral bioavailability of Albendazol.
Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N
Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole
Garcia, Hector H; Lescano, Andres G; Lanchote, Vera L; Pretell, E Javier; Gonzales, Isidro; Bustos, Javier A; Takayanagui, Osvaldo M; Bonato, Pierina S; Horton, John; Saavedra, Herbert; Gonzalez, Armando E; Gilman, Robert H
AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. PMID:21332573
Ohnishi, Kenji; Kobayashi, Ken-ichiro; Iwabuchi, Sentaro; Nakamura-Uchiyama, Fukumi
A 18-year-old Japanese woman seen as an outpatient for refractory enterobiasis had been treated with pyrantel pamoate over 40 times since the age of 11. She washed her hands and cleaned house frequently, and all family members took pyrantel pamoate, but Enterobius vermicularis eggs remained. She was orally administered 400 mg of albendazole 3 times in clinic visits, after which eggs have not been seen for 1 year. Pyrantel pamoate is used widely against enterobiasis in Japan. Our case shows albendazole to also be effective against enterobiasis. Albendazole thus appears to be a useful anti-helminthic in enterobiasis patients in whom pyrantel pamoate is not effective. This is, to our knowledge, the first case of enterobiasis treated with albendazole in Japan.
Seong, San; Moon, Daruchi; Lee, Dong Kyu; Kim, Hyung Eun; Oh, Hyun Sup; Kim, Soon Hyun; Kwon, Oh Woong; You, Yong Sung
We present a case of ocular toxocariasis treated successfully with oral albendazole in combination with steroids. A 26-year-old male visited the authors' clinic with the chief complaint of flying flies in his right eye. The fundus photograph showed a whitish epiretinal scar, and the fluorescein angiography revealed a hypofluorescein lesion of the scar and late leakage at the margin. An elevated retinal surface and posterior acoustic shadowing of the scar were observed in the optical coherence tomography, and Toxocara IgG was positive. The patient was diagnosed with toxocariasis, and the condition was treated with albendazole (400 mg twice a day) for a month and oral triamcinolone (16 mg for 2 weeks, once a day, and then 8 mg for 1 week, once a day) from day 13 of the albendazole treatment. The lesions decreased after the treatment. Based on this study, oral albendazole combined with steroids can be a simple and effective regimen for treating ocular toxocariasis.
Corba, J; Krupicer, I
The anthelmintic potential of albendazole (ABZ) in intraruminal boluses (Proftril-Captec) was investigated in sheep harbouring naturally acquired Dicrocoelium infection. The anthelmintic efficacy was assessed by coprological testing during the autumn pasture and comparison of worm counts in 22 necropsied animals (11 treated and 11 untreated) at the end of the experiment. The mean faecal egg count (EPG) in treated animals dropped significantly during week 2, and between the 4th and the 12th week the faecal samples were almost negative. The health status of treated animals improved significantly during the first 2 weeks. Helminthological dissection of livers and small intestines revealed 91.8% efficacy, but a small number of live adult flukes were found in all treated animals.
Ruiz-Olmedo, María Isabel; González-Hernández, Iliana; Palomares-Alonso, Francisca; Franco-Pérez, Javier; González F, María de Lourdes; Jung-Cook, Helgi
Background: Although albendazole is the drug-of-choice for the treatment of neurocysticercosis, its efficacy is limited due to its low bioavailability. An alternative for optimizing pharmacological treatment is through drug combinations. In vitro studies have shown that nitazoxanide and tizoxanide (the active metabolite of nitazoxanide) exhibit cysticidal activity and that the combination of tizoxanide with albendazole sulfoxide (the active metabolite of albendazole) produced an additive effect. Objectives: (1) To assess the concentration profile of tizoxanide in plasma and in cerebrospinal fluid; and (2) to evaluate the influence of nitazoxanide on the pharmacokinetics of albendazole in plasma and in cerebrospinal fluid. Methods: Two different studies were conducted. In study 1, 10 male Sprague-Dawley rats received a single oral dose of 7.5 mg/kg of nitazoxanide and serial blood and cerebrospinal fluid samples were collected over a period of 4 h. In study 2, 38 healthy male Sprague-Dawley rats were randomly divided into two groups: one of these received a single dose of albendazole (15 mg/kg) and, in the other group, albendazole (15 mg/kg) was co-administered with nitazoxanide (7.5 mg/kg). Plasma and cerebrospinal fluid samples were collected from 0 to 16 h after administration. Albendazole sulfoxide and tizoxanide levels were assayed by using HPLC or LC/MS techniques. Results: In study 1, tizoxanide reached a maximum plasma concentration of 244.42 ± 31.98 ng/mL at 0.25 h; however, in cerebrospinal fluid, this could be detected only at 0.5 h, and levels were below the quantification limit (10 ng/mL). These data indicate low permeation of tizoxanide into the blood brain barrier. In study 2, Cmax, the area under the curve, and the mean residence time of albendazole sulfoxide in plasma and cerebrospinal fluid were not affected by co-administration with nitazoxanide. Conclusion: The results of the present study indicate that in rats at the applied doses
Breijo, Martín; Isnardi, Fernanda; Brauer, Mónica; Schenker, Rudolf; Ferrari, Mariana; Ferreira, Ana M
The aim of this work was to evaluate the potential of lufenuron, a benzylphenylurea with ability to interfere with the formation of insect exoskeleton, as a therapeutic drug for larval echinococcosis (hydatid disease). For this purpose lufenuron, alone or in combination with albendazole, was administered to CD1 mice bearing Echinococcus granulosus hydatid cysts in the peritoneal cavity. Neither of the drugs alone was able to exert parasiticidal effects. However, in combination with albendazole, lufenuron reduced the growth of cysts (30-40% in cyst diameter respect to control, p<0.05). This effect was associated with ultrastructural alterations of the hydatid cyst wall and a reduction of the content of myo-inositol-hexakisphosphate, the major component of the electron dense granules of the laminated layer. Overall, this work provides evidence that lufenuron could represent a useful compound for the use in chemotherapy against larval echinococcosis, by enhancing albendazole parasiticidal activity.
Capece, Bettencourt P S; Virkel, Guillermo L; Lanusse, Carlos E
Albendazole and fenbendazole are methylcarbamate benzimidazole anthelmintics extensively used to control gastrointestinal parasites in domestic animals. These parent compounds are metabolised to albendazole sulfoxide and fenbendazole sulfoxide (oxfendazole), respectively. Both sulfoxide derivatives are anthelmintically active and are manufactured for use in animals. They metabolites have an asymmetric centre on their chemical structures and two enantiomeric forms of each sulfoxide have been identified in plasma, tissues of parasite location and within target helminths. Both the flavin-monooxygenase and cytochrome P450 systems are involved in the enantioselective biotransformation of these anthelmintic compounds in ruminant species. A relevant progress on the understanding of the relationship among enantioselective metabolism and systemic availability of each enantiomeric form has been achieved. This article reviews the current knowledge on the pharmacological implications of the enantiomeric behaviour of albendazole sulfoxide and oxfendazole in domestic animals.
Atack, John M; Kelly, David J
The microaerophilic food-borne pathogen Campylobacter jejuni is exposed to highly variable oxygen concentrations during its life cycle and employs a variety of protection mechanisms to resist oxidative stress. However, not all of the enzymes that mediate such protection have yet been identified. Two genes in strain NCTC 11168, Cj0637c and Cj1112c, are predicted to encode unrelated methionine sulphoxide reductases, which may repair oxidized methionine residues in proteins and thus contribute to oxidative stress defence. Cj0637 and Cj1112 were overexpressed, purified and shown by a coupled thioredoxin-thioredoxin reductase-NADPH assay to catalyse the stereospecific reduction of the S and R diastereoisomers, respectively, of the model compound methyl p-tolyl sulphoxide. Cj0637 is thus identified as MsrA and Cj1112 as MsrB. The contribution of these enzymes to oxidative and nitrosative stress resistance in C. jejuni was assessed by phenotypic analysis of a set of isogenic msrA, msrB and msrA/B insertion mutants. As RT-PCR data suggested a polar effect on Cj1111c in the msrB mutant, an msrB/msrB(+) merodiploid complementation strain was also constructed. The msrA/B strain was severely growth inhibited under standard microaerobic conditions, whereas the msrA and msrB strains grew normally. Agar plate disc diffusion assays showed that all mutants displayed increased sensitivity to hydrogen peroxide, organic peroxide, superoxide, and nitrosative and disulphide stress, but quantitative cell viability assays showed that the msrA/B double mutant was markedly more sensitive to both oxidative and nitrosative stress. All of the stress-sensitivity phenotypes observed for the msrB mutant were restored to wild-type in the msrB/msrB(+) merodiploid. It is concluded that MsrA and MsrB make a significant contribution to the protection of C. jejuni against oxidative and nitrosative stress.
López De Guimaraes, D; Neyra Llanos, R S; Romero Acevedo, J H
A therapeutical clinical trial was designed to study the effectiveness of Paico and Albendazole, for the treatment of ascariasis in a group of 60 children, between 3 and 14 years old, from a rural community in Huaraz. It was carried out between May and August, 2000. The sample was randomly divided into 30 cases for Paico and 30 for Albendazole, the criteria for entering the trial being a positive examination for Ascaris lumbricoides in feces. The treatment consisted in Paico juice: 1 ml/Kg for less than 10 Kg, and 2 ml/Kg in larger children, one dose before breakfast, for three consecutive days. The Albendazole was administered in a single dose of 400 mg in those over five years of age, and 200 mg in younger children. The effectiveness was evaluated qualitatively (the disappearance of the ascaris eggs from the feces) and quantitatively (decrease in the parasitic burden); in the stool examinations carried out in all cases on entering the study and 15 days after the treatment. All the stool samples were processed in the Referential Laboratory of the Regional Health Authority in Ancash. The qualitative effectiveness between Paico and Albendazole for the eradication of ascariasis was similar at 86.7%. The quantitative effectiveness was 59.5% for Paico and 58.3% for Albendazole. However, it was observed that, unlike Albedazole, Paico is 100% effective in the treatment of Hymenolepsis nana. Adverse effects were presented in 23.3% of the cases for both drugs. It is concluded that, although Paico and Albendazole have a similar effectiveness against Ascaris lumbricoides, Paico has the additional benefit of being effective against Hymenolepsis nana.
Ismail, M M; Jayakody, R L; Weil, G J; Fernando, D; De Silva, M S; De Silva, G A; Balasooriya, W K
In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations.
Solomon, N; Kachani, M; Zeyhle, E; Macpherson, C N L
The World Health Organization (WHO) treatment protocols for cystic echinococcosis (CE) are based on the standardized ultrasound (US) classification. This study examined whether the classification reflected the natural history of CE in untreated and albendazole-treated patients. Data were collected during mass US screenings in CE endemic regions among transhumant populations, the Turkana and Berber peoples of Kenya and Morocco. Cysts were classified using the WHO classification. Patient records occurring prior to treatment, and after albendazole administration, were selected. 852 paired before/after observations of 360 cysts from 257 patients were analyzed. A McNemar-Bowker χ(2) test for symmetry was significant (p<0.0001). 744 observations (87.3%) maintained the same class, and 101 (11.9%) progressed, consistent with the classification. Regression to CE3B occurred in seven of 116 CE4 cyst observations (6.0%). A McNemar-Bowker χ(2) test of 1414 paired before/after observations of 288 cysts from 157 albendazole-treated patients was significant (p<0.0001). 1236 observations (87.4%) maintained the same class, and 149 (10.5%) progressed, consistent with the classification. Regression to CE3B occurred in 29 of 206 CE4 observations (14.1%). Significant asymmetry confirms the WHO classification's applicability to the natural history of CE and albendazole-induced changes. Regressions may reflect the stability of CE3B cysts.
Adediran, Oyeduntan A.; Uwalaka, Emmanuel C.
Anthelmintic drug resistance has led to the search for alternatives in controlling helminth infections. Fifty West African Dwarf goats without history of anthelmintic treatment were divided equally into five groups. Group A was treated with ivermectin injection subcutaneously, group B with levamisole subcutaneously, group C with albendazole orally, and group D with aqueous extract of Vernonia amygdalina and group E was untreated control. Faecal samples were collected before treatment from each animal and larval culture was carried out. Faecal egg count reduction (FECR) test was carried out for each group and the data analysed using FECR version 4 to calculate percent reduction in faecal egg count. Predominant helminth infections from larval culture were Haemonchus contortus (70%), Trichostrongylus spp. (61%), and Oesophagostomum spp. (56%). Mixed infection was present in all the animals. From the FECR test Vernonia amygdalina extract was more effective against helminths (100%), compared to ivermectin 96%, levamisole 96%, and albendazole 99%. The lower 95% confidence limit was 89 for ivermectin and levamisole and 91 for albendazole. There is low resistance to ivermectin and levamisole and susceptibility to albendazole while V. amygdalina has great potentials that could be explored for the treatment of helminth diseases in goats. PMID:26579232
Dreyer, Gerusa; Addiss, David; Williamson, John; Norões, Joaquim
Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n=25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n=22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P=0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P=0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti, with no detectable enhancement in microfilarial suppression.
Atef, M; Ramadan, A; Darwish, A S; Fahim, Aisha M M
Tylosin concentrations and its disposition kinetics in serum, urine, and milk of lactating goats following a single intravenous (i.v.) or intramuscular (i.m.) injection (10 mg kg(-1) b.wt.) were carried out using high performance liquid chromatography (HPLC).The concentration-time curve of tylosin after i.v. injection could be described by a two-compartment open model. Tylosin was rapidly distributed and eliminated from goat's bodies with t(1/2(beta)) value of 1.25 h. The V((d)) was less than one litre/kg and the MRT was 1.40 h. Concomitant administration with albendazole decreased tylosin concentrations in serum after its i.v. injection and the MRT was 1.17 h. The AUC and AUMC showed a significant decrease in goats given albendazole prior to injection as compared with those given tylosin only. Following i.m. administration, the absorption half-life and the corresponding t(max) revealed rapid absorption rate with systemic bioavailability (F%) of 76.2 %. Albendazole when given concurrently with tylosin decreased its serum concentrations due to lower bioavailability (43.25 %). Following i.v. or i.m. injection, tylosin was excreted rapidly in urine in concentration much higher than those determined in serum and milk. Tylosin administered in goats pretreated with albendazole was excreted at lower concentration in urine, with a significant decrease from 1(st) to 10(th) hours as compared with animals given tylosin only. Following i.v. or i.m. administration of tylosin, the drug was excreted in high concentrations in milk. A significant decrease in milk concentrations was reported in goats pretreated with albendazole.
Fletouris, D J; Botsoglou, N A; Psomas, I E; Mantis, A I
The level and nature of the albendazole residues in milk of treated cows were determined as a function of the time of milking (12-h intervals), and the fate of those residues during cheesemaking, ripening, and storage was examined when the obtained milk was used for making Teleme cheese. Ion-pair liquid chromatographic analysis with fluorescence detection showed that the albendazole sulfoxide metabolite reached its maximum (523 +/- 199 micrograms/kg) at the 1st milking and declined below the detection limit by the 4th milking. The sulfone metabolite attained its highest level (812 +/- 99 micrograms/kg) more slowly (at the 2nd milking) and declined below detection limit by the 13th milking. The 2-aminosulfone metabolite, which was present in the milk obtained at the 1st milking, reached its maximum (128 +/- 36 micrograms/kg) at the 3rd milking, and slowly declined to a level below detection limit by the 15th milking. Whey and cheese analysis revealed that about 70% of each major metabolite initially present in milk could be distributed in the whey. The remaining 30% occurred in the cheese at residue levels higher than those initially present in the milk of the 1st or 2nd milking (688 versus 445 or 450 versus 230 micrograms/kg for albendazole sulfoxide; 890 versus 608 or 1502 versus 783 micrograms/kg for albendazole sulfone; 19 versus 15 or 161 versus 105 micrograms/kg for albendazole 2-aminosulfone). Ripening and storage of the cheeses made from milks from the 1st or 2nd milkings results in a decrease of the sulfoxide metabolite (to 225 or 206 micrograms/kg), an increase of the sulfone metabolite (to 1,181 or 1,893 micrograms/kg), and no effect on the 2-aminosulfone metabolite.
Bockarie, Moses J; Tavul, Livingstone; Ibam, Irvin; Kastens, Will; Hazlett, Fred; Tisch, Daniel J; Alpers, Michael P; Kazura, James W
The efficacy of diethylcarbamazine alone was compared with diethylcarbamazine plus albendazole in residents of an island in Papua New Guinea endemic for Wuchereria bancrofti. There was no statistically significant difference between the two drug regimens in decreasing the microfilaria positive rate at 12 and 24 months after a single-dose treatment with either regimen, e.g., 50.0% clearance of microfilaria at 24 months for diethylcarbamazine alone versus 65.7% clearance of microfilaria for diethylcarbamazine plus albendazole (P > 0.05). In contrast, diethylcarbamazine plus albendazole resulted in a significant decrease in Og4C3 antigen prevalence (17%; P = 0.003) at 24 months whereas diethylcarbamazine did not (10%; P = 0.564). These data showed no statistically significant difference in the efficacy of the two drug regimens in lowering the microfilaria reservoir, but they support the use of diethylcarbamazine combined with albendazole in mass treatment programs on the basis of greater activity against adult worms.
Kourentas, Alexandros; Vertzoni, Maria; Khadra, Ibrahim; Symillides, Mira; Clark, Hugh; Halbert, Gavin; Butler, James; Reppas, Christos
An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole.
Sangeetha, T; Quine, S Darlin
The antihyperlipidemic, antilipoperoxidative and antioxidant effects of S-allyl cysteine sulphoxide (SACS) in myocardial infarcted rats were reported previously. The present study was undertaken to evaluate the preventive role of SACS on some biochemical parameters, glycoproteins and hematology in experimentally induced myocardial infarction in rats. Myocardial infarction was induced in rats by subcutaneous injection of isoproterenol (ISO) (150 mg kg(-1)) at an interval of 24 h for 2 days. ISO-treated rats showed a significant increase in the levels of serum iron, uric acid and blood glucose, Na(+) and Ca(2+) in the heart and a significant decrease in the levels of plasma iron binding capacity, serum total protein, albumin/globulin ratio, heart K(+) and heart glycogen. The levels/concentrations of glycoproteins in serum and the heart were increased in myocardial infarcted rats. Myocardial infarcted rats also showed a significant increase in red blood cells, hemoglobin, packed cell volume, white blood cells, neutrophils, platelet count and fibrinogen level and a significant decrease in erythrocyte sedimentation rate, eosinophils, lymphocytes, bleeding, clotting and prothrombin time. Oral pretreatment with SACS (40 and 80 mg kg(-1)) daily for a period of 35 days showed a positive effect on all the biochemical parameters studied in ISO-induced rats. Thus, the study showed the protective effect of SACS on ISO-induced cardiotoxicity in male Wistar rats.
Qavi, Abdul; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita; Kumar, Neeraj; Malhotra, Kiran Preet; Srivastava, Pradeep Kumar; Verma, Rajesh; Sharma, Praveen Kumar
Abstract In this study, we describe clinical and imaging spectrum, and the natural course of patients with disseminated cysticercosis. How albendazole affects the course of disease has also been evaluated. We assessed the Toll-like receptor-4 gene polymorphisms, to know the reason for the apparently higher prevalence of disseminated cysticercosis in India. Sixty consecutive patients with disseminated cysticercosis were enrolled. Sixty age-and-sex-matched healthy controls were also enrolled for the purpose of genetic study. Twenty patients, who gave consent, were treated with albendazole along with corticosteroids. Forty patients did not give consent for antiparasitic therapy. Assessment for Toll-like receptor-4 gene polymorphisms (Asp299Gly and Thr399Ile genes) was done. Patients were followed for 6 months. We also performed a literature search of cases published in English language using PubMed electronic database and analyzed 56 cases thus available. There was an increased risk (6.63 fold and 4.61 fold) of disseminated cysticercosis in the presence of Asp299Gly and Thr399Ile polymorphisms in Toll-like receptor-4, respectively. The allelic frequency of Gly (11% vs. 3%, P = 0.024, odds ratio [OR] = 3.52) and Ile alleles (11% vs. 2%, P = 0.009, OR = 4.738) in disseminated cysticercosis was high. Albendazole resulted in complete disappearance of all cerebral lesions in 35% (7/20) patients and reduction in lesion load in remaining 65% (13/20) patients. No significant change in number of cysticercal lesion was noted in patients who did not receive albendazole. No major adverse reaction following antiparasitic treatment was noted. Three deaths were recorded in patients who did not receive antiparasitic treatment. Of the 56 cases reported in PubMed, 33 patients received antiparasitic treatment with follow-up data available for 31 patients. Most (24) of these patients received albendazole. A significant clinical and/or imaging improvements, on follow up, were observed in
Belizario, V. Y.; Amarillo, M. E.; de Leon, W. U.; de los Reyes, A. E.; Bugayong, M. G.; Macatangay, B. J. C.
OBJECTIVE: To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS: In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS: Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION: Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems. PMID:12640474
Cedillo-Rivera, R; Muñoz, O
The susceptibility of a strain of Giardia lamblia to benzimidazole carbamates, 5-nitroimidazoles, nitrofurans and other drugs was studied in vitro. Albendazole was the most active compound, with a 50% inhibitory concentration (IC50) of 0.01 mg/L and a minimal lethal concentration (MLC) of less than 0.04 mg/L; the IC50 of mebendazole was 0.06 mg/L and the MLC less than 0.5 mg/L. Among the 5-nitroimidazoles tested, ornidazole was the most effective (IC50 0.12 mg/L); tinidazole, metronidazole, secnidazole and hemezole were less active. Nifuroxazide, etofamide and nalidixic acid exhibited modest anti-giardial activity; quinfamide did not inhibit the growth of the parasite at a concentration of 200 mg/L. Albendazole and mebendazole are promising candidates for clinical use and should be further evaluated.
Taylor, D H; Morris, D L; Reffin, D; Richards, K S
The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to less than 2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes significantly more effective than mebendazole (p less than 0.05), praziquantel (p less than 0.01) or untreated controls (p less than 0.01). Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:2583567
Karagöz, Ergenekon; Selek, Mehmet Burak; Aydın, Ersin; Hatipoğlu, Mustafa; Turhan, Vedat; Acar, Ali; Öncül, Oral; Görenek, Levent
Toxocariasis is a worldwide human helminthiasis, especially seen in temperate and tropical climate regions around the world. The diagnosis of this disease is performed on the basis of clinical symptoms and laboratory findings. Albendazole is one of the treatment choices for toxocariasis, with a currently recommended regimen of 10 mg/kg/day in two doses (400 mg twice daily) for 5 days. However, there is no precise consensus about the duration of the treatment. In this article, we report a case of toxocariasis; the patient visited our infectious disease polyclinic with complaints of long-term itching and urticarial skin lesions that were resistant to routine treatment and that recurred. Then, recurrent disease was resolved and skin lesions were diminished after prolonged albendazole therapy.
AHMADI JOUYBARI, Toraj; NAJAF GHOBADI, Khadije; LOTFI, Bahare; ALAVI MAJD, Hamid; AHMADI, Nayeb Ali; ROSTAMI-NEJAD, Mohammad; AGHAEI, Abbas
Background: The aim of the study was assessment of defaults and conducted meta-analysis of the efficacy of single-dose oral albendazole against T. trichiura infection. Methods: We searched PubMed, ISI Web of Science, Science Direct, the Cochrane Central Register of Controlled Trials, and WHO library databases between 1983 and 2014. Data from 13 clinical trial articles were used. Each article was included the effect of single oral dose (400 mg) albendazole and placebo in treating two groups of patients with T. trichiura infection. For both groups in each article, sample size, the number of those with T. trichiura infection, and the number of those recovered following the intake of albendazole were identified and recorded. The relative risk and variance were computed. Funnel plot, Beggs and Eggers tests were used for assessment of publication bias. The random effect variance shift outlier model and likelihood ratio test were applied for detecting outliers. In order to detect influence, DFFITS values, Cook’s distances and COVRATIO were used. Data were analyzed using STATA and R software Results: The article number 13 and 9 were outlier and influence, respectively. Outlier is diagnosed by variance shift of target study in inferential method and by RR value in graphical method. Funnel plot and Beggs test did not show the publication bias (P=0.272). However, the Eggers test confirmed it (P=0.034). Meta-analysis after removal of article 13 showed that relative risk was 1.99 (CI 95% 1.71 – 2.31). Conclusion: The estimated RR and our meta-analyses show that treatment of T. trichiura with single oral doses of albendazole is unsatisfactory. New anthelminthics are urgently needed. PMID:28127355
Zurabian, R; Aguilar-Vega, L; Terrones Vargas, E; Cervera Hernández, M E; Willms, K; Ruíz-Velasco Acosta, S
Taenia crassiceps has been widely experimented as a model for in vitro and in vivo studies on drug responses. The purpose of this study was to treat BALB/c mice infected with T. crassiceps strain WFU with commercially available albendazole and to analyze the reduction in parasite infrapopulations. Here, we describe the reduction and apparent damage of T. crassicceps WFU cysticerci in infected mice after antihelminthic drug treatment and subsequent inoculation of those treated parasites into a naïve host. We were able to reduce significantly the parasite counts to 33 and 48% after albendazole treatment for 20 or 25 days and compared with the untreated mice. We also observed morphological damage such as the partial blebbing in the tegument and parenchyma of treated parasites, as well as disorganized musculature and the loss of cell membranes in subtegumental tissue section. However, larvae from albendazole-treated mice inoculated into the next host were able to become re-established in the next murine host due, probably, to the survival of proliferative parasite cells.
Pourgholami, Mohammad H.; Khachigian, Levon M.; Fahmy, Roger G.; Badar, Samina; Wang, Lisa; Chu, Stephanie Wai Ling; Morris, David Lawson
The angiogenic process begins with the cell proliferation and migration into the primary vascular network, and leads to vascularization of previously avascular tissues and organs as well to growth and remodeling of the initially homogeneous capillary plexus to form a new microcirculation. Additionally, an increase in microvascular permeability is a crucial step in angiogenesis. Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis. We have previously reported that albendazole suppresses VEGF levels and inhibits malignant ascites formation, suggesting a possible effect on angiogenesis. This study was therefore designed to investigate the antiangiogenic effect of albendazole in non-cancerous models of angiogenesis. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with albendazole led to inhibition of tube formation, migration, permeability and down-regulation of the VEGF type 2 receptor (VEGFR-2). In vivo albendazole profoundly inhibited hyperoxia-induced retinal angiogenesis in mice. These results provide new insights into the antiangiogenic effects of albendazole.
Nakajima, Hideaki; Huang, Tong-Yi; Sun, Kai-Yu; Chen, Shu-Ling; Chen, Ke-Bing
Background Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. Methods and Principal Findings PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10–0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24–7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. Conclusions Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available. PMID
Pérez-Rangel, Armando; Hernández, José Manuel; Castillo-Romero, Araceli; Yépez-Mulia, Lilián; Castillo, Rafael; Hernández-Luis, Francisco; Nogueda-Torres, Benjamín; Luna-Arias, Juan Pedro; Radilla, Gerardo; León-Avila, Gloria
In the present study, we evaluated the effect of an albendazole (ABZ) derivative JVG9 on cultured Giardia intestinalis. To assess the JVG9 effects, we evaluated the tubulin cytoskeleton by confocal microscopy, and we found that the characteristic staining was modified. The scanning electron microscopy images revealed extremely damaged trophozoites and cyst-like cells. The confocal images revealed that this drug triggered the expression of cyst wall protein 1 and encystation. We also found that at low doses, AL triggered the encystation process too.
Goswami, Neela D; Shah, J Jina; Corey, G Ralph; Stout, Jason E
Chronic helminth infections are common in refugee populations and may persist years after immigration. Asymptomatic Strongyloides stercoralis infection raises particular concern because of its potential for complications in immunosuppressed patients. We examined 172 Montagnard refugees resettled to Wake County, North Carolina from 2002 through 2003. Refugees were pretreated with albendazole for five days and screened for health conditions after arrival. Eosinophilia was present in 41 of 171 refugees at the first blood draw. Only 1 of 172 had a stool helminth (Fasciola) identified by microscopy. On repeat testing, 13 people had persistent eosinophilia. Results of serologic analysis for Strongyloides were available in 24 persons. Eosinophil counts decreased significantly after treatment with ivermectin in nine refugees (P = 0.039). Persistent eosinophilia, likely caused by Strongyloides infection, was common in this cohort of Montagnard refugees. Clinicians should understand the limitations of stool microscopy in diagnosis of strongyloidiasis, the limited effectiveness of albendazole in treating strongyloidiasis, and the importance of following-up refugees with persistent eosinophilia.
Albendazole, a member of benzimidazole group of compounds, has been shown to have a broad spectrum activity against all classes of helminth parasites. Although it has also been experimentally proven to be effective against cestode infection of poultry, the actual effects of the drug are not yet described. The present in vitro study demonstrated that the commercial prescription drug Zentel® was significantly effective against adult Raillietina echinobothrida Mégnin, the major cestode parasite of domestic chicken, Gallus domesticus Linnaeus. It clearly exhibited dose-dependent lethal activity at the different concentrations that were tested. Scanning electron microscopy (SEM) revealed that the drug caused extensive structural alterations on the body surface of the cestode. Severe contraction and shrinkage were evident throughout the entire length of the body. The suckers on the scolex became invaginated due to shrinkage. The distinct body segments, the proglottides, were completely distorted. The fine hairy microtriches on the tegument were obliterated and in its place were formed abnormal clumps of tissues. The results of this investigation are in favor of the use of albendazole as a drug of choice in the management of poultry helminthiasis. PMID:21264097
van Schalkwyk, P C; Geyser, T L; Récio, M; Erasmus, F P
Anthelmintic trials were carried out to evaluate the efficacy of albendazole against helmi of 2,5 to 3,8 mg/kg administered orally, resulted in a 98,8 to 100% reduction of adult parasites of the genera Haemonchus, Ostertagia, Trichostrongylus, Nematodirus, Gaigeria, Oesophagostomum, Chabertia, Marshallagia and Cooperia. Against the immature stages of these genera, except for Marshallagia and Cooperia, which were not tested, a dose level of 2,5 to 3,8 mg/kg was 83,9-100% effective. Albendazole at 2,5 mg/kg was 99,0% effective against adult stages of Dictyocaulus; its activity at a dose of 3,8 mg/kg against the immature stages of D. filaria was 89,3%. In sheep naturally infested with Moniezia, 100% elimination was obtained at a dose level of 2,5 mg/kg. Dose levels of 3,8 mg/kg and higher were more than 76% effective against adult Fasciola hepatica, while a dose of 4,8 mg/kg was 63% effective against adult Fasciola gigantica.
Bundy, D A; Thompson, D E; Cooper, E S; Blanchard, J
The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.
Romo, Matthew L; Carpio, Arturo; Kelvin, Elizabeth A
Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co-administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized.
Solaymani-Mohammadi, Shahram; Genkinger, Jeanine M.; Loffredo, Christopher A.; Singer, Steven M.
Background Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans. Methodology and Principal Findings We performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients) comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR) was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01). In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34), but limitations of the sample size precluded a definite conclusion. Conclusions/Significance The effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement
Eguale, Tadesse; Chaka, Hassen; Gizaw, Daniel
A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.
Schwab, A E; Churcher, T S; Schwab, A J; Basáñez, M-G; Prichard, R K
The Global Program for the Elimination of Lymphatic Filariasis (GPELF) intends to achieve its aims through yearly mass treatments with albendazole (ABZ) combined with ivermectin (IVM) or diethylcarbamazine (DEC). The use of ABZ and IVM separately to combat parasites of veterinary importance has, on many occasions, resulted in widespread drug resistance. In order to help predict the spread of potential ABZ resistance alleles through a population of Wuchereria bancrofti, we have developed a mathematical model that incorporates population genetics into EPIFIL, a model which examines the transmission dynamics of the parasite. Our model considers the effect of the combined treatments on the frequency of a recessive allele, which confers ABZ resistance. The model predicts that after 10 yearly treatments with ALB and DEC, 85% coverage and an initial resistance allele frequency of 5%, the frequency of the resistance genotype will increase from 0.25 to 12.7%. If non-random mating is assumed, the initial genotype frequency will be 2.34% and will increase to 62.7%. ABZ and IVM combination treatment may lead to weaker selection for this genotype. Treatment coverage, initial allele frequencies and number of treatments also affect the rate of selection.
Treatment of co-infection with bancroftian filariasis and onchocerciasis: a safety and efficacy study of albendazole with ivermectin compared to treatment of single infection with bancroftian filariasis
Makunde, William H; Kamugisha, Leo M; Massaga, Julius J; Makunde, Rachel W; Savael, Zakana X; Akida, Juma; Salum, Fred M; Taylor, Mark J
Background In order to use a combination of ivermectin and albendazole for the elimination of lymphatic filariasis, it is important to assess the potential risk of increased adverse events in individuals infected with both lymphatic filariasis and onchocerciasis. We compared the safety and efficacy of albendazole (400 mg) in combination with ivermectin (150 micrograms/kg), for the treatment of co-infections of Wuchereria bancrofti and Onchocerca volvulus with single infection of W. bancrofti. Methods The safety study on co-infections was a crossover, double blind design, while for the single infection of bancroftian filariasis an open design comparing two treatments was used. For co-infection, one group was allocated a single dose of ivermectin (150 micrograms/kg) plus albendazole (400 mg) (Group A). The other group received placebo (Group B). Five days later the treatment regime was reversed, with the Group A receiving placebo and Group B receiving treatment. For the single bancroftian filariasis infection, one group received a single dose of albendazole (400 mg) plus ivermectin (150 μg/kg) (Group C) while the other group received a single dose of albendazole (400 mg) alone (Group D). Blood and skin specimens were collected on admission day, day 0, and on days 2, 3, and 7 to assess drug safety and efficacy. Thereafter, blood and skin specimens were collected during the 12 months follow up for the assessment of drug efficacy. Study individuals were clinically monitored every six hours during the first 48 hours following treatment, and routine clinical examinations were performed during the hospitalisation period and follow-up. Results In individuals co-infected with bancroftian filariasis and onchocerciasis, treatment with ivermectin and albendazole was safe and tolerable. Physiological indices showed no differences between groups with co-infection (W. bancrofti and O. volvulus) or single infection (W. bancrofti). The frequency of adverse events in co
A sensitive LC-MS/MS method for analysis of pericyazine in presence of 7-hydroxypericyazine and pericyazine sulphoxide in human plasma and its application to a comparative bioequivalence study in Chinese healthy volunteers.
Cai, Hua Lin; Deng, Yang; Fang, Ping Fei; Cao, SiSi; Hou, Zhen Yan; Wu, Yan Qin; Chen, Xue Jiao; Yan, Miao; Zhang, BiKui
A robust and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of pericyazine in human plasma. The plasma sample was alkalized with sodium hydroxide solution and handled by liquid-liquid extraction with ethyl acetate after adding perphenazine as an internal standard (IS). The analytes were separated on an Ultimate™ AQ-C18 analytical column at 40°C, with a gradient elution consisting of A (aqueous phase: 5mM ammonium acetate buffer solution containing 0.1% formic acid) and B (organic phase: acetonitrile) at a flow rate of 0.350mL/min. The detection was conducted on an API 4000 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) transitions, m/z 366.5>142.4 for pericyazine, m/z 382.5>142.4 for its 7-hydroxy and sulphoxide metabolites and m/z 404.3>171.3 for IS were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity (LLOQ of 0.021ng/mL) and good linearity over the concentration range of 0.021-9.90ng/mL. The intra- and inter-day precision, accuracy, and stability results were within the acceptable limits and no matrix effect was observed. This method was successfully applied in a bioequivalence study to evaluate the pharmacokinetics in 20 healthy male Chinese volunteers. Additional exploratory analyses of 7-hydroxy and sulphoxide metabolites of pericyazine in the same samples suggest that the unchanged drug is predominant in the plasma and suitable for the bioequivalence comparison after a single oral administration of 10mg pericyazine.
Sinha, Santosh Kumar; Goel, Amit; Sachan, Mohit; Saraf, Sameer; Verma, Chandra Mohan
Filariasis presenting with pericardial effusion with tamponade is rare. We report a case of a 30-year-old female who was admitted with severe dyspnea and chest pain since 2 days. Echocardiogram showed massive pericardial effusion with tamponade. Pericardial fluid aspiration drained 1.2 L of hemorrhagic fluid. Cytology examination revealed microfilaria of Wuchereria bancrofti. She was treated with diethyl carbamazine and discharged. Six weeks later, she presented again with massive pericardial effusion with cardiac tamponade. Pericardiocentesis was done. Cytology examination revealed microfilaria of W. bancrofti. This time she was treated with ivermectin and albendazole and cured. Hemorrhagic effusion resolved completely. Though relatively uncommon, tropical diseases must always be considered in the etiological diagnosis of recurrent pericardial effusion.
Paredes, Alejandro Javier; Llabot, Juan Manuel; Sánchez Bruni, Sergio; Allemandi, Daniel; Palma, Santiago Daniel
Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment.
Corba, J; Krupicer, I; Legény, J; Juris, P; Veselý, L
The efficacy of intraruminal albendazole (ABZ) capsules (Profitril-Captec) and the effect of treatment on productivity were studied in 300 ewes infected with gastrointestinal nematodes and the trematode Dicrocoelium dendriticum. Coprological tests revealed that treated animals remained negative for 10 weeks after the administration of capsules. Contamination of pasture with nematode larvae was significantly reduced during the whole experiment. Necropsy of 14 animals (seven treated and seven untreated) showed 96.9-99.2% efficacy against the nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis, while efficacy was 88.5% against D. dendriticum. During the 6 month pasture season (May-October 1989), treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls. Our study confirms the reliability of the ABZ slow-release capsules over 90 days and the positive effect of treatment on nematode contamination of pasture and ewe productivity.
Ibrahim, Mohamed A.; Al-Anazi, Fars K.
Albendazole (ABZ), a broad-spectrum anthelmintic agent, is poorly absorbed after oral administration due to its low aqueous solubility. The aim of this study was to improve albendazole dissolution rate by formulating avicel pellets loaded with 10% w/w drug using extrusion/spheronization technique. In addition the wet masses were characterized by mix torque rheometry (MTR) prior to pelletization process. Different additives (i.e., lactose, Tween 80 and low molecular weight chitosan) were formulated with avicel to enhance the dissolution rate of ABZ from the produced pellets. Moreover, mix torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The produced pellets were characterized for their ABZ content, particle size, particle shape, dissolution profile and thermal behaviors. The maximum consistencies (the peak torques) of the wet granules were obtained using 0.667–1.333 ml/g of water or water containing surfactant. Also, the produced pellets have size range from 1036 to 1246 μm. The calculated drug RDR30 for 10%, 30% and 50% lactose concentrations were 1.08, 1.08 and 2.03, respectively, while that calculated for 10%, 30% and 50% w/w chitosan concentrations were 1.71, 3.62 and 3.62, respectively. The results revealed also that increasing the weight ratio of lactose and chitosan was accompanied by a significant reduction of the peak torque magnitude and this was accompanied by an enhanced ABZ dissolution rate. PMID:23960837
Hengsawas Surasarang, Soraya; Keen, Justin M; Huang, Siyuan; Zhang, Feng; McGinity, James W; Williams, Robert O
The purpose of this study was to enhance the dissolution properties of albendazole (ABZ) by the use of amorphous solid dispersions. Phase diagrams of ABZ-polymer binary mixtures generated from Flory-Huggins theory were used to assess miscibility and processability. Forced degradation studies showed that ABZ degraded upon exposure to hydrogen peroxide and 1 N NaOH at 80 °C for 5 min, and the degradants were albendazole sulfoxide (ABZSX), and ABZ impurity A, respectively. ABZ was chemically stable following exposure to 1 N HCl at 80 °C for one hour. Thermal degradation profiles show that ABZ, with and without Kollidon(®) VA 64, degraded at 180 °C and 140 °C, respectively, which indicated that ABZ could likely be processed by thermal processing. Following hot melt extrusion, ABZ degraded up to 97.4%, while the amorphous ABZ solid dispersion was successfully prepared by spray drying. Spray-dried ABZ formulations using various types of acids (methanesulfonic acid, sulfuric acid and hydrochloric acid) and polymers (Kollidon(®) VA 64, Soluplus(®) and Eudragit(®) E PO) were studied. The spray-dried ABZ with methanesulfonic acid and Kollidon(®) VA 64 substantially improved non-sink dissolution in acidic media as compared to bulk ABZ (8-fold), physical mixture of ABZ:Kollidon(®) VA 64 (5.6-fold) and ABZ mesylate salt (1.6-fold). No degradation was observed in the spray-dried product for up to six months and less than 5% after one-year storage. In conclusion, amorphous ABZ solid dispersions in combination with an acid and polymer can be prepared by spray drying to enhance dissolution and shelf-stability, whereas those made by melt extrusion are degraded.
Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie
This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole–chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome–Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID:26352932
Velázquez-Olvera, Stephanía; Salgado-Zamora, Héctor; Jiménez-Cardoso, Enedina; Campos-Aldrete, Maria-Elena; Pérez-González, Cuauhtémoc; Ben Hadda, Taibi
Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole.
Cabada, Miguel M; Lopez, Martha; Arque, Eulogia; Clinton White, A
Few data are available on the epidemiology of soil-transmitted helminths (STHs) in indigenous populations of the Peruvian Amazon. While albendazole is being increasingly used in deworming campaigns, few data exist on the impact of mass drug administration in isolated populations. We studied the prevalence of STHs, anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon. Participants had received two doses of albendazole on consecutive days, 3 months before and again 2 weeks before data collection. Overall, 290 subjects were included. Most were female (53.7%) and 63.9% were ≤19 years old. Half of the participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%), Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5-19 years (51.8 %) and 20-35 years (68.6 %) old had helminths more often than those under 5 years (38%) and older than 35 years (41.5%) (P = 0.02). Anemia was detected in 41% of children and this was more common in children under 5 years that in those of 5-19 years [odd ratio (OR) = 5.68; 95% CI: 2.71-11.88]. Overall, 72.1% of children were malnourished. Stunting was common in children (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration, this population continued to have a high prevalence of STHs, anemia, and malnutrition. In addition, we detected unusual organisms and organisms that do not respond to albendazole. Further studies are needed to assess the rationale and efficacy of mass chemotherapy for STHs in the Amazon.
Cabada, Miguel M; Lopez, Martha; Arque, Eulogia; Clinton White, A
Few data are available on the epidemiology of soil-transmitted helminths (STHs) in indigenous populations of the Peruvian Amazon. While albendazole is being increasingly used in deworming campaigns, few data exist on the impact of mass drug administration in isolated populations. We studied the prevalence of STHs, anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon. Participants had received two doses of albendazole on consecutive days, 3 months before and again 2 weeks before data collection. Overall, 290 subjects were included. Most were female (53.7%) and 63.9% were ≤19 years old. Half of the participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%), Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5–19 years (51.8 %) and 20–35 years (68.6 %) old had helminths more often than those under 5 years (38%) and older than 35 years (41.5%) (P = 0.02). Anemia was detected in 41% of children and this was more common in children under 5 years that in those of 5–19 years [odd ratio (OR) = 5.68; 95% CI: 2.71–11.88]. Overall, 72.1% of children were malnourished. Stunting was common in children (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration, this population continued to have a high prevalence of STHs, anemia, and malnutrition. In addition, we detected unusual organisms and organisms that do not respond to albendazole. Further studies are needed to assess the rationale and efficacy of mass chemotherapy for STHs in the Amazon. PMID:24934795
Humphries, Debbie; Simms, Benjamin T.; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M.; Boakye, Daniel; Wilson, Michael; Cappello, Michael
Children (n = 812) 6–11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana. PMID:23836564
Humphries, Debbie; Simms, Benjamin T; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M; Boakye, Daniel; Wilson, Michael; Cappello, Michael
Children (n = 812) 6-11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana.
Muennig, P.; Pallin, D.; Challah, C.; Khan, K.
The presumptive treatment of parasitosis among immigrants with albendazole has been shown to save both money and lives, primarily via a reduction in the burden of Strongyloides stercoralis. Ivermectin is more effective than albendazole, but is also more expensive. This coupled with confusion surrounding the cost-effectiveness of guiding therapy based on eosinophil counts has led to disparate practices. We used the newly arrived year 2000 immigrant population as a hypothetical cohort in a decision analysis model to examine the cost-effectiveness of various interventions to reduce parasitosis among immigrants. When the prevalence of S. stercoralis is greater than 2%, the incremental cost-effectiveness ratios of all presumptive treatment strategies were similar. Ivermectin is associated with an incremental cost-effectiveness ratio of 1700 dollars per QALY gained for treatment with 12 mg ivermectin relative to 5 days of albendazole when the prevalence is 10%. Any presumptive treatment strategy is cost-effective when compared with most common medical interventions. PMID:15635962
García, Agustina; Leonardi, Darío; Salazar, Mario Oscar; Lamas, María Celina
The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms. PMID:24551084
Fox, Leanne M; Furness, Bruce W; Haser, Jennifer K; Desire, Dardith; Brissau, Jean-Marc; Milord, Marie-Denise; Lafontant, Jack; Lammie, Patrick J; Beach, Michael J
This randomized, placebo-controlled trial investigated the tolerance, efficacy, and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis. Children were infected with Ascaris (30.7%), Trichuris (53.4%), and hookworm (9.7%) with 69.9% having more than one of these parasites. A total of 15.8% of the children had Wuchereria bancrofti microfilariae. Children were randomly assigned treatment with placebo, albendazole (ALB), diethylcarbamazine (DEC), or combined therapy. The combination of DEC/ALB reduced microfilarial density compared with placebo, ALB, or DEC (P < or = 0.03). Albendazole and DEC/ALB reduced the prevalence of Ascaris, Trichuris, and hookworm more than placebo or DEC (P < or = 0.03). Among Trichuris-infected children, those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo (P < or = 0.05). Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia, DEC/ALB was more effective than DEC, with no increase in severity of adverse reactions.
Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim
The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial
Boes, J; Eriksen, L; Nansen, P
The effect of anthelmintic treatment of pigs on the embryonation and infectivity of Ascaris suum eggs isolated from expelled worms was investigated. Four groups of two naturally infected pigs were dosed with albendazole, pyrantel pamoate, ivermectin or piperazine dihydrochloride, respectively. Following worm expulsion, the eggs were removed from the uteri of female worms and embryonated in sulphuric acid. The infectivity of the embryonated eggs was tested through mouse inoculation. Egg development appeared normal in cultures from worms of the piperazine. pyrantel and ivermectin treated groups. In the albendazole cultures, egg development was largely arrested at the one-cell stage (81%). Where development occurred, irregular cell division was observed and only 7% of the eggs in the culture developed into fullgrown larvae. Following mouse inoculation with 2500 embryonated eggs, significantly lower lung larval counts on day 8 post inoculation (p.i.) were observed for mice in the piperazine and pyrantel treated groups (P < 0.01) compared to untreated controls. The larvae that developed in the eggs from ivermectin and albendazole treated groups appeared fully infective for mice. It was concluded that ovicidal activity of albendazole in vivo inhibits subsequent A. suum egg development in vitro; albendazole is, therefore, not suitable to obtain worms for egg embryonation to produce experimental inoculums. The anthelmintic treatment of pigs with ivermectin had only a limited effect on both embryonation and infectivity of A. suum eggs isolated from expelled worms.
Asadi, Mohammad; Haji Shabani, Ali Mohammad; Dadfarnia, Shayessteh
A novel, simple, and rapid vortex-assisted hollow-fiber liquid-phase microextraction method was developed for the simultaneous extraction of albendazole and triclabendazole from various matrices before their determination by high-performance liquid chromatography with fluorescence detection. Several factors influencing the microextraction efficiency including sample pH, nature and volume of extraction solvent, ionic strength, vortex time, and sample volume were investigated and optimized. Under the optimal conditions, the limits of detection were 0.08 and 0.12 μg/L for albendazole and triclabendazole, respectively. The calibration curves were linear in the concentration ranges of 0.3-50.0 and 0.4-50.0 μg/L with the coefficients of determination of 0.9999 and 0.9995 for albendazole and triclabendazole, respectively. The interday and intraday relative standard deviations for albendazole and triclabendazole at three concentration levels (1.0, 10.0, and 30.0 μg/L) were in the range of 6.0-11.0 and 5.0-7.9%, respectively. The developed method was successfully applied to determine albendazole and triclabendazole in water, milk, honey, and urine samples.
Ghanbarzadeh, Saeed; Khalili, Aram; Jouyban, Abolghasem; Emami, Shahram; Javadzadeh, Yousef; Solhi, Mohammad; Hamishehkar, Hamed
Low solubility and dissolution rate are the primary challenges in the drug development which substantially impact the oral absorption and bioavailability of drugs. Due to the poor water solubility, Albendazole (ABZ) is poorly absorbed from the gastrointestinal tract and shows low oral bioavailability (5%) which is a major disadvantage for the systemic use of ABZ. To improve the solubility and dissolution rate of ABZ, different classes of hydrophilic excipients such as sugars (lactose, sucrose, and glucose), polyols (mannitol and sorbitol), ionic surfactant (sodium lauryl sulfate) and non-ionic surfactant (Cremophor A25) were co-spray dried with ABZ. The crystallinity changes in the processed drug were characterized by differential scanning calorimetry and X-Ray diffraction methods were used to interpret the enhanced solubility and dissolution rate of the drug. Results showed that the solubility and dissolution rate of ABZ were increased 1.8-2.6 folds and 3-25 folds, respectively. Unexpectedly, SLS decreased the solubility index of drug powder even lower than the unprocessed drug which was attributed to drug-SLS ionic interaction as depicted from Fourier transform infrared spectroscopy. It was concluded that by applying the facile, one-step, industrially scalable technique and the use of small amounts of excipient (only 4% of the formulation), a great improvement (21 folds) in dissolution rate of ABZ was achieved. This finding may be used in the pharmaceutical industries for the formulation of therapeutically efficient dosage forms of class II and IV drugs classified in biopharmaceutical classification system. PMID:28003836
García, Agustina; Leonardi, Darío; Piccirilli, Gisela N; Mamprin, María E; Olivieri, Alejandro C; Lamas, María C
Both an experimental design and optimization techniques were carried out for the development of chitosan-pectin-carboxymethylcellulose microspheres to improve the oral absorption of albendazole as a model drug. The effect of three different factors (chitosan, pectin and carboxy methyl cellulose concentrations) was studied on five responses: yield, morphology, dissolution rate at 30 and 60 min, and encapsulation efficiency of the microspheres. During the screening phase, the factors were evaluated in order to identify those which exert a significant effect. Simultaneous multiple response optimizations were then used to find out experimental conditions where the system shows the most adequate results. The optimal conditions were found to be: chitosan concentration, 1.00% w/v, pectin concentration 0.10% w/v and carboxymethylcellulose concentration 0.20% w/v. The bioavailability of the loaded drug in the optimized microspheres was evaluated in Wistar rats which showed an area under curve (AUC) almost 10 times higher than the pure drug.
Afonso, Sónia M S; Neves, Luis; Pondja, Alberto; Macuamule, Cristiano; Mukaratirwa, Samson; Arboix, Margarita; Cristòfol, Carles; Capece, Bettencourt P S
A controlled trial was conducted to evaluate the efficacy of three therapeutics regimes of albendazole (ABZ) against Taenia multiceps larvae in experimental infected goats. Forty-nine goats experimentally infected with 3000 T. multiceps eggs were selected and randomly divided into treatment or control groups. Treatment with 10mg/kg for 3 days for group 1 (G1), 10mg/kg for group 2 (G2) and 20mg/kg/day for group 3 (G3) was applied 2 months after infection; group 4 (G4) served as a control group. A treatment with doses of 10mg/kg/day for 3 days on group 5 (G5) and group 6 (G6) was used as control, 5 months after the infection. The efficacy of ABZ was assessed as percentage of non-viable cysts which were determined by morphologic characteristics, movement and methyl blue staining technique. The efficacy of ABZ against 2 months old cysts was significantly different from the control and were 90.3% (28/31), 72.7% (8/11) and 73.9% (14/19) for G1, G2 and G3, respectively. No differences were observed in cyst viability between treated and control groups for 5-month old cysts. The results in this study indicate that ABZ is effective in goats against 2-month-old cysts of T. multiceps larva located in tissues outside the brain.
Martinez-Marcos, Laura; Lamprou, Dimitrios A; McBurney, Roy T; Halbert, Gavin W
The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (μ-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, μ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect.
Helmy, Hanan; Weil, Gary J; Ellethy, Abou Sree T; Ahmed, Ehab S; Setouhy, Maged El; Ramzy, Reda M R
Diethylcarbamazine/albendazole (DEC/ALB) therapy is widely used in mass drug administration (MDA) programmes aimed at eliminating lymphatic filariasis. We studied the effects of repeated annual treatments with DEC/ALB on Wuchereria bancrofti microfilaraemia, filarial antigenaemia and IgG4 antibodies to Bm14 antigen. Fifty-seven subjects with asymptomatic microfilaraemia were treated with one or seven daily doses of DEC/ALB at time zero. All subjects were re-treated with single-dose DEC/ALB 12, 24 and 36 months later. The two treatment groups had comparable pre-treatment microfilaria counts. Multidose treatment cleared microfilaraemia more effectively than single-dose treatment. Filarial antigen levels decreased equally in both treatment groups. Total antigen clearance was observed in 29.6%, 52.0%, 63.6% and 79.5% of subjects at 12, 24, 36 and 48 months. These clearance rates are much higher than those observed in prior treatment trials with DEC or ivermectin. Antibody levels increased 4 weeks after treatment and then slowly decreased in most subjects. Antibody tests turned negative in 20%, 35%, 39.4% and 52.5% of treated subjects at 12, 24, 36 and 48 months post treatment. These results show that the studied parameters decline at different rates and to differing degrees following DEC/ALB treatment. These findings have important implications regarding strategies for monitoring the effects of MDA in populations.
Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno
Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from -1900% to 100%, 99% to 100%, -167% to 100%, -467% to 89%, and -200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone.
Zhang, Xuan; Zhao, Jing; Gao, Xiangyang; Pei, Dongsheng; Gao, Chao
As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis. PMID:28352336
Mattsson, Anna; Ullerås, Erik; Patring, Johan; Oskarsson, Agneta
The zebrafish embryotoxicity test has previously been combined with an external metabolic activation system (MAS) to assess developmental toxicity of metabolites produced by maternal metabolism. Due to toxicity of MAS the exposure was limited to one early and short period. We have modified the method and included additional testing time points with extended exposure durations. Using the anthelmintic drug albendazole as a model substance, we demonstrated stage-dependent toxic effects at three windows of zebrafish embryo development, i.e. 2-3, 12-14 and 24-28h post fertilization, and showed that MAS, by metabolic deactivation, reduced the toxicity of albendazole at all time points. Chemical analysis confirmed that albendazole was efficiently metabolized by MAS to the corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for assessment of metabolites at different developmental stages.
Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T
Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation.
Martínez-Espinosa, Rodrigo; Argüello-García, Raúl; Saavedra, Emma; Ortega-Pierres, Guadalupe
The control of Giardia duodenalis infections is carried out mainly by drugs, among these albendazole (ABZ) is commonly used. Although the cytotoxic effect of ABZ usually involves binding to β-tubulin, it has been suggested that oxidative stress may also play a role in its parasiticidal mechanism. In this work the effect of ABZ in Giardia clones that are susceptible or resistant to different concentrations (1.35, 8, and 250 μM) of this drug was analyzed. Reactive oxygen species (ROS) were induced by ABZ in susceptible clones and this was associated with a decrease in growth that was alleviated by cysteine supplementation. Remarkably, ABZ-resistant clones exhibited partial cross-resistance to H2O2, whereas a Giardia H2O2-resistant strain can grow in the presence of ABZ. Lipid oxidation and protein carbonylation in ABZ-treated parasites did not show significant differences as compared to untreated parasites; however, ABZ induced the formation of 8OHdG adducts and DNA degradation, indicating nucleic acid oxidative damage. This was supported by observations of histone H2AX phosphorylation in ABZ-susceptible trophozoites treated with 250 μM ABZ. Flow cytometry analysis showed that ABZ partially arrested cell cycle in drug-susceptible clones at G2/M phase at the expense of cells in G1 phase. Also, ABZ treatment resulted in phosphatidylserine exposure on the parasite surface, an event related to apoptosis. All together these data suggest that ROS induced by ABZ affect Giardia genetic material through oxidative stress mechanisms and subsequent induction of apoptotic-like events. PMID:26300866
Ismail, M M; Jayakody, R L; Weil, G J; Nirmalan, N; Jayasinghe, K S; Abeyewickrema, W; Rezvi Sheriff, M H; Rajaratnam, H N; Amarasekera, N; de Silva, D C; Michalski, M L; Dissanaike, A S
In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.
Gao, Yuhong; Li, Hongshuang; Li, Xuemei; Sun, Zhenjun
Copper (Cu) is one of the most common metal contaminants, and albendazole (ABZ) is a veterinary drug with a high efficacy against helminthes. It is believed that the two may co-exist in soil. In this study, the combined subacute toxicity of Cu exposure (0, 80, 120, 160 mg kg(-1)) and ABZ exposure (0, 3, 9 mg kg(-1)) in earthworms (Eisenia fetida) were observed using three approaches, namely chronic growth and reproduction, antioxidant enzyme activity, and earthworm Cu residue. The results have shown that the toxicity of Cu on cocoon hatching success and biomass was alleviated by presence of low concentrations of ABZ (3 mg kg(-1)) during a 56-day exposure period. However, the sensitivity of the earthworms' reproduction to Cu increased with the presence of high concentrations of ABZ (9 mg kg(-1)), indicating a reduction beginning at a Cu concentration of 80 mg kg(-1), in the cocoon number, hatching success, and biomass. In addition, the three enzyme activities exhibited different responsive patterns, indicating inducement in the catalase and glutathione peroxidase, and inhibition in the superoxide dismutase, which were dependent on the exposure times and concentrations. In regard to the earthworm Cu residue, when increasing Cu exposure concentrations, the internal Cu concentrations tended to level off, exhibited a linear pattern at the Cu concentration range of 40 to 120 mg kg(-1), and showed a stable trend above 120 mg kg(-1). The results of the present study can potentially provide important information regarding the combined toxicity of the veterinary drugs and the heavy metals in soil.
Mani, T R; Rajendran, R; Munirathinam, A; Sunish, I P; Md Abdullah, S; Augustin, D J; Satyanarayana, K
The efficacy of single-dose combination drug therapy with diethylcarbamazine (DEC) plus albendazole (ALB), and single-drug therapy with DEC alone against geohelminths was compared as part of a mass drug administration (MDA) for elimination of filariasis. This study was conducted in two blocks of Villupuram District of Tamil Nadu State, India, covering a population of 321 000 including about 100 000 children 1-15 years of age. Prevalence and intensity of geohelminth infection were determined by the Kato-Katz technique immediately before and 3 weeks after the MDA. A pre-treatment cross-sectional survey was undertaken in 18 statistically selected villages out of 204 villages, including 646 school children. About 60% were infected with one or more geohelminths. The overall prevalence rates were 53.9%, 12.4% and 5.7% for Ascaris lumbricoides, hookworms and Trichuris trichiura, respectively. Combination therapy (DEC + ALB) produced a cure rate of 74.3% and an egg reduction rate of 97.3% for geohelminths, which were higher than the corresponding rates (30.4% and 79.0%) observed in the single drug therapy arm with DEC alone. The odds of cure with combination therapy were significantly higher for roundworm (5.3 times) and hookworms (3.5 times), then odds of cure with DEC alone. Both therapies were equally effective against trichuriasis, recording cure rates >77% and egg reduction rates >83%. In combination therapy, 53.5% of the children noticed expulsion of worms after MDA, while in single drug therapy only 20.9% did. Our study indicated that MDA of combination therapy was operationally feasible at the community level, and it may secure higher community compliance because of its perceived benefits and enhanced efficacy against geohelminths than single-drug therapy.
A simple assay for the simultaneous determination of human plasma albendazole and albendazole sulfoxide levels by high performance liquid chromatography in tandem mass spectrometry with solid-phase extraction.
Wojnicz, Aneta; Cabaleiro-Ocampo, Teresa; Román-Martínez, Manuel; Ochoa-Mazarro, Dolores; Abad-Santos, Francisco; Ruiz-Nuño, Ana
A simple, reproducible and fast (4 min chromatogram) method of liquid chromatography in tandem with mass spectrometry (LC/MS-MS) was developed to determine simultaneously the plasma levels of albendazole (ABZ) and its metabolite albendazole sulfoxide (ABZOX) for pharmacokinetic and clinical analysis. Each plasma sample was extracted by solid phase extraction (SPE) using phenacetin as internal standard (IS). The extracted sample was eluted with a Zorbax XDB-CN column using an isocratic method. The mobile phase consisting of water with 1% acetic acid (40%, A) and MeOH (60%, B), was used at a flow rate of 1 mL/min. ABZ and ABZOX were detected and identified by mass spectrometry with electrospray ionization (ESI) in the positive ion and multiple-reaction monitoring (MRM) mode. The method was linear in the range of 5-1000 ng/mL for ABZ and 10-1500 ng/mL (full validation) or 10-5000 ng/mL (partial validation) for ABZOX, with 5 and 10 ng/mL lower limit of quantification (LLOQ) for ABZ and ABZOX, respectively. The tests of accuracy and precision, matrix effect, extraction recovery and stability of the samples for both ABZ and ABZOX did not deviate more than 20% for the LLOQ and no more than 15% for other quality controls (QCs), according to regulatory agencies.
Piccirilli, Gisela N; García, Agustina; Leonardi, Darío; Mamprin, María E; Bolmaro, Raúl E; Salomón, Claudio J; Lamas, María C
Encapsulation of albendazole, a class II compound, into polymeric microparticles based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve drug dissolution and oral bioavailability. The microparticles were prepared by spray drying technique and further characterized by means of X-ray powder diffractometry, infrared spectroscopy and scanning electron microscopy. The formation of a novel polymeric structure between chitosan and sodium lauryl sulfate, after the internal or external gelation process, was observed by infrared spectroscopy. The efficiency of encapsulation was found to be between 60 and 85% depending on the internal or external gelation process. Almost spherically spray dried microparticles were observed using scanning electron microscopy. In vitro dissolution results indicated that the microparticles prepared by internal gelation released 8% of the drug within 30 min, while the microparticles prepared by external gelation released 67% within 30 min. It was observed that the AUC and Cmax values of ABZ from microparticles were greatly improved, in comparison with the non-encapsulated drug. In conclusion, the release properties and oral bioavailability of albendazole were greatly improved by using spraydried chitosan-sodium lauryl sulphate microparticles.
Küster, Tatiana; Stadelmann, Britta; Aeschbacher, Denise; Hemphill, Andrew
The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.
Rajendran, R; Mani, T R; Munirathinam, A; Sunish, I P; Abdullah, S Md; Augustin, D J; Satyanarayana, K
We evaluated the long-term impact of single-dose diethylcarbamazine plus albendazole combination therapy with that of diethylcarbamazine alone on the control of soil-transmitted helminths (STH) in 2 blocks (revenue units) of Villupuram district, south India, as part of an ongoing mass drug administration (MDA) campaign for the elimination of lymphatic filariasis in 2001. The prevalence and intensities of STHs were studied in 287 children, aged 9 and 10 years (136 in the combination therapy cohort and 151 in the diethylcarbamazine alone cohort), using the Kato-Katz technique to examine stool samples at 4 time-points (baseline, and 3 weeks, 6 months and 11 months after MDA). The combination therapy showed long-term efficacy against STHs and the magnitude of control remained at a moderate and significant level for 11 months after MDA compared with the moderate gains of diethylcarbamazine alone. Single-dose MDA with albendazole and diethylcarbamazine combination therapy may prove to be a good strategy in treating multiple parasitic infections in endemic communities.
Humphries, Debbie; Nguyen, Sara; Kumar, Sunny; Quagraine, Josephine E; Otchere, Joseph; Harrison, Lisa M; Wilson, Michael; Cappello, Michael
Mass drug administration (MDA) targeting school-age children is recommended by the World Health Organization for the global control of soil-transmitted helminth (STH) infections. Although considered safe and cost-effective to deliver, benzimidazole anthelminthics are variably effective against the three most common STHs, and widespread use has raised concern about the potential for emerging resistance. To identify factors mediating response to albendazole, we conducted a cross-sectional study of hookworm infection in the Kintampo North Municipality of Ghana in 2011. Among 140 school-age children residing in five contiguous communities, the hookworm prevalence was 59% (82/140). The overall cure rate following administration of single-dose albendazole (400 mg) was 35% (27/76), with a community-wide fecal egg reduction rate (ERR) of 61% (95% confidence interval: 51.8-71.1). Significant disparities were observed in albendazole effectiveness by community, with a cure rate as low as 0% (N = 24) in Jato Akuraa and ERRs ranging from 53% to 95% across the five study sites. Individual host factors associated with response to deworming treatment included time since last meal, pretreatment blood hemoglobin level, and mid-upper arm circumference. These data demonstrate significant community-level variation in the effectiveness of albendazole, even among populations living in close proximity. Identification of host factors that influence response to albendazole, most notably the timing of drug administration and nutritional factors, creates an opportunity to enhance the effectiveness of deworming through targeted interventions. These findings also demonstrate the importance of measuring anthelminthic response as part of the monitoring and evaluation of community-based deworming programs.
Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand
In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).
Corba, J; Krupicer, I; Várady, M; Pet'ko, B
The efficacy of intraruminal albendazole (ABZ) capsules (Proftril-Captec) and the effect of treatment on productivity parameters were studied in two experiments totally on 466 ewes naturally infected with gastrointestinal nematodes and trematodes D. dendriticum. Ovoscopical tests revealed that treated animals remained negative during 10-12 weeks after the administration of capsules and that pasture contamination with helminths was significantly reduced. Necropsy revealed 96.9-99.2% efficacy against nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis. Priority finding is the efficacy of ABZ capsules against trematodes D. dendriticum which was in the first experiment 88.5% and in the second experiment 91.8%. During the 6-month pasture season treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls.
Hansen, Tina V. A.; Nejsum, Peter; Friis, Christian; Olsen, Annette; Thamsborg, Stig Milan
Background The single-dose benzimidazoles used against Trichuris trichiura infections in humans are not satisfactory. Likewise, the benzimidazole, fenbendazole, has varied efficacy against Trichuris suis whereas Oesophagostomum dentatum is highly sensitive to the drug. The reasons for low treatment efficacy of Trichuris spp. infections are not known. Methodology We studied the effect of fenbendazole, albendazole and levamisole on the motility of T. suis and O. dentatum and measured concentrations of the parent drug compounds and metabolites of the benzimidazoles within worms in vitro. The motility and concentrations of drug compounds within worms were compared between species and the maximum specific binding capacity (Bmax) of T. suis and O. dentatum towards the benzimidazoles was estimated. Comparisons of drug uptake in living and killed worms were made for both species. Principal findings The motility of T. suis was generally less decreased than the motility of O. dentatum when incubated in benzimidazoles, but was more decreased when incubated in levamisole. The Bmax were significantly lower for T. suis (106.6, and 612.7 pmol/mg dry worm tissue) than O. dentatum (395.2, 958.1 pmol/mg dry worm tissue) when incubated for 72 hours in fenbendazole and albendazole respectively. The total drug concentrations (pmol/mg dry worm tissue) were significantly lower within T. suis than O. dentatum whether killed or alive when incubated in all tested drugs (except in living worms exposed to fenbendazole). Relatively high proportions of the anthelmintic inactive metabolite fenbendazole sulphone was measured within T. suis (6–17.2%) as compared to O. dentatum (0.8–0.9%). Conclusion/Significance The general lower sensitivity of T. suis towards BZs in vitro seems to be related to a lower drug uptake. Furthermore, the relatively high occurrence of fenbendazole sulphone suggests a higher detoxifying capacity of T. suis as compared to O. dentatum. PMID:24699263
El-Metwaly, Nashwa M.; Refat, Moamen S.
This work represents the elaborated investigation for the ligational behavior of the albendazole ligand through its coordination with, Cu(II), Mn(II), Ni(II), Co(II) and Cr(III) ions. Elemental analysis, molar conductance, magnetic moment, spectral studies (IR, UV-Vis and ESR) and thermogravimetric analysis (TG and DTG) have been used to characterize the isolated complexes. A deliberate comparison for the IR spectra reveals that the ligand coordinated with all mentioned metal ions by the same manner as a neutral bidentate through carbonyl of ester moiety and NH groups. The proposed chelation form for such complexes is expected through out the preparation conditions in a relatively acidic medium. The powder XRD study reflects the amorphous nature for the investigated complexes except Mn(II). The conductivity measurements reflect the non-electrolytic feature for all complexes. In comparing with the constants for the magnetic measurements as well as the electronic spectral data, the octahedral structure was proposed strongly for Cr(III) and Ni(II), the tetrahedral for Co(II) and Mn(II) complexes but the square-pyramidal for the Cu(II) one. The thermogravimetric analysis confirms the presence or absence of water molecules by any type of attachments. Also, the kinetic parameters are estimated from DTG and TG curves. ESR spectrum data for Cu(II) solid complex confirms the square-pyramidal state is the most fitted one for the coordinated structure. The albendazole ligand and its complexes are biologically investigated against two bacteria as well as their effective effect on degradation of calf thymus DNA.
Sunish, I P; Kalimuthu, M; Rajendran, R; Munirathinam, A; Ashok Kumar, V; Nagaraj, J; Tyagi, B K
The National Programme for the Elimination of Lymphatic Filariasis is underway in the endemic districts of Tamil Nadu State, South India, since 2001. Annual mass drug administration (MDA) was carried out by the state health department to all eligible individuals. The impact of MDAs on transmission parameters was evaluated in 2 revenue blocks, viz, one with DEC alone and the other with a combination of albendazole. After 10 years with 6 annual MDAs, the transmission indices reached low levels in both treatment arms, but still persisted. However, the DEC alone arm showed higher transmission rates, compared to the DEC+ALB arm. Few villages which demonstrated persistent transmission need to be targeted with an additional control measure viz, vector control, to achieve LF elimination. It is evident from the 10 year period of the study that inclusion of albendazole along with DEC has significantly reduced the transmission indices to almost nil level, as compared to DEC alone.
Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P
Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977
García, Agustina; Leonardi, Darío; Vasconi, María D.; Hinrichsen, Lucila I.; Lamas, María C.
Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its broad spectrum activity, good tolerance and low cost. However, the drug has the disadvantage of poor bioavailability due to its very low solubility in water; as a consequence, a very active area of research focuses on the development of new pharmaceutical formulations to increase its solubility, dissolution rate, and bioavailability. The primary objective of this study was to prepare randomly methylated β-cyclodextrins inclusion complexes to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. This formulation therapeutic efficacy was contrasted with that of the pure drug by treating Trichinella spiralis infected mice during the intestinal phase of the parasite cycle, on days five and six post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral stage on day 30 post-infection, when compared with the untreated control. Thus, it could be demonstrated that the inclusion complexes improve the in vivo therapeutic activity of albendazole. PMID:25406084
Njenga, S M; Wamae, C N; Njomo, D W; Mwandawiro, C S; Molyneux, D H
Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.
Isac, Eliana; de A Picanço, Guaraciara; da Costa, Tatiane L; de Lima, Nayana F; de S M M Alves, Daniella; Fraga, Carolina M; de S Lino Junior, Ruy; Vinaud, Marina C
Nitazoxanide (NTZ) is a broad-spectrum anti-parasitic drug used against a wide variety of protozoans and helminthes. Albendazole, its active metabolite albendazole sulfoxide (ABZSO), is one of the drugs of choice to treat both intestinal and tissue helminth and protozoan infections. However little is known regarding their impact on the metabolism of parasites. The aim of this study was to compare the in vitro effect of NTZ and ABZSO in the glycolysis of Taenia crassiceps cysticerci. The cysticerci were treated with 1.2; 0.6; 0.3 or 0.15 μg/mL of NTZ or ABZSO. Chromatographic and spectrophotometric analyses were performed in the culture medium and in the cysticerci extract. Regarding the glucose concentrations was possible to observe two responses: impair of the uptake and gluconeogenesis. The pyruvate concentrations were increased in the ABZSO treated group. Lactate concentrations were increased in the culture medium of NTZ treated groups. Therefore it was possible to infer that the metabolic acidosis was greater in the group treated with NTZ than in the ABZSO treated group indicating that this is one of the modes of action used by this drug to induce the parasite death.
Burke, J M; Miller, J E; Terrill, T H; Smyth, E; Acharya, M
Control of gastrointestinal nematodes (GIN) remains a critical issue due to the prevalence of anthelmintic resistance. The objective of the experiment was to determine the efficacy of copper oxide wire particles (COWP) from three commercial sources and a combination of COWP and albendazole to control GIN and/or Haemonchus contortus in lambs. Naturally infected Katahdin lambs in early June 2014 and 2015 were randomly assigned to receive no COWP (CON; n=9 and 12) or 2g COWP in a gel capsule as Copasure(®) (COP; n=4 and 17; Animax Ltd.), copper oxide-wire form (AUS; n=7 in 2014 only; Pharmplex), Ultracruz™ (ULT; n=8 and 15; Santa Cruz Animal Health™), no COWP and albendazole (CON+alb; n=10 in 2015 only; 15mg/kg BW; Valbazen(®); Zoetis Animal Health), or COWP+alb (n=7 and 11; in 2014, lambs were administered alb on day 3). Lambs grazed grass pastures as a group and were supplemented with 227g/lamb daily of a commercial grain mix (15% crude protein) and the same amount of alfalfa pellets. Feces were collected on days 0 (day of COWP treatment), 7, and 14 for determination of fecal egg counts (FEC). Pooled (2014) or pooled treatment group feces were cultured on days 0, 7, and 14 (2015 only) to determine GIN genera. Data were analyzed using repeated measures in a mixed model, and FEC were log transformed. The predominant GIN on day 0 was H. contortus (87%) in 2014, and there was a mixed population in 2015. The mean FEC was reduced by day 7 in AUS and ULT lambs (treatment×day, P=0.001), and all of the COWP products were similar. By day 14, the AUS FEC were lower than the CON and COP groups. When examining the combination of COWP and synthetic anthelmintic, the FEC of COWP+alb were reduced to nearly 0eggs/g (back-transformed) and lower than the other groups (treatment×day, P=0.001). The percentage of H. contortus in cultured feces was reduced to a greater extent in the COWP than CON or CON+alb groups of lambs. In a mixed GIN population, the COWP products appeared to
Ash, Amanda; Okello, Anna; Khamlome, Boualam; Inthavong, Phouth; Allen, John; Thompson, R C Andrew
Taenia solium taeniasis-cysticercosis and soil-transmitted helminths (STHs) are parasitic Neglected Tropical Diseases endemic throughout Southeast Asia. Within Lao PDR, a remote northern hill tribe village had previously been identified as a hyper endemic focus for T. solium. To reduce this observed prevalence, a One Health intervention covering both pigs and humans was implemented, which included two Mass drug administrations (MDA1 and MDA2) for village residents using a triple dose albendazole 400mg treatment regime. In addition to the effect on T. solium levels, the dual impact of this anthelmintic regime on STHs within the community was also monitored. Faecal samples were collected pre and post MDA1 and MDA2 and analysed for the presence of Taenia species and the STHs Ascaris lumbricoides, Trichuris trichiura and hookworm species. The McMaster technique was used to measure the changes in both prevalence and intensity of infection. Molecular characterisation of Taenia and hookworm species was conducted to detect zoonotic species. The level of taeniasis within the sampled population decreased by 79.4% after MDA1, remained steady during the five month inter-treatment interval and decreased again by 100% after MDA2. The prevalence of STHs decreased by 65.5% and 62.8% after MDA1 and MDA2 respectively; however an increase to 62.1% of pre MDA1 levels was detected during the inter-treatment interval. Individually, hookworm prevalence decreased by 83.4% (MDA1) and 84.5% (MDA2), A. lumbricoides by 95.6% and 93.5% and T. trichiura by 69.2% and 61%. The intensity of infection within the sampled population also decreased, with egg reduction rates of 94.4% and 97.8% for hookworm, 99.4% and 99.3% for A. lumbricoides and 77.2% and 88.5% for T. trichiura. Molecular characterisation identified a T. solium tapeworm carrier from 21.6% (13/60) of households in the village. T. saginata was identified in 5% (3/60) of households. The zoonotic hookworm A. ceylanicum was detected in the
Pereira, Cíntia A J; Oliveira, Laura L S; Coaglio, Aytube L; Santos, Fernanda S O; Cezar, Rodolfo S M; Mendes, Tiago; Oliveira, Fernando L P; Conzensa, Gustavo; Lima, Walter S
Fasciolosis, a parasitic disease caused by the trematode Fasciola hepatica underreported is expanding both in human and animal population, throughout the world. The constant use of synthetic drugs to treat this condition has led to the natural selection of resistant strains of the parasite. Hence, there is a growing focus on the potential anti-helminthic properties of medicinal plants and phytopharmaceuticals. The current study assessed the potential anti-fasciolicide action of Momordica charantia leaf extracts and fractions on the eggs of F. hepatica parasites. The lyophilized crude extract (CE) of M. charantia leaves and its sub-fractions, obtained from liquid-liquid partitioning with organic solvents, were analysed by High Performance Liquid Chromatography (HPLC), suspended in 1% DMSO and used in in vitro tests. Quadruplicates of 50F. hepatica eggs were incubated at 23°C with M. charantia leaf CE in different concentrations. After 12days no larvae were formed in eggs incubated with CE concentrations above 12.5mg/mL. Eggs incubated with CE sub-fractions at concentrations of 1000, 100, 10, 1, 0.1, 0.01μg/mL affected embryonic development, with n-butanol presenting the strongest inhibition of miracidia formation. In contrast, on the 12th day, 90% of the miracidia hatched in the control experiments using 0.03% DMSO whereas embryogenesis was completely abolished with any concentration of albendazole sulphoxide ABZ(SO). Chemical analysis of the CE and sub-fractions revealed a prominent presence of flavonoids. HPLC-MS confirmed Quercetin to be one of the main flavonoids present in the CE and the n-butanol subfraction. This is the first study to analyse the potential anti-fasciolicide action of M. charantia leaf CE and subfractions.
Dvoroznáková, Emília; Porubcová, Jarmila; Snábel, Viliam; Fedorocko, Peter
The effect of liposomized muramyltripeptide phosphatidylethanolamine (L-MTP-PE) administered separately or with anthelmintic albendazole (ABZ) on cellular immunity of mice with alveolar echinococcosis was studied. The proliferative activity of splenic T and B lymphocytes was the most stimulated after combined L-MTP-PE + ABZ therapy [from weeks 8 to 14 post-infection (p.i.)] that also induced a long-term development of protective Th1 response (the highest serum concentration of IFN-gamma from weeks 8 to 18 p.i.). On the contrary, Th2 response (cytokine IL-5) in infected mice treated with L-MTP-PE was inhibited since week 8 p.i., but a significant long-term decrease in IL-5 concentration was found after combined L-MTP-PE+ABZ therapy until the end of the experiment (until week 26 p.i.). L-MTP-PE stimulated the production of superoxide anion (O2-) by peritoneal macrophages from weeks 8 to 12 p.i., but the highest O2- production was accordingly recorded after therapy L-MTP-PE+ABZ from weeks 8 to 18 p.i. Stimulation of cellular immunity of mice with alveolar echinococcis with L-MTP-PE and an interaction with ABZ's anti-parasitic effect resulted in the greatest and long-term reduction of growth of Echinococcus multilocularis cysts in the host from week 10 p.i. until the end of the experiment.
Stuchlíková Raisová, Lucie; Podlipná, Radka; Szotáková, Barbora; Syslová, Eliška; Skálová, Lenka
Albendazole (ABZ) is a benzimidazole anthelmintic widely used especially in veterinary medicine. Along with other drugs, anthelmintics have become one of a new class of micro-pollutants that disturb the environment but the information about their fate in plants remains limited. The present study was designed to test the uptake and biotransformation of ABZ in the ribwort plantain (Plantago lancelota), a common meadow plant, which can come into contact with this anthelmintic through the excrements of treated animals in pastures. Two model systems were used and compared: cell suspensions and whole plant regenerants. In addition, time-dependent changes in occurrence of ABZ and its metabolites in roots, basal parts of the leaves and tops of the leaves were followed up. Ultrahigh-performance liquid chromatography coupled with high mass accuracy tandem mass spectrometry (UHPLC-MS/MS) led to the identification of 18 metabolites of ABZ formed in the ribwort. In both model systems, the same types of ABZ biotransformation reactions were found, but the spectrum and abundance of the ABZ metabolites detected in cell suspensions and regenerants differed significantly. Cell suspensions seem to be suitable only for qualitative estimations of drug biotransformation reactions while regenerants were shown to represent an adequate model for the qualitative as well as quantitative evaluation of drug uptake and metabolism in plants.
Farid, Hoda A; Hammad, Ragaa E; Hassan, Marah M; Ramzy, Reda M R; El Setouhy, Maged; Weil, Gary J
We studied effects of combined diethylcarbamazine (DEC) and albendazole (ALB) treatment on Wuchereria bancrofti microfilaria (MF) uptake and development of infective larvae (L3) in Culex pipiens. Consenting Egyptian adults with microfilaremia (MF > 300/mL) were treated with one or seven daily doses of DEC/ALB. Laboratory-reared mosquitoes were fed on subjects before and after treatment. MF uptake and infectivity (assessed by mosquito dissection) were reduced by 89.6% and 82.9%, respectively, 12 months after single-dose treatment and by 96.2% and 99.7%, respectively, after multi-dose treatment. The L3:mosquito ratio decreased by 88% to 0.082 after single-dose treatment and by 99.8% to 0.001 after multi-dose treatment. If high coverage rates can be achieved for several annual cycles, mass drug administration (MDA) with DEC/ALB has the potential to decrease transmission to unsustainable levels and eliminate filariasis in populations. Multi-dose MDA (especially in the first year) might interrupt transmission with fewer cycles than single-dose treatment.
Liang, Jennifer L; King, Jonathan D; Ichimori, Kazuyo; Handzel, Thomas; Pa'au, Molisamoa; Lammie, Patrick J
American Samoa began a territory-wide mass drug administration (MDA) program with diethylcarbamazine and albendazole in 2000 after baseline surveys indicated that 16.5% of 2,989 residents were infected with Wuchereria bancrofti based on tests for circulating filarial antigen. Follow-up surveys were conducted in 2001, 2003, and 2006, using convenience samples of residents of sentinel villages. Antigenemia prevalence in 2001 (11.5%) and 2003 (13.5%) showed no change. After the 2003 sentinel assessment, improvements were made in the social mobilization and drug distribution strategies. In 2006, after a total of 5 years of MDA and 3 years of improved MDA participation, the antigenemia prevalence dropped from 11.5% (2001) to 0.95% (2006) (P < 0.0001). In 2006, antigenemia prevalence was greater in males (1.5%) than females (0.4%) (P = 0.04). The decline in antigenemia prevalence shows the effectiveness of MDA and changes made in social mobilization and drug distribution.
Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.
In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.
Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C.
Background Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Methodology Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. Principal Findings None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. Conclusions/ Significance The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas. PMID:26967331
Calvo, Natalia L; Arias, Juan M; Altabef, Aída Ben; Maggio, Rubén M; Kaufman, Teodoro S
Albendazole (ALB) is a broad-spectrum anthelmintic, which exhibits two solid-state forms (Forms I and II). The Form I is the metastable crystal at room temperature, while Form II is the stable one. Because the drug has poor aqueous solubility and Form II is less soluble than Form I, it is desirable to have a method to assess the solid-state form of the drug employed for manufacturing purposes. Therefore, a Partial Least Squares (PLS) model was developed for the determination of Form I of ALB in its mixtures with Form II. For model development, both solid-state forms of ALB were prepared and characterized by microscopic (optical and with normal and polarized light), thermal (DSC) and spectroscopic (ATR-FTIR, Raman) techniques. Mixtures of solids in different ratios were prepared by weighing and mechanical mixing of the components. Their Raman spectra were acquired, and subjected to peak smoothing, normalization, standard normal variate correction and de-trending, before performing the PLS calculations. The optimal spectral region (1396-1280cm(-1)) and number of latent variables (LV=3) were obtained employing a moving window of variable size strategy. The method was internally validated by means of the leave one out procedure, providing satisfactory statistics (r(2)=0.9729 and RMSD=5.6%) and figures of merit (LOD=9.4% and MDDC=1.4). Furthermore, the method's performance was also evaluated by analysis of two validation sets. Validation set I was used for assessment of linearity and range and Validation set II, to demonstrate accuracy and precision (Recovery=101.4% and RSD=2.8%). Additionally, a third set of spiked commercial samples was evaluated, exhibiting excellent recoveries (94.2±6.4%). The results suggest that the combination of Raman spectroscopy with multivariate analysis could be applied to the assessment of the main crystal form and its quantitation in samples of ALB bulk drug, in the routine quality control laboratory.
Escobedo, Angel A; Ballesteros, Javier; González-Fraile, Eduardo; Almirall, Pedro
Metronidazole is frequently used against Giardia infection; however, it has been associated with significant failure rates in clearing parasites from the gut; additionally, as it should be taken for 5 to 10 days, it is associated with poor compliance, probably due to side effects. Other drugs, including tinidazole (TNZ) and albendazole (ABZ) have been included in the antigiardial armamentarium. Our aim was to assess the efficacy of ABZ compared with TNZ in Giardia infections in children. A systematic review and a meta-analysis were carried out. PubMed, Medline, EMBASE, CENTRAL, and LILACS were searched electronically until February 2015. Also relevant journals and references of studies included therein were hand-searched for randomised controlled trials (RCTs). The meta-analysis was limited to RCTs evaluating the use of ABZ compared with TNZ in children with Giardia infection. The assessed outcome was parasitological efficacy. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Five RCTs including 403 children were included. Overall, TNZ significantly outperformed ABZ without differences between subgroups defined by ABZ dosages [relative risk, (RR) 1.61 (95% CI): (1.40-1.85); P<0.0001]. The 95% prediction interval range is 1.28-2.02. There was no significant heterogeneity (I(2)=0%; Q-test of heterogeneity P=0.4507. The number-needed-to-treat, the average number of patients who need to be treated with TNZ to gain one additional good outcome as compared with ABZ was 4, 95% CI: 3-5. Our results show that TNZ outperforms ABZ in the treatment of Giardia infections in children from developing countries.
Ramaiah, K D; Vanamail, P; Yuvaraj, J; Das, P K
Annual mass drug administration (MDA) is the recommended strategy for lymphatic filariasis (LF) elimination. We assessed the effect of six rounds of mass administration of diethylcarbamazine (DEC) and albendazole (ALB) on microfilaria (Mf) prevalence and intensity and vector infection and infectivity rates and circulating filarial antigenaemia (CFA) in a group of five villages in south India, endemic for Culex-transmitted bancroftian filariasis. During different rounds of MDA, 60-70% of the eligible population (>15 kg body weight) was treated. The MDA reduced the Mf prevalence from 8.10% (CI 6.18-10.01) to 1.01% (CI 0.31-1.71) (P<0.05) and geometric mean intensity of Mf from 0.31 (CI 0.22-0.40) to 0.02 (CI 0.00-0.04) (P<0.05), equivalent to a fall of 86% and 94% respectively. The vector infection and infectivity rates declined from 13.11% (CI 11.52-14.70) to 0.78% (CI 0.16-1.40) (P<0.05) and 1.04% (CI 0.56-1.52) to 0.13% (CI 0.00-0.39) (P<0.05), respectively. Four out of the five villages recorded <0.5% Mf prevalence and 0% vector infection rate. Circulating filarial antigenaemia (CFA) fell by 86% in the total population and 100% in 1-10 year old children. One of the five villages, which showed the highest baseline vector infection rate, showed >1.0% Mf rate. The results suggest that six rounds of mass administration of DEC and ALB, with 60-70% treatment coverage, is likely to achieve total interruption of transmission and elimination of LF in the majority of villages.
Evans, D; McFarland, D; Adamani, W; Eigege, A; Miri, E; Schulz, J; Pede, E; Umbugadu, C; Ogbu-Pearse, P; Richards, F O
Onchocerciasis, lymphatic filariasis (LF), schistosomiasis and soil transmitted, helminthiasis (STH) are all co-endemic in Nigeria. Annual mass drug administration (MDA) with ivermectin (for onchocerciasis), albendazole (for STH and with ivermectin for LF) and praziquantel (for schistosomiasis) is the WHO-recommended treatment strategy for preventive chemotherapy. Separate delivery rounds for distribution of these drugs have been the usual approach to MDA. All three drugs, however, have now been shown to be clinically and programmatically safe for co-administration with what has come to be known as triple drug administration (TDA). We examined the cost savings of converting from separate delivery rounds to TDA in two states in Nigeria. In 2008, eight local government areas received a single round of ivermectin with albendazole followed at least 1 week later by a single round of praziquantel to school-aged children. The following year, a single round was administered with TDA. The number of treated individuals was essentially unchanged during both years (1,301,864 in 2008 and 1,297,509 in 2009) and no change in adverse events was reported. The total programmatic costs for the MDA, not including drug and overhead costs, reduced by 41% from $123,624 to $72,870. Cost savings were limited in larger populations due to economies of scale. TDA is recommended for mature MDA.
McLaughlin, Steven I; Radday, Jeanne; Michel, Marie Carmel; Addiss, David G; Beach, Michael J; Lammie, Patrick J; Lammie, John; Rheingans, Richard; Lafontant, Jack
In October 2000, 71,187 persons were treated for lymphatic filariasis using albendazole and diethylcarbamazine (DEC) or DEC alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated persons reported one or more adverse reactions. There were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. Men outnumbered women 2:1 in reporting moderate problems. Three patients, representing roughly one in 25,000 persons treated, were hospitalized with severe adverse reactions judged to be treatment-associated by physician review. The cost per person treated for adverse reactions was more than twice the cost per person treated for lymphatic filariasis (dollar 1.60 versus dollar 0.71). Severe adverse reactions to lymphatic filariasis treatment using DEC with or without albendazole are uncommon. Minor and moderate reactions are more commonly reported and their management represents a challenge to lymphatic filariasis elimination programs.
Busatto, Zenaís; da Silva, Agnaldo Fernando Baldo; de Freitas, Osvaldo; Paschoal, Jonas Augusto Rizzato
This paper describes the development of analytical methods for the quantification of albendazole (ABZ) in fish feed and ABZ and its main known metabolites (albendazole sulfoxide, albendazole sulfone and albendazole aminosulfone) in fish fillet employing LC-MS/MS. In order to assess the reliability of the analytical methods, evaluation was undertaken as recommended by related guides proposed by the Brazilian Ministry of Agriculture for analytical method validation. The calibration curve for ABZ quantification in feed showed adequate linearity (r > 0.99), precision (CV < 1.03%) and trueness ranging from 99% to 101%. The method for ABZ residues in fish fillet involving the QuEChERS technique for sample extraction had adequate linearity (r > 0.99) for all analytes, precision (CV < 13%) and trueness around 100%, with CCα < 122 ng g(-)(1) and CCβ < 145 ng g(-)(1). Besides, by aiming to avoid the risk of ABZ leaching from feed into the aquatic environment during fish medication via the oral route, a promising procedure for drug incorporation in the feed involving coating feed pellets with ethyl cellulose polymer containing ABZ was also evaluated. The medicated feed had good homogeneity (CV < 3%) and a lower release of ABZ (< 0.2%) from feed to water when the medicated feed stayed in the water for up to 15 min.
Wu, Zhexue; Lee, Doohyun; Joo, Jeongmin; Shin, Jung-Hoon; Kang, Wonku; Oh, Sangtaek; Lee, Do Yup; Lee, Su-Jun; Yea, Sung Su; Lee, Hye Suk; Lee, Taeho; Liu, Kwang-Hyeon
Albendazole and fenbendazole are broad-spectrum anthelmintics that undergo extensive metabolism to form hydroxyl and sulfoxide metabolites. Although CYP3A and flavin-containing monooxygenase have been implicated in sulfoxide metabolite formation, the enzymes responsible for hydroxyl metabolite formation have not been identified. In this study, we used human liver microsomes and recombinant cytochrome P450s (P450s) to characterize the enzymes involved in the formation of hydroxyalbendazole and hydroxyfenbendazole from albendazole and fenbendazole, respectively. Of the 10 recombinant P450s, CYP2J2 and/or CYP2C19 was the predominant enzyme catalyzing the hydroxylation of albendazole and fenbendazole. Albendazole hydroxylation to hydroxyalbendazole is primarily mediated by CYP2J2 (0.34 μl/min/pmol P450, which is a rate 3.9- and 8.1-fold higher than the rates for CYP2C19 and CYP2E1, respectively), whereas CYP2C19 and CYP2J2 contributed to the formation of hydroxyfenbendazole from fenbendazole (2.68 and 1.94 μl/min/pmol P450 for CYP2C19 and CYP2J2, respectively, which are rates 11.7- and 8.4-fold higher than the rate for CYP2D6). Correlation analysis between the known P450 enzyme activities and the rate of hydroxyalbendazole and hydroxyfenbendazole formation in samples from 14 human liver microsomes showed that albendazole hydroxylation correlates with CYP2J2 activity and fenbendazole hydroxylation correlates with CYP2C19 and CYP2J2 activities. These findings were supported by a P450 isoform-selective inhibition study in human liver microsomes. In conclusion, our data for the first time suggest that albendazole hydroxylation is primarily catalyzed by CYP2J2, whereas fenbendazole hydroxylation is preferentially catalyzed by CYP2C19 and CYP2J2. The present data will be useful in understanding the pharmacokinetics and drug interactions of albendazole and fenbendazole in vivo.
Weil, Gary J.; Kastens, Will; Susapu, Melinda; Laney, Sandra J.; Williams, Steven A.; King, Christopher L.; Kazura, James W.; Bockarie, Moses J.
Background This study employed various monitoring methods to assess the impact of repeated rounds of mass drug administration (MDA) on bancroftian filariasis in Papua New Guinea, which has the largest filariasis problem in the Pacific region. Methodology/Principal Findings Residents of rural villages near Madang were studied prior to and one year after each of three rounds of MDA with diethylcarbamazine plus albendazole administered per World Health Organization (WHO) guidelines. The mean MDA compliance rate was 72.9%. Three rounds of MDA decreased microfilaremia rates (Mf, 1 ml night blood by filter) from 18.6% pre-MDA to 1.3% after the third MDA (a 94% decrease). Mf clearance rates in infected persons were 71%, 90.7%, and 98.1% after 1, 2, and 3 rounds of MDA. Rates of filarial antigenemia assessed by card test (a marker for adult worm infection) decreased from 47.5% to 17.1% (a 64% decrease) after 3 rounds of MDA. The filarial antibody rate (IgG4 antibodies to Bm14, an indicator of filarial infection status and/or exposure to mosquito-borne infective larvae) decreased from 59.3% to 25.1% (a 54.6% decrease). Mf, antigen, and antibody rates decreased more rapidly in children <11 years of age (by 100%, 84.2%, and 76.8%, respectively) relative to older individuals, perhaps reflecting their lighter infections and shorter durations of exposure/infection prior to MDA. Incidence rates for microfilaremia, filarial antigenemia, and antifilarial antibodies also decreased significantly after MDA. Filarial DNA rates in Anopheles punctulatus mosquitoes that had recently taken a blood meal decreased from 15.1% to 1.0% (a 92.3% decrease). Conclusions/Significance MDA had dramatic effects on all filariasis parameters in the study area and also reduced incidence rates. Follow-up studies will be needed to determine whether residual infection rates in residents of these villages are sufficient to support sustained transmission by the An. punctulatus vector. Lymphatic filariasis
Alvarez, L I; Mottier, M L; Lanusse, C E
The work reported here describes the comparative ability of albendazole (ABZ), fenbendazole (FBZ) and triclabendazole (TCBZ) to penetrate through the tegument of mature Fasciola hepatica, and the influence of the physicochemical composition of the incubation medium on the drug diffusion process. The data obtained from the trans-tegumental diffusion kinetic studies were complemented with the determination of lipid-to-water partition coefficients (octanol-water) for the benzimidazole (BZD) anthelmintic drugs assayed. Sixteen-week-old F. hepatica were obtained from untreated artificially infected sheep. The flukes were incubated (37 degrees C) over 60 and 90 min in incubation media (pH 7.4) prepared with different proportions of ovine bile and Krebs' Ringer Tris (KRT) buffer (100, 75, 50, 25 and 0% of bile) containing either ABZ, FBZ or TCBZ at a final concentration of 5 nmol/ml. After the incubation time expired, the liver fluke material was chemically processed and analysed by high performance liquid chromatography (HPLC) to measure drug concentrations within the parasite. Additionally, the octanol-water partition coefficients (PC) for each molecule were calculated (as an indicator of drug lipophilicity) using reversed phase HPLC. The 3 BZD molecules were recovered from F. hepatica at both incubation times in all incubation media assayed. The trans-tegumental diffusion of the most lipophilic molecules ABZ and FBZ (higher PC values) tended to be greater than that observed for TCBZ. Interestingly, the uptake of ABZ by the liver flukes was significantly greater than that measured for TCBZ, the most widely used flukicidal BZD compound. This differential uptake pattern may be a relevant issue to be considered to deal with TCBZ-resistant flukes. Drug concentrations measured within the parasite were lower in the incubations containing the highest bile proportions. The highest total availabilities of the 3 compounds were obtained in liver flukes incubated in the absence of
Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker
Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs.
Suleman, Sultan; Mohammed, Tesfaye; Deti, Habetewold; D'Hondt, Matthias; Wynendaele, Evelien; Mekonnen, Zeleke; Vercruysse, Jozef; Duchateau, Luc; De Spiegeleer, Bart; Levecke, Bruno
Background There is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia. Methodology/Principal Findings A randomized clinical trial was conducted according to the World Health Organization (WHO) guidelines to assess drug efficacy, by means of egg reduction rate (ERR), of Bendex and Ovis against STH infections in school children in Jimma, Ethiopia. In addition, the chemical and physicochemical quality of the drugs was assessed according to the United States and European Pharmacopoeia, encompassing mass uniformity of the tablets, amount of active compound and dissolution profile. Both drugs were highly efficacious against A. lumbricoides (>97%), but showed poor efficacy against T. trichiura (~20%). For hookworms, Ovis was significantly (p < 0.05) more efficacious compared to Bendex (98.1% vs. 88.7%). Assessment of the physicochemical quality of the drugs revealed a significant difference in dissolution profile, with Bendex having a slower dissolution than Ovis. Conclusion/Significance The study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the
Maganga, Lucas; Clowes, Petra; Maboko, Leonard; Hoerauf, Achim; Makunde, Williams H.; Haule, Antelmo; Mviombo, Prisca; Pitter, Bettina; Mgeni, Neema; Mabuye, Joseph; Kowuor, Dickens; Mwingira, Upendo; Malecela, Mwelecele N.; Löscher, Thomas; Hoelscher, Michael
Background Annual mass treatment with ivermectin and albendazole is used to treat lymphatic filariasis in many African countries, including Tanzania. In areas where both diseases occur, it is unclear whether HIV co-infection reduces treatment success. Methodology In a general population study in Southwest Tanzania, individuals were tested for HIV and circulating filarial antigen, an indicator of Wuchereria bancrofti adult worm burden, before the first and after 2 consecutive rounds of anti-filarial mass drug administration. Principle Findings Testing of 2104 individuals aged 0–94 years before anti-filarial treatment revealed a prevalence of 24.8% for lymphatic filariasis and an HIV-prevalence of 8.9%. Lymphatic filariasis was rare in children, but prevalence increased in individuals above 10 years, whereas a strong increase in HIV was only seen above 18 years of age. The prevalence of lymphatic filariasis in adults above 18 years was 42.6% and 41.7% (p = 0.834) in HIV-negatives and–positives, respectively. Similarly, the HIV prevalence in the lymphatic filariasis infected (16.6%) and uninfected adult population (17.1%) was nearly the same. Of the above 2104 individuals 798 were re-tested after 2 rounds of antifilarial treatment. A significant reduction in the prevalence of circulating filarial antigen from 21.6% to 19.7% was found after treatment (relative drop of 8.8%, McNemar´s exact p = 0.036). Furthermore, the post-treatment reduction of CFA positivity was (non-significantly) larger in HIV-positives than in HIV-negatives (univariable linear regression p = 0.154). Conclusion/Significance In an area with a high prevalence for both diseases, no difference was found between HIV-infected and uninfected individuals regarding the initial prevalence of lymphatic filariasis. A moderate but significant reduction in lymphatic filariasis prevalence and worm burden was demonstrated after two rounds of treatment with albendazole and ivermectin. Treatment effects were
Gayen, Prajna; Nayak, Ananya; Saini, Prasanta; Mukherjee, Niladri; Maitra, Sudipta; Sarkar, Prasanta; Sinha Babu, Santi P
In a placebo controlled field trial, the effects of doxycycline (200mg/day) for 23 days followed by doxycycline (200mg/day) in combination with albendazole (ABZ) (400mg/day) for 7 days on depletion of Wolbachia endobacteria from Wuchereria bancrofti and microfilaricidal activity were studied in 68 patients (34 males and 34 females) from West Bengal, India. The drugs in combination (i.e., doxycycline+ABZ) provided the best efficacy by totally eliminating the circulating microfilaria (mf) (in 42% cases) on day 365 with (99.8%, P<0.05) suppression even on day 365 post-treatment compared to both exclusive doxycycline (69%, P<0.05) and ABZ (89%, P<0.05) groups. Thus, our results have established that a 30-day course of doxycycline in combination with a 7-day course of ABZ is sufficient to ensure long-term reduction in mf level by depleting Wolbachia from worm tissues. Doxycycline combined with ABZ led to a greater reduction in mf density in blood at 4 months (post-treatment) in comparison to doxycycline or ABZ alone. There were significant differences between the three treatments after 12 months (post-treatment). Further, the impact of a 7-day regimen of ABZ was surprisingly good in reducing mf compared to doxycycline-alone group. Adverse reactions were mild. A 30-day course of doxycycline and ABZ in combination is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against microfilaremia.
Durgun Yetim, T; Basoglu, A; Taslak Sengul, A; Yetim, I; Serdar Bekdemir, O; Hokelek, M
Secondary hydatidosis is an important problem encountered during the surgical treatment of hydatid cysts. This study describes an experimental model of secondary hydatidosis by cyst inoculation, used to explore whether simultaneous inoculation of protoscolocidal agents could prevent secondary hydatidosis. Fertile cyst fluid was injected into the pleural space of rabbits alone (group 1, n = 8), and in combination with 2% albendazole solution (group 2, n = 8), 20% hypertonic saline (group 3, n = 8) or 10% povidone-iodine (group 4, n = 8). Computed tomography imaging of the thorax, indirect haemagglutination (IHA) titres and eosinophil counts were used to determine cyst development. After 16 months, three control rabbits had pneumothorax, seven had cysts and four had parenchymal nodules. Histopathological investigation of nodules revealed 87.5% cyst formation. Pleural thickening was observed in rabbits from all groups. Cyst formation rates, IHA titres and eosinophilia counts were higher in group 1 than in groups 2-4. This study demonstrated the experimental formation of secondary hydatidosis and found that topical protoscolocidal agents were beneficial in preventing cyst recurrence.
Pion, Sébastien D S; Chesnais, Cédric B; Bopda, Jean; Louya, Frédéric; Fischer, Peter U; Majewski, Andrew C; Weil, Gary J; Boussinesq, Michel; Missamou, François
Implementation of mass drug administration (MDA) with ivermectin plus albendazole (ALB) for lymphatic filariasis (LF) has been delayed in central Africa because of the risk of serious adverse events in subjects with high Loa loa microfilaremia. We conducted a community trial to assess the impact of semiannual MDA with ALB (400 mg) alone on LF and soil-transmitted helminth (STH) infections in the Republic of Congo. Evaluation at 12 months showed that ALB MDA had not significantly reduced Wuchereria bancrofti antigenemia or microfilaria (mf) rates in the community (from 17.3% to 16.6% and from 5.3% to 4.2%, respectively). However, the geometric mean mf count in mf-positive subjects was reduced from 202.2 to 80.9 mf/mL (60% reduction, P = 0.01). The effect of ALB was impressive in 38 subjects who were mf-positive at baseline and retested at 12 months: 37% had total mf clearance, and individual mf densities were reduced by 73.0%. MDA also dramatically reduced the hookworm infection rate in the community from 6.5% to 0.6% (91% reduction), with less impressive effects on Ascaris and Trichuris. These preliminary results suggest that semiannual community MDA with ALB is a promising strategy for controlling LF and STH in areas with coendemic loiasis.
Palomares-Alonso, Francisca; Palencia Hernández, Guadalupe; Rojas-Tomé, Irma Susana; Jung-Cook, Helgi; Pinzón-Estrada, Enrique
In the search of new alternatives for neurocysticercosis treatment, Taenia crassiceps ORF strain cysticerci have been used instead of T. solium for in vitro studies. Up to date, the main criteria for the use of the murine cysticercosis model for drug efficacy evaluation have not been assessed. The aim of the present study was to evaluate the influence of two of the main variables related to the in vivo efficacy: the length of drug treatment and the starting time of treatment after experimental infection, using albendazole (ABZ) and praziquantel (PZQ) as test drugs. Additionally, the relationship between the number of cysts and the parasite weight was assessed. For the study, female BALB/c mice were experimentally infected with T. crassiceps cysts. Three different post-infection periods (10, 20 and 30 days) and three different lengths of treatment with ABZ or PZQ (10, 20 and 30 days) were selected. The efficacy of each treatment was evaluated by comparison with a control group. Our results show that for in vivo efficacy studies, the best time to start the drug treatment is 10 days post-infection and that a minimum of 20 days of treatment is required when ABZ or PZQ are used as positive control. Moreover, in this model the parasite weight can be used as a rapid tool to measure the in vivo drug activity.
Rajendran, R; Sunish, I P; Mani, T R; Munirathinam, A; Abdullah, S Md; Arunachalam, N; Satyanarayana, K
A two-arm community-based lymphatic filariasis elimination trial is being carried out in Tamil Nadu state, India to assess the effect of 2 annual single-dose mass drug administrations of diethylcarbamazine + albendazole (DEC + ALB) on microfilaraemia and antigenaemia in one arm, and diethylcarbamazine(DEC) alone in the other arm. In a cross-sectional survey at each time-point, 450-650 subjects in childhood (2-9 years old) and young adulthood (10-25 years old) were screened from each treatment arm. After 2 annual mass drug administrations, microfilaraemia prevalence in the 2-drug arm was reduced by 54% and 62% in the 2-9 year old and 10-25 year old groups respectively; and corresponding figures for the single-drug arm were 26% and 37%. Though higher reductions were recorded for geometric mean intensity of microfilaraemia in the 2-9 year old groups for both treatment arms, reduction was more pronounced in the 2-drug arm than the single drug arm (74% vs. 24%) in the 10-25 year old group. The reduction in the antigenaemia prevalence in the 2-9 year old group was evident in both treatment arms, but in the 10-25 year old group the reduction was only 16.8% in the 2-drug arm. Our results suggest that the annual, single-dose combination (DEC + ALB) mass treatment regimen has an enhanced effect against bancroftian filariasis compared to single-drug therapy.
Khan, M A; Gaur, R L; Dixit, S; Saleemuddin, M; Murthy, P K
The responses of Mastomys coucha to re-exposure to infection with homologous infective larvae (L(3)) of Brugia malayi were investigated, after initial infections with the nematode had been treated subcutaneously for 5 days with diethylcarbamazine (DEC; 150 mg citrate/kg. day) or albendazole (ALB; 50 mg/kg. day). The parasite burdens, serum concentrations of IgG reacting with a soluble somatic extract of adult B. malayi (BmAS), and cytokine and lymphocyte-proliferative responses to filarial antigen (BmAS) or mitogen (concanavilin A or lipopolysaccharide) were studied. The results demonstrated, for the first time, that re-infection with L(3) was only successful in the DEC-treated animals, not the ALB-treated ones. When the ALB-treated animals were re-exposed, interferon-gamma production decreased, lymphocyte-proliferative responses either remained the same (with concanavilin A) or decreased (with BmAS), and concentrations of specific IgG decreased. When the DEC-treated animals were re-exposed, microfilaraemias re-appeared and, although production of interferon-gamma decreased, there were no detectable lymphocyte proliferative responses, and concentrations of specific IgG remained unchanged. Taken together, the results indicate that, at least in the M. coucha model of human filariasis, ALB but not DEC treatment may help to prevent the development of re-infections.
Children and adolescents infected with Wuchereria bancrofti in Greater Recife, Brazil: a randomized, year-long clinical trial of single treatments with diethylcarbamazine or diethylcarbamazine-albendazole.
Rizzo, J A; Belo, C; Lins, R; Dreyer, G
In filariasis-endemic areas beyond sub-Saharan Africa, the World Health Organization's recommended strategy for interrupting transmission of the causative parasites is annual, single-dose, mass treatment with a combination of diethylcarbamazine (DEC; given at 6 mg/kg) and albendazole (ALB; given at 400 mg) for 4-6 years (the minimum estimated life-span of the adult parasites). In an open, hospital-based, randomized and controlled trial, with a blinded evaluation of outcome, 82 children and adolescents from Recife, all with Wuchereria bancrofti microfilaraemias, were given either DEC alone (6 mg/kg) or the same dose of DEC combined with ALB (at 400 mg/patient). Every 90 days for 1 year after the single treatment, each patient was checked for microfilaraemia by the filtration of up to 5 ml of venous blood collected at night. One year post-treatment, 16 (39%) of the 41 patients given DEC alone and 20 (49%) of the 41 given DEC-ALB were found microfilaraemic (relative risk=0.8, with a 95% confidence interval of 0.49-1.31) and the corresponding geometric mean levels of microfilaraemia were 2.0% and 1.8% of the levels recorded immediately pre-treatment, respectively (P>0.05). In terms of the prevalences and intensities of microfilaraemia, therefore, the addition of ALB to the DEC appeared to offer no significant benefit.
A cluster-randomised controlled trial integrating a community-based water, sanitation and hygiene programme, with mass distribution of albendazole to reduce intestinal parasites in Timor-Leste: the WASH for WORMS research protocol
Nery, Susana Vaz; McCarthy, James S; Traub, Rebecca; Andrews, Ross M; Black, Jim; Gray, Darren; Weking, Edmund; Atkinson, Jo-An; Campbell, Suzy; Francis, Naomi; Vallely, Andrew; Williams, Gail; Clements, Archie
Introduction There is limited evidence demonstrating the benefits of community-based water, sanitation and hygiene (WASH) programmes on infections with soil-transmitted helminths (STH) and intestinal protozoa. Our study aims to contribute to that evidence base by investigating the effectiveness of combining two complementary approaches for control of STH: periodic mass administration of albendazole, and delivery of a community-based WASH programme. Methods and analysis WASH for WORMS is a cluster-randomised controlled trial to test the hypothesis that a community-based WASH intervention integrated with periodic mass distribution of albendazole will be more effective in reducing infections with STH and protozoa than mass deworming alone. All 18 participating rural communities in Timor-Leste receive mass chemotherapy every 6 months. Half the communities also receive the community-based WASH programme. Primary outcomes are the cumulative incidence of infection with STH. Secondary outcomes include the prevalence of protozoa; intensity of infection with STH; as well as morbidity indicators (anaemia, stunting and wasting). Each of the trial outcomes will be compared between control and intervention communities. End points will be measured 2 years after the first albendazole distribution; and midpoints are measured at 6 months intervals (12 months for haemoglobin and anthropometric indexes). Mixed-methods research will also be conducted in order to identify barriers and enablers associated with the acceptability and uptake of the WASH programme. Ethics and dissemination Ethics approval was obtained from the human ethics committees at the University of Queensland, Australian National University, Timorese Ministry of Health, and University of Melbourne. The results of the trial will be published in peer-reviewed journals presented at national and international conferences, and disseminated to relevant stakeholders in health and WASH programmes. This study is funded
ADNANI SADATI, Seyed Jafar; FARAHNAK, Ali; MOLAEI RAD, Mohammad Bagher; GOLESTANI, Abolfazl; ESHRAGHIYAN, Mohammad Reza
Background: Hydatid cysts are formed in human body can be treated clinically by surgery or drugs such as albendazole (ABZ) and mebendazole (MBZ). The purpose of this study was comparing the effects of ABZ and MBZ on glutathione-S-transferase, alkaline phosphatase and protease enzymes activities in protoscoleces of hydatid cyst. Methods: The culture supernatants containing the parasite Excretory / Secretory (E/S) products were collected every 12 h for 72 h. The E/S products of treated samples with 1μg/ml ABZ and MBZ and the control one were collected and after centrifugation then protein concentrations were measured according to Bradford method. GST, ALP and protease activities of E/S products were assessed photometrically. Results: The mean of GST specific activity level in treated protoscoleces with ABZ and MBZ and in control group were obtained 69.44, 132.83 and 225.47U/mg/protein/ml respectively. The mean ALP activity level in treated protoscoleces with ABZ and MBZ and in control group were detected 19.22, 22.27 and 27.85 U/mg/protein/ml respectively. The protease activity level in treated protoscoleces with ABZ and MBZ were not detected. While the mean of protease activity level in control group was 7.61U/mg/proteins. Statistical analysis showed the significant difference between protein concentrations, the specific activities of GST, ALP and protease enzymes in treated protoscoleces in comparison with control group (P<0.05). Also, the significant difference were seen between specific activities of GST and ALP enzymes in treated protoscoleces with ABZ in comparison with treated group with MBZ (P<0.05). Conclusion: ABZ is more effective on the enzymes activities (GST and ALP) as compared with MBZ. PMID:27114987
Samuel, Fikreslasie; Degarege, Abraham; Erko, Berhanu
Monitoring the efficacy of anthelminthic drugs is essential. The objective of this study was to assess the efficacy of a single oral dose of 400mg albendazole (ABZ) against the major soil-transmitted helminth (STH) infection in school children, Wondo Genet, southern Ethiopia. A single fresh stool sample was collected from 298 school children and examined using a duplicate smear of the Kato-Katz method. Children positive for STH infections were treated with single oral dose of 400mg ABZ and re-examined for intestinal helminth infections 21days post-treatment. The participants were interviewed for symptoms related with the drug uptake 24h after ABZ treatment. Children positive for Schistosoma mansoni infections were treated with Praziquantel (40mg/kg of body weight) after an ABZ treatment follow up survey. 51.3%, 49.7%, 44.6% and 88.3% had hookworm, Ascaris lumbricoides, Trichuris trichiura and any intestinal helminth infection, respectively. Cure rates were 97.4% for hookworm, 96.6% for A. lumbricoides and 30.8% for T. trichiura infections. Egg reduction rates (ERRs) were 99.8% for hookworm, 99.9% for A. lumbricoides and 83.1% for T. trichiura infections. Mild and transient symptoms were observed among the participants which were quite frequent. In conclusion, a 400mg single oral dose of ABZ was effective against hookworm and A. lumbricoides but less efficacious against T. trichiura infection. The drug resulted in high ERRs for hookworm, A. lumbricoides and T. trichiura. Administration of the drug in repeated doses or in combination with other drugs might be necessary.
Sunish, I. P.; Rajendran, R.; Munirathinam, A.; Kalimuthu, M.; Kumar, V. Ashok; Nagaraj, J.; Tyagi, B. K.
Background & objectives: One third of the world's population is infected with one or more of the most common soil-transmitted helminths (STH). Albendazole (ALB) is being administered with diethyl carbamazine (DEC) in filariasis endemic areas to eliminate lymphatic filariasis (LF) and helminth infections. In this study, the cumulative impact of seven annual rounds of mass drug administrations (MDA) of DEC and ALB on STH infection in school children in selected villages in southern India was determined. Methods: During 2001-2010, seven MDAs were implemented by the Tamil Nadu State Health Department, India. LF and STH infections were monitored in school children from 18 villages of the two treatment arms (viz, DEC alone and DEC+ALB). Kato-Katz cellophane quantitative thick smear technique was employed to estimate STH infections at three weeks, six months and one year post MDA. Results: Prior to treatment, an overall STH prevalence was 60 per cent. After each MDA, infection markedly reduced at three weeks post-treatment in both the arms. The prevalence increased at six months period, which was maintained up to one year. After seven rounds of MDA, the infection reduced from 60.44 to 12.48 per cent in DEC+ALB arm; while the reduction was negligible in DEC alone arm (58.77 to 52.70%). Interpretation & conclusions: Seven rounds of MDA with DEC+ALB reduced the infection load significantly, and further sustained low level of infection for 10 years. However, complete parasite elimination could not be achieved. To curtail STH infection in the community, MDA should be regularized and environmental sanitation measures need to be improved by effective community-based campaigns. PMID:25963494
El Setouhy, Maged; Ramzy, Reda M R; Ahmed, Ehab S; Kandil, Amr M; Hussain, Omar; Farid, Hoda A; Helmy, Hanan; Weil, Gary J
The Global Program for Elimination of Lymphatic Filariasis calls for mass drug administration for endemic populations outside of sub-Saharan Africa with a single dose of diethylcarbamazine (DEC) and albendazole (Alb) annually for 4-6 years. Single-dose DEC/Alb dramatically reduces blood microfilaria (MF) counts, but most treated subjects fail to completely clear MF after a single dose. A more effective regimen might reduce the number of years required for elimination programs. We performed a randomized clinical trial in Egyptian adults with asymptomatic microfilaremia to compare treatment with seven daily doses of oral DEC (6 mg/kg) and Alb (400 mg) with a single dose of the same combination. We also studied the effect of re-treatment with single-dose DEC/Alb 12 months after the first treatment course. Multi-dose DEC/Alb was significantly more effective than single-dose therapy for reducing and clearing microfilaremia (mean reduction in MF/ml relative to pretreatment counts at 12 months, 99.6% versus 85.7%, with complete clearance in 75% versus 23.1%). The two regimens had similar activity against adult filarial worms, as indicated by serial ultrasound assessments. Neither regimen resulted in complete clearance of filarial antigenemia. There was no difference in adverse events, which were mild to moderate. Blood microfilaria and parasite antigen clearance rates increased following re-treatment. Multi-dose DEC/Alb may be a useful option for filariasis elimination programs, especially in the first year (when enthusiasm for mass drug administration and coverage rates are high), to quickly reduce community MF loads and transmission rates.
Shinde, Rajshree L; Bharkad, Gopal P; Devarajan, Padma V
Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size <20nm, negative zeta potential and good stability. The docosahexaenoic acid (DHA) ME revealed high and rapid ex vivo permeation of drugs through sheep nasal mucosa. Intranasal DHA ME resulted in high brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P<0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.
Oqueka, Tim; Supali, Taniawati; Ismid, Is Suhariah; Purnomo; Rückert, Paul; Bradley, Mark; Fischer, Peter
Background Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking. Methods The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined. Results In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura. Conclusion The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren. PMID:16014169
Kshirsagar, N A; Gogtay, N J; Garg, B S; Deshmukh, P R; Rajgor, D D; Kadam, V S; Kirodian, B G; Ingole, N S; Mehendale, A M; Fleckenstein, L; Karbwang, J; Lazdins-Helds, J K
Filariasis control programmes are moving towards a strategy of repeated single-dose mass treatment of endemic populations. Using a combination, such as albendazole (ALB) to diethylcarbamazine (DEC) gives both macrofilaricidal and anti-helmintic activity. However, the safety of the combination versus DEC alone should be established in field studies in large populations prior to incorporation into national programmes. The present study compared the safety, tolerability, and efficacy of single doses of DEC 6 mg/kg + ALB placebo with DEC 6 mg/kg + ALB 400 mg in populations living in two filariasis endemic villages in the district of Wardha in western India. The study was double blind, parallel group, and randomized. Safety and tolerability study were studied in males and females older than 5 years. Safety was assessed by monitoring if adverse events (AEs) over 5 days affected daily acivities. Subjects in the 2 treatment groups experienced insignificantly different effects on daily activities and the combination was shown to be safe. Efficacy was evaluated by microfilaraemia (Mf), immunochromatographic test (ICT) and ultrasonography (USG) at 0, 3, 6, and 12 months of follow up. The efficacy study enrolled 103 male patients (aged 18-50 years) in microfilariae positive, clinical disease and asymptomatic, amicrofilaremic groups. There was no significant difference in efficacy between groups at 12 months. Within the Mf positive group, significant differences were seen in microfilaraemia (P < 0.001) with both treatments, and in USG (P < 0.001 and P < 0.004 respectively), at 12 months. The present field study has shown the combination of DEC + ALB to be as safe as the single drug DEC and thus the combination can be put in use in the national filariasis control programmes. Both drugs were adequately absorbed. The study at present does not provide evidence for the greater efficacy of the combination at 12 months follow up. While the safety of the combination has been
Williams, J C; DeRosa, A; Nakamura, Y; Loyacano, A F
An experiment was conducted to evaluate the current efficacy of albendazole (ABZ), oxfendazole (OXF) and fenbendazole (FBZ) compared with ivermectin pour-on (IVM-PO) against inhibited early fourth-stage larvae (IEL4) of Ostertagia ostertagi, other gastrointestinal nematodes and lungworm of cattle during spring in Louisiana. Twenty-five crossbred beef heifer calves of 235 kg average weight and 10-12 months of age were acquired in late winter and grazed for 9 weeks on pasture contaminated with O. ostertagi and other nematodes until May 15. The cattle were weighed and randomly allotted into 5 groups of 5 calves on May 16 (day 0) and treatments were as follows: group 1, nontreated controls (CONT); group 2, IVM-PO on mid-backline at 500 micrograms/kg; group 3, ABZ suspension (oral) at 10 mg/kg; group 4, OXF suspension (oral) at 4.5 mg/kg; group 5, FBZ suspension (oral) at 5 mg/kg. After treatment and confinement in separate pens for each group, approximately equal numbers of cattle from each group were necropsied daily between days 29-31. Mean numbers of O. ostertagi developmental stages present in CONT were: adult, 5234; developing (DL4), 3130; IEL4, 44,077. The mean percentage of IEL4 was 84.1. Cooperia spp. were the second most prevalent in CONT (20,307) and smaller numbers of abomasal and intestinal species and Dictyocaulus viviparus were present in nearly all CONT. Percent reductions for the four compounds against O. ostertagi adult, DL4 and IEL4, respectively, were IVM-PO: 99.7, 98.3, 98.1; ABZ: 74.1, 76.5, 75.3; OXF: 78.5, 42.1, 32.0; FBZ: 63.6, 17.7, 39.7. Efficacy of IVM-PO was greater (P < 0.05) against all O. ostertagi stages than the benzimidazole (BZ) drugs, except for ABZ (DL4). There were no significant differences in group means (except for C. punctata adult males, P < 0.05 lower for IVM-PO) or wide variation in reduction percentages for other abomasal and intestinal species and D. viviparus between IVM-PO and BZ drugs. The low efficacy of all three BZ
Efficacy of ivermectin and albendazole alone and in combination for treatment of soil-transmitted helminths in pregnancy and adverse events: a randomized open label controlled intervention trial in Masindi district, western Uganda.
Ndyomugyenyi, Richard; Kabatereine, Narcis; Olsen, Annette; Magnussen, Pascal
A randomized open-label trial, including 834 pregnant women, examined efficacy and recorded adverse events of ivermectin (ivc) and albendazole (alb) alone and combined (comb) on soil-transmitted helminth infections (STHs) in the second trimester of pregnancy. One abortion occurred in the alb group and 10 stillbirths (1, 5, 3, and 1) in the ivc, alb, comb, and the reference group (ref) with no STHs, respectively. Two babies were born with congenital abnormalities (1 [ivc] and 1 [ref]). The prevalence of anemia at first antenatal care (ANC) visit was 20.6% (23.7% [ivc], 21.1% [alb], 22.2% [comb], and 16.1% [ref]). Anemia was reduced to 8.5% at 36 weeks of gestation with 10.9% (ivc), 11.5% (alb), 7.7% (comb), and 6.9% (ref). Hookworm cure rates were 29.4% (ivc), 95.5% (alb), and 92.6% (comb). No severe adverse events were reported by the women after the administration of ivc, alb, or comb during the second trimester of pregnancy, but long-term pharmacovigillance is needed to assess safety of ivc, alb, or comb in pregnancy.
Fraga, Carolina Miguel; da Costa, Tatiane Luiza; de Castro, Ana Maria; Reynoso-Ducoing, Olivia; Ambrosio, Javier; Hernández-Campos, Alicia; Castillo, Rafael; Vinaud, Marina Clare
Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic benzimidazoles due to a differentiated site of action with similar outcome.
Fraga, Carolina Miguel; Da Costa, Tatiane Luiza; De Castro, Ana Maria; Reynoso-Ducoing, Olivia; Ambrosio, Javier; Hernández-Campos, Alicia; Castillo, Rafael; Vinaud, Marina Clare
Biochemical studies of benzimidazole derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.
Tsiboukis, D; Sazakli, E; Jelastopulu, E; Leotsinidis, M
Anthelmintics, such as benzimidazoles and probenzimidazoles, are veterinary drugs used against endoparasites in food producing animals. A number of these drugs are considered responsible for embryotoxicity and teratogenicity. The residue levels of Albendazole, Febantel, Fenbendazole, Mebendazole and some of their metabolites (Albendazole sulphoxide, Albendazole sulphone, Fenbendazole sulfone) were assessed in 123 (42 goat, 69 sheep, 12 bovine) raw milk samples collected from all farms throughout Southern Greece. Sample analysis was performed by HPLC with Diode Array Detector. A high percentage (27.6%) of the samples examined was found to be positive for the investigated compounds. In 14 samples (11.4%), the residues' concentration exceeded the established Maximum Residue Limits. Estimated Daily Intakes were calculated for a population of 723 children aged 10-12 years. Data on milk consumption were obtained by personal interview through a 7-day food frequency questionnaire. The maximum Estimated Daily Intakes for the anthelmintic residues, concerning raw milk, did not exceed the current Acceptable Daily Intake.
Previous studies have shown that Giardia lamblia resistance to metronidazole can be induced in the laboratory, and treatment failures with this drug have also been documented. As replacement theraples, anthelmintic benzimidazoles have antigiardial activity with few clinical side ...
Multiresidue Screening Method for Detection of Benzimidazoles and their Metabolites in Liver and Muscle by High-Performance Liquid Chromatography: Method Development and Validation According to Commission Decision 2002/657/EC
Prearo, Marino; Stella, Paola; Ostorero, Federica; Abete, Maria Cesarina
The use of veterinary drugs may cause the presence of residues in food of animal origin if appropriate withdrawal periods are not respected. A high-performance liquid chromatography (HPLC) method has been developed for the simultaneous detection of 11 benzimidazole residues, including metabolites – albendazole, albendazole sulphoxide, albendazole sulphone, fenbendazole, fenbendazole sulphoxide (oxfendazole), fenbendazole sulphone, flubendazole, mebendazole, oxibendazole, thiabendazole, 5-hydroxythiabendazole – in bovine, ovine, equine, swine, rabbit and poultry liver and in bovine, swine and fish muscle. After extraction with a dicloromethane/acetonitrile solution (35/65 v/v) containing 5% ammonium hydroxide, the solvent was evaporated to dryness, the residue was dissolved in HCl 0.1 M, defatted with hexane, purified on a strong cation exchange solid-phase extraction cartridge and analysed in HPLC with diode array and fluorescence detectors. The method was validated as screening qualitative method evaluating, according to Commission Decision 2002/657/EC criteria, specificity, CCβ and β error at cut off level of 25 μg/kg and ruggedness. PMID:27800310
Brown, Jonathan T.; Randall, Andrew D.
Dimethylsulfoxide (DMSO) is a widely used solvent in biology. It has many applications perhaps the most common of which is in aiding the preparation of drug solutions from hydrophobic chemical entities. Recent studies have suggested that this molecule may be able to induce apoptosis in neural tissues urging caution regarding its introduction into humans, for example as part of stem cell transplants. Here we have used in vitro electrophysiological methods applied to murine brain slices to examine whether a few hours treatment with 0.05% DMSO (a concentration regarded by many as innocuous) alters intrinsic excitability properties of neurones. We investigated pyramidal neurones in two distinct brain regions, namely area CA1 of the hippocampus and layer 2 of perirhinal cortex. In the former there was no effect on resting potential but input resistance was decreased by DMSO pre-treatment. In line with this action potential count for any level of depolarizing current stimulus was reduced by ∼25% following DMSO treatment. Ih-mediated “sag” was also increased in CA1 pyramids and action potential waveform analysis demonstrated that DMSO treatment moved action potential threshold towards resting potential. In perirhinal cortex a decreased action potential output for various depolarizing current stimuli was also seen. In these cells action potential threshold was unaltered by DMSO but a significant increase in action potential width was apparent. These data indicate that pre-treatment with this widely employed solvent can elicit multifaceted neurophysiological changes in mammalian neurones at concentrations below those frequently encountered in the published literature. PMID:24647720
Mottier, Lourdes; Alvarez, Luis; Lanusse, Carlos
A specific, precise and accurate high-performance liquid chromatographic (HPLC) analytical method has been developed for the quantitative determination of different benzimidazole (BZD) anthelmintics in parasite material (Moniezia benedeni). Mebendazole (MBZ), oxibendazole (OBZ), flubendazole (FLBZ), albendazole (ABZ) ricobendazole (RBZ), albendazole sulphone (ABZSO(2)), fenbendazole (FBZ), oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were measured simultaneously in M. benedeni, a sheep and cattle cestode parasite used as a model of the biological matrix. The recovery, linearity, precision, accuracy, limits of detection and quantification of the method were determined. Drug extraction from the parasite's tissue homogenate was performed using methanol (liquid phase extraction), and after solvent evaporation, the residual material was cleaned up by solid phase extraction prior to analysis by reversed-phase HPLC. The resolution of all the BZD molecules assayed was obtained on a C(18) reversed-phase (5 microm, 250 mm x 4.6 mm) column using acetonitrile and ammonium acetate as the mobile phase and ultraviolet (UV) detection at 292 nm. Regression analyses for all the BZD compounds assayed were linear at concentrations ranging from 1.61 to 64.21 nmol/100mg protein (triplicate determinations) showing correlation coefficients greater than 0.9922. The developed method is efficient for the simultaneous determination of several benzimidazole anthelmintic molecules in parasite material and useful for the ex vivo and in vivo characterisation of the kinetics of drug uptake/diffusion in target parasites, which seems to be relevant to optimise parasite control both in human and veterinary medicine.
... larvae of stomach worms (brown stomach worms including 4th stage inhibited larvae (Ostertagia ostertagi); barberpole worm (Haemonchus contortus, H. placei); small stomach worm (Trichostrongylus axei)); adult and...
... larvae of stomach worms (brown stomach worms including 4th stage inhibited larvae (Ostertagia ostertagi); barberpole worm (Haemonchus contortus, H. placei); small stomach worm (Trichostrongylus axei)); adult and...
... larvae of stomach worms (brown stomach worms including 4th stage inhibited larvae (Ostertagia ostertagi); barberpole worm (Haemonchus contortus, H. placei); small stomach worm (Trichostrongylus axei)); adult and...
... tapeworms (Moniezia benedeni and M. expansa); adult and 4th stage larvae of stomach worms (brown stomach... flukes (Fasciola hepatica and Fascioloides magna); heads and segments of common tapeworms (Moniezia expansa) and fringed tapeworm (Thysanosoma actinioides); adult and fourth stage larvae of stomach...
... tapeworms (Moniezia benedeni and M. expansa); adult and 4th stage larvae of stomach worms (brown stomach... flukes (Fasciola hepatica and Fascioloides magna); heads and segments of common tapeworms (Moniezia expansa) and fringed tapeworm (Thysanosoma actinioides); adult and fourth stage larvae of stomach...
... tapeworms (Moniezia benedeni and M. expansa); adult and 4th stage larvae of stomach worms (brown stomach... flukes (Fasciola hepatica and Fascioloides magna); heads and segments of common tapeworms (Moniezia expansa) and fringed tapeworm (Thysanosoma actinioides); adult and fourth stage larvae of stomach...
Thomas, C P; Dunn, M J; Mattera, R
The human leukaemic cell line K562 is a pluripotent stem cell with the potential to mature along a megakaryocytic or erythroid line. In these cells, thrombin and U46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F2 alpha), a thromboxane A2 analogue, increased intracellular Ca2+ in a rapid and concentration-dependent manner. The peak transient observed with both thrombin and U46619 was preserved upon stimulation in the absence of extracellular calcium and blunted with phorbol myristate acetate, suggestive of activation of phospholipase C. Short-term treatment with leupeptin abolished the calcium response to thrombin, but did not alter that to U46619. Both pertussis toxin (PT) and DMSO pretreatment inhibited thrombin- but not U46619-stimulated intracellular calcium elevation, indicating that these agonists signal through different G-proteins. Western blot analysis of crude membranes from K562 cells revealed the presence of G12 alpha and G13 alpha; the other known PT-substrates, Gi1 alpha and G0 alpha, were not detected. Consistent with this observation, ADP-ribosylation experiments revealed the presence of two PT substrates which co-migrated with human erythrocyte G12 alpha and G13 alpha. An antibody raised against Gq/11 alpha, a subfamily of G-protein alpha subunits unmodified by PT, specifically recognized 42 kDa protein(s) in K562 cells. PCR amplification of reverse-transcribed K562 RNA followed by DNA sequencing showed that these cells express messages for both Gq alpha and G11 alpha. Treatment of K562 cells with DMSO reduced the levels of thrombin receptor mRNA, without simultaneous changes in the expression of G12 alpha and G13 alpha. We have thus identified Ca(2+)-mobilizing agonists and related G-proteins in K562 cells, together with changes induced by DMSO in this signalling pathway. Images Figure 5 Figure 6 Figure 7 Figure 9 PMID:7492305
Mariano, A C; Alexandre, G M; Silva, L C; Romeiro, A; Cameron, L C; Chen, Y; Chase, P B; Sorenson, M M
In the catalytic cycle of skeletal muscle, myosin alternates between strongly and weakly bound cross-bridges, with the latter contributing little to sustained tension. Here we describe the action of DMSO, an organic solvent that appears to increase the population of weakly bound cross-bridges that accumulate after the binding of ATP, but before P(i) release. DMSO (5-30%, v/v) reversibly inhibits tension and ATP hydrolysis in vertebrate skeletal muscle myofibrils, and decreases the speed of unregulated F-actin in an in vitro motility assay with heavy meromyosin. In solution, controls for enzyme activity and intrinsic tryptophan fluorescence of myosin subfragment 1 (S1) in the presence of different cations indicate that structural changes attributable to DMSO are small and reversible, and do not involve unfolding. Since DMSO depresses S1 and acto-S1 MgATPase activities in the same proportions, without altering acto-S1 affinity, the principal DMSO target apparently lies within the catalytic cycle rather than with actin-myosin binding. Inhibition by DMSO in myofibrils is the same in the presence or the absence of Ca(2+) and regulatory proteins, in contrast with the effects of ethylene glycol, and the Ca(2+) sensitivity of isometric tension is slightly decreased by DMSO. The apparent affinity for P(i) is enhanced markedly by DMSO (and to a lesser extent by ethylene glycol) in skinned fibres, suggesting that DMSO stabilizes cross-bridges that have ADP.P(i) or ATP bound to them. PMID:11535124
The present study provides a great insight into the major new research areas like Plasma research (which is yielding a greater understanding of the universe) and Nano Technology Research (which provides many practical uses like Drug Delivery System). The Ultrasonic Velocities, Viscosities and Refractive indices of Poly (Acrylic Acid) and Poly (Vinyl Alcohol) blends in DMSO solutions have been measured over a wide range of composition, concentration and at different temperatures. The variation of Ultrasonic Velocity, derived acoustical parameters, adiabatic compressibility, acoustic impedance, Rao number, molar compressibility and relaxation strength with composition of blend solution was found not linear. This non-linearity has been attributed to incompatibility in conformity with the earlier findings. This behavior was confirmed by Viscometric and interaction parameters studies, as well as by investigation of Refractive index studies. These investigations offer an entirely new and simple approach to the study of the compatibility of polymer blends which is in general obtained by sophisticated techniques of thermal dynamic mechanical and electron microscopic analysis.
Mkupasi, Ernatus Martin; Sikasunge, Chummy Sikalizyo; Ngowi, Helena Aminiel; Johansen, Maria Vang
Porcine cysticercosis, an infection caused by Taenia solium metacestodes, is continuously being reported in low-income countries of Latin America, Asia, and sub-Saharan Africa. The disease was declared eradicable by the International Task Force for Diseases Eradication (ITFDE) in 1993, and it is listed among the 17 WHO Neglected Tropical Diseases and Neglected Zoonoses that are potentially eradicable. In view of that, WHO has proposed a step-wise approach to its elimination, including chemotherapy of infected pigs. Different drugs have been tested on porcine cysticercosis with varying efficacies. These include flubendazole, fenbendazole, albendazole, albendazole sulphoxide, oxfendazole, praziquantel, and nitazoxanide. This review summarises available information on the efficacies and adverse effects shown by these drugs in pigs. Oxfendazole has shown to be effective for the control of porcine cysticercosis; however, it needs to be integrated with other control approaches. There is a need for standardised guidelines for evaluating the efficacy of anthelmintics against porcine cysticercosis, and more efficacy studies are needed since the conclusions so far are based on a limited number of studies using few infected pigs. PMID:23936558
Munguía, Beatriz; Michelena, Mauricio; Melian, Elisa; Saldaña, Jenny; Ures, Ximena; Manta, Eduardo; Domínguez, Laura
In the search for new anthelmintics able to overcome the resistance problem against all available drugs in livestock, the synthesis of novel valerolactam-benzimidazole hybrid compounds was reported. This allowed us to obtain these in vitro and in vivo bioactive compounds using Nippostrongylus brasiliensis rat model by integrating physiology-based assays and ex vivo diffusion studies. In order to further study those novel hybrid molecules, Haemonchus contortus (a sheep gastrointestinal nematode of interest) and Mesocestoides vogae tetrathyridia (a useful system to study the efficacy of anthelmintic drugs against cestoda) were used as parasite models to compare the ex vivo patterns of diffusion and biotransformation of benzimidazoles and their valerolactam-benzimidazole hybrid derivatives. On average, a nine-fold higher intraparasitic concentration of compounds was found in M. vogae compared with H.contortus, with similarities regarding the order of entry of compounds, highlighting febendazole (FEB) and its hybrid compound 10, while valerolactam compound 2 practically did not penetrate the parasites. Interestingly, sulphoxidation drug metabolism was observed and measured, revealing percentages of oxidation of 8.2% and 14.5% for albendazole (ABZ) and febendazole respectively in M. vogae, while this effect was more relevant in H. contortus parasite. More importantly, significant differences were observed between anthelmintic-susceptible adult parasites (Hc S) and those from sheep farms (Hc U). In fact, the percentages of oxidation of FEB and the hybrid compound 8 were higher in Hc U (25.5%, 54.1%, respectively) than in Hc S (8.8%, 38.2%). Interestingly, sulphoxidation of hybrid compound 10 was neither observed in M. vogae nor in H. contortus parasites, suggesting that increased drug metabolism (oxidation reactions) could not be used by these parasites as a defense mechanism against this novel drug.
STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that...suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading...are a diverse group of infectious diseases including STH infections , lymphatic filariasis (LF), schistosomiasis, onchocerciasis, and at least 13
Environmental enteropathy (EE) is a subclinical condition among children in the developing world, characterized by T-cell infiltration of the small-bowel mucosa and diffuse villous atrophy. EE leads to macronutrient and micronutrient malabsorption and stunting, with a resultant increased risk for in...
Association of two single-isomer anionic CD in NACE for the chiral and achiral separation of fenbendazole, its sulphoxide and sulphone metabolites: application to their determination after in vitro metabolism.
Rousseau, Anne; Gillotin, Florian; Chiap, Patrice; Crommen, Jacques; Fillet, Marianne; Servais, Anne-Catherine
A NACE method was developed for the separation of fenbendazole (FBZ), a prochiral drug giving rise to chiral (oxfendazole or OFZ) and nonchiral (FBZ sulphone or FBZSO(2)) metabolites. First, the effect of the nature and the concentration of CD as well as that of the acidic BGE on the enantiomeric separation of OFZ were studied. OFZ enantiomers were completely resolved using a BGE made up of 10 mM ammonium formate and 0.5 M TFA in methanol containing 10 mM heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-CD and 10 mM heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-CD. Moreover, the NACE method was found to be particularly well suited to the simultaneous determination of FBZ, OFZ enantiomers, and FBZSO(2). Thiabendazole was selected as an internal standard. The CD-NACE potential was then evaluated for in vitro metabolism studies using FBZ as a model case. The OFZ enantiomers and FBZSO(2) could be detected after incubation of FBZ in the phenobarbital-induced male rat liver microsomes systems.
Loos, Julia A.; Cumino, Andrea C.
-AMPKɑ was observed in the developmental structures during the de-differentiation process from protoscoleces to microcysts. Therefore, the Eg-AMPK expression during the asexual development of E. granulosus, as well as the in vitro synergic therapeutic effects observed in presence of Met plus albendazole sulfoxide (ABZSO), suggest the importance of carrying out chemoprophylactic and clinical efficacy studies combining Met with conventional anti-echinococcal agents to test the potential use of this drug in hydatidosis therapy. PMID:25965910
Waring, R H
1. The metabolism of S-carboxymethylcysteine (Mucodyne) has been studied in the rat, rabbit, guinea-pig, marmoset and human. All species studied, except the rabbit, excrete large amounts of the parent compound. 2. Rabbits and humans give S-carboxymethylcysteine sulphoxide, rats form N-acetyl-S-carboxymethylcysteine while marmosets excrete methylmercapturic acid as other major metabolites. Traces of methylmercapturic acid sulphoxide, methylcysteine, methylcysteine sulphoxide and 3-(S-carboxymethylthio)lactic acid were also found.
Waring, R H
The metabolism of an oral dose of S-carboxymethylcysteine (SCMC) has been studied in man; the principal urinary component after 24 h was the unchanged compound (29.4-83.7%, 20 subjects). Markers variation was found between individuals; SCMC sulphoxide, S-methylcysteine, N-acetyl-S-carboxymethylcysteine, N-acetyl-S-methylcysteine with the corresponding sulphoxides and dicarboxymethylsulphide were also found as metabolites.
Itoh, Makoto; Weerasooriya, Mirani V; Yahathugoda, Thishan C; Takagi, Hidekazu; Samarawickrema, Wilfred A; Nagaoka, Fumiaki; Kimura, Eisaku
ELISA for filaria-specific IgG4 in urine (urine ELISA) was applied to children in 7 schools in Sri Lanka, before and after 5 rounds of annual mass drug administration (MDA). The pre-treatment IgG4 prevalence in 2002 was 3.20%, which decreased to 0.91% in 2003 after the first MDA (P<0.001), and finally to 0.36% in 2007 after the 5th MDA. Among 5-10 year-old children, the prevalence decreased from 3.37% in 2002 to 0.51% in 2003 (P=0.009). A pattern of IgG4 titer distribution according to age and its yearly change could also provide useful information in drug efficacy analysis. In 2008, new samples from eleven 2006/07 urine ELISA-positive students and their family members (total n=56) were examined by ICT antigen test, microfilaria test, and urine ELISA. No infection was confirmed among them. Urine ELISA will be useful in monitoring elimination/resurgence in a post-MDA low endemic situation.
Albendazole in the Treatment of Ancylostoma duodenale and AscAris lumbricoides Infections. Trans. R. Soc. Trop. Med. Hyg., 77(2):160-11 1983. 1340 MANSOUR...synthesis 1345 CHEMOTHERAPY Albendazole in the treatment of Ancylostoma duodenale infection 1339 Albendazole in the treatment of Ascaris lumbricoides ...tuberculous-meningitis 1350 PARASITOLOGY Amoebic.liver abscess 1330 Ancylostoma duodenale 1339 Ascaris lumbricoides 1339 Fasciola gigantica 1342
Lake, Brian G; Price, Roger J; Walters, David G; Phillips, John C; Young, Philip J; Adams, Timothy B
The metabolism of two thiofurans, namely furfuryl mercaptan (FM) and 2-methyl-3-furanthiol (MTF), to their corresponding methyl sulphide and methyl sulphoxide derivatives has been studied in male Sprague-Dawley rat hepatocytes and liver microsomes. Rat hepatocytes converted FM to furfuryl methyl sulphoxide (FMSO) and MTF to 2-methyl-3-(methylthio)furan sulphoxide (MMFSO). Liver microsomes catalysed the NADPH-dependent metabolism of furfuryl methyl sulphide (FMS) to FMSO and 2-methyl-3-(methylthio)furan sulphide (MMFS) to MMFSO. FMS and MMFS metabolism to their thiofuran methyl sulphoxide derivatives was induced by the treatment of rats with Aroclor 1254 and inhibited in liver microsomes treated with 1-aminobenzotriazole. The NADPH-dependent metabolism of FM to FMSO and MTF to MMFSO in liver microsomes was observed in the presence of S-adenosylmethionine. In summary, both thiofurans can be metabolised in rat liver to their thiofuran methyl sulphide derivatives which can be subsequently S-oxidised to form thiofuran methyl sulphoxides. FM and MTF appear to be substrates for rat hepatic microsomal thiol methyltransferase and the S-oxidation of FMS and MMFS appears to be primarily catalysed by cytochrome P450 forms.
John, P P; Mazumder, Avijit; Mazumder, R; Bhatnagar, S P
The anthelmintic activity of the Imethanolic extract of the root bark of Carissa carandas was evaluated on adult Indian earthworm (Pheretima posthuma) using albendazole as a reference standard. The extract caused paralysis followed by the death of worm at the tested dose level. The extract at the highest tested concentration has anthelmintic activity comparable with that of standard drug albendazole.
John, P.P.; Mazumder, Avijit; Mazumder, R.; Bhatnagar, S.P.
The anthelmintic activity of the Imethanolic extract of the root bark of Carissa carandas was evaluated on adult Indian earthworm (Pheretima posthuma) using albendazole as a reference standard. The extract caused paralysis followed by the death of worm at the tested dose level. The extract at the highest tested concentration has anthelmintic activity comparable with that of standard drug albendazole. PMID:22557253
Singh, Aloukick K; Singh, Satyendra K; Singh, Amrita; Gupta, Kamlesh K; Khatoon, Jahanarah; Prasad, Amit; Rai, Ravi P; Gupta, Rakesh K; Tripathi, Mukesh; Husain, Nuzhat; Prasad, Kashi N
Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci.
Vizcaino-Caston, Isaac; Kelly, Catherine A; Fitzgerald, Annabel V L; Leeke, Gary A; Jenkins, Mike; Overton, Tim W
We describe a novel method of Polyhydroxyalkanoate (PHA) extraction using dimethyl sulphoxide (DMSO) for use in screening studies. Compared to conventional chloroform extraction, the DMSO method was shown to release comparable quantities of PHA from Cupriavidus necator cells, with comparable properties as determined using Fourier transform infrared spectroscopy and differential scanning calorimetry.
... active ingredients: D Desmopressin acetate Diflunisal Dipyridamole H Hydrochlorothiazide; lisinopril...-specific BE recommendations for drug products containing the following active ingredients: A Abiraterone acetate Albendazole Amlodipine besylate, hydrochlorothiazide, and olmesartan medoxomil C...
Márquez-Navarro, Adrián; Nogueda-Torres, Benjamín; Hernández-Campos, Alicia; Soria-Arteche, Olivia; Castillo, Rafael; Rodríguez-Morales, Sergio; Yépez-Mulia, Lilián; Hernández-Luis, Francisco
The anthelmintic activity of 11 benzimidazole derivatives (A1-A11) and 2 thioureides N,N'-disubstituted (B1-B2) was determined. Each compound and albendazole was tested in vitro against Toxocara canis larvae and in vivo against Hymenolepis nana adult. Compounds A1-A6 and B1-B2 were designed as albendazole prodrugs. Compounds A8-A11 were designed as direct analogues of A7, which had previously proved to be an effective agent against Fasciola hepatica. Results of the in vitro screening showed that A6 was more active than albendazole at 0.18 microM (relative mobility 40% and 80%, respectively). Whereas that the in vivo evaluation against H. nana, compounds A7-A11 demonstrated significant activity in terms of removing cestode adults in the range of 88-97%, displaying better efficacy than albendazole (83%).
... the parasites, such as albendazole or praziquantel Powerful anti-inflammatories (steroids) to reduce swelling If the cyst is ... eat uncooked foods while traveling, and always wash fruits and vegetables well.
Ram, H; Rasool, T J; Sharma, A K; Meena, H R; Singh, S K
A trial using albendazole, albendazole plus rafoxanide combination, ivermectin and doramectin was conducted in Pashmina goats having history of fenbendazole resistance to Haemonchus spp. and maintained at high altitude (>2350 m above sea level). Day 0 infection level was variable in different groups of animals and their larval cultures indicated Haemonchus, Trichostrongylus, Ostertagia and Oesophagostomum spp. infection, in addition to Nematodirus spp. as observed in egg counts. Efficacy of drugs was calculated on day 14 post treatment by faecal egg count reduction test (FECRT). Albendazole was least effective (14%) followed by its combination with rafoxanide (54%). However, ivermectin and doramectin were 96% and 94% effective against gastrointestinal nematodes of Pashmina goats. It was concluded that use of albendazole and its combination with rafoxanide are ineffective in controlling the nematodes of goats at this farm; hence, future use must be avoided. However, regular monitoring of the efficacy of ivermectin and doramectin is needed.
Daniel, Wladyslawa A; Syrek, Maciej; Haduch, Anna; Wójcikowski, Jacek
Because of serious side-effects of thioridazine and tricyclic antidepressants (cardiotoxicity), a possible influence of imipramine and amitriptyline on the pharmacokinetics and metabolism of thioridazine was investigated in a steady state (2-week treatment) in rats. Imipramine and amitriptyline (5 and 10 mg kg−1 i.p., respectively) elevated 30 and 20 fold, respectively, the concentration of thioridazine (10 mg kg−1 i.p.) and its metabolites (N-desmethylthioridazine, 2-sulphoxide, 2-sulphone, 5-sulphoxide) in blood plasma. Similar, yet weaker increases in the thioridazine concentration were found in the brain. Moreover, an elevation of thioridazine/metabolite ratios was observed. Imipramine and amitriptyline added to control liver microsomes in vitro inhibited the metabolism of thioridazine via N-demethylation (an increase in Km), mono-2-sulphoxidation (an increase in Km and a decrease in Vmax) and 5-sulphoxidation (mainly a decrease in Vmax). Amitriptyline was a more potent inhibitor than imipramine of the thioridazine metabolism. The varying concentration ratios of antidepressant/thioridazine in vivo appear to be more important to the final result of the pharmacokinetic interactions than are relative direct inhibitory effects of the antidepressants on thioridazine metabolism observed in vitro. Besides direct inhibition of the thioridazine metabolism, the decreased activity of cytochrome P-450 towards 5-sulphoxidation, produced by chronic joint administration of thioridazine and the antidepressants, seems to be relevant to the observed in vivo interaction. The obtained results may also point to inhibition of another, not yet investigated, metabolic pathway of thioridazine, which may be inferred from the simultaneous elevation of concentrations of both thioridazine and the measured metabolites. PMID:10991922
Background Soil-transmitted helminth (STH) infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority. Methods We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the Trichuris muris model. Drug combinations were first tested in vitro and additive and synergistic combinations investigated further in vivo in female mice using ratios based on the ED50 of the respective drugs. Results In vitro all 10 combinations of the standard anthelmintics tested against T. muris revealed synergistic behavior. We identified three drug combinations in vivo as strongly synergistic, namely mebendazole-ivermectin (Combination index (CI)=0.16), mebendazole-levamisole (CI=0.17) and albendazole-mebendazole (CI=0.23). For albendazole-ivermectin, moderate synergism was observed (CI=0.81) and for albendazole-levamisole a nearly additive effect was documented (CI=0.93) in vivo. Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin) were antagonistic in vivo. Conclusion Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies. PMID:23231753
Flohr, Carsten; Tuyen, Luc Nguyen; Lewis, Sarah; Minh, Truong Tan; Campbell, Jim; Britton, John; Williams, Hywel; Hien, Tran Tinh; Farrar, Jeremy; Quinnell, Rupert J
Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI -9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30-81%) for triple mebendazole, 75% (47-88%) for single albendazole, and 88% (58-97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs.
Bonnett, R; Buckley, D G; Hamzetash, D; Hawkes, G E; Ioannou, S; Stoll, M S
An improved preparation of photobilirubin II in ammoniacal methanol is described. Evidence is presented which distinguishes between the two structures proposed earlier for photobilirubin II in favour of the cycloheptadienyl structure. Nuclear-Overhauser-enhancement measurements with bilirubin IX alpha and photobilirubin II in dimethyl sulphoxide are complicated by the occurrence of negative and zero effects. The partition coefficient of photobilirubin II between chloroform and phosphate buffer (pH 7.4) is 0.67. PMID:6743241
Virkel, G; Lifschitz, A; Sallovitz, J; Ballent, M; Scarcella, S; Lanusse, C
Understanding the disposition kinetics and the pattern of metabolism is critical to optimise the flukicidal activity of triclabendazole (TCBZ) in ruminants. TCBZ is metabolised by both flavin-monooxygenase (FMO) and cytochrome P450 (P450) in the liver. Interference with these metabolic pathways may be useful to increase the systemic availabilities of TCBZ metabolites, which may improve the efficacy against Fasciola hepatica. The plasma disposition of TCBZ metabolites was evaluated following TCBZ co-administration with FMO [methimazole (MTZ)] and P450 [piperonyl butoxyde (PB) and ketoconazole (KTZ)] inhibitors in sheep. Twenty (20) healthy Corriedale x Merino weaned female lambs were randomly allocated into four experimental groups. Animals of each group were treated as follow: Group A, TCBZ alone (5 mg/kg, IV route); Group B, TCBZ (5 mg/kg, IV) + MTZ (3 mg/kg, IV); Group C, TCBZ (5 mg/kg, IV) + PB (30 mg/kg, IV) and Group D, TCBZ (5 mg/kg, IV) + KTZ (10 mg/kg, orally). Blood samples were taken over 240 h post-treatment and analysed by HPLC. TCBZ sulphoxide and sulphone were the main metabolites recovered in plasma. MTZ did not affect TCBZ disposition kinetics. TCBZ sulphoxide Cmax values were significantly increased (P < 0.05) after the TCBZ + PB (62%) and TCBZ + KTZ (37%) treatments compared to those measured in the TCBZ alone treatment. TCBZ sulphoxide plasma AUCs were higher (P < 0.05) in the presence of both PB (99%) and KTZ (41%). Inhibition of TCBZ P450-mediated oxidation in the liver accounted for the increased systemic availability of its active metabolite TCBZ sulphoxide. This work contributes to the search of different strategies to improve the use of this flukicidal drug in ruminants.
Keiser, Jennifer; Manneck, Theresia; Kirchhofer, Carla; Braissant, Olivier
Isothermal microcalorimetry (IMC) is an analytical tool that continuously measures the heat flow generated by chemical, physical or biological processes. We have demonstrated that IMC is a useful tool to analyze drug effects on helminths, including adult Fasciola hepatica. Here, we used IMC to examine the activity of triclabendazole and its metabolites triclabendazole sulphone and triclabendazole sulphoxide on juvenile and adult F. hepatica. Worms (one adult or 2-3 juveniles) were placed in 4 or 20 ml glass ampoules containing RPMI 1640 and the test compound (25-100 μg/ml) and the heat flow and motility of worms was examined with TAM48 and TAMIII isothermal microcalorimetry instruments. IMC was found to be precisely document drug effects on juvenile F. hepatica and confirmed the pronounced effect of the benzimidazole derivatives on the motor activity of F. hepatica. Juvenile F. hepatica incubated with 100 μg/ml triclabendazole, triclabendazole sulphone and triclabendazole sulphoxide showed no movements 8.3, 35 and 6h post-incubation (all p<0.001). The metabolic heat of triclabendazole sulphoxide treated worms (100 μg/ml) was reduced by 50% and 76% 24 and 120 h post-incubation, respectively. Limitations of calorimetric measurements were observed using adult F. hepatica as only three worms could be measured simultaneously and also control worms showed a considerable decrease in heat flow. Adult F. hepatica exposed to triclabendazole, triclabendazole sulphone and triclabendazole sulphoxide showed no movements after 31 (p=0.009), 49 (p>0.05) and 88 (p>0.05)h. In conclusion, IMC is useful to document drug effects on juvenile F. hepatica and since rapid technological developments in this field are occurring IMC might also hold promise to study adult F. hepatica in the near future.
soman intoxication included repetitive chewing , facial and forepaw clonus, motor stereotypy, and wet- dog shakes. Overt motor convulsions were...and secured by dental cement. On the morning of the fifth or sixth day following surgeries, electrode-implanted animals were connected to an ECoG...dimethyl sulphoxide (DMSO) for the dog , pig, rat and rabbit. Toxicology. 1975; 3:143-69. Olney JW, Labruyere J, Price MT. Pathological changes
Gonzalez, Armando E.; Bustos, Javier A.; Jimenez, Juan A.; Rodriguez, Mary L.; Ramirez, Mercy G.; Gilman, Robert H.; Garcia, Hector H.
Taenia solium cysticercosis infects pigs and humans. Because antiparasitic treatment for human cysticercosis has sub-optimal efficacy, alternative regimes are needed. Seven antiparasitic regimens were tested in 42 naturally infected pigs with cysticercosis, and compared with prednisone alone (n = 6) or no treatment (n = 6). The numbers of viable cysts in muscles and in the brain were examined after necropsy and were significantly decreased in pigs receiving combined albendazole plus praziquantel, albendazole alone, or oxfendazole. Pigs receiving praziquantel alone and nitazoxanide had numerous surviving cysts. Control (untreated) pigs and prednisone-treated pigs had many more viable cysts, suggesting no effect. Combined albendazole plus praziquantel, and oxfendazole, showed a strong cysticidal effect and provide suitable alternative treatments to be further explored for their use for treatment of human neurocysticercosis. PMID:22855760
Hartati; Aryanti, S.; Muherman, S. Y.
The main purpose study was to find out the effect of once a year of 400 mg albendazole on the nutritional status and learning achievement of elementary school students in Sukarami Palembang. Methods study used quasi experimental research with non -equivalent control group pretest-posttest design. This study was conducted in Palembang, South Sumatera for one year. Samples of this study were 1914 students deriving from a systematic stratified random sampling and divided into 2 groups: 986 students for the treatment samples were given 400 mg albendazole and 928 students for the controlled samples were given placebo. The result of this study found that there was a decrease in the prevalence of worm infection both in the treatment and controlled samples. However the number of infected students in the treatment samples decreased. The implication research is the drug albendazole worm declared as the most effective drug to treat intestinal worm infections.
Van Schalkwyk, P C; Geyser, T L; Davies, P V; Récio, M
Two field cases of apparent inefficacy of albendazole against cestodes in lambs were investigated. In both farms Thysaniezia giardi was identified and 2 critical controlled trials were conducted to determine the efficacy of 5 anthelmintics against T. giardi. Albendazole dosed at 3,8 mg/kg or 7,6 mg/kg live mass, mebendazole at 15 mg/kg were totally ineffective against T. giardi. Treatment with resorantel at 65 mg/kg or niclosamide at 50 mg/kg however, caused expulsion of the strobilae within 16--24 hours after treatment and at autopsy, lambs were free of scoleces of T. giardi.
Ramli, Inssaf; Amarouch, Hajar; Mael-Ainin, Maha; Aitourhroui, Mohammed; Senouci, Karima; Hassam, Badredine
L'anguillulose intestinale est rare. Les formes malignes surviennent généralement au cours d'une immunodépression. Notre observation souligne la gravité de l'anguillulose en cas de maladie auto-immune notamment le pemphigus et l'inefficacité de l'Albendazole dans ces situations à risque. PMID:26161186
The combined effect of the Lymphatic Filariasis Elimination Programme and the Schistosomiasis and Soil-transmitted Helminthiasis Control Programme on soil-transmitted helminthiasis in schoolchildren in Tanzania.
Massa, Khalid; Magnussen, Pascal; Sheshe, Amir; Ntakamulenga, Robert; Ndawi, Benedict; Olsen, Annette
The combined effect of the Lymphatic Filariasis Elimination Programme (LFEP) and the National Schistosomiasis and Soil-transmitted Helminthiasis Control Programme (NSSCP) on soil-transmitted helminthiasis (STH) was evaluated. In September 2004, before mass drug administration (MDA) with ivermectin and albendazole by the LFEP in October, the prevalence and intensity of STH were recorded in 228 pupils in one primary school. After 8 months, all available pupils were re-examined, and the prevalence of Ascaris lumbricoides, Trichuris trichiura and hookworm had decreased from 0.9 to 0.7% (P=0.84), from 4.8 to 0.7% (P=0.004) and from 45.6 to 11.9% (P<0.001), respectively. Overall, 81.2% of the schoolchildren stated that they were treated by the LFEP in October 2004. After the 8 months follow-up, pupils were treated with praziquantel and albendazole by the present project (substitute for the NSSCP). After another 4 months (at 12 months follow-up), the prevalence of hookworm infection was reduced to 4.8% (P=0.003), while the prevalence of T. trichiura was reduced to 0.3% (P=0.54) and the prevalence of A. lumbricoides remained unchanged. Mass co-administration of ivermectin and albendazole by the LFEP had a significant effect on STH, which was further amplified by treatment with praziquantel and albendazole 4 months later.
Ghosh, D; Dubey, T; Prabhakar, S
The coexistence of brain parenchymal cysts at various stages of evolution, both intraventricular and subarachnoid racemose, is reported in a patient with neurocysticercosis. The condition has a variety of presentations, depending on the location of the cyst. This case is of particular interest because of the rarity of this condition in India. Keywords: brain parenchymal cyst; cysticercosis; albendazole PMID:10448497
Ha, Kyung Ho; Song, Jung Eun; Kim, Byung Seok; Lee, Chang Hyeong
AIM: To evaluate the clinical characteristics and progression of liver abscess caused by toxocara. METHODS: We retrospectively reviewed the medical records of patients with serum IgG antibody to Toxocara canis and liver abscess diagnosed using abdominal computed tomography between February 2010 and February 2015. Among 84 patients exhibiting serum IgG antibody to Toxocara canis, 34 patients were diagnosed with liver asbscess and treated with albendazole. A follow-up period of 1 year was conducted. RESULTS: Mean patient age was 53 (34-79) years, with 26 (76.5%) patients being male. Twenty-one (61.7%) patients were moderate or heavy drinkers, 23 (67.6%) patients had a history of eating raw meat or liver and 6 (17.6%) patients owned pet dogs or cats. Main patient symptoms consisted of right upper quadrant pain, fever, and fatigue; 18 (52.9%) patients, however, presented with no symptoms. Lung involvement was detected in 444 (11.7%) patients. The eosinophil count increased in 29 (85.3%) patients at initial diagnosis, and decreased in most patients after albendazole treatment. The initial serum IgE level increased in 25 (73.5%) patients, but exhibited various response levels after albendazole treatment. Liver abscess formation improved in all patients. CONCLUSION: The liver abscess was improved with albendazole treatment. PMID:27366302
Reid, Michael J.; Halabi, Cathra; Wietek, Natalie; LaRiviere, Alejandro; Shah, Maulik; Wilson, Michael R.; Chin-Hong, Peter; Douglas, Vanja; Kazacos, Kevin R.; Babik, Jennifer M.
After severe neurocognitive decline developed in an otherwise healthy 63-year-old man, brain magnetic resonance imaging showed eosinophilic meningoencephalitis and enhancing lesions. The patient tested positive for antibodies to Baylisascaris spp. roundworms, was treated with albendazole and dexamethasone, and showed improvement after 3 months. Baylisascariasis should be considered for all patients with eosinophilic meningitis. PMID:27434260
Martínez, Dalila Y; Seas, Carlos; Bravo, Francisco; Legua, Pedro; Ramos, Cesar; Cabello, Alfonso M; Gotuzzo, Eduardo
Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris is an uncommon infection for which there is no optimal therapy. We describe a young, female patient who presented with extensive cutaneous and neurological involvement and who recovered after receiving prolonged treatment with miltefosine, fluconazole, and albendazole.
Attia, Rasha A H; Mahmoud, Abeer E; Farrag, Haiam Mohammed Mahmoud; Makboul, Rania; Mohamed, Mona Embarek; Ibraheim, Zedan
Trichinellosis is a serious disease with no satisfactory treatment. We aimed to assess the effect of myrrh (Commiphora molmol) and, for the first time, thyme (Thymus vulgaris L.) against enteral and encysted (parenteral) phases of Trichinella spiralis in mice compared with albendazole, and detect their effect on inducible nitric oxide synthase (iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%), respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated mice showed the highest iNOS expression followed by albendazole, then thyme. On the other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of inflammatory cells infiltrating and surrounding encapsulated T. spiralis larvae than albendazole treated group. In conclusion, myrrh and thyme extracts are highly effective against both phases of T. spiralis and showed strong iNOS expressions, especially myrrh which could be a promising alternative drug. This experiment provides a basis for further exploration of this plant by isolation and retesting the active principles of both extracts against different stages of T. spiralis.
Attia, Rasha AH; Mahmoud, Abeer E; Farrag, Haiam Mohammed Mahmoud; Makboul, Rania; Mohamed, Mona Embarek; Ibraheim, Zedan
Trichinellosis is a serious disease with no satisfactory treatment. We aimed to assess the effect of myrrh (Commiphora molmol) and, for the first time, thyme (Thymus vulgaris L.) against enteral and encysted (parenteral) phases of Trichinella spiralis in mice compared with albendazole, and detect their effect on inducible nitric oxide synthase (iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%), respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated mice showed the highest iNOS expression followed by albendazole, then thyme. On the other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of inflammatory cells infiltrating and surrounding encapsulated T. spiralis larvae than albendazole treated group. In conclusion, myrrh and thyme extracts are highly effective against both phases of T. spiralis and showed strong iNOS expressions, especially myrrh which could be a promising alternative drug. This experiment provides a basis for further exploration of this plant by isolation and retesting the active principles of both extracts against different stages of T. spiralis. PMID:26676322
Chafik, A.; Benjelloun, A.; El Khadir, A.; El Barni, R.; Achour, A.; Ait Benasser, M. A.
The hydatid cyst is not rare in our country, but bone lesions are less common. The disease often takes the appearance of abscess or malignant lesion. We report a case of a 35-year-old man with a hydatid cyst of the rib complicated with cutaneous fistula. The surgery allowed both diagnosis and treatment. Albendazole was then administered to prevent relapse. PMID:20182633
Fraga, Carolina Miguel; Costa, Tatiane Luiza; Bezerra, José Clecildo Barreto; de Souza Lino Junior, Ruy; Vinaud, Marina Clare
Human cysticercosis caused by Taenia crassiceps is rare however it is considered of zoonotic risk. The treatment of the infected patients was successful when using albendazole or praziquantel. The active forms of albendazole inhibit the glucose uptake and the active forms of praziquantel alter glycogen levels and nutrients absorption. The aim of this study was to analyze the production of organic acids that indicate the oxidation of fatty acids and the use of alternative energy sources from T. crassiceps cysticerci removed from the peritoneal cavity of mice treated with low dosages of albendazole (5.75 and 11.5mg/kg) or praziquantel (3.83 and 7.67 mg/kg). The beta-hydroxibutyrate production was higher by the larval stage cysticerci in all treated groups and the propionate production was higher in final stage cysticerci treated with 11.5mg/kg of albendazole when compared to the control group. The larval stages of cysticerci from the groups treated with 5.75 mg/kg of albendazole and 3.83 mg/kg of praziquantel produced more urea than the initial and final stages which indicate amino acids breakdown. We conclude that it was possible to detect the fatty acid oxidation and amino acids breakdown which indicate the use of alternative energy production sources as the used dosages only cause a partial blockage of the glucose uptake and leads to metabolic alterations in the cysticerci. The metabolic behavior observed after host treatment was different from former descriptions of the in vitro one which indicates great host-parasite interaction.
Bashir, S.; Khan, B. M.; Babar, M.; Andleeb, S.; Hafeez, M.; Ali, S.; Khan, M. F.
This study was carried out as a prerequisite to evaluate the therapeutic potential of Camellia varieties. The crude extracts of six different plants of green tea Camellia assamica and Camellia sinensis were tested against three Gram-positive and four Gram-negative bacteria using agar disk diffusion method at 50 mg/ml concentration. 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and diphenyl-(2,4,6-trinitrophenyl)iminoazanium free radical scavenging methods were performed to evaluate the antioxidant potential. Phytochemical constituents and trace metals were detected through thin layer chromatography and Inductively Coupled Plasma Atomic Emission Spectrophotometer, respectively. The maximum inhibition of Staphylococcus aureus was recorded by dimethyl sulphoxide extracts of green tea varieties. The measured zone of inhibition of dimethyl sulphoxide extracts by Qimen was (10.00±0.0 mm), Japanese (10.00±0.0 mm), Turkish (10.00±0.0 mm), Indonesian (8.33±1.0 mm), P3 clone (10.00±0.0 mm) and Sri Lankan (10.00±0.0 mm). Maximum scavenging potential activity was found with ethanol, methanol and dimethyl sulphoxide extracts. Spot screening of TLC-developed plates indicated that the presence of active biological compounds such as flavonoids, proteins, phenols, alkaloids and glycosides also exhibited strong activity against tested bacterial strains. This study reveals the potential biological activities of Camellia assamica and Camellia sinensis having massive phytochemical constituents and trace elements. PMID:25284935
Cardona-Costa, J; García-Ximénez, F
Cryopreservation of fish embryos may play an important role in biodiversity preservation and in aquaculture, but it is very difficult. In addition, the cryopreservation of fish embryo blastomeres makes conservation strategies feasible when they are used in germ-line chimaerism, including interspecific chimaerism. Fish embryo blastomere cryopreservation has been achieved by equilibrium procedures, but to our knowledge, no data on vitrification procedures are available. In the present work, zebrafish embryo blastomeres were successfully vitrified in microvolumes: a number of 0.25 microl drops, sufficient to contain all the blastomeres of an embryo at blastula stage (from 1000-cell stage to oblong stage), were placed over a 2.5 cm loop of nylon filament. In this procedure, where intracellular cryoprotectant permeation is not required, blastomeres were exposed to cryoprotectants for a maximum of 25 sec prior vitrification. The assayed cryoprotectants (ethylene glycol, propylene glycol, dimethyl sulphoxide, glycerol and methanol) are all frequently used in fish embryo and blastomere cryopreservation. Methanol was finally rejected because of the excessive concentration required for the vitrification (15M). All other cryoprotectants were prepared (individually) at 5 M in Hanks' buffered salt solution (sigma) plus 20% FBS (vitrification solutions: vs). After direct thawing in Hanks' buffered salt solution plus 20% FBS, acceptable survival rates were obtained with ethylene glycol: 82.8%, propylene glycol: 87.7%, dimethyl sulphoxide: 93.4%, and glycerol: 73.9% (p < 0.05). Dimethyl sulphoxide showed the highest blastomere survival rate and allowed the rescue of as much as 20% of the total blastomeres from each zebrafish blastula embryo.
Meese, C O; Fischer, P
A direct structural identification, and quantitative assessment below the 50 nmol/ml level, of the full pattern of renally excreted metabolites is made possible by 13C NMR measurements of untreated urine samples when stable isotope-labelled (13C) drug analogues are administered to humans. The full potential of the new ex vivo NMR approach is exemplified by a study, for a group of volunteers, of S-carboxymethyl-L-cysteine metabolism. The metabolic sulphoxidation pathway of S-carboxymethyl-L-cysteine in man, accepted so far, needs to be profoundly revised on the basis of the 13C NMR results.
Velcheva, Evelina A; Juchnovski, Ivan N; Binev, Ivan G
Fourier-transform IR frequencies nu(C=O) and integrated intensities A(C=O) of the carbonyl groups of a series of benzaldehydes (53 compounds) have been measured in dimethyl sulphoxide. Excellent and satisfactory correlations have been found between nu(C=O) and sigma(+) substituent constants of the m- and p-substituted compounds. Diortho-substituted compounds deviate strongly from the correlation lines because of the steric ortho-effects mainly. sigma(+) constants of ionic substituents (10 examples) have proved satisfactorily valid in the series studied.
Maskery, Brian; Coleman, Margaret S.; Weinberg, Michelle; Zhou, Weigong; Rotz, Lisa; Klosovsky, Alexander; Cantey, Paul T.; Fox, LeAnne M.; Cetron, Martin S.; Stauffer, William M.
Background Many U.S.-bound refugees travel from countries where intestinal parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides stercoralis) are endemic. These infections are rare in the United States and may be underdiagnosed or misdiagnosed, leading to potentially serious consequences. This evaluation examined the costs and benefits of combinations of overseas presumptive treatment of parasitic diseases vs. domestic screening/treating vs. no program. Methods An economic decision tree model terminating in Markov processes was developed to estimate the cost and health impacts of four interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) “No Program,” 2) U.S. “Domestic Screening and Treatment,” 3) “Overseas Albendazole and Ivermectin” presumptive treatment, and 4) “Overseas Albendazole and Domestic Screening for Strongyloides”. Markov transition state models were used to estimate long-term effects of parasitic infections. Health outcome measures (four parasites) included outpatient cases, hospitalizations, deaths, life years, and quality-adjusted life years (QALYs). Results The “No Program” option is the least expensive ($165,923 per cohort) and least effective option (145 outpatient cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for a one-year cohort). The “Overseas Albendazole and Ivermectin” option ($418,824) is less expensive than “Domestic Screening and Treatment” ($3,832,572) or “Overseas Albendazole and Domestic Screening for Strongyloides” ($2,182,483). According to the model outcomes, the most effective treatment option is “Overseas Albendazole and Ivermectin,” which reduces outpatient cases, deaths and hospitalization by around 80% at an estimated net cost of $458,718 per death averted, or $2,219/$24,036 per QALY/life year gained relative to “No Program”. Discussion Overseas presumptive treatment for U.S.-bound refugees is a cost
Arafa, Waleed M; Shokeir, Khalid M; Khateib, Abdelrahman M
This study aimed to compare between the efficiency of in vivo fecal egg reduction test (FERT) and in vitro egg hatching assay (EHA) in evaluating of the anti-Fasciola activity of albendazole, triclabendazole, oxyclozanide and praziquantel. A field trial was carried out on fifty naturally Fasciola infected cattle that were divided equally into 5 groups (A-E). On day zero; groups A-D were drenched with albendazole, triclabendazole, oxyclozanide or praziquantel, respectively, while the remaining one, group E, was kept as untreated control. Fecal egg counts of the different groups were conducted weekly over a period of one month post-treatment. In vitro, commercial albendazole and oxyclozanide were diluted to 0.0002, 0.002, 0.02, 0.2 and 2.0 μg/ml, while commercial triclabendazole and praziquantel were diluted to concentrations of 25, 50, 75 and 100 μg/ml with dimethyl sulfoxide (DMSO). In vivo, at the 2nd week post-treatment, triclabendazole and oxyclozanide showed 100% fecal egg reduction (FER), and albendazole had a maximum of 73.7% reduction (P < 0.0001), however, praziquantel did not record any reduction of Fasciola egg counts. In vitro, triclabendazole treated Fasciola gigantica eggs showed early embryonic lysis with zero% hatching at the different concentrations (P < 0.01). In albendazole, the hatching varied according to the drug concentration. At the highest two concentrations; 0.2 and 2.0 μg/ml, the hatching percentages were 7.4 ± 1.6 and 5.6 ± 1.5 (P < 0.01) respectively. On the contrary, there were no significant differences in egg development and hatching percentage of oxyclozanide or praziquantel treated groups. In conclusion, the efficacy of triclabendazole and albendazole as fasciolicdes could be predicted by Egg Hatching Assay (EHA). Meanwhile fasciolicide activity of oxyclozanide could not be assessed with EHA. Based on in vivo and in vitro findings, paraziquantel did not show any fasciolicide effect.
Coulibaly, Yaya Ibrahim; Dicko, Ilo; Keita, Modibo; Keita, Mahamadou Minamba; Doumbia, Moussa; Daou, Adama; Haidara, Fadima Cheick; Sankare, Moussa Hama; Horton, John; Whately-Smith, Caroline; Sow, Samba Ousmane
Background Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas. Methodology/Findings 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and “other signs/symptoms”). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone. Conclusions These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between
Patil, Pranali G.; Kamble, S. H.; Shah, T. S.; Iyer, K. R.
Organic solvents used for solubilization of the substrates/NCEs are known to affect the activity of cytochrome P450 enzymes. Further, this effect varies with the solvents used, the substrates and CYP450 isoforms in question. In the present study, we have investigated the effect of ten commonly used water miscible organic solvents (methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, acetone, dimethyl sulphoxide, N,N-dimethyl formamide, dioxane and polyethylene glycol 400) on p-nitrophenol hydroxylase activity at 0, 0.1, 0.25, 0.5, 0.75 and 1% v/v concentration in rat liver microsomes. All the solvents studied showed concentration dependent inhibition of the p-nitrophenol hydroxylase activity except acetonitrile which showed activation of the activity at concentration range studied. Out of ten solvents studied, dioxane was found to be the most inhibitory solvent (inhibition >90% at 0.25% v/v concentration). Overall, solvents like dimethyl sulphoxide, dimethyl formamide and dioxane appeared to be unsuitable for characterizing p-nitrophenol hydroxylase (CYP2E1-mediated) reactions due to a high degree of inhibition. On the other hand, methanol and acetonitrile at concentrations <0.5% v/v appeared to be appropriate solvents for substrate solubilization while evaluating CYP2E1-mediated catalysis. The results of this study imply that caution should be exercised while choosing solvents for dissolution of substrate during enzyme studies in liver microsomes. PMID:26180273
Baraquet, Claudine; Théraulaz, Laurence; Iobbi-Nivol, Chantal; Méjean, Vincent; Jourlin-Castelli, Cécile
Shewanella oneidensis uses a wide range of terminal electron acceptors for respiration. In this study, we show that the chemotactic response of S. oneidensis to anaerobic electron acceptors requires functional electron transport systems. Deletion of the genes encoding dimethyl sulphoxide and trimethylamine N-oxide reductases, or inactivation of these molybdoenzymes as well as nitrate reductase by addition of tungstate, abolished electron acceptor taxis. Moreover, addition of nigericin prevented taxis towards trimethylamine N-oxide, dimethyl sulphoxide, nitrite, nitrate and fumarate, showing that this process depends on the DeltapH component of the proton motive force. These data, together with those concerning response to metals (Bencharit and Ward, 2005), support the idea that, in S. oneidensis, taxis towards electron acceptors is governed by an energy taxis mechanism. Surprisingly, energy taxis in S. oneidensis is not mediated by the PAS-containing chemoreceptors but rather by a chemoreceptor (SO2240) containing a Cache domain. Four other chemoreceptors also play a minor role in this process. These results indicate that energy taxis can be mediated by new types of chemoreceptors.
Cardona-Costa, J; Roig, J; Perez-Camps, M; García-Ximénez, F
No data on vitrification of tissue samples are available in fishes. Three vitrification solutions were compared: V1: 20% ethylene glycol and 20% dimethyl sulphoxide; V2: 25% propylene glycol and 20% dimethyl sulphoxide, and; V3: 20% propylene glycol and 13% methanol, all three prepared in Hanks' buffered salt solution plus 20 percent FBS, following the same one step vitrification procedure developed in mammals. Caudal fin tissue pieces were vitrified into 0.25 ml plastic straws in 30s and stored in liquid nitrogen for 3 days minimum, warmed (10s in nitrogen vapour and 5s in a 25 degree C water bath) and cultured (L-15 plus 20% FBS at 28.5 degree C). At the third day of culture, both attachment and outgrowing rates were recorded. V3 led to the worst results (8% of attachment rate). V1 and V2 allow higher attachment rates (V1: 63% vs V2: 50%. P < 0.05) but not significantly different outgrowing rates (83% to 94%). Vitrification of caudal fin pieces is advantageous in fish biodiversity conservation, particularly in the wild, due to the simplicity of procedure and equipment.
McDonagh, A F; Palma, L A
Amorphous isomerically pure biliverdin IX alpha is readily prepared in more than 70% yield by dehydrogenation of bilirubin with 2,3-dichloro-5,6-dicyanobenzoquinone in dimethyl sulphoxide under carefully controlled conditions. Crystalline biliverdin IX alpha and amorphous [14C]biliverdin can be obtained similarly in more than 40+ yield. The pure crystalline pigment was characterized by elemental analysis, methylation, chemical and enzymic reduction to bilirubin, i.r.- and u.v.-visible-absorption spectroscopy, n.m.r. spectroscopy and field-desorption mass spectrometry, and its solubility was determined. Under certain conditions, dehydrogenation, gave biliverdin contaminated with III alpha and XIII alpha isomers as a result of disproporationation of bilirubin. Formation of non-IX alpha isomers depends on the concentrations of the reagents and the order in which they are mixed, and occurs under neutral anaerobic conditions. Free-radical reactions probably are responsible, suggesting that the first step in the deydrogenation of bilirubin with 2,3-dichloro-5,6-dicyanobenzoquinone in dimethyl sulphoxide is formation of a bilirubin cation radical, rather than hydride ion abstraction. Images Fig. 1. Fig. 2. PMID:7458909
Patil, Pranali G; Kamble, S H; Shah, T S; Iyer, K R
Organic solvents used for solubilization of the substrates/NCEs are known to affect the activity of cytochrome P450 enzymes. Further, this effect varies with the solvents used, the substrates and CYP450 isoforms in question. In the present study, we have investigated the effect of ten commonly used water miscible organic solvents (methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, acetone, dimethyl sulphoxide, N,N-dimethyl formamide, dioxane and polyethylene glycol 400) on p-nitrophenol hydroxylase activity at 0, 0.1, 0.25, 0.5, 0.75 and 1% v/v concentration in rat liver microsomes. All the solvents studied showed concentration dependent inhibition of the p-nitrophenol hydroxylase activity except acetonitrile which showed activation of the activity at concentration range studied. Out of ten solvents studied, dioxane was found to be the most inhibitory solvent (inhibition >90% at 0.25% v/v concentration). Overall, solvents like dimethyl sulphoxide, dimethyl formamide and dioxane appeared to be unsuitable for characterizing p-nitrophenol hydroxylase (CYP2E1-mediated) reactions due to a high degree of inhibition. On the other hand, methanol and acetonitrile at concentrations <0.5% v/v appeared to be appropriate solvents for substrate solubilization while evaluating CYP2E1-mediated catalysis. The results of this study imply that caution should be exercised while choosing solvents for dissolution of substrate during enzyme studies in liver microsomes.
Quihui-Cota, Luis; Morales-Figueroa, Gloria Guadalupe
Background Intestinal parasitism remains a public health challenge in northwestern Mexico even when a twice yearly single dose of albendazole (400 mg) is administered to schoolchildren. We aimed to determine the current prevalence of intestinal parasitic infections in schoolchildren of northwestern Mexico. Methods The Faust and Kato Katz techniques were used to detect and identify the intestinal parasite species. One thousand two hundred and seventy eight children from 12 public schools were invited to participate in this study; 312 children participated in September 2003. Results Sixty eight percent of the subjects had intestinal parasites, 63% had protozoan infections, and 29%, 16% and 10% were infected with Giardia duodenalis, Hymenolepsis nana, and Entamoeba histolytica/dispar/moshkovskii respectively. Fifty children excreted eggs of Hymenolepsis nana. Conclusion Educational strategies should be considered to support the national de-worming campaign, because albendazole alone will not sufficiently improve the health conditions of vulnerable populations. PMID:24714136
Blish, Catherine A; Sangaré, Laura; Herrin, Bradley R; Richardson, Barbra A; John-Stewart, Grace; Walson, Judd L
Albendazole treatment of individuals with human immunodeficiency virus type 1 (HIV-1) and Ascaris lumbricoides co-infection has led to significantly improved CD4(+) cell counts and a trend for lower plasma HIV-1 RNA levels in a previous randomized placebo-controlled trial. To define mechanisms by which deworming contributed to changes in markers of HIV-1 disease progression, plasma cytokine levels were evaluated. Albendazole treatment, compared with placebo, was associated with significantly decreased plasma interleukin (IL) 10 levels (P = .01)ot associated with significant changes in levels of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-12p70, IL-13, interferon gamma, tumor necrosis factor alpha, or thymic stromal lymphopoietin. Treatment of A. lumbricoides co-infection may delay HIV-1 disease progression by reducing helminth-induced, IL-10-mediated immunosuppression.
Sunish, I P; Rajendran, R; Mani, T R; Munirathinam, A; Reuben, R; Dash, A P
The impact of single dose mass drug administration of diethylcarbamazine (DEC), DEC with albendazole (ALB), and ivermectin (IVR) with albendazole, was examined on the human bancroftian filarial infections in village scale trials in south India, from a follow-up study after 2 years. The treatment arms administered with DEC alone and DEC+ALB demonstrated long-term benefits in reducing microfilaraemia significantly (P<0.05), while antigenaemia reduction was negligible. The arm with ALB+IVR did not show such reductions. Among the antigenaemic and microfilaraemic individuals, 87% became amicrofilaraemic in DEC+ALB arm, which were higher than that observed in the other 2 treatment arms. Among amicrofilaraemics (but Ag+), nearly 35% cleared of infection in DEC+ALB, while 26% and 6% in DEC alone and IVR+ALB arms, respectively. The drug combination DEC+ALB was observed to demonstrate a significant impact in reducing filarial infection even after 2 years post treatment.
Küster, Tatiana; Stadelmann, Britta; Hermann, Corina; Scholl, Sabrina; Keiser, Jennifer; Hemphill, Andrew
Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis and causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated the in vitro and in vivo efficacy of mefloquine against E. multilocularis metacestodes. Treatment using mefloquine (20 μM) against in vitro cultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. The in vitro activity of mefloquine was dependent on the dosage. In vitro culture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriate in vivo studies. PMID:21135182
Spaldonová, R; Corba, J
The efficacy of seven more recently developed anthelmintics of the benzimidazolecarbamate group, i. e., parbendazole, mebendazole, fenbendazole, oxibendazole, cambendazole, oxfendazole and albendazole, has been tested in a series of experiments on white mice artifically infected with Trichinella spiralis. Our results disclosed a relationship between their anthelmintic effect and their chemical structure. This finding might be of importance in a targeted synthesis of new, effective, derivates of benzimidazole, e. g., in the therapy of trichinellosis and in the choice of the most effective drug.
Várady, M; Praslicka, J; Corba, J
Moxidectin was demonstrated to have a high efficacy in lambs against Ostertagia spp. which were resistant to albendazole, levamisole and ivermectin in goats. Moxidectin reduced the number of eggs in faeces by 99.6% and the number of worms found at post-mortem dissection of the lambs by 99.9%. Of the adult worms found in abomasa, 91% were identified as Ostertagia circumcincta and 9% as Ostertagia trifurcata.
Ólafsson, Guðmundur Dagur; Sigurðsson, Emil L; Sigurðardóttir, Bryndís
One of the more common reasons patients seek medical advice after traveling in tropical countries are skin eruptions. Here we describe two cases of individuals who, after traveling to south east Asia, developed a skin eruption later diagnosed as cutaneous larva migrans. This particular skin condition is common among travelers to countries where the hookworm responsible is endemic. The diagnosis is based on travel history and clinical examination. The patients were treated with albendazole with good results and complete resolution of the symptoms.
Almalik, Abdulrahman; Alsharidi, Aynaa; Al-Sheef, Mohammed; Enani, Mushirah
Hydatid disease is one of the most geographically widespread zoonoses with substantial disease burden. In this report we are discussing an unusual case of intra-abdominal HD that was ongoing for 22 years despite two surgical interventions. Significant symptomatic relief was achieved within the first two months of combination therapy with albendazole and praziquantel. HD is still of public health concern in the Middle East that needs optimized care. PMID:25114815
HAMIDI MADANI, Ali; ENSHAEI, Ahmad; POURREZA, Farshid; ESMAEILI, Samaneh; HAMIDI MADANI, Mohammad
Isolated renal hydatid disease is a rare endemic infestation caused by larval form of Echinococcus granulosus. Hydatiduria is an uncommon presentation of renal hydatid disease. In 2012 a 34-year-old female referred to Razi Hospital, Rasht, Iran with complaints of right flank pain and grape-like material in urine. Diagnosis was made by ultrasonography and CT scan. The patient was treated surgically with nephrectomy in combination with perioperative chemotherapy with albendazol. PMID:26587504
Raghavamma, S. T. V.; Rao, N. Rama
Antianthelmintic activity of successive extracts (chloroform, acetone, ethanol and aqueous) of Nauclea orientalis leaves were evaluated separately on adult Indian earthworm (Pheretima posthuma) and compared with that of albendazole. It was found that the extracts exhibited, respectively dose-dependent action and inhibition of spontaneous motility (paralysis) and death of earthworms. The results indicated that the chloroform, ethyl acetate and ethanol extracts were more potent. PMID:21218070
Dhanaraj, Manoharan; Ramalingam, Manoharan
A 25-year-old male was seen with complaints of itchy skin lesions over left thigh. On examination multiple annular scaly plaques with wavy borders, peripheral papules and central clearing was seen. Closer examination revealed multiple forked tracts with excoriated papules. A diagnosis of cutaneous larva migrans was made and the patient treated using T.Albendazole 400 mg twice daily for 7 days which resulted in complete clinical cure.
Küster, Tatiana; Stadelmann, Britta; Hermann, Corina; Scholl, Sabrina; Keiser, Jennifer; Hemphill, Andrew
Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis and causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated the in vitro and in vivo efficacy of mefloquine against E. multilocularis metacestodes. Treatment using mefloquine (20 μM) against in vitro cultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. The in vitro activity of mefloquine was dependent on the dosage. In vitro culture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriate in vivo studies.
Erdem Kivrak, Esra; Sıpahi, Oğuz Reşat; Korkmaz, Metin; Işikgöz Taşbakan, Meltem; Pullukçu, Hüsnü; Arda, Bilgin; Yamazhan, Tansu; Ulusoy, Sercan
Toxocariasis in man is associated with three syndromes which are visceral larva migrans, ocular larva migrans and covert toxocariasis. Although neurotoxocariasis is defined as the fourth syndrome of toxocariasis, it is usually considered as a neurological disease which is usually concomitant with visceral larva migrans. In this report, a case of brain abscess caused by toxocariasis was presented. A 56 years-old female patient was admitted to our hospital with headache, pain referring to right side of her face and teeth, numbness of forth and fifth finger of her right hand. Cranial diffusion weighted, dynamic magnetic resonance imaging (MRI) revealed a few non-specific intensities at supratentorial white matter, an approximately 13 x 12 mm lesion without contrast enhancement and a significant edema around the white matter in the left frontal cortex. Histologic examination after stereotactic biopsy of the lesion revealed diffuse histiocyte infiltration. A specific agent could not be detected in the histochemical examination. Western-blot test for toxocariasis in serum and cerebrospinal fluid samples were found positive. She was transferred to the infectious diseases clinic, and albendazole therapy (400 mg, q12h) was started. Albendazole treatment was completed for a total of one month following the regression of the cranial MRI findings on the 14th day of therapy. The patient is recalled for cranial MRI control three months later. However, it was noted that she continued albendazole for three months. Compared to the previous MRI, there were two stabilized T2A hyperintense lesions in left cranial hemisphere and minimally regressed lesions at the level of left frontal centrum semiovale. The patient was successfully treated with albendazole. There was no relapse after six month follow-up. This case was presented to withdraw attention to neurotoxocariasis which may be encountered although rarely in the etiology of encephalitis/ brain abscess.
Loos, Julia A; Dávila, Valeria A; Rodrígues, Christian R; Petrigh, Romina; Zoppi, Jorge A; Crocenzi, Fernando A; Cumino, Andrea C
Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.
Loos, Julia A.; Dávila, Valeria A.; Rodrígues, Christian R.; Petrigh, Romina; Zoppi, Jorge A.; Crocenzi, Fernando A.; Cumino, Andrea C.
Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy. PMID:28182659
Zevallos, Karine; Vergara, Katherine C.; Vergara, Antonio; Vidal, Carlos; Garcia, Hector H.; Evans, Carlton A.
The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Stool microscopy diagnosed helminths in 98% and co-infection with multiple species in 24% of study subjects. The TST was positive (≥ 10 mm) for 49%, and responses increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P = 0.01), and tuberculosis contact (P = 0.05). TST results had no association with helminth-egg concentrations, species, or co-infections (all P > 0.1). One month after deworming with albendazole (three daily 400-mg doses), helminths were reduced, but 63% remained infected with helminths. Albendazole did not cause a change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species. PMID:20682875
Shibazaki, Shunichi; Eguchi, Shunsuke; Endo, Takashi; Wakabayashi, Tadamasa; Araki, Makoto; Gu, Yoshiaki; Imai, Taku; Asano, Kouji; Taniuchi, Norihide
Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case 1, whereas a corticosteroid and albendazole were used in Case 2 as induction therapy. Both patients recovered. Albendazole was also used in Case 1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole. PMID:27123346
Wen, Li-Yong; Yan, Xiao-Lan; Sun, Feng-Hua; Fang, Yue-Yi; Yang, Ming-Jin; Lou, Lei-Jun
To assess the efficacy of ivermectin against intestinal nematode infections, a randomized, double-blind, multicenter clinical trial was carried out in a total of 816 human individuals infected with different nematodes from three counties in China. The subjects were randomly assigned into experimental and control groups and orally given a single dose of 0.1, 0.2, 0.2 and 0.2mg/kg ivermectin against Ascaris lumbricoides, hookworm, Trichuris trichiura and Enterobius vermicularis, respectively. Parallel control groups to each of the ivermectin groups were given a single oral dose of 6.7 mg/kg albendazole. The cure rates with ivermectin and albendazole were 100% (102/102) and 99.0% (101/102) for Ascaris, and 66.7% (68/102) and 67.7% (69/102) for Trichuris, respectively, with no significant difference (P>0.05) between the two treatments. The parasitological cure rates of albendazole were 69.6% (71/102) for hookworm and 94.1% (96/102) for Enterobius, which were significantly higher than ivermectin (33.3% and 52.9%, respectively, P<0.0001). The expulsion of worm in the feces reached its peak 1-2 days after ivermectin treatment. The study showed that ivermectin, with few side effects, could be used as an additional treatment tool for intestinal nematodes, especially for the treatment of Ascaris and Trichuris infections in China.
Carvalho, Karina Penedo; Gadelha, Ana Paula Rocha
Tritrichomonas foetus is a venereal pathogen of cattle, which causes infertility, early embryonic death or abortion. In order to evaluate the potential trichomonicidal activity of benzimidazoles, the effects of thiabendazole, mebendazole and albendazole were analyzed on the multiplication, general morphology and ultrastructure of T. foetus. It was found that mebendazole presented the highest IC(50%) (2.3 microM), when compared with albendazole (IC(50%)=9.4 microM) and thiabendazole (IC(50%)=142.6 microM), and that such effects were irreversible. Concerning microscopic analysis, thiabendazole- and mebendazole-treated cells presented increased volume, internalization of the flagella, disruption or multiplication of the nucleus, multiple organelles and cytoplasmic vacuolization. Albendazole-treated cells exhibited slight alterations, because the parasite became slightly rounded, its flagella were not internalized but the cytoplasm was vacuolated. Mebendazole was indeed highly effective as an in vitro trichomonicidal agent, and this might open up new possibilities for the use of mebendazole in the therapy of bovine trichomoniasis.
Maroto, R.; Jiménez, A. E.; Romero, J. J.; Alvarez, V.; De Oliveira, J. B.; Hernández, J.
As the prevalence and severity of anthelmintic resistance continue to rise, nematode infections in sheep correspondingly reduce the profitability of the sheep industry. In Costa Rica, sheep production systems are increasing in both number and importance. A field trial study was carried out to detect the level of anthelmintic resistance to albendazole and ivermectin in gastrointestinal nematodes (GIN) of sheep from seven farms in Costa Rica. Resistance was determined using the fecal egg count reduction test (FECRT). Three treatment groups were assessed on each farm: control, albendazole, and ivermectin. Haemonchus spp. (71%), Strongyloides sp. (57%), and Trichostrongylus spp. (43%) presented resistance levels to albendazole, whereas Strongyloides sp. (43%), Haemonchus spp. (29%), and Trichostrongylus spp. (29%) were resistant to ivermectin. Haemonchus spp., Strongyloides sp., and Trichostrongylus spp. were the most resistant GIN to both products. This study suggests that frequency of treatment, exclusive chemical control, and visual estimation of animal weight to calculate dosage may contribute to the high levels of anthelmintic resistance that were observed on the farms analyzed herein. PMID:21772962
Van Schalkwyk, P C; Geyser, T L; Rezin, V S
Two field isolates of Ostertagia spp. of sheep from the Swellendam and Malmesbury districts in the south-western Cape were shown to be resistant to benzimidazole anthelmintics. At therapeutic dosage rates albendazole was 32,5%, thiabendazole 0%, oxfendazole 14,9% and morantel 91,4% effective against the adult stage of Ostertagia spp. in naturally infested lambs at Swellendam. Efficacy against the adult stage of the same isolate of Ostertagia spp. in artificially infested sheep in the laboratory was tested at dosage rates of albendazole 3,8% mg/kg or 7,6 mg/kg, mebendazole 15 mg/kg, levamisole 7,5 mg/kg and morantel 14,5 mg/kg and varied from 0%, 0%, 1,9% 53,9% and 87,0% respectively. Albendazole, the only anthelmintic tested against the Malmesbury strain of Ostertagia spp. was 9,8% effective against the adult stage in naturally infested lambs. Trichostrongylus spp. and Nematodirus spp. simultaneously present in these animals were fully susceptible to all the anthelmintics tested.
Shukla, Geeta; Kaur, Hemjeet; Sharma, Lalita
Various antiprotozoal drugs have been used to counteract the spread of giardiasis. However, due to increase in resistance to these compounds, there is an urgent need to find a natural biocompatible product to fight the pathogen in more healthy and effective way. The present study was designed to compare the therapeutic effect of probiotic Lactobacillus casei alone and in conjunction with antiprotozoal drugs on the outcome of giardiasis in murine model. BALB/c mice were challenged with Giardia intestinalis trophozoites, and 1 day after infection, these mice were treated with either probiotic alone or in conjunction with antiprotozoal drugs. Cyst, trophozoite, and lactobacilli counts were monitored vis-a-vis histopathological alterations in the small intestine. It was found that albendazole administered orally 1 day after Giardia infection was the most effective antiprotozoal drug among albendazole, tinidazole, metronidazole, and nitazoxanide. It reduced both the severity and duration of giardiasis. More specifically, oral administration of the probiotic L. casei in conjunction with albendazole further reduced the Giardia infection as was evident by the restored normal gut morphology. This suggests that probiotics and antiprotozoal drugs in combination may be the better alternative therapy for treatment of gastrointestinal diseases and enhanced recovery.
Kumsa, Bersissa; Abebe, Girma
A study was conducted to determine the presence of anthelmintic resistance on Hawassa University goat farm in southern Ethiopia. The 180 goats were stratified by age and sex and randomly assigned to treatment groups (albendazole, tetramisole and ivermectin and untreated control). Each treatment group included 15 goats and treatments were administered according to weight of each goat with 7.5 mg/kg bw albendazole, 22.5 mg/kg bw tetramisole and 0.2 mg/kg bw ivermectin dose rates recommended by scientists. Faecal samples were collected on day 0 before treatment, and again on day 12 post treatment. Efficacy of all the drugs was assessed on day 12 post treatment by faecal egg count reduction test (FECRT). Multiple anthelmintic resistance in Haemonchus spp. against albendazole, tetramisole and ivermectin was recorded in all age categories of the goats. Likewise, Trichostrongylus/Teladorsagia spp. showed resistance against ivermectin. Coprocultures from all pre- and post-treatments revealed the predominance of Haemonchus spp. Resistance against anthelmintics is attributed to the high frequency of treatment and low dosage of treatment practices on the farm. Large scale studies, however, are needed to assess the current status of anthelmintic resistance against the most commonly used anthelmintics in different agroecology, species of animals and management systems in Ethiopia.
Molina, I; Duque, C C; Alfonso, J; Cervera, R P; Romeu, A
The present study was undertaken to compare the developmental capacity of human embryos derived from abnormally fertilised zygotes (1 PN, > 3 PN; 16-18 hours after ICSI) cryopreserved using two techniques: ultra rapid freezing and vitrification. At 2-4 cell stage, (48 hours after ICSI), these abnormally fertilised embryos were then distributed in three groups: a) embryos that were cryopreserved by ultra rapid freezing (URF Group), b) embryos cryopreserved by vitrification (V Group) and c) embryos that were not cryopreserved (Control group). Survival rates and embryo development after 24 hours of in vitro culture (72 hours after ICSI) were compared. 42 embryos were cryopreserved by ultra rapid freezing in 0.5 mL straws, using a mixture of dimethyl sulphoxide (3M) and sucrose (0.25M) in a base solution consisting of IVF medium plus 20 percent (v/v) of Human Serum Albumin (HSA), and 24 embryos were vitrified in 0.25 ml straws, using a two step protocol with an equilibration solution consisting of 10 percent ethylene glycol (1.79 M) and 10 percent dimethyl sulphoxide (1.41 M) in a base solution of modified phosphate buffered saline (PBS) with 20 percent of HSA and a vitrification solution consisting of 20 percent ethylene glycol (3.58 M), 20 percent dimethyl sulphoxide (2.82 M) and 0.5 M sucrose in base solution. The recovery rate after thawing/warming was lower for the vitrification group (75 percent V; 83 percent URF). The number of embryos with less than 50 percent of intact blastomeres after cryopreservation was significantly higher for the URF group (0 percent V; 34 percent URF). After in vitro culture, the rate of embryos not cryopreserved (Control group) that developed in vitro (72 hours after ICSI) was the highest (86 percent), followed by group V (50 percent), while group URF was the lowest (13 percent). These differences were statistically significant. This straw method of vitrification is successful and safe.
Kintz, P; Cirimele, V
A method for cannabis testing in human whole blood is presented. The procedure involves extraction of a 2 mL specimen acidified with 0.2 mL of 10% acetic acid in a silanized vial in presence of deuterated internal standards into hexane:ethyl acetate. After evaporation to dryness the drug and its metabolite were derivatized by methylation with iodomethane in tetrabutylammonium hydroxide-dimethyl sulphoxide (DMSO). The derivatives were extracted into isoocatane for analysis by gas chromatography-mass spectrometry (GC-MS). The limit of quantification was 1.0 and 0.5 ng/mL for delta 9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THC-COOH), respectively.
Torregrosa-Crespo, J; Martínez-Espinosa, R M; Esclapez, J; Bautista, V; Pire, C; Camacho, M; Richardson, D J; Bonete, M J
A number of species of Haloferax genus (halophilic archaea) are able to grow microaerobically or even anaerobically using different alternative electron acceptors such as fumarate, nitrate, chlorate, dimethyl sulphoxide, sulphide and/or trimethylamine. This metabolic capability is also shown by other species of the Halobacteriaceae and Haloferacaceae families (Archaea domain) and it has been mainly tested by physiological studies where cell growth is observed under anaerobic conditions in the presence of the mentioned compounds. This work summarises the main reported features on anaerobic metabolism in the Haloferax, one of the better described haloarchaeal genus with significant potential uses in biotechnology and bioremediation. Special attention has been paid to denitrification, also called nitrate respiration. This pathway has been studied so far from Haloferax mediterranei and Haloferax denitrificans mainly from biochemical point of view (purification and characterisation of the enzymes catalysing the two first reactions). However, gene expression and gene regulation is far from known at the time of writing this chapter.
Guha, S K; Singh, G; Anand, S; Ansari, S; Kumar, S; Koul, V
Earlier studies on the rat and the monkey had demonstrated that an injection of styrene maleic anhydride (SMA) in a solvent vehicle of dimethyl sulphoxide (DMSO) into the lumen of the vas deferens is toxicologically safe and has contraceptive action. Phase I clinical trial was therefore undertaken on 38 male volunteers giving varying doses of SMA, ranging between 5 mg and 140 mg, into each vas deferens. A dose of 70 mg is the predicted therapeutic dose based on animal data. That the compound is within the vas deferens lumen during the period of the safety assessment is inferred from the effect on the spermatozoa count in ejaculates which reach azoospermic levels in the higher dose ranges. The treatment is well tolerated with only minimal side effects in a few cases and no long-term adverse effects.
Kreiner-Møller, A; Stracke, F; Zimmermann, H
Various cryoprotective agents (CPA) are added to cell media in order to avoid cell injury during cryo preservation. The resulting complex environment of the preserved cell, consisting of crystalline and liquid phases can however not be investigated non-invasively by established methods in cryobiology. This study shows how scanning confocal Raman microscopy can non-invasively extract information on chemical composition, phase domain and distribution at cryogenic temperatures. The formation of the salt hydrate, hydrohalite NaCl∙H2O, in solutions comprised of phosphate buffered saline (PBS) and dimethyl sulphoxide (DMSO) is studied in particular. Scanning confocal Raman microscopy can be used to unambiguously identify hydrohalite in a medium containing DMSO and saline. The confocal Raman microscopy imaging along with differential scanning calorimetric measurements further show that the hydrohalite is formed without eutectic formation. This method also allows for discrimination between closely packed hydrohalite crystals that are oriented differently.
Dekker, A.; Houx, N.W.
A method for determining residues of aldicarb, aldicarb sulphoxide, aldoxycarb, oxamyl and methomyl in soil, groundwater and surface water is described. Subsoils were extracted with water and topsoils were extracted with acetone. The aqueous samples were either directly injected after acidification or concentrated by extraction with chloroform. The organic extracts were evaporated to dryness and redissolved in acidified mobile phase. The compounds were detected with a variable wavelength U.V. detector or with a fluorometric detector after a post-column reaction. Compounds within a concentration range from 0.5 ng/ml to 200 micrograms/ml could be determined with a maximum coefficient of variation of 7.5%. Recoveries varied from 77.0% to 98.8%.
Dix, K M; van der Pauw, C L; McCarthy, W V
Dose of 1.5 and 4.0 mg/kg/day of HEOD in corn oil and 0.25, 0.5 and 1.0 mg/kg/day of HEOD in dimethyl sulphoxide (DMSO) were administered to pregnant CF1 mice on days 6 to 14 (inclusive) of gestation. Some maternal and foetal toxicity was seen in the HEOD in DMSO and DMSO control groups compared with the untreated controls, such as reduced body weight gains, some maternal deaths, lower foetal body weights and increased incidence of delayed ossification of the foetal bones. No maternal or foetal toxicity was seen in the HEOD in corn oil or the corn oil control groups. No compound-related teratogenic effects were observed.
Development of an on-line coupling of liquid-liquid extraction, normal-phase liquid chromatography and high-resolution gas chromatography producing an analytical marker for the prediction of mutagenicity and carcinogenicity of bitumen and bitumen fumes.
Blomberg, J; de Groot, P C; Brandt, H C; van der Does, J J; Schoenmakers, P J
A fast and fully automated system for the determination of polycyclic aromatic compounds (PACs) is described. The system has been developed to produce an analytical 'marker', correlating chemical characteristics (including PAC analysis) with mutagenicity and carcinogenicity. The products of interest are bitumen fumes, bitumen and other (heavy or even residual) oil products, regardless of their boiling range. Dimethyl sulphoxide (DMSO) extractables obtained from a flow-injection analysis (FIA) system are introduced on-line in a normal-phase liquid chromatographic (NPLC) system. Here, the PACs are separated from the DMSO and possible co-extracted heavy residual species. The final step incorporates on-line gas chromatographic analysis of the three-to-six-ring PAC fraction, followed by flame-ionisation detection for quantification. It was demonstrated that data obtained from samples in the distillate lubrication-oil range correlate well with data obtained from the manual DMSO-extraction method standardised by the Institute of Petroleum as IP346.
Mahato, T H; Prasad, G K; Singh, Beer; Srivastava, A R; Ganesan, K; Acharya, J; Vijayaraghavan, R
Reactions of sulphur mustard and sarin were studied on the surface of V(1.02)O(2.98) nanotubes by gas chromatography and gas chromatography-mass spectrometry techniques. The V(1.02)O(2.98) nanotube samples were made by using hydrothermal method and characterized by scanning electron microscopy, nitrogen adsorption, X-ray diffractometry and thermogravimetry. Later, they were exposed to sulphur mustard and sarin separately at ambient temperature (30+/-2 degrees C). The data explored the formation of sulphoxide of sulphur mustard, thiodiglycol for sulphur mustard and isopropyl methyl phosphonic acid for sarin on V(1.02)O(2.98) nanotubes illustrating the role of oxidation and hydrolysis reactions in the decontamination.
Massoud, Ahmad Mohamed; Shalaby, Hatem Abdel Mawgoud; El Khateeb, Rabab Mohamed; Mahmoud, Mona Said; Kutkat, Mohamed Abdel Aziz
Objective To evaluated the histological changes within the tegument of adult Fasciola gigantica (F. gigantica) that led to the gross changes that were visible externally. Methods The effects of oleoresin extract of myrrh (Mirazid®), myrrh volatile oil and triclabendazole sulphoxide (reference drug) on the tegumental structure of adult F. gigantica following treatment in vitro had been determined by light microscopy. Results The internal changes in the tegument observed in this study were compatible with surface changes seen in the previous scanning electron microscopy study, using the same drugs. The swelling of tegumental syncytium was a particular feature of their action, but its level was much greater with myrrh volatile oil, in which vacuolization of the tegument and loss of spines were observed. Conclusions The present study demonstrated the fasciocidal properties of Mirazid® oleoresin extract, and it might be possible to reinforce its fasciocidal activity by increasing its content of myrrh volatile oil. PMID:23730566
de Siqueira, Adriana; Salvagni, Fernanda Auciello; Yoshida, Alberto Soiti; Gonçalves-Junior, Vagner; Calefi, Atilio Sersun; Fukushima, André Rinaldi; Spinosa, Helenice de Souza; Maiorka, Paulo César
The intentional and accidental poisoning of animals and people is a threat to public health and safety worldwide. Necropsies and histopathological examinations of 26 cats and 10 dogs poisoned by the carbamates aldicarb and carbofuran, confirmed by thin layer chromatography (TLC) and high performance liquid chromatography with diode-array detector (HPLC-DAD) were analysed, with variable post mortem interval and conservation of the carcass. Biological matrices were collected for toxicological and histopathological analyses. High performance liquid chromatography with diode-array detector (HPLC-DAD) was utilized to detect aldicarb and its metabolites, aldicarb sulphoxide and aldicarb sulphone, and carbofuran. The variable post mortem interval and the method of conservation of the carcass may be harmful to toxicological, necroscopic and histopathological analyses, that should be performed in order to provide reliable evidences to investigate possible poisoning of animals, which is cruel crime, and are usually linked to domestic or social conflict.
Darlewski, Witold; Popiel, Stanisław; Nalepa, Tomasz; Gromotowicz, Waldemar; Szewczyk, Rafał; Stankiewicz, Romuald
A process of dibutyl sulphide (DBS) electro-oxidation using electrolysis and cyclic voltamperometry was investigated in water-methanol solution using different electrodes (platinum, boron doped diamond, graphite and glassy carbon). Obtained results indicate that the DBS electro-oxidation process is irreversible in voltamperometric conditions. It was shown that during DBS electrolytic oxidation on Pt, at the low anode potential (1.8 V), DBS was oxidized to sulphoxide and sulphone. Electrolysis at higher potential (up to 3.0 V) resulted in complete DBS oxidation and formation of various products, including: butyric acid, sulphuric acid, butanesulphinic acid, butanesulphonic acid, identified using gas chromatography (GC-AED) and mass spectrometry (GC-MS) methods.
Thanacoody, H K R
The emergence of multiresistant bacterial strains and the continuing burden of infectious disease globally point to the urgent need for novel affordable antimicrobial drugs. Thioridazine is a phenothiazine antipsychotic drug with well-recognized antimicrobial activity, but this property has not been harnessed for clinical use as a result of its central nervous system and cardiac side-effects. The cardiotoxicity of thioridazine has recently been shown to be structurally specific at a molecular level, whereas its antimicrobial properties are shared by a number of phenothiazine analogues. This raises the possibility that its enantiomers or its inactive metabolite, the ring sulphoxide, may act as a lead compound in the future development of antimicrobial drugs to face the new challenges in infectious disease. PMID:17764469
Giffin, Shirin M.; McKinnie, Iain T.; Wadsworth, William J.; Woolhouse, Anthony D.; Smith, Gerald J.; Haskell, Tim G.
The laser performance of a range of solid state dye lasers based on rhodamine 590-doped co-polymers of 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) has been investigated. The optimisation of preparation conditions, including polymerisation initiator and solvent for dye delivery is discussed in detail. Laser efficiency is compared for different polymeric hosts and dye concentrations with a range of output couplers, cavity lengths and repetition rates. Passive and dynamic loss have been determined for each host medium. Laser efficiencies of optimised polymers are among the highest reported for rhodamine 590-doped solid state dye lasers under these operating conditions. Highest slope efficiency of 35% and lowest threshold fluence of 0.06 J cm -2 were obtained with dimethyl sulphoxide (DMSO) additive in MPMMA at 10 Hz repetition rate.
Rogge, G D; Viana, A M; Randi, A M
Spores of Dicksonia sellowiana (Presl.) Hook., an endangered tree fern, were stored in liquid nitrogen. Surface sterilized spores were placed in 1 ml sterile polypropylene cryotubes and were plunged into liquid nitrogen cryo-cans for 15 minutes, 15 days, 1 month and 3 months. In all, of the treatments the percentage of germination was higher than the control (fresh spores). Germination in Dyer and MS media supplement with 10 (-7) M and 5 x 10(-7) M BA was also promoted as comparing to control. There was no difference between the germination of spores thawed rapidly in a water bath at 45 degree C during 5 minutes or slowly at room temperature. Cryopreservation seems to promote germination of some dormant spores of D. sellowiana. The pre-treatment in cryoprotective solution of dimethyl sulphoxide 15%(v/v) in 1 M glycerol inhibited the germination of cryopreserved spores
Brewer, S. A.; Artiles, C. Perdomo; Taylor, J. A.; Dennis, M.
The photochemical destruction of 2-(phenylthio)ethanol, a benign model for the toxic chemical, sulphur mustard, was investigated in both aqueous solution, and on a textile substrate. In both cases the first formed product was the sulphoxide, 2-(phenylsulphinyl)ethanol. Increasing the concentration of sensitiser did not necessarily lead to an increase in the rate of destruction of sulphide; which is attributed to the self-quenching of the reaction in the presence of higher concentrations of Rose Bengal. The oxidation of sulphide was more efficient on nylon fabric that had been dyed with Rose Bengal, than in aqueous solution; however, a significant quantity of sulphone was also formed on the fabric. The dyed fabric could be used repeatedly to destroy the model sulphide, although the Rose Bengal itself was gradually destroyed, but at a much slower rate than the model sulphide. The ability for the fabric dyed with Rose Bengal to destroy a biological organism was also demonstrated.
Kaneti, J.; Nazir, A. Fattah; Binev, I. G.; Radomirska, V. B.; Juchnovski, I. N.
The IR spectra of cyanoacetic acid, ethyl cyanoacetate and cyanoacetamide as well as those of related mono- and, whenever possible, dianions have been studied in dimethyl-sulphoxide (DMSO) and DMSO- d6.The observed nitrile and carbonyl absorption frequencies correlate linearly with the corresponding Wiberg bond indices given by CNDO/2 calculations with full geometry optimization. These calculations predict carbanionic structures throughout except in the case of the dinegative ion of cyanoacetamide, which could be considered as originating from the aminoacetylenic tautomer of NCCH 2CONH 2. Parallel MINDO/3 calculations, however, predict that the latter dianion is again a carbanion. This result is in reasonable agreement with normal coordinate calculations and the experimental isotopic shifts of vibrational frequencies of the dianion 15NCCH -CONH -.
Bindra, Ravindar M.; Imhof, Robert E.; Xiao, P.; Andrews, Jeremy J.
Although the direct measurement of in-vivo stratum corneum hydration is relatively straightforward using the technique of opto-thermal transient emission radiometry, assessing the effect of a topically applied substance can be complex. The substance itself may change over time and may also contribute to the measured opto-thermal signal. The method developed to account for these changes uses concurrent in-vivo and in-vitro measurements. It is illustrated with topically applied petroleum jelly, dimethyl sulphoxide (DMSO) and an anti- perspirant. The petroleum jelly caused an increase in stratum corneum hydration, whilst DMSO caused a decrease, which recovers over 90 minutes. The anti-perspirant was applied before exercising and, whilst an untreated site became more hydrated, the treated site was found to become drier.
Vousdouka, Venetia I; Papapanagiotou, Elias P; Angelidis, Apostolos S; Fletouris, Dimitrios J
A simple, rapid and sensitive liquid chromatographic method that allows for the quantitative determination of fenbendazole residues in fermented dairy products is described. Samples were extracted with a mixture of acetonitrile-phosphoric acid and the extracts were defatted with hexane to be further partitioned into ethyl acetate. The organic layer was evaporated to dryness and the residue was reconstituted in mobile phase. Separation of fenbendazole and its sulphoxide, sulphone, and p-hydroxylated metabolites was carried out isocratically with a mobile phase containing both positively and negatively charged pairing ions. Overall recoveries ranged from 79.8 to 88.8%, while precision data, based on within and between days variations, suggested an overall relative standard deviation of 6.3-11.0%. The detection and quantification limits were lower than 9 and 21μg/kg, respectively. The method has been successfully applied to quantitate fenbendazole residues in Feta cheese and yoghurt made from spiked and incurred ovine milk.
Zhao, Qiang; Lee, Dong Woog; Ahn, B. Kollbe; Seo, Sungbaek; Kaufman, Yair; Israelachvili, Jacob N.; Waite, J. Herbert
Polyelectrolyte complexation is critical to the formation and properties of many biological and polymeric materials, and is typically initiated by aqueous mixing followed by fluid-fluid phase separation, such as coacervation. Yet little to nothing is known about how coacervates evolve into intricate solid microarchitectures. Inspired by the chemical features of the cement proteins of the sandcastle worm, here we report a versatile and strong wet-contact microporous adhesive resulting from polyelectrolyte complexation triggered by solvent exchange. After premixing a catechol-functionalized weak polyanion with a polycation in dimethyl sulphoxide (DMSO), the solution was applied underwater to various substrates whereupon electrostatic complexation, phase inversion, and rapid setting were simultaneously actuated by water-DMSO solvent exchange. Spatial and temporal coordination of complexation, inversion and setting fostered rapid (~25 s) and robust underwater contact adhesion (Wad >= 2 J m-2) of complexed catecholic polyelectrolytes to all tested surfaces including plastics, glasses, metals and biological materials.
Moret, Séverine; Dyson, Paul J.; Laurenczy, Gábor
The chemical transformation of carbon dioxide into useful products becomes increasingly important as CO2 levels in the atmosphere continue to rise as a consequence of human activities. In this article we describe the direct hydrogenation of CO2 into formic acid using a homogeneous ruthenium catalyst, in aqueous solution and in dimethyl sulphoxide (DMSO), without any additives. In water, at 40 °C, 0.2 M formic acid can be obtained under 200 bar, however, in DMSO the same catalyst affords 1.9 M formic acid. In both solvents the catalysts can be reused multiple times without a decrease in activity. Worldwide demand for formic acid continues to grow, especially in the context of a renewable energy hydrogen carrier, and its production from CO2 without base, via the direct catalytic carbon dioxide hydrogenation, is considerably more sustainable than the existing routes. PMID:24886955
Teyssier, Jean-Raymond; Ragot, Sylviane; Chauvet-Gélinier, Jean-Christophe; Trojak, Benoit; Bonin, Bernard
To test the hypothesis that the oxidative stress consistently detected in the peripheral blood of patients with depressive disorder impacts on the functionally relevant brain region, the expression level of nine major genes of the stress response and repair systems has been quantified in the prefrontal cortex of 24 depressive and 12 control subjects. These genes were: superoxide dismutase (SOD1), SOD2, catalase (CAT), gluthatione peroxidase 1 (GPx1), 8-oxoguanine DNA glycosylase (OGG1), nei-like 1 (NEIL1), methionine sulphoxide reductase A (MSRA), telomere repeat-binding factor 2 (TERF2) and C-FOS. Telomere length (a maker of chronic exposure to oxidative stress) has been measured in the DNA of the occipital cortex. No significant difference has been found between the compared groups. It must be concluded that the pathogenic role of the oxidative stress in the cerebral mechanism of depression cannot be inferred from the alteration of peripheral parameters.
Flor, Sabrina; Huala Juan, Martin; Tripodi, Valeria; Lucangioli, Silvia
A stereoselective CD-MEKC system has been developed for the quality control of Montelukast (MK), commercialized as a pure enantiomer. The proposed method is the first one that allows the simultaneous determination of MK, its enantiomeric form, diasteroisomers and its main degradation compound (MK sulphoxide). CD-MEKC system is composed of 10 mM SDS, 10 mM sulfobutylether-β-CD, 10 mM TM-β-CD, and 20 mM borate buffer at pH 9.0. Combination of these two CDs allows high baseline enantioresolution between MK and its enantiomeric impurity, but also, between the diasteroisomeric forms. Moreover, a multivariate design was applied to optimize operational parameters. The method was designed to meet with requirements of the official pharmacopoeias and fully validated according to international guidelines. Linearity of MK was demonstrated in the range from 10.0 to 100.0 μg/mL (r(2) = 0.9908) with a LOD and LOQ of 0.30 and 0.90 μg/mL, respectively. Intra and interday precision were evaluated and RSD values were below 2%, and also, accuracy expressed as percentage of recovery was in a range from 99.0 to 101.9 for the three assayed levels. The method allows determining 0.02% w/w of the enantiomeric and diasteroisomeric impurities, and 0.01% w/w of MK sulphoxide. Robustness was evaluated by a Plackett and Burman design. Finally, the CD-MEKC system was successfully applied to the determination of related substances in MK bulk drug and its quantification in two pediatric pharmaceutical dosage forms.
Midwinter, Robyn G; Cheah, Fook-Choe; Moskovitz, Jackob; Vissers, Margret C; Winterbourn, Christine C
Hypochlorous acid (HOCl) is produced by the neutrophil enzyme, myeloperoxidase, and reacts with amines to generate chloramines. These oxidants react readily with thiols and methionine and can affect cell-regulatory pathways. In the present study, we have investigated the ability of HOCl, glycine chloramine (Gly-Cl) and taurine chloramine (Tau-Cl) to oxidize IkappaBalpha, the inhibitor of NF-kappaB (nuclear factor kappaB), and to prevent activation of the NF-kappaB pathway in Jurkat cells. Glycine chloramine (Gly-Cl) and HOCl were permeable to the cells as determined by oxidation of intracellular GSH and inactivation of glyceraldehyde-3-phosphate dehydrogenase, whereas Tau-Cl showed no detectable cell permeability. Both Gly-Cl (20-200 muM) and HOCl (50 microM) caused oxidation of IkappaBalpha methionine, measured by a shift in electrophoretic mobility, when added to the cells in Hanks buffer. In contrast, a high concentration of Tau-Cl (1 mM) in Hanks buffer had no effect. However, Tau-Cl in full medium did modify IkappaBalpha. This we attribute to chlorine exchange with other amines in the medium to form more permeable chloramines. Oxidation by Gly-Cl prevented IkappaBalpha degradation in cells treated with TNFalpha (tumour necrosis factor alpha) and inhibited nuclear translocation of NF-kappaB. IkappaBalpha modification was reversed by methionine sulphoxide reductase, with both A and B forms required for complete reduction. Oxidized IkappaBalpha persisted intracellularly for up to 6 h. Reversion occurred in the presence of cycloheximide, but was prevented if thioredoxin reductase was inhibited, suggesting that it was due to endogenous methionine sulphoxide reductase activity. These results show that cell-permeable chloramines, either directly or when formed in medium, could regulate NF-kappaB activation via reversible IkappaBalpha oxidation.
Diez-Rodrĩguez, Gabriela I; de Baptista, Gilberto C; Trevizani, Luiz R P; Haddad, Marinéia L; Nava, Dori E
The coffee leaf miner Leucoptera coffeella (Guérin-Mèneville), one of the major pests of coffee crops in Brazil, is mainly controlled with insecticides. The objective of this study was to evaluate the residues and the translocation of the insecticide thiamethoxam in coffee leaves, as well as to study its effect on the coffee leaf miner control, comparing it with aldicarb, used as standard. One experiment was set up in the county of Garça, SP from December/2001 to August/2002. The treatments used were: aldicarb 150 G at the rates of 2.25 and 4.50 g a.i./pit, thiamethoxam 10 GR, at the rates of 0.15 and 0.30 g a.i./pit and check. Twig samples were collected prior to and 30 , 60, 90, 120, 150, 180, 210 and 240 days after the application, at three coffee plant heights (lower, middle and upper third), and the percentage of mined leaves was evaluated. The determination of aldicarb residues, including their sulphoxide and sulfone metabolites and of thiamethoxam were performed by gas chromatography with a nitrogen-phosphorus and mass spectrometer detectors, respectively. The results indicated a uniform translocation of both insecticides in all three thirds of the coffee plants when applied to the soil. A higher persistence of thiamethoxam was verified with its residues being found for as far long as eight months following the application, while aldicarb residues, including the sulphoxide and sulfone metabolites, were found only until four to six months after the application. Control of the coffee leaf miner was observed with both insecticides.
Fanigliulo, Ameriga; De Filippis, Piero; Curcuruto, Ornella; Repeto, Paolo; Roveda, Davide; Hartenstein, Matthew; Adams, Erwin; Cabooter, Deirdre
A stability-indicating method for the determination of S-carboxymethyl-L-cysteine and related degradation impurities in Exputex® 250mg/5mL syrup was developed in anion-exchange liquid chromatography mode. A forced degradation study supported the method development to ensure stability indicating conditions. Aqueous solutions of the active pharmaceutical ingredient and syrup samples at different pH-values were stress-tested in different thermal, light exposure and headspace conditions. One degradation product was detected in thermal stress studies at 60°C and 80°C in the pH range 5.0-7.0 and was identified by mass spectrometry as 5-oxo-thiomorpholine-3-carboxylic acid (lactam of carbocysteine). A second degradation product was only generated in moderately strong oxidizing conditions (0.5% H2O2 aqueous solution) and was identified as S-carboxymethyl-L-cysteine-(R/S)-sulphoxide (carbocysteine sulphoxide). The method was developed on a Zorbax SAX column, in isocratic mode. The mobile phase consisted of 200mM phosphate solution at pH 4.0 and acetonitrile (50:50 v/v) and UV detection was performed at a wavelength of 205nm. The method was linear for carbocysteine (R>0.9982) over a concentration range of 2.5-50μg/mL and 0.4-0.6mg/mL. Linearity for the impurities was shown from the LOQ to 50μg/mL. Specificity was verified and accuracy demonstrated for the active ingredient and its degradation products in syrup samples at 3 levels around their respective specification limits. Repeatability, intermediate precision and inter-laboratory reproducibility were assessed on three commercial batches, analyzed in triplicate by two operators at both the transferring and the receiving site and demonstrated a successful method transfer to the manufacturing quality control laboratory.
Opoku, Ernest Cudjoe; Olsen, Annette; Browne, Edmund; Hodgson, Abraham; Awoonor-Williams, John K.; Yelifari, Lawrence; Williams, John; Magnussen, Pascal
Background The benefits of integrated control of malaria, schistosomiasis, and soil-transmitted helminth infections have not been fully explored in Ghanaian schoolchildren. Objective To assess the impact of co-administered artemether-lumefantrine plus albendazole, and artemether-lumefantrine plus albendazole plus praziquantel compared to albendazole plus praziquantel on anaemia, sustained attention, and recall in schoolchildren. Design This three-arm, open-label intervention study was carried out in Ghana among class three schoolchildren. Artemether-lumefantrine and albendazole were co-administered to 131 schoolchildren in Study Arm 1; artemether-lumefantrine, albendazole, and praziquantel to 90 children in Study Arm 2 versus albendazole and praziquantel to 127 children in Control Arm 3. Medicines were administered to all children at least 30 min after a meal. A HemoCue® photometer was used to measure haemoglobin (Hb), while the code transmission test (CTT), adapted from the Test of Everyday Attention for Children (TEA-Ch), was used to measure sustained attention and recall before-and-after interventions in June 2011 and June 2012. Results We observed significant malaria parasite prevalence reductions of 62.8 and 59.2% in Study Arm 1 from 24.2 to 9.0%, p<0.01, and 59.2% in Study Arm 2 from 26.7 to 10.9%, p<0.01), respectively, compared to 8.93% in Control Arm 3 (from 34.7 to 31.6%, p>0.05). Meanwhile, anaemia prevalence reduced significantly (p<0.01) in all three study arms after interventions by 38.4% (from 19.8 to 12.2%), 20.7% (from 26.6 to 21.1%), and 36.0% (from 28.3 to 18.1%) in Study Arms 1, 2, and 3, respectively. Although the interventions had no significant effects on Hb levels, anaemia prevalence reduced insignificantly by 38.4 and 20.7% in Study Arms 1 and 2, respectively, compared to 36.0% in Control Arm 3. Among schoolchildren in Study Arms 1 and 2, mean CTT score improved significantly after interventions by 10.4% (from 3.18 to 3.55, p=0.01) and 20
Kumar, Ranjeet; Doharey, Pawan Kumar; Saxena, Jitendra Kumar; Rathaur, Sushma
Phosphoglycerate kinase (PGK) is a glycolytic enzyme present in many parasites. It has been reported as a candidate molecule for drug and vaccine developments. In the present study, a full-length cDNA encoding the Brugia malayi 3-phosphoglycerate kinase (BmPGK) with an open reading frame of 1.3 kb was isolated and PCR amplified and cloned. The exact size of the BmPGK's ORF is 1377 bps. The BmPGK gene was subcloned into pET-28a (+) expression vector, the expressed enzyme was purified by affinity column and characterized. The SDS-PAGE analysis revealed native molecular weight of recombinant Brugia malayi 3-phosphoglycerate kinase (rBmPGK) to be ∼45 kDa. The enzyme was found sensitive to temperature and pH, it showed maximum activity at 25 °C and pH 8.5. The Km values for PGA and ATP were 1.77 and 0.967 mM, respectively. The PGK inhibitor, clorsulon and antifilarial drugs albendazole and ivermectin inhibited the enzyme. The specific inhibitor of PGK, clorsulon, competitively inhibited enzyme with Ki value 1.88 μM. Albendazole also inhibited PGK competitively with Ki value 35.39 μM. Further these inhibitory studies were confirmed by docking and molecular simulation of drugs with enzyme. Clorsulon interacted with substrate binding site with glutamine 37 as well as in hinge regions with aspartic acid 385 and valine 387 at ADP binding site. On the other hand albendazole interacted with asparagine 335 residues. These effects were in good association with binding interactions. Thus current study might help in designing and synthesis of effective inhibitors for this novel drug target and understanding their mode of interaction with the potent anthelmintic drugs.
Domínguez-Álvarez, Javier; Mateos-Vivas, María; García-Gómez, Diego; Rodríguez-Gonzalo, Encarnación; Carabias-Martínez, Rita
Benzimidazoles (BZDs) are anthelmintic agents widely used in veterinary medicine. Their use in food-producing animals increases the possibility of residues appearing in animal tissues and products. Most analytical procedures reported for the determination of BZDs have been developed based on liquid chromatography (LC) because of their polar nature - zwitterionic - and thermal lability. To our knowledge, the determination of these compounds by capillary electrophoresis coupled to mass spectrometry (CE-MS) has not yet been described. In this work CE-MS is proposed for the identification and simultaneous quantification of several benzimidazoles in egg samples. The target compounds were 2-aminobenzimidazole, carbendazim, albendazole-2-aminosulphone, 5-hydroxy-thiabendazole, oxibendazole, albendazole, fenbendazole, oxfendazole, albendazole-sulphone, fenbendazole-sulphone. Optimization of the composition and nature - organic/aqueous - of both the electrophoretic separation buffer and the injection medium was carried out with a view to obtaining the best sensitivity and separation efficiency for the CE-MS coupling. A comparative study was carried out on different sample treatments for analyte extraction from egg samples. Two of them comprised a solvent extraction step followed by clean-up using a new commercial polymeric sorbent (Evolute ABN(©)), and the third was a particularization of the general extractive method so called Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS). Different modifications of the QuEChERS method were assayed, which included a later preconcentration step based on either SPE with MCX(©) sorbents or evaporation. The whole optimized method (QuEChERS with preconcentration prior to CE-MS) was validated according to the 2002/657/EC decision obtaining a CE-MS method sufficiently reliable and robust to determine residues of these compounds in egg samples of different origins with limits of detection between 3 and 51 μgL(-1) (S/N=3) and
Background Saponins isolated from plant sources have a number of traditional and industrial applications. Saponins have pharmacological effects like anti-inflammatory, molluscicidal, antimicrobial, antispasmodic, antidiabetic, anticancer, anticonvulsant, anthelmintic, antitussive and cytotoxic activities. The current work describes the anthelmintic and cytotoxic activities of crude saponins of Achillea Wilhelmsii and Teucrium Stocksianum as these plants are rich with saponins. Methods Brine shrimp cytotoxic activity of crude saponins was determined by Meyer et al. (1982) at test concentrations of 1000 μg/ml, 100 μg/ml, 10 μg/ml, 7.5 μg/ml, 5.0 μg/ml, 2.5 μg/ml and 1.25 μg/ml. Percentage mortality of test concentrations was determined. Similarly, in vitro anthelmintic activity was determined against roundworms, tapeworms and earthworms. Albendazole and piperazine citrate at concentration 10 mg/ml were used as standard anthelmintic drugs. Results Crude saponins of Achillea wilhelmsii (CSA) and Teucrium stocksianum (CST) had, respectively, cytotoxic activity with LC50 values 2.3 ± 0.16 and 5.23 ± 0. 34 μg/ml. For in vitro anthelmintic activity, time for paralysis and death of parasites (parasiticidal activity) was noted. At concentration 40 mg/ml, crude saponins of Achillea wilhelmsii are 1.96 and 2.12 times more potent than albendazole against Pheretima posthuma and Raillietina spiralis, respectively. Similarly, at concentration 40 mg/ml, crude saponins of Teucrium stocksianum (CST) has 1.89, 1.96 and 1.37 times more parasiticidal activity than albendazole against Pheretima posthuma, Raillietina spiralis and Ascardia galli, respectively. Conclusion Crude saponins of Achillea wilhelmsii and Teucrium stocksianum have cytotoxic and anthelmintic activity. The crude saponins may be excellent sources of cytotoxic and anthelmintic constituents that warrant its isolation and purification for new drug development. PMID:22051373
Boix, Nuria; Teixido, Elisabet; Vila-Cejudo, Marta; Ortiz, Pedro; Ibáñez, Elena; Llobet, Juan M.; Barenys, Marta
Background Fascioliasis and paragonimiasis are widespread foodborne trematode diseases, affecting millions of people in more than 75 countries. The treatment of choice for these parasitic diseases is based on triclabendazole, a benzimidazole derivative which has been suggested as a promising drug to treat pregnant women and children. However, at the moment, this drug is not approved for human use in most countries. Its potential adverse effects on embryonic development have been scarcely studied, and it has not been assigned a pregnancy category by the FDA. Thus, to help in the process of risk-benefit decision making upon triclabendazole treatment during pregnancy, a better characterization of its risks during gestation is needed. Methodology The zebrafish embryo test, a preimplantation and a postimplantation rodent whole embryo culture were used to investigate the potential embryotoxicity/teratogenicity of triclabendazole and its first metabolite triclabendazole sulfoxide. Albendazole and albendazole sulfoxide were included as positive controls. Principal Findings Triclabendazole was between 10 and 250 times less potent than albendazole in inducing dysmorphogenic effects in zebrafish or postimplantation rodent embryos, respectively. However, during the preimplantation period, both compounds, triclabendazole and triclabendazole sulfoxide, induced a dose-dependent embryolethal effect after only 24 h of exposure in rodent embryos and zebrafish (lowest observed adverse effect concentrations = 10 μM). Conclusions/Significance In humans, after ingestion of the recommended doses of triclabendazole to treat fascioliasis and paragonimiasis (10 mg/kg), the main compound found in plasma is triclabendazole sulfoxide (maximum concentration 38.6 μM), while triclabendazole concentrations are approximately 30 times lower (1.16 μM). From our results it can be concluded that triclabendazole, at concentrations of the same order of magnitude as the clinically relevant ones, does
Kang, In-Soon; Kim, Dong-Hee; An, Hye-Gyung; Son, Hyun-Mi; Cho, Min Kyoung; Park, Mi-Kyung; Kang, Shin Ae; Kim, Bo Young; Yu, Hak Sun
Health education has been shown to be effective in slowing the spread of the disease, infectious disease in particular. To evaluate the impact of health education on the prevalence and pattern of new infection of enterobiasis, children from 6 kindergartens in Ulsan city, South Korea, were recruited after undergoing a screening for enterobiasis, and then divided into three groups, including group medication (GM), education (Edu), and control group. All children in GM group received medical treatment with 500 mg albendazole twice, with 15 days interval. In the Edu group, only children diagnosed positive for Enterobius vermicularis eggs received medical treatment with 500 mg albendazole twice, with 15 days interval and all parents in the group received brochures providing information about enterobiasis. In the control group, only children diagnosed positive for E. vermicularis eggs received medical treatment with 500 mg albendazole twice, with 15 days interval, and no information about enterobiasis was provided to parents. Two post-treatment examinations were performed at three and six months after treatment. The infection rate in the GM group was dramatically decreased at 3 months, and this rate was almost the same as at 6 months after treatment. Infection rate of children in the Edu group was shown to drop from 9.9% to 3.0% at 3 months, and to 2.7% at 6 months after treatment; however, the infection rate in the control group continued to be higher than in the other two groups at both 3 and 6 months, with smaller change at 3 months compared to the other two groups. In addition, both new infection and re-infection cases in the Edu group were fewer, compared to those in the control group. In conclusion, although GM is the best method for eradication of enterobiasis, providing health information about enterobiasis to parents could reduce the prevalence, as well as the rate of new infection or re-infection with E. vermicularis in their children.
It has been argued that targeting delivery of anthelmintics to school-children by taking advantage of the existing education infrastructure and administrative system can be one of the most cost-effective approaches in minimizing the intensity of infections with both schistosomiasis and major intestinal nematodes in many developing countries. The study was conducted in January 1997, shortly after the completion of the drug intervention programme. This paper provides an analysis of the costs of providing age-targeted treatment of school-children for urinary schistosomiasis using praziquantel and for intestinal nematodes using albendazole as an integral part of the School Health Programme in Tanga Region, Tanzania. The analysis shows that the total financial cost of the intervention programme in 1996 prices was US$54 252.28 (exchange rate: TSH 573 = US$1). Of this amount, the cost of drugs constitutes 80.6%, while the delivery cost appears relatively low, representing just below 20%. Even when the opportunity cost of unpaid days of labour input is included, the cost of drugs still remains the highest cost component of the intervention (55.8%). In the current epidemiological and logistic setting of Tanzania, the financial cost per child treated using praziquantel, which involved prior screening at the school level, was US$0.79, while treatment using albendazole was as low as US$0.23, of which US$0.20 was drug purchase cost. It is concluded that the base cost of delivering a universal, standard, school-based health intervention such as albendazole can be as low as US$0.03 per child tested, but even a very slight increase in the complexity of delivery can have a very significant impact on the cost of intervention.
Lee, Caroline A; Neul, David; Clouser-Roche, Andrea; Dalvie, Deepak; Wester, Michael R; Jiang, Ying; Jones, J P; Freiwald, Sascha; Zientek, Michael; Totah, Rheem A
Several antihistamine drugs including terfenadine, ebastine, and astemizole have been identified as substrates for CYP2J2. The overall importance of this enzyme in drug metabolism has not been fully explored. In this study, 139 marketed therapeutic agents and compounds were screened as potential CYP2J2 substrates. Eight novel substrates were identified that vary in size and overall topology from relatively rigid structures (amiodarone) to larger complex structures (cyclosporine). The substrates displayed in vitro intrinsic clearance values ranging from 0.06 to 3.98 mul/min/pmol CYP2J2. Substrates identified for CYP2J2 are also metabolized by CYP3A4. Extracted ion chromatograms of metabolites observed for albendazole, amiodarone, astemizole, thioridazine, mesoridazine, and danazol showed marked differences in the regioselectivity of CYP2J2 and CYP3A4. CYP3A4 commonly metabolized compounds at multiple sites, whereas CYP2J2 metabolism was more restrictive and limited, in general, to a single site for large compounds. Although the CYP2J2 active site can accommodate large substrates, it may be more narrow than CYP3A4, limiting metabolism to moieties that can extend closer toward the active heme iron. For albendazole, CYP2J2 forms a unique metabolite compared with CYP3A4. Albendazole and amiodarone were evaluated in various in vitro systems including recombinant CYP2J2 and CYP3A4, pooled human liver microsomes (HLM), and human intestinal microsomes (HIM). The Michaelis-Menten-derived intrinsic clearance of N-desethyl amiodarone was 4.6 greater in HLM than in HIM and 17-fold greater in recombinant CYP3A4 than in recombinant CYP2J2. The resulting data suggest that CYP2J2 may be an unrecognized participant in first-pass metabolism, but its contribution is minor relative to that of CYP3A4.
Fraga, Carolina Miguel; Costa, Tatiane Luiza; Bezerra, José Clecildo Barreto; de Souza Lino, Ruy; Vinaud, Marina Clare
Human cysticercosis by Taenia crassiceps is rare although it is considered of zoonotic risk, especially to immunocompromised individuals. Albendazole and praziquantel are widely used and effective in its treatment. Their active forms inhibit the glucose uptake by the parasite and induce muscle contractions that alter its glycogen levels interfering in the energetic metabolism of the parasite and leading to its death. The aim of this study was to evaluate alterations in glycolysis, the tricarboxylic acid cycle and glucose concentrations caused by low dosage treatments of the hosts with albendazole and praziquantel. Therefore, T. crassiceps intraperitoneally infected mice were treated by gavage feeding with 5.75 or 11.5 mg/kg of albendazole and 3.83 or 7.67 mg/kg of praziquantel. The treated mice were euthanized after 24 h and the cysticerci collected were morphologically classified into initial, larval or final phases. Concentrations of the organic acid produced and glucose were evaluated to detect alterations into the glycolysis and the tricarboxylic acid cycle pathways through chromatography and spectrophotometry. The low dosage treatment caused a partial blockage of the glucose uptake by the cysticerci in spite of the non significant difference between its concentrations. An activation of the tricarboxylic acid cycle was noted in the cysticerci that received the treatment due to an increase in the production of citrate, malate and α-ketoglutarate and the consumption of oxaloacetate, succinate and fumarate. The detection of α-ketoglutarate indicates that the cysticerci which were exposed to the drugs after host treatment present different metabolic pathways than the ones previously described after in vitro treatment.
Richards, Frank O.; Eigege, Abel; Miri, Emmanuel S.; Jinadu, M. Y.; Hopkins, Donald R.
PROBLEM: Annual mass drug administration (MDA) with safe oral anthelminthic drugs (praziquantel, ivermectin and albendazole) is the strategy for control of onchocerciasis, lymphatic filariasis (LF) and schistosomiasis. District health officers seek to integrate treatment activities in areas of overlapping disease endemicity, but they are faced with having to merge different programmatic guidelines. APPROACH: We proceeded through the three stages of integrated MDA implementation: mapping the distribution of the three diseases at district level; tailoring district training and logistics based on the results of the mapping exercises; and implementing community-based annual health education and mass treatment where appropriate. During the process we identified the "know-do" gaps in the MDA guidelines for each disease that prevented successful integration of these programmes. LOCAL SETTING: An integrated programme launched in 1999 in Plateau and Nasarawa States in central Nigeria, where all three diseases were known to occur. RELEVANT CHANGES: Current guidelines allowed onchocerciasis and LF activities to be integrated, resulting in rapid mapping throughout the two states, and states-wide provision of over 9.3 million combined ivermectin-albendazole treatments for the two diseases between 2000 and 2004. In contrast, schistosomiasis activities could not be effectively integrated because of the more restrictive guidelines, resulting in less than half of the two states being mapped, and delivery of only 701,419 praziquantel treatments for schistosomiasis since 1999. LESSONS LEARNED: Integration of schistosomiasis into other MDA programmes would be helped by amended guidelines leading to simpler mapping, more liberal use of praziquantel and the ability to administer praziquantel simultaneously with ivermectin and albendazole. PMID:16917658
Palomares-Alonso, Francisca; Rojas-Tomé, Irma Susana; Palencia Hernández, Guadalupe; Jiménez-Arellanes, María Adelina; Macías-Rubalcava, Martha Lydia; González-Maciel, Angélica; Ramos-Morales, Andrea; Santiago-Reyes, Rosalba; Castro, Nelly; González-Hernández, Iliana; Rufino-González, Yadira; Jung-Cook, Helgi
Currently, neurocysticercosis treatment involves two drugs: albendazole and praziquantel; however, their efficacy is suboptimal and new cysticidal drugs are needed. The present paper reports the cysticidal activity of extracts of the bark from Prunus serotina against Taenia crassiceps cysts and the isolation and identification of the main components of the most active extract. Results showed that all extracts displayed in vitro cysticidal activity (EC50=17.9-88.5μg/mL), being the methanolic the most active and selective. Also, methanolic extract exhibited in vivo efficacy at 300mg/kg which was similar to that obtained with albendazole. Bio-guided fractionation of methanolic extract led the isolation of 2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one (naringenin, NGN), 3,4,5-trimethoxybenzoic acid and 1,3,5-trimethoxybenzene. NGN exhibited in vitro activity, in a time-concentration-dependent manner (EC50=89.3μM]. Furthermore, NGN at a dose of 376.1μmol/kg displayed similar in vivo efficacy than those obtained with albendazole at 188.4μmol/kg. NGN also caused a high level of damage in all parasite tissue in a similar manner than that observed with the methanolic extract. This study represents the first report of the cysticidal properties of the bark of P. serotina. NGN was identified as the main active compound of this specie and other studies are required to explore the potential of this flavanone as cysticidal agent.
Diani-Moore, Silvia; Papachristou, Fotini; Labitzke, Erin; Rifkind, Arleen B
Cytochrome P450 (P450) enzymes metabolize the membrane lipid arachidonic acid to stable biologically active epoxides [eicosatrienoic acids (EETs)] and 20-hydroxyeicosatetraenoic acid (20-HETE). These products have cardiovascular activity, primarily acting as vasodilators and vasoconstrictors, respectively. EET formation can be increased by the prototype CYP1A or CYP2 inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or phenobarbital (PB), respectively. We report here that imidazole derivative drugs: the anthelminthics, albendazole and thiabendazole; the proton pump inhibitor, omeprazole; the thromboxane synthase inhibitor, benzylimidazole; and the aromatase (CYP19) inhibitor vorozole (R76713, racemate; and R83842, (+) enantiomer) increased hepatic microsomal EET formation in a chick embryo model. Albendazole increased EETs by transcriptional induction of CYP1A5 and the others by combined induction of CYP1A5 and CYP2H, the avian orthologs of mammalian CYP1A2 and CYP2B, respectively. All inducers increased formation of the four EET regioisomers, but TCDD and albendazole had preference for 5,6-EET and PB and omeprazole for 14,15-EET. Vorozole, benzylimidazole, and TCDD also suppressed 20-HETE formation. Vorozole was a remarkably effective and potent inducer of multiple hepatic P450s at a dose range which overlapped its inhibition of ovarian aromatase. Increased CYP1A activity in mouse Hepa 1-6 and human HepG2 cells by vorozole and other imidazole derivatives demonstrated applicability of the findings to mammalian cells. The findings suggest that changes in P450-dependent arachidonic acid metabolism may be a new source of side effects for drugs that induce CYP1A or CYP2. They demonstrate further that in vivo induction of multiple hepatic P450s produces additive increases in arachidonic acid epoxygenase activity and can occur concurrently with inhibition of ovarian aromatase activity.
Eguale, T; Tilahun, G; Debella, A; Feleke, A; Makonnen, E
In vitro anthelmintic activities of crude aqueous and hydro-alcoholic extracts of the seeds of Coriandrum sativum (Apiaceae) were investigated on the egg and adult nematode parasite Haemonchus contortus. The aqueous extract of Coriandrum sativum was also investigated for in vivo anthelmintic activity in sheep infected with Haemonchus contortus. Both extract types of Coriandrum sativum inhibited hatching of eggs completely at a concentration less than 0.5 mg/ml. ED(50) of aqueous extract of Coriandrum sativum was 0.12 mg/ml while that of hydro-alcoholic extract was 0.18 mg/ml. There was no statistically significant difference between aqueous and hydro-alcoholic extracts (p>0.05). The hydro-alcoholic extract showed better in vitro activity against adult parasites than the aqueous one. For the in vivo study, 24 sheep artificially infected with Haemonchus contortus were randomly divided into four groups of six animals each. The first two groups were treated with crude aqueous extract of Coriandrum sativum at 0.45 and 0.9 g/kg dose levels, the third group with albendazole at 3.8 mg/kg and the last group was left untreated. Efficacy was tested by faecal egg count reduction (FECR) and total worm count reduction (TWCR). On day 2 post treatment, significant FECR was detected in groups treated with higher dose of Coriandrum sativum (p<0.05) and albendazole (p<0.001). On days 7 and 14 post treatment, significant FECR was not detected for both doses of Coriandrum sativum (p>0.05). Significant (p<0.05) TWCR was detected only for higher dose of Coriandrum sativum compared to the untreated group. Reduction in male worms was higher than female worms. Treatment with both doses of Coriandrum sativum did not help the animals improve or maintain their PCV while those treated with albendazole showed significant increase in PCV (p<0.05).
Cernanská, D; Várady, M; Corba, J
The prevalence of anthelmintic resistance on 27 sheep farms in Slovakia was investigated in 2003 and 2004 using the faecal egg count reduction test (FECRT) according to the WAAVP guidelines. Resistance to albendazole was detected on one farm (3.7%) and suspected on two farms (7.4%) out of 27 sheep flocks. Resistance to ivermectin was tested on 26 farms. On six (23.1%) farms, results indicated the presence of ivermectin resistance. Resistance to ivermectin was suspected on eight farms (30.8%). However, it is also possible that generic ivermectin anthelmintics used in survey have a lower efficacy against sheep nematodes.
Várady, M; Praslicka, J; Corba, J
A multiple resistant field strain of gastro-intestinal nematodes was detected in Cashmere and Angora goats imported from New Zealand. Different treatments with three types of broad spectrum anthelmintics (albendazole, levamisole/tetramisole and ivermectin) at various dose rates are described. Satisfactory effect in Angora goats was not achieved until all three anthelmintics were administered simultaneously at twice the normal sheep dose. Post mortem worm counts and identification revealed that the resistant population consisted of 89% Ostertagia circumcincta, 6% Ostertagia ostertagi and 5% Ostertagia trifurcata. However, egg hatch assay carried out seven months later detected the presence of resistant nematodes again.
Tritten, Lucienne; Silbereisen, Angelika; Keiser, Jennifer
Background Few effective drugs are available for soil-transmitted helminthiases and drug resistance is of concern. In the present work, we tested the efficacy of the veterinary drug monepantel, a potential drug development candidate compared to standard drugs in vitro and in parasite-rodent models of relevance to human soil-transmitted helminthiases. Methodology A motility assay was used to assess the efficacy of monepantel, albendazole, levamisole, and pyrantel pamoate in vitro on third-stage larvae (L3) and adult worms of Ancylostoma ceylanicum, Necator americanus and Trichuris muris. Ancylostoma ceylanicum- or N. americanus-infected hamsters, T. muris- or Ascaris suum-infected mice, and Strongyloides ratti-infected rats were treated with single oral doses of monepantel or with one of the reference drugs. Principal Findings Monepantel showed excellent activity on A. ceylanicum adults (IC50 = 1.7 µg/ml), a moderate effect on T. muris L3 (IC50 = 78.7 µg/ml), whereas no effect was observed on A. ceylanicum L3, T. muris adults, and both stages of N. americanus. Of the standard drugs, levamisole showed the highest potency in vitro (IC50 = 1.6 and 33.1 µg/ml on A. ceylanicum and T. muris L3, respectively). Complete elimination of worms was observed with monepantel (10 mg/kg) and albendazole (2.5 mg/kg) in A. ceylanicum-infected hamsters. In the N. americanus hamster model single 10 mg/kg oral doses of monepantel and albendazole resulted in worm burden reductions of 58.3% and 100%, respectively. Trichuris muris, S. ratti and A. suum were not affected by treatment with monepantel in vivo (following doses of 600 mg/kg, 32 mg/kg and 600 mg/kg, respectively). In contrast, worm burden reductions of 95.9% and 76.6% were observed following treatment of T. muris- and A. suum infected mice with levamisole (200 mg/kg) and albendazole (600 mg/kg), respectively. Conclusions/Significance Monepantel reveals low or no activities against N. americanus
Jara, W; Sumano, H; Ocampo, L
The effects of albendazole, fenbendazole and oxfendazole on the fermentation ability of the rumen were assessed in 12 Dorset sheep, using as parameters volatile fatty acid concentration, percentage digestibility of cellulose in vitro and pH. Although the digestibility of cellulose was affected only at high concentrations, volatile fatty acid concentrations were markedly reduced after treatment. Correlation coefficient analysis revealed a significant correlation between digestibility of cellulose and volatile fatty acids, as well as between volatile fatty acids and pH. Despite an evident decrease in volatile fatty acids and digestibility of cellulose, it is suggested that this does not outweigh the advantages derived from the use of these benzimidazoles.
Patel, Bhupeshwari; Sharma, Tanya; Bhatt, Girish Chandra; Dhingra Bhan, Bhavna
Enterobius vermicularis, the pinworm, is one of the most prevalent intestinal parasites in the world. Ectopic infestations in the genital or urinary tracts rarely occur and chronic enterobiasis of the urinary tract has rarely been reported. Here we present such a case in a 7-year-old girl presenting with fever, pain in the abdomen, vomiting and burning micturition. Ultrasonography and micturating cystourethrogram (MCU) studies were normal. The ova were demonstrated from both the patient's urine and stool specimen. This child was treated successfully with Albendazole and Ivermectin.
Lozada, Heiler; Daza, Jorge E
Strongyloidiasis is an infection caused by the parasite Strongyloides stercoralis, which can be asymptomatic and means a high morbidity and mortality in immunocompromised hosts, severe malnutrition and coinfection with HTLV-1 virus. The parasite has the potential to produce and multiply internal autoinfection in humans, thus an hyperinfection can be developed. A case of pulmonary infection by this parasite is presented in this study, infection which advanced into a respiratory failure and required mechanical ventilation and hemodynamic support in an intensive care unit. The standard treatment combined with ivermectin and albendazole was provided, achieving an appropriate response.
Deesomsak, M; Sawanyawisuth, K; Prachayakul, V
We report a patient presenting with chronic diarrhoea of unidentified etiology. Laboratory results showed microcytic anemia, peripheral eosinophilia with negative results of stool sample smears and stool concentration technique. Ancylostoma duodenale was found in the caecum and terminal ileum during colonoscopy. The patient was treated with a 3-day course of 400 mg albendazole and iron supplement. The diarrhoea disappeared shortly after treatment. Physicians particularly in tropical areas should be aware of hookworms as causative agents of chronic diarrhoea and it may be found in the large intestine.
Siddalingappa, Karjigi; Murthy, Sambasiviah Chidambara; Herakal, Kallappa; Kusuma, Marganahalli Ramachandra
Cutaneous larva migrans or creeping eruptions is a cutaneous dermatosis caused by hookworm larvae, Ancylostoma braziliense. A 2-month-old female child presented with a progressive rash over the left buttock of 4 days duration. Cutaneous examination showed an urticarial papule progressing to erythematous, tortuous, thread-like tract extending a few centimeters from papule over the left gluteal region. A clinical diagnosis of cutaneous larva migrans was considered. Treatment with albendazole led to complete resolution, confirming the diagnosis. This is to the best of our knowledge, the youngest age at which this condition is being reported. PMID:26538729
Whittaker, John H; Robertson, Alan P; Kimber, Michael J; Day, Tim A; Carlson, Steve A
The objective of this study was to investigate an interaction between nematodes and gut Enterobacteriaceae that use benzimidazoles as a carbon source. By addressing this objective, we identified an anthelmintic resistance-like mechanism for gastrointestinal nematodes. We isolated 30 gut bacteria (family Enterobacteriaceae) that subsist on and putatively catabolize benzimidazole-class anthelmintics. C. elegans was protected from the effects of benzimidazoles when co-incubated with these Enterobacteriaceae that also protect adult ascarids from the effects of albendazole. This bacterial phenotype represents a novel mechanism by which gastrointestinal nematodes are potentially spared from the effects of benzimidazoles, without any apparent fitness cost to the parasite. PMID:28066686
Christen, Jacques-Robert; Mura, Marie; Roudaut, Gwenaëlle; Drogoul, Anne-Sophie; Demar, Magalie; Briolant, Sébastien; Garnotel, Eric; Simon, Fabrice; Pommier De Santi, Vincent
Two cross-sectional studies were performed 2 years apart in French military personnel deployed from France to French Guiana. In 2011, military medical centres in French Guiana reported 40 cases of intestinal parasitism in service members returning from illegal gold mining sites in the rainforest. In 2013, 48 out of 132 service members returning from French Guiana after a 4-month mission had eosinophilia and seven were infected with hookworm. A presumptive first-line treatment with albendazole could be the most pragmatic strategy.
Human anisakiasis is acquired through eating raw or undercooked saltwater fish or squid. Infestation with living larvae caused by eating parasitized fish often times results in gastroenteritis. It mainly involves the stomach and small intestine with no reported cases of eosinophilic esophagitis caused by Anisakidea. A 41-year-old man presented for the evaluation of 1 year of dysphagia to solid foods and was found to have endoscopic findings consistent with eosinophilic esophagitis with pathology showing 100 eosinophils per high-power field. During endoscopy, a roundworm, later identified as Anisakidae species, was found. Patient was treated with a 6-week course of albendazole with symptomatic, endoscopic, and histologic improvement. PMID:28144618
Tirnea, Livius; Minciu, Radu; Olariu, Tudor Rares; Dumitrascu, Victor; Neghina, Adriana Maria; Neghina, Raul
Hydatid cyst of a solitary congenital kidney is a rare entity because of the small percentage of cases with renal hydatidosis and the reduced number of cases with this renal anomaly. We report a case presenting this extremely rare combination and having a favorable outcome. The diagnosis was confirmed based on an association of imagistic techniques and positive serology. The case was managed using a minimal invasive surgical technique (PAIR) that reduced the operative risks. Additionally, an antihelminthic agent (albendazole) was administered. To our knowledge, this is the first case with such comorbidity and treated through percutaneous approach.
Shivekar, S; Senthil, K; Srinivasan, R; Sureshbabu, L; Chand, P; Shanmugam, J; Gopal, R
Intestinal maggots were isolated from a patient, who had reported to the Department of General Medicine of Sri Manakula Vinayagar Medical College, Puducherry, in southern India with complaints of abdominal distress, bloating of abdomen and intestinal hurry following a meal. He was diagnosed as a case of intestinal myiasis. Maggots obtained from his stool were identified to be Muscina stabulans based on characteristic patterns of posterior spiracles. He was treated with purgatives and albendazole. This intestinal myiasis case caused by M. stabulans is reported here because of its rare occurrence and the need to establish a correct diagnosis.
Park, Eun Jin; Song, Joon Young; Choi, Min Ju; Jeon, Ji Ho; Choi, Jah-Yeon; Yang, Tae Un; Hong, Kyung Wook; Noh, Ji Yun; Cheong, Hee Jin; Kim, Woo Joo
A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.
Vallentin, Blandine; Carsin, Ania; Dubus, Jean-Christophe
Toxocara canis, one of the most frequent parasites worldwide, rarely triggers respiratory symptoms. We report the case of a 5-year-old girl hospitalized for a unilateral eosinophilic pleural effusion due to Toxocara canis. Besides the fact that she was living in a squat, no other medical condition was reported. There was no other site of infection caused by the parasite and she was successfully treated with albendazole. This case report is obviously unique as very few cases of pleural effusion due to Toxocara canis are reported in literature, all in adult patients.
Ranasuriya, G; Mian, A; Boujaoude, Z; Tsigrelis, C
Toxocariasis is a parasitic disease caused by Toxocara canis or T. cati. We report a patient with toxocariasis who presented with dyspnea, high-grade eosinophilia, and bilateral pulmonary nodules. To further characterize the pulmonary manifestations of toxocariasis, we have reviewed 11 previously published pulmonary toxocariasis cases. The most common pulmonary symptoms in our review were cough and dyspnea, and the most common finding on chest imaging was bilateral pulmonary nodules. Risk factors for Toxocara infection primarily included exposure to dogs. Most patients received albendazole and responded well. A high index of suspicion is needed to diagnose this otherwise preventable parasitic disease.
Hem, S; Tarantola, A; Chheang, R; Nop, P; Kerléguer, A
A live intraocular nematode was identified from a 37 year-old man presented with iritis, pain, redness, lacrimation, swelling, vision loss and intermittent blindness during many hours per day of the left eye. By using slit lamp examination, a worm was removed from iris in an ophthalmology outpatient department setting and sent to the Medical Microbiology Laboratory, Institut Pasteur du Cambodge. Gnathostoma spinigerum was identified, based on its typical morphology via microscopic examination. Based on our diagnosis, the patient was treated by oral albendazole and responded well to this therapy.
Küster, Tatiana; Hermann, Corina; Hemphill, Andrew; Gottstein, Bruno; Spiliotis, Markus
Alveolar echinococcosis (AE) in humans is a parasitic disease characterized by severe damage to the liver and occasionally other organs. AE is caused by infection with the metacestode (larval) stage of the fox tapeworm Echinococcus multilocularis, usually infecting small rodents as natural intermediate hosts. Conventionally, human AE is chemotherapeutically treated with mebendazole or albendazole. There is, however still the need for improved chemotherapeutical options. Primary in vivo studies on drugs of interest are commonly performed in small laboratory animals such as mice and Mongolian jirds, and in most cases, a secondary infection model is used, whereby E. multilocularis metacestodes are directly injected into the peritoneal cavity or into the liver. Disadvantages of this methodological approach include risk of injury to organs during the inoculation and, most notably, a limitation in the macroscopic (visible) assessment of treatment efficacy. Thus, in order to monitor the efficacy of chemotherapeutical treatment, animals have to be euthanized and the parasite tissue dissected. In the present study, mice were infected with E. multilocularis metacestodes through the subcutaneous route and were then subjected to chemotherapy employing albendazole. Serological responses to infection were comparatively assessed in mice infected by the conventional intraperitoneal route. We demonstrate that the subcutaneous infection model for secondary AE facilitates the assessment of the progress of infection and drug treatment in the live animal. PMID:23717701
Corba, J; Várady, M; Praslicka, J; Veselý, L
Multiple resistant strains of Ostertagia and Trichostrongylus were detected in a flock of cashmere and angora goats imported from New Zealand. The ED50 values detected by in vitro EHA test were from 0.27 to 0.36 micrograms/ml (while the reference value of sensitivity is 0.10 microgram/ml TBZ). Multiple resistance to all the types of currently used anthelmintics was confirmed by in vivo FECRT, when the efficacy of recommended doses was lower than 90% (albendazole 74%, levamisole 86%, ivermectin 83%). Two control schemes were investigated. In the simultaneous application of anthelmintics in the double or triple of recommended doses (0.4 mg/kg ivermectin s.c., 30 mg/kg levamisole and 20 mg/kg albendazole p.o.) was effective. Examination of goats 7 and 8 months after treatment revealed the repeated presence of multiple resistant gastrointestinal nematodes. It is the first published case of intercontinental transfer of resistant strains of nematodes when importing small ruminants.
Noland, Gregory S.; Blount, Stephen; Gonzalez, Manuel
The Dominican Republic is one of four remaining countries in the Americas with lymphatic filariasis (LF). Annual mass drug administration (MDA) with albendazole and diethylcarbamazine was conducted in La Ciénaga, an impoverished urban barrio in Santo Domingo, from 2004 to 2006. Eight years after the last MDA, a transmission assessment survey (TAS) was conducted in November–December 2014 to determine if LF transmission remains absent. Of 815 first and second grade primary school students (mean age: 6.51 years; range 5–9) tested by immunochromatographic test (ICT), zero (0.0%) were positive. This is below the TAS critical cutoff of nine, indicating that the area “passed” TAS and that transmission remains interrupted in La Ciénaga. Importantly, this also provides evidence that three rounds of effective (> 65% coverage) MDA, likely aided by environmental improvements and periodic school-based albendazole monotherapy MDA, achieved interruption of LF transmission from a relatively low-transmission setting. PMID:26503279
Bénéré, E; VAN Assche, T; Cos, P; Maes, L
This study investigated the molecular and biological variation among different Giardia duodenalis assemblages. In vitro growth and susceptibility to albendazole, fenbendazole, flubendazole, metronidazole, tinidazole and furazolidone was studied for laboratory (AI: WB, AII: G1 and B: GS/M-83-H7) and 6 field isolates of assemblage subtype AI, AII, B and EIII. Additionally, isolates of the 3 assemblages were evaluated in the gerbil upon 3-day oral treatment with albendazole (6 mg/kg), flubendazole (5 mg/kg) and metronidazole (20 mg/kg). Assemblage AI grew significantly faster than all other assemblage subtypes, which showed comparable generation times. The assemblage A laboratory strains displayed altered in vitro drug susceptibilities compared to their matching AI or AII field isolate. No variation in drug susceptibility was observed between field isolates of assemblages A and E. However, assemblage A laboratory strains were more susceptible to the benzimidazoles and less susceptible to the nitro-imidazoles and furazolidone than the assemblage B laboratory strain. In the gerbil, no markedly different drug susceptibilities were observed. In conclusion, the Giardia assemblage subtype can be associated with differences in growth characteristics rather than in drug susceptibility.
Bugeme, Marcellin; Mukuku, Olivier
Nous rapportons une observation de neurocysticercose parenchymateuse chez un homme de 38 ans, consommant régulièrement la viande de porc, qui a présenté une épilepsie réfractaire. Le diagnostic de NCC était basé sur la présence de lésions kystiques montrant le scolex sur les images du scanner cérébrale, la présence de signes cliniques évocateurs de NCC (épilepsie faite des crises convulsives focales évoluant vers des crises bilatérales), la réponse clinique au traitement à l'albendazole et le fait que notre patient vit dans une zone reconnue endémique à la cysticercose. Après un traitement fait d'albendazole et de prednisolone, l’évolution est marquée par la disparition complète des crises épileptiques. PMID:26090052
Tsotetsi, Ana Mbokeleng; Njiro, Stephen; Katsande, Tendai Charles; Moyo, Gugulethu; Baloyi, Faculty; Mpofu, Jaison
The present study was conducted to determine the prevalence and distribution of gastrointestinal helminths, to detect the presence of anthelmintic resistance in livestock from small-scale farms and to determine the level of helminthosis awareness among small-scale farmers in Gauteng Province, South Africa. Blood and faecal samples were collected from cattle (n = 314), sheep (n = 256) and goats (n = 311). Faecal egg counts and cultures were done, helminth genera identified and packed cell volume was assessed to detect anaemia. A faecal egg count reduction test was used to determine anthelmintic resistance against albendazole (7.5 mg/kg), levamisole (5 mg/kg) and ivermectin (0.2 mg/kg) on five small ruminant farms. A high prevalence of both nematodes and trematodes was observed; however, only 1 % of cattle had high nematode egg counts compared to goats (30 %) and sheep (32 %). Only 5 % of the animals were anaemic. Haemonchus and Calicophoron were the most dominant helminth genera in the studied ruminants. Anthelmintic resistance was detected against the three tested drugs on all the screened farms, except against albendazole and levamisole in sheep from Hammanskraal and Nigel, respectively. About 88 % of interviewed farmers were aware of veterinary helminthosis, 67 % treated against helminths and 83 % provided their livestock with nutritional supplements. This study showed that a high prevalence of helminthosis and anthelmintic resistance does occur in the study area, thus relevant strategic interventions are recommended.
Kovalenko, F P; Kukhaleva, I V; Shkolyar, N A; Legonkov, Yu A; Musaev, G Kh; Bulanova, T E; Samochatova, E I
The problem of echinococcosis has acquired special urgency in Russia in the last 10 years. The dramatically worse epidemiological situation of echinococcosis in the country is suggested by just frequent cases of cystic echinococcosis in the indigenous population of Moscow and its region, including children. Currently, albendazole that is less toxic than mebendazole remains the drug of choice, However, some authors note that E. granulosus larval cysts are moresusceptible to mebendazole than to albendazole. Both drugs mainly show parasitological activity and have no larvicidal effect particularly in larval alveococcosis. Analysis of the results of chemotherapy, with a group of benzimidazole carbamates for echinococcosis in 6 clinical centers from 5 European countries (Italy, Bulgaria, Romania, Greece, and Turkey) over the past 30 years showed that the evaluation of therapeutic effectiveness was overestimated; thus, 40% of all parasitic larval cysts that were considered dead became active again after, 2 years after the treatment. The original oil micronized mebendazole suspension tested by us in albino mice with late-stage larval cystic echinococcosis showed the properties of a highly effective and safe systemic larvicide that caused prompt death in the entire parasite population in the treated animals even in extreme hyperinvasion when the baseline parasite weight was greater than the host's one.
Siza, Julius E.; Kaatano, Godfrey M.; Chai, Jong-Yil; Eom, Keeseon S.; Rim, Han-Jong; Yong, Tai-Soon; Min, Duk-Young; Chang, Su Young; Ko, Yunsuk; Changalucha, John M.
The objective of this study was to carry out a community survey on schistosomiais and soil-transmitted helminth (STH) infections in order to suggest feasible and effective intervention strategies in Lake Victoria basin, Tanzania. A total of 37 communities selected from 23 districts of the 4 regions in the Lake Victoria basin of Tanzania were involved in the study. From each of the selected locality, 50 adult community members, 25 males and 25 females, were recruited for the study. Each study participant was requested to submit stool and urine specimens. From each stool specimen, duplicate Kato-Katz thick smears were prepared and microscopically examined for Schistosoma mansoni and STH eggs. Urine specimens were processed by the filtration technique and microscopically examined for Schistosoma haematobium eggs. Ultrasound examination for morbidity due to schistosomiasis was performed. Mass treatment was done using praziquantel and albendazole for schistosome and STHs infections, respectively. Out of 1,606 adults who provided stool specimens, 199 (12.4%) were positive for S. mansoni, 349 (21.7%) for hookworms, 133 (8.3%) for Ascaris lumbricoides, and 33 (2.0%) for Trichuris trichiura. Out of 1,400 participants who provided urine specimens, 25 (1.8%) were positive for S. haematobium eggs. Because of the co-endemicity of these afflictions and their impact on vulnerable population groups, the helminthiasis could be simultaneously treated with 2 drugs, praziquantel for schistosomiasis and albendazole for STHs. PMID:26537031
Bailey, M S; Thomas, R; Green, A D; Bailey, J W; Beeching, N J
One hundred and fifty-three British soldiers and 86 Royal Air Force (RAF) personnel were deployed on a hostage rescue operation in Sierra Leone. For 3 days they were exposed to various infection risks and 6 weeks later some of the soldiers presented with gastrointestinal complaints. Both groups were screened with structured questionnaires, blood investigations and (where indicated) faecal microscopy and charcoal culture for helminths. Definite and probable cases of helminth infection were treated with albendazole and all soldiers were screened again after 3 months. Among the soldiers investigated, 73/145 (50%) reported gastrointestinal symptoms and 70/139 (50%) had eosinophilia. Among these, 17/66 (26%) had hookworm infection, 6/66 (9%) had Strongyloides stercoralis infection and 1/66 (2%) had Giardia lamblia infection. Eosinophilia was most strongly associated with entering the enemy camp and being in the platoon that attacked the area around the camp latrines. Among RAF personnel, who were not involved in activities on the ground, 3/86 (3%) had borderline eosinophilia. Treatment of 105/153 (69%) soldiers with albendazole was well tolerated and, on follow-up screening 3 months later, 23/124 soldiers (19%) had gastrointestinal symptoms and 18/121 (15%) had eosinophilia. Faecal investigations and schistosomiasis serology tests were all negative at this stage.
Rinaldi, Laura; Morgan, Eric R; Bosco, Antonio; Coles, Gerald C; Cringoli, Giuseppe
To determine how far management practices on small ruminant dairy flocks in southern Italy have influenced the development of anthelmintic resistance (AR), faecal egg count (FEC) reduction tests were run on 54 sheep farms using the FLOTAC technique with a sensitivity of 2 eggs per gram of faeces. Tests were run on groups of sheep (12-20 animals per group) using six anthelmintics administered orally: levamisole on 8 farms, ivermectin (half and full dose) on 8 farms, moxidectin on 3 farms, monepantel on 8 farms, netobimin on 22 farms (pooled samples) and albendazole on 5 farms (pooled samples). Different formulae and statistics were used to calculate FEC reductions and confidence intervals based on the presence of a control group and/or the use of pooled samples. A very high average efficacy was obtained with all anthelmintics tested as follows: levamisole 99.3% (range across farms 98-100%), ivermectin half dose 99.5% (98.0-100%), ivermectin full dose 99.9% (99.3-100%), moxidectin 100% (99.9-100%), monepantel 99.4% (97-100%), netobimin 99.1% (92-100%) and albendazole 100%. The results suggest that the development of AR in small ruminants could be limited in countries with a Mediterranean type of climate provided that refugia of the nematode populations are maintained, anthelmintic use is restricted and movement of animals is not permitted to spread resistance.
Longo, Monica; Zanoncelli, Sara; Colombo, Paolo Angelo; Harhay, Michael Oscar; Scandale, Ivan; Mackenzie, Charles; Geary, Timothy; Madrill, Nicole; Mazué, Guy
Filarial diseases affect millions of people in poverty-stricken areas. In 2011, an investigation of the potential of flubendazole as a safe, highly efficacious, and field-usable macrofilaricidal drug was begun by Drug for Neglected Diseases initiative. As part of the preclinical development program, whole embryo culture was used to investigate the potential embryotoxicity of flubendazole and its metabolites, reduced and hydrolyzed flubendazole. Albendazole was included as a comparator. Flubendazole and albendazole showed similar potency in affecting rat embryonic development in vitro, inducing retardation of growth and dysmorphogenic effects at concentrations ≥0.5 μg/mL. The head, optic and otic systems, branchial arches and posterior body portion were affected. Diffuse areas of cell death were seen in various embryonic districts. The No Observed Effect Level (NOEL) was 0.25 μg/mL for both drugs. Reduced and hydrolyzed flubendazole were less embryotoxic than the parent compound, with NOELs 4-fold and >40-fold higher than that of flubendazole, respectively.
Robinson, Elizabeth L.; Zavalij, Peter Y.; Isaacs, Lyle
Cucurbituril (CB) is currently being investigated as a solubilizing agent for insoluble drugs. We recently found that acyclic CB[n]-type receptors that bear sulfonate solubilizing groups are well suited for this application. Herein, we report cucurbituril derivative (1) that bears two sulfonate groups on its convex face that we hypothesized would be a superior solubilizing excipient for insoluble drugs. Before using 1 for drug solubilization experiments we showed that 1 does not self-associate and that it retained its ability to bind to diammonium compounds as common guests for CB sized cavities. X-ray crystallography shows that 1 maintains the key structural features of CB with only minor ellipsoidal deformations at the equator and carbonyl portals of 1. Unfortunately, the aqueous solubility of 1 (20 mM) is slightly lower than CB (20-30 mM) which limits its potential as a solubilizing excipient for insoluble drugs. We created phase solubility diagrams for the solubilization of three drugs (camptothecin, albendazole, cinnarizine) with two different containers (1 and CB). CB and 1 exhibit comparable solubilization abilities (e.g. Ka and maximum solubility) toward camptothecin and albendazole but 1 is an inferior solubilizing agent for cinnarizine because of the low solubility exhibited by the 1•cinnarizine complex. PMID:25937787
Vieira, J N; Maia, F S; Ferreira, G F; Mendes, J F; Gonçalves, C L; Villela, M M; Pereira, D I B; Nascente, P S
The fast anthelmintic resistance development has shown a limited efficiency in the control of animal's endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.
Robson, N Z; Othman, S
Despite being a common skin dermatosis in the tropics, physicians in the tropics may miss the diagnosis of cutaneous larva migrans for other pruritic skin manifestation. This is especially in those who live in urban housing with no history of travel. Cutaneous larva migrans, an intensely pruritic skin pathology is mainly contracted by people with history of beach holiday or contact with moist soft sand which had been contaminated with dog or cat faeces. This article reports a patient who presented with intensely itchy papular spots over the dorsum of his foot after walking barefooted in an urban toilet soiled with cat faeces. The patient had initially seen an urban general practitioner who diagnosed the papular skin lesion as an allergic reaction, and prescribed antihistamines. The patient subsequently developed creeping skin lesions and was seen by the author who prescribed albendazole 400 mg twice daily for three days. The patient reported reduction in itching after two days of albendazole treatment and a follow up at ten days revealed a healed infection.
Vinaud, Marina Clare; Ferreira, Cirlane Silva; Lino Junior, Ruy de Souza; Bezerra, José Clecildo Barreto
Cysticerci metabolic studies demonstrate alternative pathways responsible for its survival, such as energy sources, fatty acids oxidation and excretion of beta-hydroxybutyrate, which indicates the capability of energy production from proteins. The aim of this study was to detect alternative metabolic pathways for energy production and its end products in Taenia crassiceps cysticerci in vitro exposed to praziquantel and albendazole, in sub-lethal doses. Spectrophotometer and chromatographic analysis were performed to detect: propionate, acetate, beta-hydroxybutyrate, total proteins, urea and creatinine, SE by cysticerci in vitro exposed to praziquantel and albendazole. The drugs influenced the metabolism by inducing the creatinine phosphate phosphorylation as an alternative energy source, inhibiting the use of proteins and amino acids in the acid nucleic synthesis; and preventing the budding and replication of the cysticerci. This study also highlights the description of urea excretion, which is an important metabolic pathway to excrete toxic products such as ammonia, and the fatty acid oxidation as an alternative energy source in cysticerci exposed to anthelmintic drugs.
Siza, Julius E; Kaatano, Godfrey M; Chai, Jong-Yil; Eom, Keeseon S; Rim, Han-Jong; Yong, Tai-Soon; Min, Duk-Young; Chang, Su Young; Ko, Yunsuk; Changalucha, John M
The objective of this study was to carry out a community survey on schistosomiais and soil-transmitted helminth (STH) infections in order to suggest feasible and effective intervention strategies in Lake Victoria basin, Tanzania. A total of 37 communities selected from 23 districts of the 4 regions in the Lake Victoria basin of Tanzania were involved in the study. From each of the selected locality, 50 adult community members, 25 males and 25 females, were recruited for the study. Each study participant was requested to submit stool and urine specimens. From each stool specimen, duplicate Kato-Katz thick smears were prepared and microscopically examined for Schistosoma mansoni and STH eggs. Urine specimens were processed by the filtration technique and microscopically examined for Schistosoma haematobium eggs. Ultrasound examination for morbidity due to schistosomiasis was performed. Mass treatment was done using praziquantel and albendazole for schistosome and STHs infections, respectively. Out of 1,606 adults who provided stool specimens, 199 (12.4%) were positive for S. mansoni, 349 (21.7%) for hookworms, 133 (8.3%) for Ascaris lumbricoides, and 33 (2.0%) for Trichuris trichiura. Out of 1,400 participants who provided urine specimens, 25 (1.8%) were positive for S. haematobium eggs. Because of the co-endemicity of these afflictions and their impact on vulnerable population groups, the helminthiasis could be simultaneously treated with 2 drugs, praziquantel for schistosomiasis and albendazole for STHs.
Johny, Shajahan; Merisko, Amber; Whitman, Douglas W
Background The Apicomplexa are a diverse group of obligate protozoan parasites infesting a wide range of invertebrate and vertebrate hosts including humans. These parasites are notoriously difficult to control and many species continue to evolve resistance to commercial antibiotics. In this study, we sought to find an effective chemotherapeutic treatment against arthropod gregarines (Apicomplexa), and to identify candidate compounds for testing against other groups of protozoan parasites. Methods We tested eleven commercial antibiotics against a gregarine parasite of Romalea microptera grasshoppers. Infected insects were fed daily, lettuce containing known amounts of specific antibiotics. On Days 15 or 20, we measured the number of gregarines remaining in the digestive tract of each grasshopper. Results Treatment with metronidazole and griseofulvin in host insects significantly reduced gregarine counts, whereas, gregarine counts of insects fed, albendazole, ampicillin, chloramphenicol, fumagillin, quinine, streptomycin, sulfadimethoxine, thiabendazole or tetracycline, were not significantly different from the controls. However, albendazole produced a strong, but non-significant reduction in gregarine count, and streptomycin exhibited a non-significant antagonistic trend. Conclusion Our results confirm that gregarine infections are difficult to control and suggest the possibility that streptomycin might aggravate gregarine infection. In addition, the insect system described here, provides a simple, inexpensive, and effective method for screening antibiotics. PMID:17997852
Feitosa, Thais Ferreira; Vilela, Vinícius Longo Ribeiro; Athayde, Ana Célia Rodrigues; Braga, Fábio Ribeiro; Dantas, Elaine Silva; Vieira, Vanessa Diniz; de Melo, Lídio Ricardo Bezerra
The aim of this study was to verify the in vivo effectiveness of pumpkin seed (Curcubita pepo Linnaeus, 1753) in naturally infected ostriches in the Cariri zone, semiarid region of Paraíba State, Brazil. Forty-eight ostriches were used, African Black breed, of 14 to 36 months old, naturally infected by gastrointestinal nematodes. These animals were divided into four groups of 12 ostriches. Group 1 consists of animals treated with 0.5 g/kg live weight (l. w.) of pumpkin seed meal; group 2 received 1 g/kg l. w. of pumpkin seed meal; group 3 was treated with Albendazole 5 %, at the dosage of 1 mL/10 kg l. w.; and Group 4 was the control group and do not received treatment. Groups 1 and 2 received the treatment for three consecutive days, orally, at intervals of 7 days, totaling nine administrations. The Albendazole 5 % was administered one time, at the beginning of the experiment, according to the manufacturer's recommendations. The groups treated with pumpkin seed showed a significant decrease in egg counts per gram of feces (EPG), wherein group 2 (1 g/kg l. w.) was the most effective. The control and drug groups showed no reduction in EPG. The results of the present study demonstrate that the administration of pumpkin seed was effective in controlling gastrointestinal helminths in naturally infected ostriches.
Robinson, R D; Williams, L A; Lindo, J F; Terry, S I; Mansingh, A
In vitro bioassay of (a) aqueous methanol extracts (AME) of the green leaves of mimosa (Mimosa pudica), love weed (Cuscuta americana), vervine (Stachytarpheta jamaicensis), chicken weed (Salvia serotina) and breadfruit (Artocarpus altilis); (b) methanol-water fraction (MWF) of breadfruit leaves, and (c) commercially available drugs albendazole, thiabendazole and levamisole were assayed for nematode inactivating potential, using filariform larvae of Strongyloides stercoralis. Test larvae were obtained from a 10-day-old charcoal coproculture. Bioassays were conducted in Locke's solution, using 100 larvae in each of three replicates. Inactivation was recorded microscopically at 1, 3, 6 and 12 hours, then every 24 hours up to 5 days' incubation. It50 (time for inactivation of 50% of larvae) values read: levamisole and mimosa extract less than 1 hour; love weed extract, approximately 2 hours; breadfruit (MWF), 9.5 hours; chicken weed, 20 hours; albendazole, 35 hours; breadfruit (AME), 49 hours; thiabendazole, 74 hours and vervine extract, 81.5 hours. It95 values followed a similar, trend, and were approximately double the It50 measures. A potential role for locally available natural products in the treatment of strongyloidiasis is highlighted.
Ar Latin-Small-Letter-Dotless-I bas, Bilgin Kadri Dingil, Guerbuez; Koeroglu, Mert; Uenguel, Uemit; Zaral Latin-Small-Letter-Dotless-I , Aliye Ceylan
The aim of this case study is to present effectiveness of percutaneous drainage as a treatment option of ruptured lung and liver hydatid cysts. A 65-year-old male patient was admitted with complicated liver and lung hydatid cysts. A liver hydatid cyst had ruptured transdiaphragmatically, and a lung hydatid cyst had ruptured both into bronchi and pleural space. The patient could not undergo surgery because of decreased respiratory function. Both cysts were drained percutaneously using oral albendazole. Povidone-iodine was used to treat the liver cyst after closure of the diaphragmatic rupture. The drainage was considered successful, and the patient had no recurrence of signs and symptoms. Clinical, laboratory, and radiologic recovery was observed during 2.5 months of catheterization. The patient was asymptomatic after catheter drainage. No recurrence was detected during 86 months of follow-up. For inoperable patients with ruptured liver and lung hydatid cysts, percutaneous drainage with oral albendazole is an alternative treatment option to surgery. The percutaneous approach can be life-saving in such cases.
Nabukenya, Immaculate; Rubaire-Akiiki, Chris; Olila, Deogracious; Muhangi, Denis; Höglund, Johan
Gastrointestinal nematodes (GIN) are a challenge to goat production globally causing reduced growth, morbidity and mortality. We report here results of the first nation-wide anthelmintic resistance (AR) study and validation of assessment of clinical anaemia with FAMACHA eye scores in goats in Uganda. From August to December 2012 the efficacy of albendazole (7.5mg/kg), levamisole (10.5mg/kg) and ivermectin (0.3mg/kg) against strongyle nematodes was tested on 33 goat farms in Soroti, Gulu, Mpigi, Mbarara and Ssembabule districts of Uganda. Altogether 497 goats were subjected to a total of 45 different faecal egg count reduction tests (FECRT), each involving 5-20 goats. On one farm all substances were tested. Faecal and blood samples were collected and FAMACHA eye scores evaluated on the day of treatment and 15 days later. A questionnaire survey was conducted on frequency, type and dose of anthelmintics used, farm size and grazing management system. Examination of infective third stage larvae (L3) from pooled faecal cultures demonstrated Haemonchus to be the predominant genus (>75%). Resistance to at least one anthelmintic group was detected on 61% of the 33 farms and in 49% of the 45 test groups. Prevalence of resistance to ivermectin, levamisole and albendazole was respectively 58%, 52% and 38%. Correlation between pre-treatment packed cell volume determinations and FAMACHA scores (r(498) = -0.89) was significant. Paddock grazing system (Odds ratio 4.9, 95% CI 1.4-17.3) and large farm size of >40 goats (odds ratio 4.4, 95% CI 1.2-16.1) were significant predictors of AR. In all districts, resistance to all three anthelmintics was higher on large-scale goat farms practising mostly paddock grazing. Interestingly, resistance to albendazole, the most commonly used anthelmintic in Uganda, was lower than that to ivermectin and levamisole. We recommend adaptation of FAMACHA to goats to help restrict anthelmintic treatment to heavily infected individuals. This will limit
Steinmann, Peter; Yap, Peiling; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Ran; Wu, Fang-Wei; Chen, Jia-Xu; Zhou, Hui; Zhou, Xiao-Nong
The current global strategy for the control of soil-transmitted helminthiasis emphasises periodic administration of anthelminthic drugs to at-risk populations. However, this approach fails to address the root social and ecological causes of soil-transmitted helminthiasis. For sustainable control, it has been suggested that improvements in water, sanitation and hygiene behaviour are required. We designed a 5-year multi-intervention trial in Menghai county, Yunnan province, People's Republic of China. Three different interventions were implemented, each covering a village inhabited by 200-350 people. The interventions consisted of (i) initial health education at study inception and systematic treatment of all individuals aged ≥2 years once every year with a single dose of albendazole; (ii) initial health education and bi-annual albendazole administration; and (iii) bi-annual treatment coupled with latrine construction at family level and regular health education. Interventions were rigorously implemented for 3 years, whilst the follow-up, which included annual albendazole distribution, lasted for 2 more years. Before the third round of treatment, the prevalence of Ascaris lumbricoides was reduced by only 2.8% in the annual treatment arm, whilst bi-annual deworming combined with latrine construction and health education resulted in a prevalence reduction of 53.3% (p<0.001). All three control approaches significantly reduced the prevalence of Trichuris trichiura and hookworm, with the highest reductions achieved when chemotherapy was combined with sanitation and health education. The prevalence of T. trichiura remained at 30% and above regardless of the intervention. Only bi-annual treatment combined with latrine construction and health education significantly impacted on the prevalence of Taenia spp., but none of the interventions significantly reduced the prevalence of Strongyloides stercoralis. Our findings support the notion that in high-endemicity areas
Wei, Yongfang; Hong, Qing; Chen, Daixiong; Liang, Chenjie; Liu, Haiying; Luo, Xiaodong; Zhu, Xunmin
The Mongolian gerbil (Meriones unguiculatus) has been indicated to be a useful experimental model host for studying nematode. To understand the possibility of the Mongolian gerbil as an animal model of Angiostrongylus cantonensis infection, we investigated the development, migration, and tissue distribution of A. cantonensis and pathological changes in the brain and lungs of the infected Mongolian gerbils. The first stage larvae of A. cantonensis in the stool of the infected gerbils were examined by direct smear method at 45th day postinfection (PI). In addition, a group of the infected gerbils were orally fed with albendazole (100 mg/kg/day/gerbil) at the 8th day PI and continued for 3 consecutive days. The results showed that mortality rate of Mongolian gerbils infected with 10 third stage larvae of A. cantonensis was about 62% at the 30th day PI; the peak period of death was from the 23rd to 30th day PI. About 93% (27/29) of the worms in survivors of infected gerbils could develop to complete sexual maturity at the 46th day PI, and the examinations of 12 gerbils in G3 group revealed that first stage larvae of A. cantonensis could be found in the feces of 4 gerbils at the 45th day PI. About 80% of the worms were in the brain of infected gerbils and 20% in the lungs from the 23rd to 25th day PI; during migration of the worms from the brain to lungs, more than 90% of the worms arrived to the lungs and less than 10% of them still stayed in the brain during from the 45th to 46th day PI. Pathological examination revealed that injuries induced by A. cantonensis in infected gerbils were characterized by eosinophilic meningitis and granulomatous pneumonia. Otherwise, albendazole exhibited a good larvicidal activity in the infected Mongolian gerbils. In contrast with infected control group, no gerbils died in administering albendazole, no worms were recovered, and no nervous system symptoms caused by the infection occurred at the 26th day PI. These findings clearly
Ottesen, Eric A.; Hooper, Pamela J.; Bradley, Mark; Biswas, Gautam
Background In its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) achieved an unprecedentedly rapid scale-up: >1.9 billion treatments with anti-filarial drugs (albendazole, ivermectin, and diethylcarbamazine) were provided via yearly mass drug administration (MDA) to a minimum of 570 million individuals living in 48 of the 83 initially identified LF-endemic countries. Methodology To assess the health impact that this massive global effort has had, we analyzed the benefits accrued first from preventing or stopping the progression of LF disease, and then from the broader anti-parasite effects (‘beyond-LF’ benefits) attributable to the use of albendazole and ivermectin. Projections were based on demographic and disease prevalence data from publications of the Population Reference Bureau, The World Bank, and the World Health Organization. Result Between 2000 and 2007, the GPELF prevented LF disease in an estimated 6.6 million newborns who would otherwise have acquired LF, thus averting in their lifetimes nearly 1.4 million cases of hydrocele, 800,000 cases of lymphedema and 4.4 million cases of subclinical disease. Similarly, 9.5 million individuals—previously infected but without overt manifestations of disease—were protected from developing hydrocele (6.0 million) or lymphedema (3.5 million). These LF-related benefits, by themselves, translate into 32 million DALYs (Disability Adjusted Life Years) averted. Ancillary, ‘beyond-LF’ benefits from the >1.9 billion treatments delivered by the GPELF were also enormous, especially because of the >310 million treatments to the children and women of childbearing age who received albendazole with/without ivermectin (effectively treating intestinal helminths, onchocerciasis, lice, scabies, and other conditions). These benefits can be described but remain difficult to quantify, largely because of the poorly defined epidemiology of these latter infections. Conclusion The GPELF has earlier
Sensitive chiral high-performance liquid chromatographic determination of anthelmintic flubendazole and its phase I metabolites in blood plasma using UV photodiode-array and fluorescence detection Application to pharmacokinetic studies in sheep.
Nobilis, Milan; Vybíralová, Zuzana; Krízová, Veronika; Kubícek, Vladimír; Soukupová, Marie; Lamka, Jirí; Szotáková, Barbora; Skálová, Lenka
Although benzimidazole anthelmintic flubendazole, methyl ester of [5-(4-fluorobenzoyl)-1H-benzimidazol-2-yl]carbamic acid, is extensively used in veterinary and human medicine for the treatment of gastrointestinal parasitic helminth infections, reliable data about its pharmacokinetics in various species have not been reported. Our previous work [M. Nobilis, Th. Jira, M. Lísa, M. Holcapek, B. Szotáková, J. Lamka, L.Skálová, J. Chromatogr. A 1149 (2007) 112-120] had described the stereospecificity of carbonyl reduction during phase I metabolic experiments in vitro. For in vivo pharmacokinetic studies, further improvement and optimization of bioanalytical HPLC method in terms of sensitivity and selectivity was necessary. Hence, a modified chiral bioanalytical HPLC method involving both UV photodiode-array and fluorescence detection for the determination of flubendazole, both enantiomers of reduced flubendazole and hydrolyzed flubendazole in the extracts from plasma samples was tested and validated. Albendazole was used as an internal standard. Sample preparation process involved a pH-dependent extraction of the analytes from the blood plasma into tert-butylmethyl ether. Chromatographic separations were performed on a Chiralcel OD-R 250 mm x 4.6mm column with mobile phase methanol-1M NaClO(4) (75:25, v/v) at the flow rate 0.5 ml min(-1). In quantitation, selective UV absorption maxima of 290 nm (for reduced flubendazole), 295 nm (for albendazole), 310 nm (for flubendazole) and 330 nm (for hydrolyzed flubendazole) were used in the UV photodiode-array detection, and lambda(exc.)/lambda(emis.)=228 nm/310 nm (for reduced flubendazole) and lambda(exc.)/lambda(emis.)=236 nm/346 nm (for albendazole) were set on the fluorescence detector. The fluorescence detection was approximately 10-times more sensitive than the UV detection. Each HPLC run lasted 27 min. The validated chiral HPLC-PDA-FL method was employed in the pharmacokinetic studies of flubendazole in sheep. The
das Neves, José Henrique; Carvalho, Nadino; Rinaldi, Laura; Cringoli, Giuseppe; Amarante, Alessandro F T
The occurrence of anthelmintic resistance to levamisole, albendazole, ivermectin and moxidectin was investigated in cattle from 10 farms located in São Paulo State, Brazil, using two techniques for counting eggs in faeces: McMaster with a sensitivity of 50 eggs per gram (EPG) and FLOTAC with a sensitivity of two EPG. We also evaluated the use of different mathematical and test design approaches to determine the efficacy of the anthelmintic treatments: one formula/design that compares post-treatment arithmetic mean EPG counts for the treated and control groups (FECRT1) and two methods to analyse data from pre- and post-treatment EPG counts in the same group (FECRT2 and FECRT3, respectively). Treatment groups received either ivermectin (0.2 mg/kg of body weight (BW); moxidectin (0.2 mg/kg BW); albendazole (2.5 mg/kg BW); levamisole (4.7 mg/kg BW); or no treatment (control group). The number of animals in each group ranged from 8 to 11. Faecal samples from each animal were collected 2 days before the treatment and again 10 and 28 days post-treatment. The FEC reduction (FECR) confidence intervals were usually wider when based on data obtained using the McMaster method than when data were obtained using the FLOTAC method. Efficacy estimated from pre- and post-treatment EPG counts in the same group presented smaller confidence intervals. Ivermectin proved to be totally ineffective in all herds evaluated. Cooperia spp. was the major parasite displaying resistance, followed by Haemonchus spp. The results also indicated the presence of Oesophagostomum spp. and Trichostrongylus spp., meaning they, too, were resistant to ivermectin. Resistance to moxidectin was found on nine of the 10 farms investigated; however, only three farms had previously used moxidectin. In contrast, albendazole and levamisole demonstrated high efficacy on the majority of farms. In surveys for anthelmintic resistance in cattle, the use of a diagnostic method with higher sensitivity to detect eggs is
Mohamed, Abdel-Maaboud I; Abdelmageed, Osama H; Salem, Hesham; Nagy, Dalia M; Omar, Mahmoud A
A validated simple and sensitive spectrofluorimetric method was developed for the determination of chlorpromazine hydrochloride, promethazine hydrochloride, trifluperazine hydrochloride, thioridazine hydrochloride, perazine maleate and oxomemazine. The method was based on condensation of malonic acid/acetic anhydride (MAA) under the catalytic effect of the tertiary amine moiety of the studied phenothiazines to provide a deep yellow to brown colour with green fluorescence. Relative fluorescence intensity of the products was measured at λ exc 398 nm and λ em 432 nm. Different variables affecting the reaction were studied and optimized. The method was successfully applied for the determination of the studied drugs in commercial dosage forms. The lower detection limits allowed the application of this method for the determination of the compounds in plasma as an example of a biological fluid. In addition, the method was considered specific for the determination of tertiary amines in the presence of primary and secondary amines; as a result, it was deemed suitable for the determination of the cited drugs in the presence of their degradation products resulting from N-dealkylation or oxidation of the corresponding sulphoxides or sulphones.
McClean, Rhett; Zee, Yeng Peng; Holt, William V; Johnston, Stephen D
Alternative techniques for the cryopreservation of kangaroo spermatozoa that reduced or eliminated the need for glycerol were investigated including; (1) freezing spermatozoa with 20% glycerol in pre-packaged 0.25 mL Cassou straws to enable rapid dilution of the glycerol post-thaw, (2) investigating the efficacy of 20% (v/v) dimethyl sulphoxide (DMSO) and dimethylacetamide (DMA-10%, 15% and 20% v/v) as cryoprotectants and (3) vitrification of spermatozoa with or without cryoprotectant (20% v/v glycerol, 20% v/v DMSO and 20% v/v DMA). Immediate in-straw post-thaw dilution of 20% glycerol and cryopreservation of spermatozoa in 20% DMSO produced no significant improvement in post-thaw viability of kangaroo spermatozoa. Spermatozoa frozen in 20% DMA showed post-thaw motility and plasma membrane integrity of 12.7+/-1.9% and 22.7+/-5.4%, respectively, while kangaroo spermatozoa frozen by ultra-rapid freezing techniques showed no evidence of post-thaw viability. The use of 10-20% DMA represents a modest but significant improvement in the development of a sperm cryopreservation procedure for kangaroos.
Meyer, Jesse G.; A. Komives, Elizabeth
We report the effects of supercharging reagents dimethyl sulphoxide (DMSO) and m-nitrobenzyl alcohol ( m-NBA) applied to untargeted peptide identification, with special emphasis on non-tryptic peptides. Peptides generated from a mixture of five standard proteins digested with trypsin, elastase, or pepsin were separated with nanoflow liquid chromatography using mobile phases modified with either 5 % DMSO or 0.1 % m-NBA. Eluting peptides were ionized by online electrospray and sequenced by both CID and ETD using data-dependent MS/MS. Statistically significant improvements in peptide identifications were observed with DMSO co-solvent. In order to understand this observation, we assessed the effects of supercharging reagents on the chromatographic separation and the electrospray quality. The increase in identifications was not due to supercharging, which was greater for the 0.1 % m-NBA co-solvent and not observed for the 5.0 % DMSO co-solvent. The improved MS/MS efficiency using the DMSO modified mobile phase appeared to result from charge state coalescence.
Bagiu, Radu Vasile; Vlaicu, Brigitha; Butnariu, Monica
The objective of the study was to summarize the methods for isolating and identifying natural sulfur compounds from Allium ursinum (ramson) and to discuss the active constituents with regard to antifungal action. Using chromatographic techniques, the active constituents were isolated and subsequently identified. Analyses by high-performance liquid chromatography (HPLC) suggested that these compounds were sulfur constituents, with a characteristic absorbance at 250 nm. Gas chromatography-mass spectrometry (GC-MS) analyses allowed the chemical structures of the isolated constituents to be postulated. We adopted the same methods to identify the health-giving profiling of ramsons and the effects are thought to be primarily derived from the presence and breakdown of the alk(en)ylcysteine sulphoxide, alliin and its subsequent breakdown to allicin (sulfur-compounds of ramson) in connection with antifungal action. The aim of the study was the characterization of the chemical composition of ramsons and the testing of the action of the in vitro extracts, on different strains of Candida albicans. The main goal was to highlight the most efficient extracts of Allium ursinum that can provide long-term antifungal activity without remissions. The extracts from Allium ursinum plants, inhibited growth of Candida spp. cells at concentrations ranging from 0.5 to 4.0 mg/mL, while that of adherent cells at concentrations ranging from 1.0 to > 4.0 mg/mL, depending on the yeast and plant species. PMID:22408399
Bagiu, Radu Vasile; Vlaicu, Brigitha; Butnariu, Monica
The objective of the study was to summarize the methods for isolating and identifying natural sulfur compounds from Allium ursinum (ramson) and to discuss the active constituents with regard to antifungal action. Using chromatographic techniques, the active constituents were isolated and subsequently identified. Analyses by high-performance liquid chromatography (HPLC) suggested that these compounds were sulfur constituents, with a characteristic absorbance at 250 nm. Gas chromatography-mass spectrometry (GC-MS) analyses allowed the chemical structures of the isolated constituents to be postulated. We adopted the same methods to identify the health-giving profiling of ramsons and the effects are thought to be primarily derived from the presence and breakdown of the alk(en)ylcysteine sulphoxide, alliin and its subsequent breakdown to allicin (sulfur-compounds of ramson) in connection with antifungal action. The aim of the study was the characterization of the chemical composition of ramsons and the testing of the action of the in vitro extracts, on different strains of Candida albicans. The main goal was to highlight the most efficient extracts of Allium ursinum that can provide long-term antifungal activity without remissions. The extracts from Allium ursinum plants, inhibited growth of Candida spp. cells at concentrations ranging from 0.5 to 4.0 mg/mL, while that of adherent cells at concentrations ranging from 1.0 to > 4.0 mg/mL, depending on the yeast and plant species.
Koh, Ivan Chong Chu; Yokoi, Ken-Ichi; Tsuji, Masaharu; Tsuchihashi, Yasushi; Ohta, Hiromi
In the present study, we examined methods for the cryopreservation of Epinephelus septemfasciatus spermatozoa. The percent motility, average path velocity, and linearity of movement (LIN) of fresh and corresponding post-thaw sperm were evaluated. Sperm motility was investigated using computer-assisted sperm analysis. Five percent dimethyl sulphoxide (Me₂SO) with 95% fetal bovine serum (FBS) was the most successful cryoprotectant diluent with a comparative post-thaw motility of 77.6±8.5%; 5% dimethyl formamide was also effective. Fetal bovine serum was significantly better as an extender when compared with artificial seminal plasma, glucose, and trehalose solution. Sperm tolerated a wide range of cooling rates (from 27.1 to 94.3 °C min⁻¹); however, the post-thaw motility of sperm cooled to -30 °C was significantly lower than that of other cooled temperatures (-40 to -70 °C). The velocity of post-thaw sperm was significantly lower than that of fresh sperm, although LIN remained the same. For effective cryopreservation of seven-band grouper sperm, samples should be diluted in 5% Me₂SO with 95% FBS and cooled to at least -40 °C before immersion in liquid nitrogen.
Rieger, T J; de Oliveira, C T; Pereira, J Q; Brandelli, A; Daroit, D J
1. Feathers are recalcitrant protein-rich wastes produced in huge amounts by poultry processing for meat production. Hence, feather bioconversion and protease production by Bacillus sp. CL18 were investigated. 2. Bacillus sp. CL18 demonstrated a remarkable feather-degrading potential. Through cultivations on feather broth (10 g l(-1) feathers), 94.5% ± 3% of whole feathers were degraded after 4 d. Increases in soluble protein contents were observed and protease production was maximal also at d 4. This strain produced diverse proteolytic enzymes during growth. 3. Crude protease displayed optimal activity at 55°C (50-62°C), pH 8.0 (7.0-9.0) and a low thermal stability. Proteolytic activity increased in the presence of Ca(2+), Mg(2+), Triton X-100, Tween 20 and dimethyl sulphoxide. Inhibition profile indicated that crude protease contains, mainly, serine proteases. Enzyme preparation hydrolysed mainly casein and soy protein isolate. 4. The keratinolytic capacity of Bacillus sp. CL18 at moderate temperatures (30°C) might be appropriate for feather conversion, resulting in protein hydrolysates and proteolytic enzymes. Proteases are postulated to be added-value products that can be obtained from such a bioprocess.
Freshney, R I
There is now clear evidence that cells cultured from human and animal tumours can be induced to differentiate in vitro by recognised hormones, regulatory peptides, polar solvents and cytotoxic drugs. Examples can be found from several different types of tumour with the bulk of the data deriving from neuroblastoma and myeloid leukaemia. There is no clear correlation of inducer with cell type, other than some specific peptides like MSH, and agents such as dimethyl sulphoxide and dexamethasone have wide ranging activity. Steroid hormone action may require interaction between different cell types, and the inability of tumours to differentiate in situ may implicate reduced cell-cell interaction, possibly due to degradation of extracellular matrix, or to alteration of the stromal phenotype by tumour-derived factors such as peptides or prostaglandins. When differentiation has been demonstrated, it has been possible, in some cases, to correlate increased differentiation with reduced malignancy by in vitro characterisation or tumorigenicity. Conditions which induce differentiation in rat mammary carcinoma and mouse myeloma also reduce tumour growth in vivo. Clinical trials have not provided any conclusive evidence for a therapeutic benefit so far, but relatively few trials have been carried out. There is clearly a need for further investigation both in vitro and in vivo to select optimal conditions and combinations of agents for clinical evaluation.
Skriver, L; Nilsson, J R
The induction of high rates of food vacuole formation in Tetrahymena pyriformis increased the rate of respiration in exponentially growing cells by 17% and in starving cells by 47.5%. The increased rate of oxygen uptake was caused by phagocytosis itself, as shown by comparing the rates of respiration of a Tetrahymena mutant exposed to particles at the permissive or restrictive temperatures for food vacuole formation. During cell division, heat-synchronized cells in rich, particle-supplemented medium showed a significant decrease in the rate of respiration. Furthermore, dimethyl sulphoxide, in concentrations sufficient to block food vacuole formation, suppressed the rate of respiration to a level similar to that of starved cells. Cytochalasin B, fowever, did not reduce the rate of oxygen uptake despite the inability of the cells to complete the formation of food vacuoles during treatment; a possible explanation for this finding is discussed. There was a strong correlation between formation of food vacuoles and a high metabolic rate in Tetrahymena.
Jha, Rakhi K; Jha, Pradeep K; Guha, Sujoy K
The rationale and technique underlying a novel concept of noninvasive fertility control by a new Cuproferrogel contraceptive drug, iron oxide-copper-styrene maleic anhydride-dimethyl sulphoxide (Fe3O4-Cu-SMA-DMSO) composite named 'Smart RISUG' (smart reversible inhibition of sperm under guidance) in presence of pulsed magnetic field (PMF; 1 mT to 800 mT) is explained. It was synthesized by dispersing iron oxide particles and copper particles into SMA-DMSO (male contraceptive RISUG) and characterized for particle distribution, particle size measurement and transmittance peaks, etc. Interaction of the RISUG particles as well as Smart RISUG particles with Albino rat sperm cell was studied in presence as well as absence of PMF. To find an explanation to increased reaching of the Smart RISUG drug into sperm under influence of magnetic field, the transport properties were characterized by high resolution transmission electron microscopy and atomic force microscopy. Smart RISUG could be mobilized into sperm cell membrane at the PMF, 760 mT in about 50 seconds. Adoption of novel drug Smart RISUG involving new technique may open the pathway for non surgical control of drug distribution, detection and restoration of the normal fertility after removal of the contraceptive from the male/female reproductive tube in presence of electromagnetic field.
Parhi, Rabinarayan; Suresh, Podilam; Pattnaik, Subasini
In the present study, pluronic lecithin organogel (PLO) of diltiazem hydrochloride (DZH) was developed by taking different ratios of organic phase to aqueous phase (1:3, 1:4, and 1:5) with varying concentration of soya lecithin (20, 30, and 40 % w/w) in organic phase (isopropyl myristate, IPM) and pluronic (20, 25, and 30 % w/w) in aqueous phase, respectively, and characterized for in vitro parameters and ex vivo permeation study. The results of in vitro parameters were found to be within permissible limit and all the PLOs were physically stable at refrigeration and ambient temperature. The influence of phase ratio and different concentrations of soya lecithin on DZH release from the PLOs was found to be significant (p < 0.05), whereas the influences of different concentrations of pluronic were insignificant. The effect of different solvents/penetration enhancers viz. IPM, propylene glycol (PG), dimethyl sulphoxide (DMSO), and D-limonene, in combination and alone, on the permeation of DZH across the dorsal skin of rat was studied. Among all, formulation containing IPM (PLO6) exhibited highest flux of 147.317 μg/cm(2)/h. Furthermore, histopathology section of treated skin sample illustrated that lipid bilayer disruption was the mechanism for the DZH permeation. The above results indicated that PLO6 may serve as a promising alternative delivery system for DZH in the effective treatment of hypertension.
Mashtalir, Olha; Naguib, Michael; Mochalin, Vadym N; Dall'Agnese, Yohan; Heon, Min; Barsoum, Michel W; Gogotsi, Yury
Intercalation and delamination of two-dimensional solids in many cases is a requisite step for exploiting their unique properties. Herein we report on the intercalation of two-dimensional Ti3C2, Ti3CN and TiNbC-so called MXenes. Intercalation of hydrazine, and its co-intercalation with N,N-dimethylformamide, resulted in increases of the c-lattice parameters of surface functionalized f-Ti3C2, from 19.5 to 25.48 and 26.8 Å, respectively. Urea is also intercalated into f-Ti3C2. Molecular dynamics simulations suggest that a hydrazine monolayer intercalates between f-Ti3C2 layers. Hydrazine is also intercalated into f-Ti3CN and f-TiNbC. When dimethyl sulphoxide is intercalated into f-Ti3C2, followed by sonication in water, the f-Ti3C2 is delaminated forming a stable colloidal solution that is in turn filtered to produce MXene 'paper'. The latter shows excellent Li-ion capacity at extremely high charging rates.
Benítez, Vanesa; Mollá, Esperanza; Martín-Cabrejas, María A; Aguilera, Yolanda; López-Andréu, Francisco J; Cools, Katherine; Terry, Leon A; Esteban, Rosa M
The food industry produces a large amount of onion wastes, making it necessary to search for possible ways for their utilization. One way could be to use these onion wastes as a natural source of high-value functional ingredients, since onion are rich in several groups of compounds, which have perceived benefits to human health. The objective of this work is to gain knowledge of any differences between the different onion wastes obtained from industry and non-commercial bulbs to use them as food ingredients rich in specific compounds. The results showed that brown skin and top-bottom could be potentially used as functional ingredient rich in dietary fibre, mainly in insoluble fraction, and in total phenolics and flavonoids, with high antioxidant activity. Moreover, brown skin showed a high concentration of quercetin aglycone and calcium, and top-bottom showed high concentration of minerals. Outer scales could be used as source of flavonols, with good antioxidant activity and content of dietary fibre. However, inner scales could be an interesting source of fructans and alk(en)yl cystein sulphoxides. In addition, discarded onions (cvs Recas and Figueres) could be used as a good source of dietary fibre, and cv Recas also as a source of phenolics compounds.
Fasano, G; Vannin, A S; Biramane, J; Delbaere, A; Englert, Y
This study investigated whether failed maturation oocytes could be used to evaluate different cryopreservation procedures. A total of 289 failed maturation oocytes (GV and MI stages), obtained from 169 patients undergoing IVF treatment (mean age 33.84±5.0) were divided into two different slow-cooling groups (1.5 mol/l 1,2-propanediol+0.2 mol/l sucrose in either NaCl (group A) or choline chloride (ChCl) (group B) based cryopreservation solutions) and one vitrification group (15% ethylene glycol+15% dimethyl sulphoxide). Survival rate, in vitro maturation (IVM) rate, fertilization and developmental rate of cryopreserved oocytes were assessed. Regardless of the stage at which cryopreservation was performed (GV+MI), the slow cooling with ChCl based medium always gave significantly lower survival rate than the slow cooling in NaCl based medium (p=0.01) and vitrification (p<0.001). An extended study also showed statistically reduced survival rate between slow-cooling NaCl based medium and vitrification (p<0.05). Global results of in vitro maturation and fertilization showed worse results between both slow-cooling NaCl and ChCl based media versus vitrification. In conclusion, for oocytes that had failed to mature, vitrification gave better survival, maturation, fertilization and also cleavage rates than the slow-cooling protocols. Four cells embryos were obtained only from vitrified in vitro matured MI oocytes.
Primo, Fernando L.; Cordo, Paloma L. A. G.; Neto, Alberto F.; Morais, Paulo C.; Tedesco, Antonio C.
This study report on the synthesis and characterization of molybdenum chlorophyllin (Mo-Chl) compounds associated in a complex with magnetic nanoparticles (citrate-coated cobalt ferrite), the latter prepared as a biocompatible magnetic fluid (MF). The complex material was developed for application as a synergic drug for cancer treatment using Photodynamic Therapy (PDT) and Hyperthermia (HPT). Chlorophyllin was obtained from alkaline extraction of Ilex paraguariensis following molybdenum insertion from hydrolysis with molybdate sodium. Fluorescence quantum yield (Φf) of Mo-Chl/dimethyl-sulphoxide (DMSO) was lower than 0.1, with a lifetime of 5.0 ns, as obtained from time-correlated single-photon counting technique. The oxygen quantum yield of Mo-Chl was carried out using laser flash-photolysis studies in homogeneous medium saturated with O2(g) (ΦΔ = 0.50). Cellular viability was also evaluated via the classical MTT assay using gingival fibroblasts cells as a biological model. Studies performed with the complex Mo-Chl (5.0 μmol.L-1)/MF at different magnetic nanoparticle concentrations (ranging from 1012 to 1015 particle.mL-1) revealed a cellular viability of approximately 95% for the ideal magnetic material concentration of 1×10 particle.mL-1. The present study shows that natural photosensitizers molecules Mo-Chl used in association with magnetic nanoparticles represent a promising generation of drug developed to work synergistically in the treatment of neoplastic tissues using PDT and HPT.
Cristòfol, C; Virkel, G; Alvarez, L; Arboix, M; Lanusse, C E
The enantioselective disposition kinetics of the benzimidazole anthelmintic, ricobendazole (RBZ), have been characterized after its intravenous (iv) and subcutaneous (sc) administration as a racemic formulation to cattle. The (+) and (-) RBZ enantiomeric forms were recovered in plasma after iv and sc administration of the racemic RBZ formulation, using a chiral phase based HPLC method. A biexponential plasma concentration versus time curve was observed for both RBZ enantiomers following the iv treatment. Total body clearance was higher for (-) RBZ (150.4 mL/h. kg) compared with that obtained for the (+) RBZ antipode (78.1 mL/h. kg). The elimination half-life of the (-) RBZ enantiomer was shorter (T1/2beta: 2.67 h) compared with the (+) enantiomer (T1/2beta: 5.41 h). The plasma availability (expressed as AUC) was significantly higher for (+) RBZ compared with that obtained for the (-) antipode following both treatments. The enantiomeric ratio in plasma at T(0) was close to unity (50% of each enantiomer); the analysis of the concentration ratios (+) RBZ/(-) RBZ, demonstrated an increase in the proportion of (+) RBZ during the time course of the kinetics after both iv and sc treatments. The results presented herein show the enantioselective disposition kinetics of RBZ in cattle and are a further contribution to the understanding of the kinetic behaviour of these sulphoxide-containing benzimidazole anthelmintics in ruminants.
Hunt, Charles J; Pegg, David E; Armitage, Susan E
Current cryopreservation protocols for haematopoietic cells have developed largely empirically and there is no consensus on an optimal method of preservation. These protocols, though providing sufficient cells to permit engraftment, can lead to cell loss of the order of 50 percent. In the context of umbilical cord blood such losses are unacceptable. Whilst an empirical approach can provide an acceptable level of recovery, the cryopreservation process can only be optimised by adopting a methodological approach. This paper provides an overview of just such an approach as illustrated by a study on CD34 cells from umbilical cord blood. It involves firstly the determination of membrane permeability parameters that can then be used to model safe addition and elution protocols for the chosen cryoprotectant, in this case dimethyl sulphoxide. This in turn permits cryoprotectant toxicity to be evaluated free from the confounding effect of osmotic damage caused by inappropriate addition and elution protocols. Finally, non-toxic concentrations of cryoprotectant may be investigated in a cooling rate study to provide an optimal cryopreservation protocol. Using the model, the effect on CD34 cells of current addition and elution protocols was also examined.
Tao, Yong; Liu, Jianming; Zhang, Yunhai; Zhang, Meiling; Fang, Junshun; Han, Wei; Zhang, Zhizhong; Liu, Ya; Ding, Jianping; Zhang, Xiaorong
In evolution, the red panda (Ailurus fulgens) plays a pivotal role in the higher level phylogeny of arctoides carnivore mammals. The red panda inhabits certain Asian countries only and its numbers are decreasing. Therefore, the development of feasible ways to preserve this species is necessary. Genetic resource cryopreservation and somatic cell nuclear transfer (SCNT) have been used extensively to rescue this endangered species. The present study describes the establishment, for the first time, of a red panda ear fibroblast cell line, which was then cryopreserved, thawed and cultured. Through micromanipulation, interspecies embryos were reconstructed using the cryopreserved-thawed fibroblasts of the red panda as the donor and rabbit oocytes as recipients. A total of 194 enucleated rabbit oocytes were reconstructed with red panda ear fibroblasts; enucleated oocytes were activated without fusion as the control. The results show that the fibroblast cell line was established successfully by tissue culture and then cryopreserved in liquid nitrogen. Supplementation with 20% fetal bovine serum and 8% dimethyl sulphoxide in basic medium facilitated the cryopreservation. The interspecies embryos were successfully reconstructed. The cleavage, morulae and blastocyst rates after in vitro culture were 71, 47 and 23% (31/194), respectively. This study indicated that a somatic cell line could be established and cryopreserved from red panda and that rabbit cytoplast supports mitotic cleavage of the red panda karyoplasts and is capable of reprogramming the nucleus to achieve blastocysts.
Zheng, Wenli; Jiang, Zhaoling; Zhang, Lifang; Zhang, Chong; Zhang, Xiao; Fei, Chenzhong; Zhang, Keyu; Wang, Xiaoyang; Wang, Mi; Li, Tao; Xiao, Sui; Wang, Chunmei; Xue, Feiqun
A reliable method for the simultaneous determination of toltrazuril and its main metabolites (toltrazuril sulphone and toltrazuril sulphoxide) in chicken and pig skin+fat was developed and validated. Analytes were extracted from skin+fat with acetonitrile. The crude extracts were subjected to liquid-liquid extraction with n-hexane, and then further cleaned using primary secondary amine and Oasis™ MAX solid phase extraction cartridges. Chromatographic separation by UPLC-UV was performed on a C18+ reversed-phase column with gradient elution. Relative recovery from the spiked samples ranged from 84.8% to 109.1%. Limits of detection and quantification for the analytes were within 25-37.5μgkg(-1) and 50-75μgkg(-1), respectively. The developed method has been successfully applied to the depletion study of toltrazuril drug residues in chicken skin+fat. The recommended withdrawal period with oral administration based on our research is 24.18 days.
Saranya, P; Sukanya Kumari, H; Prasad Rao, B; Sekaran, G
The thermo-tolerant and extreme acidophilic microorganism Bacillus pumilus was isolated from the soil collected from a commercial edible-oil extraction industry. Optimisation of conditions for the lipase production was conducted using response surface methodology. The optimum conditions for obtaining the maximum activity (1,100 U/mL) of extremely acidic thermostable lipase were fermentation time, 96 h; pH, 1; temperature, 50 °C; and concentration of palm oil, 50 g/L. After purification, a 7.1-fold purity of lipase with specific activity of 5,173 U/mg protein was obtained. The molecular weight of the thermo-tolerant acidophilic lipase (TAL) was 55 kDa. The predominant amino acid in the TAL was glycine. The functional groups of lipase were determined by Fourier transform infrared spectroscopy. TAL exhibited enhanced activity (114 %) with dimethyl sulphoxide (20 %, v/v), and it showed a moderate activity with methanol, hexane and benzene. The optimum conditions for the treatment of palm oil in wastewater using the TAL were found to be time, 3 h; pH, 1; temperature, 50 °C with pseudo second-order kinetic constant of 1.88 × 10(-3) L mol(-1) min(-1). The Michaelis-Menten enzyme kinetic model and the nonlinear kinetic model were evaluated for the TAL. TAL established hydrolysis efficiency of 96 % for palm oil in wastewater at 50 °C.
Doronina, Victoria A.; Staniforth, Gemma L.; Speldewinde, Shaun H.; Tuite, Mick F.
Summary Prions are self‐perpetuating amyloid protein aggregates which underlie various neurodegenerative diseases in mammals and heritable traits in yeast. The molecular basis of how yeast and mammalian prions form spontaneously into infectious amyloid‐like structures is poorly understood. We have explored the hypothesis that oxidative stress is a general trigger for prion formation using the yeast [PSI +] prion, which is the altered conformation of the Sup35 translation termination factor. We show that the frequency of [PSI +] prion formation is elevated under conditions of oxidative stress and in mutants lacking key antioxidants. We detect increased oxidation of Sup35 methionine residues in antioxidant mutants and show that overexpression of methionine sulphoxide reductase abrogates both the oxidation of Sup35 and its conversion to the [PSI +] prion. [PSI +] prion formation is particularly elevated in a mutant lacking the Sod1 Cu,Zn‐superoxide dismutase. We have used fluorescence microscopy to show that the de novo appearance of [PSI +] is both rapid and increased in frequency in this mutant. Finally, electron microscopy analysis of native Sup35 reveals that similar fibrillar structures are formed in both the wild‐type and antioxidant mutants. Together, our data indicate that oxidative stress is a general trigger of [PSI +] formation, which can be alleviated by antioxidant defenses. PMID:25601439
Gugler, R; Müller-Liebenau, B; Somogyi, A
1 The pharmacokinetics and bioavailability of cimetidine were studied after 200 mg oral and intravenous doses in 14 patients with liver cirrhosis, and results were compared to a control group of 12 ulcer patients. 2 In cirrhotic patients, the volume of the central compartment (0.41 +/- 0.06 v 0.19 +/- 0.09 1/kg) and the volume of distribution at steady-state (1.02 +/- 0.17 v 0.80 +/- 0.24 1/kg) were significantly increased. No differences were observed in the area volume of distribution, the total systemic plasma clearance and renal clearance. The non-renal clearance was significantly decreased from 191 +/- 46 to 123 +/- 102 ml/min. 3 The bioavailability of cimetidine (area method) was significantly increased from 60 +/- 23% to 77 /+- 18% in the cirrhotic patients. Also increased was the time during which plasma levels exceeded 0.5 microgram/ml. 4 Urinary excretion of cimetidine was increased in liver cirrhosis by 32% after intravenous and by 36% after oral administration, while the amount of the sulphoxide metabolite decreased accordingly. Creatinine clearance in the cirrhotic patients was highly correlated with the renal clearance of cimetidine as well as its total plasma clearance. PMID:7126415
Gilmore, J A; Liu, J; Woods, E J; Peter, A T; Critser, J K
Previous reports have left unresolved discrepancies between human sperm cryopreservation methods developed using theoretical optimization approaches and those developed empirically. This study was designed to investigate possible reasons for the discrepancies. Human spermatozoa were exposed to 1 mol/l glycerol, 1 mol/l dimethyl sulphoxide (DMSO), 1 mol/l propylene glycol (PG) or 2 mol/l ethylene glycol (EG) at 22, 11 and 0 degrees C, then returned to isosmotic media while changes in cell volume were monitored. Activation energies (E(a)) of the hydraulic conductivity (L(p)) in the presence of cryoprotective agents (CPA) (L(p)(CPA)) were 22.2 (DMSO), 11.9 (glycerol), 15.8 (PG), and 7.8 (EG) kcal/mol. The E(a) values of the membrane permeability to CPA (P(CPA)) were 12.1 (DMSO), 10.4 (glycerol), 8.6 (PG) and 8.0 (EG) kcal/mol. These data indicated that even at low temperatures, EG permeates fastest. The high L(p)(CPA) in the presence of EG and low associated E(a) would allow spermatozoa to remain closer to equilibrium with the extracellular solution during slow cooling in the presence of ice. Collectively, these data suggest that the increase of the E(a) of L(p) in the presence of CPA at low temperature is the likely reason for the observed discrepancy between theoretical predictions of spermatozoa freezing response and empirical data.
Challam, M; Roy, B; Tandon, V
The alcoholic extract of Lysimachia ramosa Wall (Primulaceae) was tested in vitro against helminth parasites, Fasciolopsis buski and Ascaris suum, from porcine hosts and Raillietina echinobothrida from domestic fowl. The live adult parasites, collected from a freshly autopsied host, were exposed to different concentrations (5-50mg) of the test plant extract in physiological phosphate-buffered saline (PBS) having 0.1% dimethyl sulphoxide (DMSO) at 37+/-1 degrees C. The treated parasites revealed complete inactivation and flaccid paralysis that was followed by death at varying periods of time. A dose-dependent loss of motility and mortality was observed in all the treated parasites. Scanning electron microscopic observations revealed conspicuous deformity of the surface architecture in all the parasites exposed to the test plant extract. The general tegument in F. buski showed shrinkage and loss of scale-like spines; proglottides all along the strobilar length in R. echinobothrida appeared shrunken and deformed and the cuticular surface of A. suum appeared disorganised, having lost transverse striations. The botanicals of the test plant seem to be effective against all the three types of helminth parasites.
Wang, Tingting; Chen, Yihui; Ma, Junfeng; Zhang, Xiaodan; Zhang, Lihua; Zhang, Yukui
In the current study, a novel ionic liquid-based zwitterionic organic polymer monolithic column was developed by copolymerizing 1-vinyl-3-(butyl-4-sulfonate) imidazolium, acrylamide and N,N'-methylenebisacrylamide in a quaternary porogenic solvent consisting of formamide, dimethyl sulphoxide, polyethylene glycol 8000 and polyethylene glycol 10,000 for capillary hydrophilic interaction chromatography. The monolithic stationary phase was optimized by adjusting the amount of monomer in the polymerization solution along with the composition of porogenic solvent. The optimized monolith exhibited excellent selectivity and favorable retention for nucleosides and benzoic acid derivatives. The primary factors affecting the separation efficiency of the monolithic column (including acetonitrile content, pH, and buffer salt concentration in the mobile phase) have been thoroughly evaluated. Excellent reproducibility of the retention times for five nucleosides was achieved, with relative standard deviations of run-to-run (n = 3), column-to-column (n = 3) and batch-to-batch (n = 3) in the range of 0.18-0.48%, 2.33-4.20% and 3.07-6.50%, respectively.
Slater, M R; Hood, D M; Carter, G K
A descriptive and matched case-control study of laminitis was conducted in 7 private practices and at the Texas Veterinary Medical Centre (TVMC) between May 1992 and July 1993. Out of 108 horses with laminitis, 19 acute (49%) and 20 chronic (51%) cases were seen in private practice and 16 acute (23%) and 53 (77%) cases at the TVMC. Gastrointestinal disease was the most common problem in 19/35 horses (54%), occurring just prior to the onset of acute laminitis in all hospitals. Among all horses in the study, most commonly used drugs were phenylbutazone (68%), acepromazine (34%), dimethyl sulphoxide (DMSO) (27%), antibiotics of various types (19%) and flunixin meglumine (19%). Acepromazine, DMSO and flunixin meglumine were used more commonly in acute cases of laminitis compared to chronic cases. In acutely affected horses, DMSO and flunixin meglumine were used significantly more often at the TVMC. In chronic cases, phenylbutazone and antibiotics were used more often in private practice. Shoeing and trimming were more commonly part of the treatment protocol for chronic cases. There were no significant associations between age, breed, sex or weight and the occurrence of acute laminitis. Horses with chronic laminitis were significantly older (P=0.04) and more females tended to be affected (P=0.08).
Warloe, Trond; Peng, Qian; Heyerdahl, Helen; Moan, Johan; Steen, Harald B.; Giercksky, Karl-Erik
Seven hundred sixty three basal cell carcinomas (BCCs) in 122 patients were treated by photodynamic therapy by 5-aminolevulinic acid (ALA) in cream topically applied, either alone, in combination with dimethyl sulphoxide (DMSO) and ethylenediaminetetraacetic acid disodium salt (EDTA), or with DMSO as a pretreatment. After 3 hours cream exposure 40 - 200 Joules/cm2 of 630 nm laser light was given. Fluorescence imaging of biopsies showed highly improved ALA penetration depth and doubled ALA-induced porphyrin production using DMSO/EDTA. Treatment response was recorded after 3 months. After a single treatment 90% of 393 superficial lesions responded completely, independent of using DMSO/EDTA. In 363 nodulo-ulcerative lesions the complete response rate increased from 67% to above 90% with DMSO/EDTA for lesions less than 2 mm thickness and from 34% to about 50% for lesions thicker than 2 mm. Recurrence rate observed during a follow-up period longer than 12 months was 2 - 5%. PDT of superficial thin BCCs with ALA-induced porphyrins and DMSO/EDTA equals surgery and radiotherapy with respect to cure rate and recurrence. Cosmetic results of ALA-based PDT seemed to be better than those after other therapies. In patients with the nevoid BCC syndrome the complete response rate after PDT was far lower.
ThermoTRPs, a subset of the Transient Receptor Potential (TRP) family of cation channels, have been implicated in sensing temperature. TRPM8 and TRPA1 are both activated by cooling. TRPM8 is activated by innocuous cooling (<30 °C) and contributes to sensing unpleasant cold stimuli or mediating the effects of cold analgesia and is a receptor for menthol and icilin (mint-derived and synthetic cooling compounds, respectively). TRPA1 (Ankyrin family) is activated by noxious cold (<17 °C), icilin, and a variety of pungent compounds. Extensive amount of medicinal chemistry efforts have been published mainly in the form of patent literature on various classes of cooling compounds by various pharmaceutical companies; however, no prior comprehensive review has been published. When expressed in heterologous expression systems, such as Xenopus oocytes or mammalian cell lines, TRPM8 mediated currents are activated by a number of cooling compounds in addition to menthol and icilin. These include synthetic p-menthane carboxamides along with other class of compounds such as aliphatic/alicyclic alcohols/esters/amides, sulphones/sulphoxides/sulphonamides, heterocyclics, keto-enamines/lactams, and phosphine oxides. In the present review, the medicinal chemistry of various cooling compounds as activators of thermoTRPM8 channel will be discussed according to their chemical classes. The potential of these compounds to emerge as therapeutic agents is also discussed. PMID:22860192
Juárez-Hernández, J.; Zavala-Soto, M. E.; Bibbins-Martínez, M.; Delgado-Macuil, R.; Díaz-Godinez, G.; Rojas-López, M.
We have used FTIR with attenuated total reflectance (ATR) technique to analyze the decolourization process of Remazol Blue dye (RB19) caused by the oxidative activity of laccase enzyme. It is known that laccases catalyze the oxidation of a large range of phenolic compounds and aromatic amines carrying out one-electron oxidations, although also radicals could be formed which undergo subsequent nonenzymatic reactions. The enzyme laccase is a copper-containing polyphenol oxidase (EC 18.104.22.168) which has been tested as a potential alternative in detoxification of environmental pollutants such as dyes present in wastewaters generated for the textile industry. In order to ensure degradation or avoid formation of toxic compounds it is important to establish the mechanism by which laccase oxidizes dyes. In this research individual ATR-FTIR spectra have been recorded for several reaction times between 0 to 236 hours, and the temporal dependence of the reaction was analyzed through the relative diminution of the intensity of the infrared band at 1127 cm-1 (associated to C-N vibration), with respect to the intensity of the band at 1104 cm-1 (associated to S = O) from sulphoxide group. Decolourization process of this dye by laccase could be attributed to its accessibility on the secondary amino group, which is a potential point of attack of laccases, abstracting the hydrogen atom. This decolourization process of remazol blue dye by laccase enzyme might in a future replace the traditionally high chemical, energy and water consuming textile operations.
Zain, Mariani Mohd; Yahaya, Zary Shariman; Him, Nik Ahmad Irwan Izzauddin Nik
To date, the ivermectin resistance in nematode parasites has been reported and many studies are carried out to determine the causes of this problem. A free-living Caenorhabditis elegans is used as a model system for this study to investigate the response of C. elegans to ivermectin exposure by using larval development assay. Worms were exposed to ivermectin at concentration from 1 ng/mL to 10 ng/mL and dimethyl sulphoxide (DMSO) as a control. The developments of the worms were monitored for 24, 48, 72, and 96 hours until the worms become adults. Results indicated that worms’ growth began to be affected by ivermectin at a concentration of 5 ng/mL, while at the concentration of 6, 7, 8, 9, and 10 ng/mL, the growth of worms were inhibited compared to control worms. Further study of the protein expression in C. elegans should be done to investigate the up-regulated and down-regulated proteins involve in ivermectin resistance. PMID:27965734
Sato, Hiromu; Hirai, Toshihiro
A soft dielectric polymer, plasticized poly(vinyl chloride) (PVC gel), has been known as a characteristic actuator with electrotactic creep deformation. The deformation can be applied for bending and contraction. The mechanism of the deformation has been attributed to the colossal dielectric constant of the gel induced by dc field. The dielectric constant at 1 Hz, jumps from less than10 to thousand times larger value. The huge dielectric constant suggests the gel can have electro-optic function. In this paper, we introduce the gel can bend light direction by applying a dc electric field. The PVC gel can bend light direction depending on the electric field. Detailed feature of the light bending will be introduced and discussed. Bending angle can be controlled by dielectric plasticizer and electric field. The components of the gel, PVC and plasticizer themselves, did not show any effect of electro-optical function like the PVC gel. The same feature can be observed in other polymer, like poly(vinyl alcohol)-dimethyl sulphoxide gel, too.
Franchini, M K; Carstensen, J T
The effect of sparging with an inert gas (argon) was evaluated during the investigation of the solution kinetics of an oxidation-prone amphiphilic drug containing a sulphide moiety. Samples stored with an air headspace in pH7 and 8 phosphate buffers at elevated temperatures and in the absence of light degraded to two main products, a sulphoxide and a cinnamic acid analogue. Initially, this appeared to be a sequential mechanism which could be blocked by removing oxygen. Instead, argon-sparge forced the direct degradation to the cinnamate, which was evidenced by the formation of a strong odour of sulphide. In addition, argon-sparged samples remained colourless, while those sparged with oxygen or stored with an air headspace turned yellow and had negligible odour. The half-lives for samples stored in pH 8 buffers at 93 degrees C at an initial drug concentration of 25 mg mL(-1) were 128 days (argon sparged), 86 days (air headspace), and 65 days (oxygen sparged). The results indicated that for the drug under study, sparging with an inert gas affected the mechanism as well as the rate of the reaction at elevated temperatures.
Beseli, Aydin; Goulart da Silva, Marilia; Daub, Margaret E
The photosynthetic bacterium Rhodobacter sphaeroides and plant pathogenic fungus Cercospora nicotianae have been used as models for understanding resistance to singlet oxygen ((1)O(2)), a highly toxic reactive oxygen species. In Rhodobacter and Cercospora, (1)O(2) is derived, respectively, from photosynthesis and from the (1)O(2)-generating toxin cercosporin which the fungus produces to parasitize plants. We identified common genes recovered in transcriptome studies of putative (1)O(2)-resistance genes in these two systems, suggesting common (1)O(2)-resistance mechanisms. To determine if the Cercospora homologs of R. sphaeroides (1)O(2)-resistance genes are involved in resistance to cercosporin, we expressed the genes in the cercosporin-sensitive fungus Neurospora crassa and assayed for increases in cercosporin resistance. Neurospora crassa transformants expressing genes encoding aldo/keto reductase, succinyl-CoA ligase, O-acetylhomoserine (thiol) lyase, peptide methionine sulphoxide reductase and glutathione S-transferase did not have elevated levels of cercosporin resistance. Several transformants expressing aldehyde dehydrogenase were significantly more resistant to cercosporin. Expression of the transgene and enzyme activity did not correlate with resistance, however. We conclude that although the genes tested in this study are important in (1)O(2) resistance in R. sphaeroides, their Cercospora homologs are not involved in resistance to (1)O(2) generated from cercosporin.
Rivers-Auty, Jack; Ashton, John C
The delivery of some classes of drugs is challenging. Solubility, absorption, distribution, and duration of action may all be altered by combination with vehicle molecules. It has already been discovered that polyethylene glycol - which is used as a stabiliser in peptide drug formulations - has biological activity in its own right, including potential neuroprotective properties. In this article we review the evidence for confounding activity for four distinct compounds that have been used as solvents and/or carrier molecules for the delivery of lipophilic drugs under investigation for potential neuroprotective properties. We discuss the evidence that cyclodextrins, ethanol, dimethyl sulphoxide, and a castor oil derivative - Cremophor™ EL - have all been found to have mild to moderate neuroprotective effects. We argue that this has probably reduced the statistical power and increased the Type II error rates of neuroprotection experiments that have employed these vehicles, and suggest experimental design considerations to help correct the problem. However, we also note that the properties of these compounds may represent an opportunity for drug development, particularly for the newer compounds that have been subject to only limited experimental investigation.
Gayatri, Gaddamanugu; Sastry, G Narahari
Density functional theory calculations are performed to examine the regio and stereoselective preferences in [4+2] cycloaddition reactions of vinyl cyclopentadiene (1 and 2) and vinyl heterocyclic (1-N, 1-O, 1-S, 2-N, 2-O and 2-S) systems with maleic anhydride. Stepwise and concerted pathways of model systems 1 and 2 as dienes with ethylene as dienophile reveal that the reactions proceed through asynchronous and concerted pathway. 3-Vinyl systems (2) are predicted to be more reactive compared to 2-vinyl systems (1). The regio and stereoselective preferences are evaluated based on activation energies, reaction energies, density functional based descriptors and atoms in molecules analysis. In all cases, extra-annular cycloadducts are more feasible compared to intra-annular cycloadducts. Stereoselectivity depends on the favorable secondary orbital interactions. Solvents such as water, tetrahydrofuran, acetone, and dimethyl sulphoxide are employed to understand the effects of solvents on the cycloadduct formation. The computational results thus obtained are compared with the earlier experimental observations that are available.
Enantiomers of chiral compounds may express various biological activities and also different toxicities. Examples of different pharmacological effects of some chiral drugs such as fluoxetine, penicillamine, ibuprofen and albuterol are provided in this paper. Due to possible differences in activity, the chiral drugs are required to be pure enantiomeric compounds in order to be more effective and safer to use. In the laboratory, enantiomers are mainly synthesized as racemates (an equimolar mixture of enantiomers) while in biological pathways only one enantiomeric form is produced, such as amino acids, sugars and lipids. This paper presents the principles of chirality, general information about enantiomers and their biological aspects. It gives an outline of stereoselective methods for chromatographic resolution of enantiomers with stereoselective protein stationary phases, i.e. capillary electrochromatography (CEC) and high performance liquid chromatography (HPLC). The use of enzyme biotransformations (hydrolysis, oxidation and reduction) in chiral syntheses of carboxyl-, phosphoryl- or beta-hydroxy esters, alcohols, epoxides and cis-carboxyl sulphoxide is described. This article also includes an example of lipase stereoselectivity improvement by amino acid mutations within the enzyme active site.
Hafez, Mohamed M.; Al-Shabanah, Othman A.; Al-Harbi, Naif O.; Al-Harbi, Mohamed M.; Al-Rejaie, Salim S.; Alsurayea, Saad M.; Sayed-Ahmed, Mohamed M.
Objectives. The purpose of the study is to evaluate the hepatoprotective effect of rutin in carbon tetrachloride- (CCl4-) induced liver injuries in rat model. Methods. Forty male Wistar albino rats were divided into four groups. Group I was the control group and received dimethyl sulphoxide (DMSO) and olive oil. Group II received rutin. Groups III was treated with CCl4. Group IV was administered rutin after 48 h of CCl4 treatment. Liver enzymes level, lipid profile, lipid peroxidation, and hydrogen peroxide were measured. The genes expression levels were monitored by real time RT-PCR and western blot techniques. Results. CCl4 group showed significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBAR), hydrogen peroxide (H2O2), and lipid profile and a significant decrease in glutathione peroxidase (GPx), glutathione S transferase (GST), catalase (CAT), paraoxonase-1 (PON-1), paraoxonase-3 (PON-3), peroxisome proliferator activated receptor delta (PPAR-δ), and ATP-binding cassette transporter 1 (ABAC1) genes expression levels. Interestingly, rutin supplementation completely reversed the biochemical and gene expression levels induced by CCl4 to control values. Conclusion. CCl4 administration causes aberration of genes expression levels in oxidative stress pathway resulting in DNA damage and hepatotoxicity. Rutin causes hepatoprotective effect through enhancing the antioxidant genes. PMID:25478064
Cairnie, A.B.; Leach, K.E.
Rats, trained to drink water during a single 30-min period each day, were then given 0.1% saccharin twice a week and water on other days for 30 min. If 20 rad of radiation (0.2 Gy) were given each time 30 to 40 min after the saccharin the rats developed a profound aversion to saccharin during the course of three weeks, whereas control groups failed to do so. This paradigm was then used to test the ability of drugs, given twice weekly immediately after the saccharin, to prevent the development during three weeks of an aversion when 20 rad was given, 30 to 40 min later. Insulin, domperidone, haloperidol, acetylsalicylic acid, naloxone, chlorpheniramine, cimetidine, and dimethyl sulphoxide were tested without notable success. However dexamethasone, at doses ranging from 0.013 mg/kg to 1.3 mg/kg, significantly attenuated the conditioned taste aversion by up to 60 percent. The results are discussed in terms of a search for an antinauseant and antiemetic drug effective against radiation in man.
Seo, Sungbaek; Kaufman, Yair; Israelachvili, Jacob N.; Waite, J. Herbert
Polyelectrolyte complexation is critical to the formation and properties of many biological and polymeric materials, and is typically initiated by aqueous mixing1 followed by fluid–fluid phase separation, such as coacervation2–5. Yet little to nothing is known about how coacervates evolve into intricate solid microarchitectures. Inspired by the chemical features of the cement proteins of the sandcastle worm, here we report a versatile and strong wet-contact microporous adhesive resulting from polyelectrolyte complexation triggered by solvent exchange. After premixing a catechol-functionalized weak polyanion with a polycation in dimethyl sulphoxide (DMSO), the solution was applied underwater to various substrates whereupon electrostatic complexation, phase inversion, and rapid setting were simultaneously actuated by water–DMSO solvent exchange. Spatial and temporal coordination of complexation, inversion and setting fostered rapid (~25 s) and robust underwater contact adhesion (Wad ≥ 2 J m−2) of complexed catecholic polyelectrolytes to all tested surfaces including plastics, glasses, metals and biological materials. PMID:26779881
Liu, Kai; Sun, Yinghui; Lin, Xiaoyang; Zhou, Ruifeng; Wang, Jiaping; Fan, Shoushan; Jiang, Kaili
High-strength and conductive carbon nanotube (CNT) yarns are very attractive in many potential applications. However, there is a difficulty when simultaneously enhancing the strength and conductivity of CNT yarns. Adding some polymers into CNT yarns to enhance their strength will decrease their conductivity, while treating them in acid or coating them with metal nanoparticles to enhance their conductivity will reduce their strength. To overcome this difficulty, here we report a method to make high-strength and highly conductive CNT-based composite yarns by using a continuous superaligned CNT (SACNT) yarn as a conductive framework and then inserting polyvinyl alcohol (PVA) into the intertube spaces of the framework through PVA/dimethyl sulphoxide solution to enhance the strength of yarns. The as-produced CNT/PVA composite yarns possess very high tensile strengths up to 2.0 GPa and Young's moduli more than 120 GPa, much higher than those of the CNT/PVA yarns reported. The electric conductivity of as-produced composite yarns is as high as 9.2 × 10(4) S/m, comparable to HNO(3)-treated or Au nanoparticle-coated CNT yarns. These composite yarns are flexible, lightweight, scratch-resistant, very stable in the lab environment, and resistant to extremely humid ambient and as a result can be woven into high-strength and heatable fabrics, showing potential applications in flexible heaters, bullet-proof vests, radiation protection suits, and spacesuits.
Sagoo, J K; Bose, C; Beeley, N R; Tendler, S J
High-field n.m.r. studies were undertaken upon a peptide fragment of the C-terminal region of human beta-calcitonin-gene-related peptide (beta-hCGRP). Studies on the antigenic [Bu(t)-Cys18]beta-hCGRP-(19-37)-fragment revealed that several elements of secondary structure were present when the peptide was dissolved in [2H6]dimethyl sulphoxide. In particular an unspecified turn in the region of Ser19-Gly20 and a type I beta-turn in the region of Asn31-Val32-Gly33 were identified. Through-space connections between the terminal Phe37 amide group and the beta-protons of Thr50 suggest that the peptide may be folded into a loop-type conformation. These structural elements appear to overlap with the epitopes of a number of monoclonal antibodies and provide a molecular basis for understanding the role of the terminal Phe37 amide residue in the immune recognition of beta-hCGRP. Images Fig. 3. PMID:1741742
Koo, Ok Jae; Hossein, Mohammad Shamim; Hong, So Gun; Martinez-Conejero, Jose A; Lee, Byeong Chun
Cycle synchronization of donor cells in the G0/G1 stage is a crucial step for successful somatic cell nuclear transfer. In the present report, we evaluated the effects of contact inhibition, serum starvation and the reagents - dimethyl sulphoxide (DMSO), roscovitine and cycloheximide (CHX) - on synchronization of canine fibroblasts at the G0/G1 stage. Ear fibroblast cells were collected from a beagle dog, placed into culture and used for analysis at passages three to eight. The population doubling time was 36.5 h. The proportion of G0/G1 cells was significantly increased by contact inhibition (77.1%) as compared with cycling cells (70.1%); however, extending the duration of culture did not induce further synchronization. After 24 h of serum starvation, cells were effectively synchronized at G0/G1 (77.1%). Although synchronization was further increased gradually after 24 h and even showed significant difference after 72 h (82.8%) of starvation, the proportion of dead cells also significantly increased after 24 h. The percentage of cells at the G0/G1 phase was increased (as compared with controls) after 72 h treatment with DMSO (76.1%) and after 48 h treatment with CHX (73.0%) or roscovitine (72.5%). However, the rate of cell death was increased after 24 and 72 h of treatment with DMSO and CHX, respectively. Thus, we recommend the use of roscovitine for cell cycle synchronization of canine ear fibroblasts as a preparatory step for SCNT.
Özkara, Arzu; Akyıl, Dilek; Eren, Yasin; Erdoğmuş, S Feyza; Konuk, Muhsin; Sağlam, Esra
The present study evaluates the cytotoxic and genotoxic potential of pyracarbolid using both micronuleus (MN) assay, in human lymphocytes, and Allium cepa assay, in the root meristem cells. In Allium test, EC50 value was determined in order to selecting the test concentrations for the assay and the root tips were treated with 25 ppm (EC50/2), 50 ppm (EC50) and 100 ppm (EC50 × 2) concentrations of pyracarbolid. One percent of dimethyl sulphoxide (DMSO) and methyl methane sulfonate (MMS) were used as negative and positive controls, respectively. In the micronucleus assay, the cultures were treated with four concentrations (250, 500, 750 and 1000 µg/ml) of pyracarbolid for 24 and 48 h, negative and positive controls were also used in the experiment parallely. The results showed that mitotic index (MI) significantly reduced with increasing the pyracarbolid concentration at each exposure time. It was also obtained that prophase and metaphase index decreased significantly in all concentration at each exposure time. Anaphase index decreased as well and results were found to be statistically significant, except 24 h. A significant increase was observed in MN frequency in all concentrations and both treatment periods when compared with the controls. Pyracarbolid also caused a significant reduction in the cytokinesis block proliferation index (CBPI) in all concentration and both exposure time.
Ji, Xiuling; Chen, Guiyuan; Zhang, Qi; Lin, Lianbing; Wei, Yunlin
An extracellular cold-adapted alkaline lipase from the psychrotrophic Yersinia enterocolitica strain KM1 was purified 26-fold to homogeneity. The enzyme was active over a broad range spanning 0-60 °C with an optimum activity at 37 °C, and it was found to be alkaline-preferring with an optimum activity at pH 9.0. The molecular weight was estimated to be 34.3 KDa and monomeric. The lipase could be activated by Ca(2+) and low concentration (10%) of ethanol, dimethyl sulphoxide, methanol, and acetonitrile, whereas it was strongly inhibited by Zn(2+), Cu(2+), SDS, EDTA, and PMSF. Using p-nitrophenyl butyrate as a substrate at 37 °C, the Km and Vmax of the enzyme were found to be 16.58 mM and 5.24 × 10(5) μM · min(-1), respectively. This extracellular cold-adapted alkaline lipase may be a good candidate for detergents and biocatalysts at low temperature.
Verma, Sunita; Boucher, O.; Reddy, M. S.; Upadhyaya, H. C.; Le van, P.; Binkowski, F. S.; Sharma, O. P.
An "online" aerosol dynamics and chemistry module is included in the Laboratoire de Météorologie Dynamique general circulation model (LMDZ), so that the chemical species are advected at each dynamical time step and evolve through chemical and physical processes that have been parameterized consistently with the meteorology. These processes include anthropogenic and biogenic emissions, over 50 gas/aqueous phase chemical reactions, transport due to advection, vertical diffusion and convection, dry deposition and wet scavenging. We have introduced a size-resolved representation of aerosols which undergo various processes such as coagulation, nucleation and dry and wet scavenging. The model considers 16 prognostic tracers: water vapor, liquid water, dimethyl sulfide (DMS), hydrogen sulfide (H2S), dimethyl sulphoxide (DMSO), methanesulphonic acid (MSA), sulfur dioxide (SO2), nitrogen oxides (NOX), carbon monoxide (CO), nitric acid (HNO3), ozone (O3), hydrogen peroxide (H2O2), sulfate mass and number for Aitken and accumulation modes. The scheme accounts for two-way interactions between tropospheric chemistry and aerosols. The oxidants and chemical species fields that represent the sulfate aerosol formation are evolved interactively with the model dynamics. A detailed description on the coupled climate-chemistry interactive module is presented with the evaluation of chemical species in winter and summer seasons. Aqueous phase reactions in cloud accounted for 71% of sulfate production rate, while only 45% of the sulfate burden in the troposphere is derived from in-cloud oxidation.
Patikarnmonthon, Nisa; Nawapan, Sirikan; Buranajitpakorn, Sarinya; Charoenlap, Nisanart; Mongkolsuk, Skorn; Vattanaviboon, Paiboon
Copper (Cu)-based biocides are important chemical controls for both fungal and bacterial diseases in crop fields. Here, we showed that Cu ions at a concentration of 100 μM enhanced t-butyl hydroperoxide (tBOOH) and hydrogen peroxide (H(2) O(2) ) killing of Xanthomonas campestris pv. campestris through different mechanisms. The addition of an antilipid peroxidation agent (α-tocopherol) and hydroxyl radical scavengers (glycerol and dimethyl sulphoxide) partially protected the bacteria from the Cu-enhanced tBOOH and H(2) O(2) killing, respectively. Inactivation of the alkyl hydroperoxide reductase gene rendered the mutant vulnerable to lethal doses of copper sulphate, which could be alleviated by the addition of an H(2) O(2) scavenger (pyruvate) and α-tocopherol. Taken together, the data suggest that Cu ions influence the killing effect of tBOOH through the stimulation of lipid peroxidation, while hydroxyl radical production is the underlying mechanism responsible for the Cu-ion-enhanced H(2) O(2) killing effects.
Moreira, L.; Leitäo, R. E.; Martins, F.
Molar conductivity values (Λm) of 2,6-lutidinium chloride at ten different concentrations ranging from 0.001 to 0.01 mol dm-3, in several solvents and temperatures are reported for: seven solvents (dimethyl sulphoxide, acetonitrile, propylene carbonate, N,N-dimethylacetamide, ethanol, 1-propanol and 1-butanol) at five different temperatures (60.00, 65.00, 70.00, 75.00 and 80.00°C) and three additional solvents (nitromethane, 2-methyl-1-propanol and 2-ethoxyethanol) at 60.00°C. Molar conductivities at infinite dilution ( ), association constants (KA) and respective errors are also determined. The temperature dependence of ILM0002 and KA shows positive, negative and negligible trends. ILM0003 versus viscosity plots reveal a breakdown of Walden's rule. KA is markedly dependent on the solvent's features, revealing strong deviations from the predictions of classical dielectric theories. It is reasoned that specific ion-solvent-solvent interactions may play an important role.
Amps, K J; Jones, M; Baker, D; Moore, H D
The development of efficient and robust methods for the cryopreservation of human embryonic stem cells (hESCs) is important for the production of master and working cell banks for future clinical applications. Such methods must meet requirements of good manufacturing practice (GMP) and maintain genetic stability of the cell line. We investigated the culture of four Shef hESC lines in gas permeable 'culture cassettes' which met GMP compliance. hESCs adhered rapidly to the membrane and colonies displayed good proliferation and expansion. After 5-7 days of culture, hESCs were cryopreserved in situ using 10% dimethyl sulphoxide in foetal calf serum at approximately 1 degrees C/min. This method was compared with a control of standard flask culture and cryopreservation in vials. Post-thaw cassette culture displayed relative proliferation ratios (fold increase above flask/cryovial culture) of 114 (Shef 4), 8.2 (Shef 5), 195 (shef 6) and 17.5 (Shef 7). The proportion of cells expressing pluripotency markers after cryopreservation was consistently greater in cassette culture than for the control with the markers SSEA3 and SSEA4 exhibiting a significant increase (P> or =0.05). The efficiency of cell line culture in cassette was associated with the overall passage number of the cell line. The procedure enables cryopreservation of relatively large quantities of hESCs in situ, whilst returning high yields of viable, undifferentiated stem cells, thereby increasing capacity to scale up with greater efficacy.
Fábián, Balázs; Idrissi, Abdenacer; Marekha, Bogdan; Jedlovszky, Pál
Molecular dynamics simulations of the liquid-vapour interface of dimethyl sulphoxide (DMSO)-water mixtures of 11 different compositions, including two neat systems are performed on the canonical (N, V, T) ensemble at 298 K. The molecules constituting the surface layer of these systems are selected by means of the identification of the truly interfacial molecules (ITIM) method, and their local lateral environment at the liquid surface is investigated by performing Voronoi analysis. The obtained results reveal that both molecules prefer to be in a mixed local environment, consisting of both kinds of molecules, at the liquid surface, and this preference is even stronger here than in the bulk liquid phase. Neat-like patches, in which a molecule is surrounded by like neighbours, are not found. However, vacancies that are surrounded solely by water molecules are observed at the liquid surface. Our results show that strongly hydrogen bonded DMSO·H2O complexes, known to exist in the bulk phase of these mixtures, are absent from the liquid surface.
He, Fei; Liu, Weirong; Zheng, Shengchao; Zhou, Li; Ye, Benlan; Qi, Zhi
It is well known that dimethyl sulphoxide (DMSO) increases membrane permeability, which makes it widely used as a vehicle to facilitate drug delivery across biological membranes. However, the mechanism of how DMSO increases membrane permeability has not been well understood. Recently, molecular dynamics simulations have demonstrated that DMSO can induce water pores in biological membranes, but no direct experimental evidence is so far available to prove the simulation result. Using FluxOR Tl⁺ influx assay and intracellular Ca²⁺ imaging technique, we studied the effect of DMSO on Tl⁺ and Ca²⁺ permeation across cell membranes. Upon application of DMSO on CHO-K1 cell line, Tl⁺ influx was transiently increased in a dose-dependent manner. The increase in Tl⁺ permeability induced by DMSO was not changed in the presence of blockers for K⁺ channel and Na⁺-K⁺ ATPase, suggesting that Tl⁺ permeates through transient water pores induced by DMSO to enter into the cell. In addition, Ca²⁺ permeability was significantly increased upon application of DMSO, indicating that the transient water pores induced by DMSO were non-selective pores. Furthermore, similar results could be obtained from RAW264.7 macrophage cell line. Therefore, this study provided experimental evidence to support the prediction that DMSO can induce transient water pores in cell membranes, which in turn facilitates the transport of active substances across membranes.
Avachat, Amelia M; Kapure, Sayali S
Biodegradable injectable in-situ forming implants (ISFI) correspond to an alternative parenteral depot system to microspheres and surgical implants. Objective of present work was to formulate and evaluate long acting implant of asenapine maleate (ASM) using PLGA which would release drug uniformly for 21 days. PLGA 50:50 with different drug: polymer ratios were tried. N-methyl-2-pyrrolidone and dimethyl sulphoxide were used as organic solvents. The influence of various parameters viz. polymer concentration, solvent ratio, viscosity and morphology on formation of implant was investigated. In-vitro dissolution studies indicated that drug: polymer ratio of 1:2 and N-methyl-2-pyrrolidone (0.3ml) gave desired release profile, total cumulative drug released being 97.66% at the end of 21 days. Mathematical models point towards erosion mechanism with zero order kinetics. Ex-vivo studies confirmed the formation of implant in extensor digitorum muscle with desired drug release profile. In-vivo study was performed in Sprague- Dawley rats. Compared to marketed sublingual formulation area under curve of ASM implant was found to increase 2.215 fold. The Cmax was found to be 11ng/ml. Thus long acting ISFI of ASM was successfully formulated showing improved therapeutic results for the treatment of schizophrenia and bipolar disorders which could be a potentialsubstitute to marketed sublingual tablets.
Jia, J B; Green, C S; Cohen, A J; Helmy, M
Onyx(®) (ev3, Irvine, CA, USA) is a liquid embolic agent composed of ethylene vinyl alcohol copolymer dissolved in dimethyl sulphoxide used for the treatment of intracranial arteriovenous malformations. Onyx is a preferred embolizing agent due to its unique properties, non-adhesive nature, and durability. In addition to its approved intracranial application, Onyx is also being used successfully in extracranial embolization in areas including extracranial aneurisms and vascular malformations, trauma, gastrointestinal bleeding, and neoplasms. Because of its increasing utilization, it is important for reporting radiologists to be able to recognize its extracranial appearance across different imaging techniques and to be familiar with its uses. The goal of this review is to describe the extracranial uses of Onyx and its appearance in various extracranial locations at radiography and CT, while providing didactic examples. Onyx appears radiodense at CT and plain radiography and has a curvilinear pattern following the expected path of the vessel embolized. At CT, Onyx creates streak artefact that may obstruct the view of surrounding tissues consistent with descriptions of other tantalum devices.
Sharma, U; Chaudhury, K; Jagannathan, N R; Guha, S K
Nuclear magnetic resonance (NMR) spectroscopy was used to quantify citrate, glucose, lactate, glycerophosphorylcholine and choline in seminal plasma from subjects injected with a new male contraceptive RISUG, a copolymer of styrene maleic anhydride dissolved in dimethyl sulphoxide, and in seminal plasma from normal ejaculates. No significant difference in the concentration of citrate was observed between the groups, indicating that the prostate is not affected by the contraceptive. The concentrations of glucose, lactate, glycerophosphorylcholine and choline were significantly lower (P < 0.01) in subjects injected with RISUG compared with controls. In addition, metabolite ratios such as choline:citrate, citrate:lactate, choline:lactate and glycerophosphorylcholine:choline were calculated. Citrate:lactate and glycerophosphorylcholine:choline ratios were significantly lower in RISUG-injected subjects than in controls (P < 0.01), thereby indicating the occurrence of partial obstructive azoospermia. The most important finding of the present study was that the intervention of RISUG in the vas deferens even for a period as long as 8 years is absolutely safe and does not lead to prostatic diseases.
Jha, Rakhi K; Jha, Pradeep K; Guha, Sujoy K
The rationale and technique underlying a novel concept of noninvasive fertility control by a new Cuproferrogel contraceptive drug, iron oxide–copper–styrene maleic anhydride–dimethyl sulphoxide (Fe3O4–Cu–SMA–DMSO) composite named ‘Smart RISUG’ (smart reversible inhibition of sperm under guidance) in presence of pulsed magnetic field (PMF; 1 mT to 800 mT) is explained. It was synthesized by dispersing iron oxide particles and copper particles into SMA-DMSO (male contraceptive RISUG) and characterized for particle distribution, particle size measurement and transmittance peaks, etc. Interaction of the RISUG particles as well as Smart RISUG particles with Albino rat sperm cell was studied in presence as well as absence of PMF. To find an explanation to increased reaching of the Smart RISUG drug into sperm under influence of magnetic field, the transport properties were characterized by high resolution transmission electron microscopy and atomic force microscopy. Smart RISUG could be mobilized into sperm cell membrane at the PMF, 760 mT in about 50 seconds. Adoption of novel drug Smart RISUG involving new technique may open the pathway for non surgical control of drug distribution, detection and restoration of the normal fertility after removal of the contraceptive from the male/female reproductive tube in presence of electromagnetic field. PMID:19421370
Tijet, N; Helvig, C; Pinot, F; Le Bouquin, R; Lesot, A; Durst, F; Salaün, J P; Benveniste, I
The chemical tagging of a cytochrome P-450-dependent lauric acid omega-hydroxylase from clofibrate-treated Vicia sativa seedlings with [1-14C]11-dodecynoic acid allowed the isolation of a full-length cDNA designated CYP94A1. We describe here the functional expression of this novel P-450 in two Saccharomyces cerevisiae strains overproducing their own NADPH-cytochrome P-450 reductase or a reductase from Arabidopsis thaliana. The results show a much higher efficiency of the yeast strain overproducing the plant reductase compared with the yeast strain overproducing its own reductase for expressing CYP94A1. The methyl end of saturated (from C-10 to C-16) and unsaturated (C18:1, C18:2 and C18:3) fatty acids was mainly oxidized by CYP94A1. Both E/Z and Z/E configurations of 9, 12-octadecadienoic acids were omega-hydroxylated. Lauric, myristic and linolenic acids were oxidized with the highest turnover rate (24 min-1). The strong regioselectivity of CYP94A1 was clearly shifted with sulphur-containing substrates, since both 9- and 11-thia laurate analogues were sulphoxidized. Similar to animal omega-hydroxylases, this plant enzyme was strongly induced by clofibrate treatment. Rapid CYP94A1 transcript accumulation was detected less than 20 min after exposure of seedlings to the hypolipidaemic drug. The involvement of CYP94A1 in the synthesis of cutin monomers and fatty acid detoxification is discussed.
Praslicka, J; Pilko, P; Várady, M; Corba, J
Two experiments were carried out with sheep naturally infected with gastrointestinal nematodes to evaluate efficacy of anthelmintics using in vivo faecal egg count reduction (FECR) test. In experiment 1 with 28 ewes, the following efficacy of anthelmintics given at recommended dose rates was observed: albendazole 99.4%, ivermectin 99.3% and levamisole 81.8%. In experiment 2 with 18 ewes, tetramisole exhibited 71.3% efficacy. Suspected resistance to imidothiazole anthelmintics was confirmed by in vitro larval development test (LDT)--minimal inhibition concentration (MIC) values were estimated at 2.0 micrograms/ml. Infective larvae L3 cultivated from eggs produced by the population of resistant helminths were identified as Ostertagia and Trichostrongylus spp.
Raccurt, C P; El Samad, Y; Chouaki, T; Borel, A; Agnamey, P; Totet, A; Schmit, J L
The purpose of this report is to describe a case of febrile hypereosinophilic syndrome in a traveler three weeks after returning from a sightseeing trip to Guinea. Laboratory testing demonstrated an inflammatory response syndrome and hepatic cytolysis. Parasite serology led to suspicion of toxocariasis that was treated using albendazole. Follow-up tests at two months showed the presence of Schistosoma mansoni eggs in stools despite negative standard serodiagnostic testing (hemagglutination). Secondarily Western blot testing of serum samples at one, two and 14 months after returning from Guinea continued to show only protein bands specific to toxocariasis with no bands specific to bilhariziasis. These findings provide further evidence of the limitations of serological testing for detection of bilharziasis in travelers and the difficulty of diagnosis. Guinea is a high-risk tourist destination. Intestinal and urinary bilharziasis are endemic over three-fourths of country. Travelers planning even short stays in areas where bilharziasis is endemic should be advised on preventive measures.
Diawara, Aïssatou; Schwenkenbecher, Jan M; Kaplan, Ray M; Prichard, Roger K
In endemic countries with soil-transmitted helminths mass drug administration with albendazole or mebendazole are being implemented as a control strategy. However, it is well known in veterinary helminths that the use of the same benzimidazole drugs can place selection on the β-tubulin gene, leading to resistance. Given the concern that resistance could arise in human soil-transmitted helminths, there is an urgent need to develop accurate diagnostic tools for monitoring resistance. In this study, we developed molecular assays to detect putative resistance genetic changes in Ascaris lumbricoides, Trichuris trichiura, and hookworms, and we optimized an egg hatch assay for the canine hookworm Ancylostoma caninum and applied it to Necator americanus. Both assays were tested on field samples. The molecular assays demonstrated their reproducibility and capacity to detect the presence of worms carrying putative resistance-associated genetic changes. However, further investigations are needed to validate our molecular and biological tests on additional field isolates.
Fraser, Margaret; Taleo, George; Taleo, Fasihah; Yaviong, James; Amos, Morris; Babu, Mark; Kalkoa, Morris
This report presents the results of the Vanuatu mid-term evaluation of the lymphatic filariasis elimination program being implemented countrywide. Vanuatu is one of the first countries to initiate this program as part of the Global Program for Elimination of Lymphatic Filariasis, based on a five-year annual mass drug administration (MDA) of albendazole and diethylcarbamazine and complemented in Vanuatu by extensive coverage with bed nets. This paper reports results of 561 persons tested at eight sentinel sites following two years of MDA. Coverage was 72% and bed net use was more than 70%. Antigen prevalence was reduced by 63% (from 22% to 8%) and prevalence of microfilaremia prevalence was reduced by 93% (from 12% to 0.8%). Results of surveys of health workers and the community are also reported, and the methodology used for this evaluation is discussed.
Baple, Katy; Clayton, James
Hookworm-related cutaneous larva migrans (HrCLM) is a skin disease caused by infection with the larvae of animal hookworms. With conditions for infection more favourable in tropical climates, HrCLM in the UK is classically diagnosed in the returning traveller. We present two cases of clinically diagnosed UK-acquired HrCLM from a district general hospital in the south of England. A 68-year-old woman presented with a pruritic serpiginous tract on the right hand. She was a keen gardener and had been handling compost. A 50-year-old man, a long distance runner, presented with a similar lesion on the dorsum of his foot. Both patients were treated with a single dose of albendazole. These cases may represent an emerging infection in the UK. In the absence of a suggestive travel history, early recognition followed by efficient access to therapy is vital for treating HrCLM transmitted in the UK.
Neurocysticercosis (NCC) is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis) can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug) may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues. PMID:28139530
Okello, Anna L; Thomas, Lian; Inthavong, Phouth; Ash, Amanda; Khamlome, Boualam; Keokamphet, Chattouphone; Newberry, Kim; Gauci, Charles G; Gabriël, Sarah; Dorny, Pierre; Thompson, Rc Andrew; Lightowlers, Marshall W; Allen, John
Following confirmation that a remote village of approximately 300 inhabitants in northern Lao PDR was hyperendemic for the Neglected Tropical Disease Taenia solium, a pilot human-porcine therapeutic control intervention was implemented between October 2013 and November 2014. Mass drug administration with a three day albendazole 400mg protocol was offered to all eligible humans in October 2013 and March 2014. At these times, and again in October 2014, eligible village pigs received the anti-cysticercosis TSOL18 vaccination and an oral dose of oxfendazole anthelmintic at 30mg/kg, both repeated one month later. Community and individual human taeniasis prevalences were estimated via copro-antigen ELISA of volunteered human faecal samples prior to October 2013, and again in January 2015, in order to examine the short term impact of the intervention.
Okello, Anna L; Thomas, Lian; Inthavong, Phouth; Ash, Amanda; Khamlome, Boualam; Keokamphet, Chattouphone; Newberry, Kim; Gauci, Charles G; Gabriël, Sarah; Dorny, Pierre; Thompson, Rc Andrew; Lightowlers, Marshall W; Allen, John
Following confirmation that a remote village of approximately 300 inhabitants in northern Lao PDR was hyperendemic for the Neglected Tropical Disease Taenia solium, a pilot human-porcine therapeutic control intervention was implemented between October 2013 and November 2014. Mass drug administration with a three day albendazole 400mg protocol was offered to all eligible humans in October 2013 and March 2014. At these times, and again in October 2014, eligible village pigs received the anti-cysticercosis TSOL18 vaccination and an oral dose of oxfendazole anthelmintic at 30mg/kg, both repeated one month later. Community and individual human taeniasis prevalences were estimated via copro-antigen ELISA of volunteered human faecal samples prior to October 2013, and again in January 2015, in order to examine the short term impact of the intervention.
Kukhaleva, I V; Kovalenko, F P; Shkolyar, N A; Legonkov, Yu A; Musaev, A Kh; Bulanova, T E; Samochatova, E I
The incidence of trichinosis in Russia was 0.07 per 100,000 population in 2014, which was 2.9-fold higher than that in 2013. Two WHO recommended medications mebendazole and albendazole are now used to treat humari trichinosis. The drugs are active against only mature helminths and non-encysted muscle larvae. The original oil suspension of micronized mebendazole was.found to have 100% efficacy against trichinosis in albino mice in the late muscular phase (encysted larvae) of hyperinvasion after intensive therapy under lifetime diagnostic guidance during and after a treatment cycle. The lifetime diagnostic method used to evaluate the larvicidal activity of anti-trichinosis agents in animals with experimental trichinosis revealed the signs of viaility, established a trend for deatih of Trichinella larvae, and determined their destructive changes.
Qu, Ting-Ting; Yang, Qing; Yu, Mei-Hong; Wang, Jie
Strongyloides stercoralis hyperinfection syndrome is a rare but fatal disease, which occurs commonly in immunocompromised patients. Strongyloidiasis among patients with chronic kidney disease is rarely reported.A 55-year-old Chinese male presented to hospital with diarrhea and abdominal pain. He developed acute respiratory failure and progressed to diffuse alveolar hemorrhage owing to disseminated strongyloidiasis immediately. The bronchoalveolar lavage revealed filariform larvae of Strongyloides stercoralis.This patient was diagnosed with Strongyloides hyperinfection syndrome. Although albendazole, mechanical ventilator support, fluid resuscitation, vasopressor support, extracorporeal membrane oxygenation, hydrocortisone, and broadspectrum antimicrobials were actively used, the patient eventually died.Similar cases in patients with chronic kidney disease in the literature are also reviewed. Through literature review, we recommend that strongyloidiasis should be routinely investigated in patients with chronic kidney disease who will undergo immunosuppressive therapy.
Mrabet, D; Rekik, S; Khiari, H; Mizouni, H; Meddeb, N; Cheour, I; Elleuch, M; Mnif, E; Mrabet, A; Sahli, H; Sellami, S
Hydatidosis, also known as echinococcosis, is a rare but serious parasitic disease in endemic areas. Primary spinal location is extremely rare. This case report describes a rare instance of hydatid cyst that caused severe and progressive low-back pain and neurologic dysfunction. Spine MRI showed a unique vertebral collapse of Th12 body with multicystic lesions filling the spinal canal. In addition, hydatidosis serodiagnostic test was positive at 1/725. Treatment depended on the actual surgical removal of the cysts. Surgery consisted in excision and extirpation of the cysts, associated with decompressive laminectomy. The diagnosis was confirmed on the basis of histological results. No coincidental hydatid visceral involvement was found. Antihelminthic drugs (Albendazole) were promptly given before surgery for a long period. The outcome was satisfactorily marked by total regression of the motor deficit and sphincter disorders. PMID:22699469
Hussain, Shabbir; Hussain, Kosar; Hussain, Sahar
Neurocysticercosis is recognised as a significant cause of neurological morbidity in endemic regions. The wide range of pleomorphic and non-specific neurological manifestations of neurocysticercosis must be kept in mind by physicians, as the disease has shown resurgence in developed countries. When an atypical presentation of an unusual tropical disease occurs in non-endemic regions, the diagnosis is often missed. We describe a case of a 4-year-old girl who presented with a history of transient bilateral loss of vision with headache and vomiting. Brain MRI revealed the presence of a single cysticercus granuloma in the occipital lobe. A diagnosis of symptomatic occipital lobe seizure secondary to neurocysticercosis was made. She was given a course of albendazole. There was no recurrence of symptoms at 3 years follow-up. Occipital seizures that are associated with ictal amaurosis closely mimic basilar migraine. Such cases benefit from neuroimaging in order to rule out the underlying structural causes.
Prasad, Rajniti; Thakur, Neha; Mohanty, C; Singh, M K; Mishra, O P; Singh, Utpal Kant
The authors report a 6-year-old boy, who had presented with low-grade fever, altered sensorium, headache and seizure for 5 days. On examination, he had features of raised intracranial pressure with left VI cranial-nerve palsy and bilateral extensor plantar response. CT scan showed multiple calcifications in cerebral cortex. MRI cranium showed multiple cysts involving whole of the brain. He was diagnosed as having cysticercal encephalitis, based on immunological and imaging study. He was managed with 20% mannitol, phenytoin and albendazole, and regained consciousness 7 days later, but had residual neurological deficit as left-lower-limb monoparesis and visual acuity of just projection of rays (PR+) and perception of light (PL+).
Gustavsen, K M; Bradley, M H; Wright, A L
More than 1000 million people in 82 countries are at risk of contracting the tropical disease lymphatic filariasis (LF). Although the disease is wide-spread, transmission of the causative parasites can be stopped through mass drug administrations based on a combination of anti-parasitic medicines. For more than 10 years, the pharmaceutical companies GlaxoSmithKline (GSK) and Merck & Co., Inc., have participated in a unique private-sector collaboration to support the global efforts to eliminate LF, through donations of drugs to prevent the disease. GSK's albendazole and Merck's ivermectin (Mectizan) now reach hundreds of millions of people each year, through national LF-elimination programmes carried out in collaboration with Ministries of Health, the World Health Organization, non-governmental organizations and local communities. Working in support of the Global Programme to Eliminate Lymphatic Filariasis, GSK and Merck not only provide donated medicines but also offer financial, programmatic and management expertise to support LF-elimination efforts worldwide.
Vásquez Tsuji, O; Rodríguez Herrera, R; Campos Rivera, T; Mora Tiscareño, M A; Aguirre Maldonado, E; Yamazaki Nakashimada, M A; Valencia Rojas, S; Martínez Barbosa, I
We present the case of a four-year-old boy with a history of repeated upper respiratory tract infections and pyoderma. He presented fever, seizures, inability to talk, loss of swallowing, fine tremor in the upper extremities; positive bilateral Babinski reflex and quadriparesis. The diagnosis of Bruton's disease and generalized microporidiosis was based on immunologic analysis, smear tests with chromotrope R2 stain and indirect immunofluorescense with monoclonal 3B6 antibody for Encephalitozoon species in samples of spinal fluid, bronchial and paranasal sinus aspirates and stool, which were all positive. The patient was treated with albendazol during 72 days; he left the hospital in a good condition, walking, talking and able to swallow. His laboratory test controls were negative; he is followed up in the outpatient department.
Miller, J E; Barras, S R
Fifteen weaned crossbred (Suffolk x Louisiana Native) lambs were treated with albendazole (10 mg kg-1) to remove existing nematode infections. They were inoculated with Haemonchus contortus infective larvae from a residual population surviving treatment with the oral formulation of ivermectin (0.2 mg kg-1). One group of five lambs remained untreated, another group of five was treated with the injectable formulation of ivermectin (0.2 mg kg-1), and a third group of five was treated with the oral formulation of ivermectin (0.2 mg kg-1). Subsequent to the treatments, there was essentially no difference in mean fecal egg count or mean number of H. contortus recovered at necropsy between the three groups.
Ramanathan, Roshan; Nutman, Thomas B.
Strongyloides stercoralis is an intestinal nematode acquired in the tropics or subtropics. Most often, it causes chronic, asymptomatic infection, but a change in immune status can increase parasite numbers, leading to hyperinfection syndrome, dissemination, and death if unrecognized. Corticosteroid use is most commonly associated with hyperinfection syndrome. Diagnosis of Strongyloides infection is based on serology and serial stool examinations for larvae. The treatment of choice for chronic, asymptomatic infection is oral ivermectin. Alternative pharmacologic agents include albendazole and thiabendazole. For hyperinfection syndrome, ivermectin remains the drug of choice, though therapy duration must be individualized with the end point being complete parasite eradication. Recurrent strongyloidiasis should prompt an evaluation for human T-cell lymphotropic virus type 1 coinfection. No test of cure is currently available, although immunoglobulin G antibody levels have been shown to decline within 6 months of successful treatment. PMID:18462583
Human neurocysticercosis is a severe disease caused by the installation of Taenia solium larvae in the CNS. A wide variety of clinical manifestations are related to neurocysticercosis. These are determined by a number of important factors, including the number and location of the cysts, the stage of cystercerci and the host response to the infection. Epilepsy, focal neurological signs and increased intracranial pressure are the most common clinical manifestations of the disease. Neurocysticercosis is still deeply rooted in Latin America, Africa and Asia. Albendazole and praziquantel are the drugs used in the treatment of cysticercosis. Both drugs have limited solubility and extensive metabolism, and thus great interindividual variability in plasma levels is found. This article focuses on current knowledge of the pharmacokinetics and the drug interactions of the anthelmintic drugs and the perspectives in the treatment of this parasitic disease.
Tanowitz, Herbert B.; Weiss, Louis M.; Wittner, Murray
Tapeworms are among the oldest afflictions of humans. They continue, even today, to be an important cause of morbidity and mortality, worldwide. Taenia saginata and Taenia solium infections are still common in many developing countries. Diphyllobothrium latum infections, are decreasing, but this tapeworm, transmitted to humans through the eating of raw salmon, can cause severe anemia. Hymenolepis and Dipylidium infections may occur to children. Hydatid disease is a common cause of morbidity, especially among immigrant groups from endemic areas of the Mediterranean; the liver is the most common site of a hydatid cyst. Although surgery has been the mainstay of therapy, drug therapy and percutaneous aspiration have been used more frequently in recent years. praziquantel and albendazole are the two most useful drugs against various tapeworm infections.
Kulik, Anna; Białecka, Wanda; Podolska, Marzena; Kwiatkowska-Puchniarz, Barbara; Mazurek, Aleksander
The subject of the study was to develop a versatile HPLC system for identification and determination of four benzimidazole derivatives in the antiparasitic drugs. The tests covered: Zentel, Panacur, Vermox tablets and Systamex suspension. A satisfactory separation was obtained using the Nucleosil C8 column in the gradient system composed of mobile phase A: 85% orthophosphoric acid / water / acetonitrile in 0.05:75:25, v/v/v ratio, and mobile phase B: 85% orthophosphoric acid / water / acetonitrile in 0.05:50:50, v/v/v ratio. Both phases were adjusted to pH = 4.5 with 15% sodium hydroxide solution. A detection at 288 nm for oxfendazole and 254 nm for albendazole, fenbendazole and mebendazole was applied. The correlation coefficients in the range 0,9997 - 0,9999 proved that the calibration curves were linear. The method was validated in terms of selectivity, accuracy and precision.
Chan, Renee C.F.; Cheong, Elaine Y.L.; Brammah, Susan; Clezy, Kate R.; Tong, Chiwai; Marriott, Deborah; Webb, Cameron E.; Chacko, Bobby; Tobias, Vivienne; Outhred, Alexander C.; Field, Andrew S.; Prowse, Michael V.; Bertouch, James V.; Stark, Damien; Reddel, Stephen W.
The insect microsporidian Anncaliia algerae was first described in 2004 as a cause of fatal myositis in an immunosuppressed person from Pennsylvania, USA. Two cases were subsequently reported, and we detail 2 additional cases, including the only nonfatal case. We reviewed all 5 case histories with respect to clinical characteristics, diagnosis, and management and summarized organism life cycle and epidemiology. Before infection, all case-patients were using immunosuppressive medications for rheumatoid arthritis or solid-organ transplantation. Four of the 5 case-patients were from Australia. All diagnoses were confirmed by skeletal muscle biopsy; however, peripheral nerves and other tissues may be infected. The surviving patient received albendazole and had a reduction of immunosuppressive medications and measures to prevent complications. Although insects are the natural hosts for A. algerae, human contact with water contaminated by spores may be a mode of transmission. A. algerae has emerged as a cause of myositis, particularly in coastal Australia. PMID:24447398
Fernando, Sumadhya Deepika; Rodrigo, Chaturaka; Rajapakse, Senaka
Many trials have explored the efficacy of individual drugs and drug combinations to treat bancroftian filariasis. This narrative review summarizes the current evidence for drug management of bancroftian filariasis. Diethylcarbamazine (DEC) remains the prime antifilarial agent with a well-established microfilaricidal and some macrofilaricidal effects. Ivermectin (IVM) is highly microfilaricidal but minimally macrofilaricidal. The role of albendazole (ALB) in treatment regimens is not well established though the drug has a microfilaricidal effect. The combination of DEC+ALB has a better long-term impact than IVM+ALB. Recent trials have shown that doxycycline therapy against Wolbachia, an endosymbiotic bacterium of the parasite, is capable of reducing microfilaria rates and adult worm activity. Followup studies on mass drug administration (MDA) are yet to show a complete interruption of transmission, though the infection rates are reduced to a very low level. PMID:21234244
Corti, N; Taegtmeyer, A B
Most medicines are taken with breakfast which is usually unproblematic and has the advantage of improving adherence through establishment of a daily routine. However, due to alterations in absorption from the gastrointestinal tract, there are a number of medicines that either lose (such as bisphosphonates) or gain (such as albendazole) efficacy if taken together with food. Food components can also affect drug-metabolising enzymes and even cause drug toxicity (alcohol and grapefruit juice are notable examples). Conversely, drugs such as monoamine oxidase inhibitors can inhibit the metabolism of tyramine in tyramine-rich foods and lead to adverse circulatory reactions. These and other examples of when the ingestion of medication together with food can cause clinically relevant problems are discussed in this article.
Çiçek, Ayşegül Çopur; Gündoğdu, Deniz; Direkel, Sahin; Öztürk, Çinar
Ascaris lumbricoides is a comman intestinal helminths in humans. It is a parasite which commonly affects society with a low socioeconomic status, especially in tropical and rural areas. Ascaris lumbricoides infestation can lead to serious complications because of the mobility of the worms. The parasite can cause a variety of complications like intestinal obstruction, perforation, biliary obstruction, pancreatitis, peritonitis, liver abscess, cholangiohepatitis, volvulus, and gangrene, etc. A 59-year-old female patient hospitalized with the diagnosis of mesenteric ischemia was operated on for jejunal resection. On the 6th postoperative day, a worm was noticed emerging through the nasogastric tube. Ascaris lumbricoides was determined as a result of the examination microbiology laboratory. The patient was treated successfully with one dose of albendazole 200 mg 1x2. Our case describes a clinical situation of ascariasis observed after jejunal resection and emphasizes the importance of remaining aware of this rare complication of ascariasis.
Prieto-Pérez, Laura; Pérez-Tanoira, Ramón; Cabello-Úbeda, Alfonso; Petkova-Saiz, Elizabet; Górgolas-Hernández-Mora, Miguel
Millions of people in in rural areas and deprived tropical and subtropical regions are infected by soil-transmitted helminths: Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus), and Strongyloides stercoralis. Large migratory flows have made their worldwide distribution easier. Besides being debilitating and producing a significant mortality, they cause high morbidity, leading to physical and intellectual impairment in millions of children who live in poverty. Along with the use of benzimidazoles (albendazole and mebendazole), large-scale international campaigns for treatment and prevention have decreased the number of affected individuals. However, re-infestations and benzimidazole-resistance are frequent, so there needs to be awareness about the importance and consequences of these neglected parasites.
Dolenc-Voljč, Mateja; Žgavec, Borut; Vizjak, Alenka; Tenyi, Viktor; Luzar, Boštjan
Figurate erythema can appear in a wide spectrum of dermatological diseases. Rarely, it can present as an atypical manifestation of bullous pemphigoid. Among eosinophilic dermatoses, figurate erythema may appear in Wells syndrome, which has been occasionally reported in association with Toxocara infection. We present the case of an older female patient diagnosed with bullous pemphigoid, who presented with an unusual combination of blisters and figurate erythema outside the area of blister formation. In addition, high blood eosinophilia associated with lymph node and bone marrow eosinophilia was diagnosed and was causally related to Toxocara canis infection. The patient was treated with dapsone for bullous pemphigoid and with albendazole for toxocariosis, with complete regression of all skin lesions and blood eosinophilia. This paper discusses the possible etiopathogenesis of figurate erythema in our patient and summarizes previous clinical and histological findings in bullous pemphigoid and eosinophilic dermatoses presenting with figurate erythema lesions.
Williams, Andrew R.; Soelberg, Jens; Jäger, Anna K.
Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA) with synthetic anthelmintic drugs such as albendazole, however continual re-infection and the threat of drug resistance mean that complementary treatment options would be highly valuable. Here, we screened ethanolic extracts from 29 medicinal plants used in Africa (Ghana) and the Caribbean (US Virgin Islands) for in vitro anthelmintic properties against Ascaris suum, a swine parasite that is very closely related to the human A. lumbricoides. A wide variety of activities were seen in the extracts, from negligible to potent. Extracts from Clausena anisata, Zanthoxylum zanthoxyloides and Punica granatum were identified as the most potent with EC50 values of 74, 97 and 164 μg/mL, respectively. Our results encourage further investigation of their use as complementary treatment options for ascariasis, alongside MDA. PMID:27301442
Darocha, Szymon; Wawrzyńska, Liliana; Oniszh, Karina; Dziewulska, Barbara
Cutaneous larva migrans is a parasitic dermatosis imported by travelers returning from tropical and subtropical regions. In cutaneous larva migrans syndrome humans are incidental hosts and the larvae are unable to complete their natural cycle. Adult hookworms live in the intestines of dogs and cats, shedding eggs in feces that hatch and mature into larvae that can remain infective for months in the soil. Larvae penetrate the skin after contact with infected soil and cause an itchy creeping eruption. Cutaneous larva migrans is not usually associated with systemic symptoms and is rarely accompanied by peripheral blood eosinophilia. We report a patient who had both cutaneous larva migrans syndrome caused by Ancylostoma brasiliense and eosinophilic pneumonia after returning from Sri Lanka. The patient has been applied intravenous corticosteroids and local treatment with albendazole ointment with a very good clinical response.
Hochberg, Natasha S; Hamer, Davidson H
Anisakidosis, human infection with nematodes of the family Anisakidae, is caused most commonly by Anisakis simplex and Pseudoterranova decipiens. Acquired by the consumption of raw or undercooked marine fish or squid, anisakidosis occurs where such dietary customs are practiced, including Japan, coastal regions of Europe, and the United States. Severe epigastric pain, resulting from larval invasion of the gastric mucosa, characterizes gastric anisakidosis; other syndromes are intestinal and ectopic. Allergic anisakidosis is a frequent cause of foodborne allergies in areas with heavy fish consumption or occupational exposure. Diagnosis and treatment of gastric disease is usually made by a compatible dietary history and visualization and removal of the larva(e) on endoscopy; serologic testing for anti-A. simplex immunoglobulin E can aid in the diagnosis of intestinal, ectopic and allergic disease. Intestinal and/or ectopic cases may require surgical removal; albendazole has been used occasionally. Preventive measures include adequately freezing or cooking fish.
Kobayashi, Ken-ichiro; Nakamura-Uchiyama, Fukumi; Nishiguchi, Takeshi; Isoda, Kenichi; Kokubo, Yasumasa; Ando, Katsuhiko; Katurahara, Masaki; Sako, Yasuhito; Yanagida, Tetsuya; Ito, Akira; Iwabuchi, Sentaro; Ohnishi, Kenji
We report disseminated cysticercosis concurrent with taeniasis in a 31-year-old male Japanese, who had visited India three times and stayed for 1 month each time during the previous 1 year. The patient presented increasing numbers of subcutaneous nodules and expelled proglottids, although numerous cysts were also found in the brain in imaging findings, though no neurological symptoms were observed. Histopathological and serological findings strongly indicated cysticercosis. We found taeniid eggs in his stool by microscopic examination and revealed them as the Indian haplotype of Taenia solium by mitochondrial DNA analysis. We concluded that disseminated cysticercosis was caused by the secondary autoinfection with eggs released from the tapeworm carrier himself. After confirming the absence of adult worms in the intestine by copro-polymerase chain reaction, the patient was successfully treated with albendazole at a dose of 15 mg/kg/day for 28 days. Subcutaneous and intracranial lesions had completely disappeared by the end of the treatment period.
Sanchez-Larsen, Alvaro; Monteagudo, Maria; Lozano-Setien, Elena; Garcia-Garcia, Jorge
Neurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.
Sharma, Ravinder; Gautam, Prachi; Kumar, Sanjay; Elhence, Poonam; Bansal, Rani; Gupta, Gaurav
Human cysticercosis is an infection by the larval stage of the tapeworm. We encountered a rare case of isolated cysticercosis of sternocleidomastoid muscle in a 25 year old female. She presented with 2.5 × 1.5 cm firm, dull aching swelling with ill defined margins in right upper part of neck. It appeared to arise in sternocleidomastoid muscle. The diagnosis was established by FNAC, USG and CT scan. Patient was admitted and started on medical treatment. There was complete resolution of symptoms and patient improved to normal after 1 month of therapy with albendazole. The case is reported because it is a rare one and to reinforce the fact that parasitic etiology should be kept in mind while dealing with a case of neck swelling.
Verma, Rajesh; Jaiswal, Anupam
An 8-year-old girl presented to the neurology department with a complaint of insidious onset of left-sided ptosis and restricted elevation of the left eye. A CT scan orbit and brain revealed a ring-enhancing lesion in the levator palpebral superioris (LPS) and superior rectus (SR) muscle complex of the left eye and left parietal and right temporal region. She was started on steroid, followed by albendazole with improvement. The LPS/SR complex is the least common site of involvement among extraocular muscles in ocular cysticercosis. Specially, with brain neurocysticercosis (NCC), it is extremely rare. We report an unusual association of multiple brain NCC with ocular cysticercosis involving LPS and SR muscle. PMID:23355567
Kumar, M. L. Vijaya; Thippeswamy, B.; Kuppust, I. L.; Naveenkumar, K. J.; Shivakumar, C. K.
Objective: To assess the anthelmintic acivity of Bacillus cereus and Bacillus pumilus metabolites. Materials and Methods: The successive solvent extractions with petroleum ether, ethyl acetate and methanol. The solvent extracts were tested for anthelmintic activity against Pheretima posthuma at 20 mg/ml concentration. The time of paralysis and time of death of the worms was determined for all the extracts. Albendazole was taken as a standard reference and sterile water as a control. Results: All the sample extracts showed significant anthelmintic activity in paralyzing the worms comparable with that of the standard drug. The time of death exhibited by BP metabolites was close to the time exhibited by standard. Conclusion: The study indicates both bacteria Bacillus cereus and Bacillus pumilus have anthelmintic activity indicating potential metabolites in them. PMID:25598639
Georgiu, Carmen; Nicolau, Dan; Sabha, Wissam; Surariu, Miruna; Precup, Dorel
The hydatid disease is a zoonosis endemic to rural countries, such as those in the Mediterranean region, South America, North Africa, Central Asia and China. Hydatid cysts commonly affect liver and lungs, but less than 100 cases of costal hydatidosis have been reported in the literature. While diagnosis of the disease in commonly affected organs is relatively easy, uncommon locations can prove to be challenging as is the case with costal hydatidosis. Imaging techniques can suggest the diagnosis, but sometimes it remains uncertain until surgery. The treatment is surgical, assisted by long-time Albendazole chemotherapy. We present a rare case of costal hydatidosis, the first one to be reported in Romania according to our review of the literature. PMID:26004107
Saavedra, Herbert; Gonzales, Isidro; Alvarado, Manuel A; Porras, Miguel A; Vargas, Victor; Cjuno, Román A; Garcia, Hector H; Martinez, S Manuel
Neurocysticercosis (NCC) is the most common parasitic disease of the central nervous system and is caused by larvae of the tapeworm Taenia solium. NCC is endemic in almost all developing countries. It presents as intraparenchymal forms associated with seizures or as extraparenchymal forms associated with intracranial hypertension. The clinical and epidemiological suspicion are important but the diagnosis is made primarily by images and confirmed by serology. Computed tomography (CT) and magnetic resonance imaging tests are used. Immunodiagnosis by Western Blot, which is currently perform in the Instituto Nacional de Ciencias Neurológicas in serum and cerebrospinal fluid serves as confirmatory test. Treatment involves symptomatic measures (control of seizures or intracranial hypertension) and anticysticercal medications (albendazole and praziquantel). Anticysticercal treatment should be used under hospital conditions because of secondary effects.
Cerruto, Maria Angela; D'Elia, Carolina; Artibani, Walter
Eosinophilic cystitis is a rare inflammatory disease with controversial aetiology and treatment. We report the case of a 61-year-old man presented with lower quadrant abdominal pain and lower urinary tract symptoms, non responsive to antibiotics and nonsteroidal antiinflammatory drugs. Physical examination was substantially negative, such as laboratory parameters, microscopic, bacteriological and serological evaluations. Cystoscopy revealed red areas involving the mucosa of the bladder and transurethral biopsies revealed infiltrating eosinophils. The patient was treated with corticosteroids and montelukast sodium with improving of the symptoms, and at 5 weeks postoperative pain score was reduced. After discontinuing corticosteroids dysuria recurred with the development of hyperemia at the genital skin; the specific enzyme-linked immunosorbent assay (ELISA) to detect antibodies against several parasites was slightly positive for Toxocara species. Montelukast sodium was discontinued and corticosteroid therapy was started together with albendazole, with improving of patient’s symptoms and pain decreasing after one week.
Karabay, Ozalp; Onen, Ahmet; Yildiz, Fidan; Yilmaz, Erkan; Erdal, Cenk A; Sanli, Aydin; Kilci, Göksel; Algin, Ibrahim; Itil, Oya; Açikel, Unal
The ratio of cardiac involvement of Echinoccocus granulosus is 0.02-2% and although seen rarely, involvement of the interatrial septum has also been reported in the published literature. The present case was a 19-year-old male university student admitted to hospital with complaints of headache and dizziness. Computerized tomography of the cranium revealed a cystic mass located at the frontal region and enucleation of the cyst was performed during surgery. A cystic lesion 5 x 4 cm in size was detected within the interatrial septum on two-dimensional transthoracic echocardiography during the postoperative period and the patient was referred to our clinic. Open heart surgery was performed and a hydatid cyst that involved the interatrial septum was enucleated. The cyst wall was sutured to the interatrial septum. No complications developed during the postoperative period. The patient was discharged on the fifth day of hospitalization and medical therapy was started with albendazole.
Khuroo, Mehnaaz S
Strongyloidiasis is infection caused by the nematode Strongyloides stercoralis. Chronic uncomplicated strongyloidiasis is known to occur in immunocompetent individuals while hyperinfection and dissemination occurs in selective immunosuppressed hosts particularly those on corticosteroid therapy. We report two cases of hyperinfection strongyloidiasis in renal transplant recipients and document endoscopic and pathological changes in the involved small bowel. One patient presented with features of dehydration and malnutrition while another developed ileal obstruction and strangulation, requiring bowel resection. Oesophagogastroduodenoscopy showed erythematous and thickened duodenal mucosal folds. Histopathological examination of duodenal biopsies revealed S. stercoralis worms, larvae and eggs embedded in mucosa and submucosa. Wet mount stool preparation showed filariform larvae of S. stercoralis in both cases. Patients were managed with anthelmintic therapy (ivermectin/albendazole) and concurrent reduction of immunosuppression. Both patients had uneventful recovery. Complicated strongyloidiasis should be suspected in immunocompromised hosts who present with abdominal pain, vomiting and diarrhoea, particularly in endemic areas. PMID:25150235
Chang, Alicia H; Perry, Sharon; Du, Jenny N T; Agunbiade, Abdulkareem; Polesky, Andrea; Parsonnet, Julie
Beginning in 2005, the Centers for Disease Control and Prevention (CDC) expanded the overseas presumptive treatment of intestinal parasites with albendazole to include refugees from the Middle East. We surveyed the prevalence of helminths and protozoa in recent Middle Eastern refugees (2008-2010) in comparison with refugees from other geographical regions and from a previous survey (2001-2004) in Santa Clara County, California. Based on stool microscopy, helminth infections decreased, particularly in Middle Eastern refugees (0.1% versus 2.3% 2001-2004, P = 0.01). Among all refugees, Giardia intestinalis was the most common protozoan found. Protozoa infections also decreased somewhat in Middle Eastern refugees (7.2%, 2008-2010 versus 12.9%, 2001-2004, P = 0.08). Serology for Strongyloides stercoralis and Schistosoma spp. identified more infected individuals than stool exams. Helminth infections are increasingly rare in refugees to Northern California. Routine screening stool microscopy may be unnecessary in all refugees.
Kabego, Landry; Kasengi, Joe Bwija; Mirindi, Patrick; Ruhanya, Vurayai; Lupande, David; Bulabula, André; Ngoma, Patrick
Introduction Mansonella perstans is a human filarial parasite transmitted by biting midges (Diptera: Ceratopogonidae) belonging to the genus Culicoides and it is widely spread in sub-Saharan Africa. While most cases are asymptomatic, mansonelliasis can be associated with angioedema, arthralgia, swellings, pain in the scrotum or in serous cavities such as the pleura, the peritoneum, the pericardium, etc. Mansonelliasis can be really hard to treat, but it has been shown that an intensive treatment using albendazole can clear the parasite. Case report Here we describe a case of a 16 months-old malnourished child with pneumonia due to M. perstans in the east of the Democratic Republic of Congo. Conclusion Although our investigations confirmed M. perstans infection, this case shows that it is very difficult to come to a conclusive diagnosis. PMID:28053918
Speare, Rick; Bradbury, Richard Stewart; Croese, John
A 26-year-old male member of the Australian Defense Force presented with a history of central abdominal pain of 4 weeks duration and peripheral eosinophilia consistent with eosinophilic enteritis. Acute hookworm disease was diagnosed as the cause. Adult worms recovered from feces after therapy with albendazole were morphologically consistent with Ancylostoma ceylanicum. As the patient had been deployed with the Regional Assistance Mission to Solomon Islands for 6 months prior to this presentation, it is very likely that the A. ceylanicum was acquired in Solomon Islands. Until now, it has been assumed that any Ancylostoma spp. recovered from humans in Solomon Islands is A. duodenale. However, this case demonstrates that human hookworm infection acquired in the Solomon Islands could be caused by A. ceylanicum. PMID:27658607
Canyigit, Murat Gumus, Mehmet; Cay, Nurdan; Erol, Bekir; Karaoglanoglu, Mustafa; Akhan, Okan
A 27-year-old female with a type 2 hydatid cystic lesion in the liver according to the Gharbi classification (CE 3A according to the WHO classification) was referred for percutaneous treatment after albendazole treatment for 1 year. A catheterization technique was performed but hypertonic saline and alcohol were not given into the cavity due to cystobiliary leakage. During the 4-month follow-up period, sequential cavitography revealed biliary fistula, and bile-stained drainage had not been ceased despite the sphincterotomy, nasobiliary drainage catheter, and plastic stent. Since the patient refused to surgery, we embolized the biliary fistula using N-butyl 2-cyanoacrylate for the first time in the literature. At the 3-month follow-up, the patient's course was uneventful and ultrasound, multidetector-row CT, and MRI examinations revealed no collection in or adjacent to the cavity.
Khaldi, M; Mohamed, S; Kallel, J; Khouja, N
Among a series of 155 brain hydatid disease patients hospitalized between 1965 and 1998, 117 were children. The mean age was approximately 7.2 years, with a slight male predominance. Eighteen patients presented with another visceral localization. Symptoms and signs of intracranial hypertension are currently encountered (75%) followed by hemiparesis, epilepsy, mental changes, skull deformities and, more rarely, dyskinetic phenomenon. Brain hemispheric localization is the rule, with some exceptions. CT scans reveal an intra-parenchymal lesion with clearly defined, rarely enhanced margins. Medical treatment has virtually no place in the management of cerebral solitary cyst. Albendazole has been used in cases of multiple involvement, with controversial results. Surgical hydrostatic expulsion is the only effective treatment. Recovery is expected when the cyst is extracted completely unruptured.
Khine, Yee Yee; Jiang, Yanyan; Dag, Aydan; Lu, Hongxu; Stenzel, Martina H
A series of thermo-and pH-responsive poly(methyl methacrylate)-block-poly[methacrylic acid-co-di(ethylene glycol) methyl ether methacrylate] PMMA-b-P[MAA-co-DEGMA] block copolymers were synthesized by RAFT polymerization and self-assembled into micelles. The molar ratio of MAA was altered from 0-12% in order to modulate the lower critical solution temperature (LCST) of PDEGMA. The release of the drug albendazole from the micelle was strongly dependent on the temperature and the LCST value of the polymer. Systems below the LCST released the drug slowly while increasing the temperature above the LCST or decreasing the pH value to 5 resulted in the burst-like release of the drug. ABZ delivered in this pH-responsive drug carrier had a higher toxicity than the free drug or the drug delivered in a non-responsive drug carrier.
George, N; Persad, K; Sagam, R; Offiah, V N; Adesiyun, A A; Harewood, W; Lambie, N; Basu, A K
In Trinidad, small ruminant farms are semi-intensively managed under tropical conditions which support the development and survival of the infective stages of the helminths. Local farmers use anthelmintics to control gastrointestinal nematodes frequently. Frequent use of anthelmintics has the potential to select for populations of nematodes resistance to those chemicals. Hence, an attempt was made to study the efficacy of commonly used drugs on gastrointestinal nematodes of sheep. Three farms situated in different counties in Trinidad were selected. Sheep aged 6-15 months and not treated with anthelmintics for a minimum of six months previous and with faecal egg count (FEC)>150 eggs per gram were selected for study. They were allocated into 5 groups, each consisting 10 animals. The Group TA animals were treated once with albendazole (5mg/kg. b.wt.), group TF with fenbendazole (5mg/kg.b.wt.), group TI animals with ivermectin (200 μg/kg b.wt.), group TL with levamisol (7.5mg/kg b.wt.). The group NTC animals were not given any drug and served as control. The number of nematode eggs per gram of faeces from each animal was determined before treatment and at 14 days after treatment. The anthelmintic susceptibility to different drugs was detected by FECRT (in vivo) with EPG recorded at 14 day post-treatment. The data analysis using FECRT revealed that efficacy of albendazole (46-62%), fenbendazole (44-61%) and levamisol (53-81%) were reduced compared to ivermectin (95-97%). An attempt has also been made to find a suitable method for calculation of FECR (%).
Domke, Atle V Meling; Chartier, Christophe; Gjerde, Bjørn; Höglund, Johan; Leine, Nils; Vatn, Synnøve; Stuen, Snorre
In the period of 2008–2009, the efficacies of the benzimidazole (BZ) albendazole and the macrocyclic lactone (ML) ivermectin against gastrointestinal nematodes (GIN) of small ruminants were evaluated by means of the fecal egg count reduction (FECR) test and by post-treatment identification of surviving third stage (L3) larvae after coproculture. Sheep (n=28) and goat (n=28) flocks from three areas of Norway were randomly selected to assess the prevalence of anthelmintic resistance (AR), whereas only lambs from non-randomly selected sheep flocks (n=32) with a farm management that could select for AR were investigated the second year. Only flocks with a mean excretion of nematode eggs per gram feces (EPG) ≥ 150 at time of treatment were included in the survey. In total, 48 (80%) and 13 (46.4%) of the selected sheep and goat flocks, respectively, fulfilled the inclusion criteria. The proportions of flocks classified as resistant (i.e., FECR <95% and with a lower 95% confidence interval of <90%) for the BZ drug albendazole were 10.5% and 31.0% in the randomly and non-randomly selected sheep flocks, respectively. When restricting the area to Rogaland County, eight flocks out of ten (80%) non-randomly selected sheep flocks showed BZ resistance. The efficacy of ML was 100% in all surveyed sheep and goat flocks. In post-treatment coprocultures from the non-randomly selected flocks, the main nematode genera were Teladorsagia/Trichostrongylus in five flocks, Haemonchus in two flocks, and a mixture of these genera in the remaining two flocks. In the goat flocks, the pre-treatment infection levels of GIN were low compared to what was found in the sheep flocks. Still, in one flock, AR against BZ in Teladorsagia/Trichostrongylus was found. New strategies and recommendations to face the emerging AR situation in Rogaland County in order to limit the spread of resistant nematodes within and into other areas are urgently needed.
Novobilský, Adam; Höglund, Johan
Control of Fasciola hepatica infection in livestock is based on annual treatment using flukicides such as triclabendazole, albendazole and closantel. However, triclabendazole resistant F. hepatica populations are emerging worldwide and resistance is emerging to albendazole, whereas it has until now never been described for closantel. In Sweden, a topical formulation containing a combination of closantel and ivermectin (Closamectin Pour On) has been registered for use in cattle only since 2011. This study evaluated the efficacy of closantel against F. hepatica in naturally infected beef cattle using both coproantigen and faecal egg count reduction tests. Faecal egg counts (FEC) and coproantigen ELISA examinations were conducted in February 2014 in three beef cattle herds (A, B, C) in south-western Sweden. On each farm, 10 F. hepatica coproantigen-positive and F. hepatica egg-positive animals were allocated after 12–16 weeks of housing into groups and treated topically with a minimum of 20 mg closantel per kg body weight. Faecal samples were collected from selected animals on 0, 7 and 21 day post-treatment (PT). Based on FEC, closantel efficacy 21 days PT was 72% (95% CI: 65–77%) and 97% (95% CI: 95–98%) on farms A and B, respectively. No FEC reduction at all was observed on farm C. In total, 4, 1 and 6 animals remained coproantigen-positive at 21 days PT on farms A, B and C, respectively. Closantel treatment failure was confirmed on two of the farms. As the animals were housed 12–16 weeks before treatment and thereafter during the entire study, failure due to the presence of juvenile flukes was excluded. Although the cause of closantel failure currently remains unclear, development of resistance or/and absorption failure of topical administration should be considered. To our knowledge, this is the first report of closantel treatment failure against F. hepatica in cattle. PMID:26448903
Eris, Cengiz; Akbulut, Sami; Yildiz, Mehmet Kamil; Abuoglu, Hasan; Odabasi, Mehmet; Ozkan, Erkan; Atalay, Suleyman; Gunay, Emre
The benefits and risks of surgery for splenic hydatid cyst (SHC) remain controversial. We aimed to share our experience about a surgical approach for SHC. Sixteen consecutive patients with SHC disease who underwent open splenectomy at our hospital between January 2006 and July 2012 were retrospectively evaluated. Data on the patients' demographic features, clinical findings, radiological and serological diagnostic methods, and surgical and medicinal treatment options were collected and used to generate descriptive profiles of diagnosis, treatment course, and outcome. The patient population was composed of 6 females and 10 males, with an age range of 18 to 79 years (mean age: 47.0 ± 18.0). Radiological examinations detected hydatid cysts in spleen alone (n = 7) or both spleen and liver (n = 9). Preoperative serological testing identified 13 of the patients as IHA positive. All except 1 patient received a 10- to 21-day preoperative course of albendazole therapy and all patients received vaccination 1 week prior to surgery. Seven patients underwent splenectomy. The remaining patients underwent splenectomy with partial cystectomy and omentopexy (n = 6), partial cystectomy and unroofing (n = 1), pericystectomy (n = 1), or pericystectomy with partial nephrectomy (n = 1). All except one patient received a 10- to 45-day postoperative course of albendazole. No patients developed serious complications or signs of recurrence during the follow-up. The clinical profile of SHC disease at our hospital includes diagnosis by radiological methods, splenectomy treatment by simple or concomitant procedures according to the patient's symptoms, cyst size, number and localization, and compression of adjacent organs, and adjunct vaccination to decrease risk of postoperative septic complications. This profile is associated with low risk of complications and high therapeutic efficacy.
Bloemhoff, Yris; Danaher, Martin; Andrew Forbes; Morgan, Eric; Mulcahy, Grace; Power, Clare; Sayers, Ríona
Dictyocaulus viviparus, Ostertagia ostertagi (nematode parasites), and Fasciola hepatica (trematode parasite) result in productivity losses on dairy farms and impact on animal health through clinical and sub-clinical disease. Parasite control in livestock systems is largely based on the use of chemoprophylactic agents (anthelmintics), grazing management, or a combination of both. The objective of this study was to document current parasite control measures employed by Irish dairy farmers in a predominantly pasture-based livestock system. A questionnaire survey of 312 geographically representative farmers was completed in 2009 with a follow up survey completed in 2011. Statistical analysis highlighted significant differences in chemoprophylactic usage between 2009 and 2011. In particular, an increase in the use of albendazole for both trematode (19% in 2009 to 36% in 2011) and nematode (30% in 2009 to 58% in 2011) control was observed. This was most likely due to flukicide restrictions introduced in the Republic of Ireland in 2010 for dairy animals. Logistic regression highlighted regional differences in chemoprophylactic use. Farmers in southern parts of Ireland, an area with good quality soil, less rainfall, and a higher density of dairy farms than other regions, were approximately half as likely to dose for F. hepatica and were more likely (OR>2.0) to use albendazole for both nematode and fluke control. Approximately 30% of respondents who used a chemoprophylactic treatment for nematodes, used a product which was 'unsuitable for purpose' (e.g. ivermectin for the treatment of F. hepatica), highlighting the need for increased awareness, continuing research, and regionally targeted education tools regarding optimal parasite control.
Leitsch, David; Müller, Joachim; Müller, Norbert
The antioxidative enzyme thioredoxin reductase (TrxR) has been suggested to be a drug target in several pathogens, including the protist parasite Giardia lamblia. TrxR is also believed to catalyse the reduction of nitro drugs, e.g. metronidazole and furazolidone, a reaction required to render these compounds toxic to G. lamblia and other microaerophiles/anaerobes. It was the objective of this study to assess the potential of TrxR as a drug target in G. lamblia and to find direct evidence for the role of this enzyme in the activation of metronidazole and other nitro drugs. TrxR was overexpressed approximately 10-fold in G. lamblia WB C6 cells by placing the trxR gene behind the arginine deiminase (ADI) promoter on a plasmid. Likewise, a mutant TrxR with a defective disulphide reductase catalytic site was strongly expressed in another G. lamblia WB C6 cell line. Susceptibilities to five antigiardial drugs, i.e. metronidazole, furazolidone, nitazoxanide, albendazole and auranofin were determined in both transfectant cell lines and compared to wildtype. Further, the impact of all five drugs on TrxR activity in vivo was measured. Overexpression of TrxR rendered G. lamblia WB C6 more susceptible to metronidazole and furazolidone but not to nitazoxanide, albendazole, and auranofin. Of all five drugs tested, only auranofin had an appreciably negative effect on TrxR activity in vivo, albeit to a much smaller extent than expected. Overexpression of TrxR and mutant TrxR had hardly any impact on growth of G. lamblia WB C6, although the enzyme also exerts a strong NADPH oxidase activity which is a source of oxidative stress. Our results constitute first direct evidence for the notion that TrxR is an activator of metronidazole and furazolidone but rather question that it is a relevant drug target of presently used antigiardial drugs.
Wammes, Linda J.; Hamid, Firdaus; May, Linda; Kaisar, Maria M. M.; Prasetyani-Gieseler, Margaretta A.; Djuardi, Yenny; Wibowo, Heri; Kruize, Yvonne C. M.; Verweij, Jaco J.; Tsonaka, Roula; Houwing-Duistermaat, Jeanine J.; Sartono, Erliyani; Luty, Adrian J. F.; Supali, Taniawati; Yazdanbakhsh, Maria
In cross-sectional studies, chronic helminth infections have been associated with immunological hyporesponsiveness that can affect responses to unrelated antigens. To study the immunological effects of deworming, we conducted a cluster-randomized, double-blind, placebo-controlled trial in Indonesia and assigned 954 households to receive albendazole or placebo once every 3 mo for 2 y. Helminth-specific and nonspecific whole-blood cytokine responses were assessed in 1,059 subjects of all ages, whereas phenotyping of regulatory molecules was undertaken in 121 school-aged children. All measurements were performed before and at 9 and 21 mo after initiation of treatment. Anthelmintic treatment resulted in significant increases in proinflammatory cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) and mitogen, with the largest effect on TNF responses to PfRBCs at 9 mo—estimate [95% confidence interval], 0.37 [0.21–0.53], P value over time (Ptime) < 0.0001. Although the frequency of regulatory T cells did not change after treatment, there was a significant decline in the expression of the inhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on CD4+ T cells of albendazole-treated individuals, –0.060 [–0.107 to –0.013] and –0.057 [–0.105 to –0.008] at 9 and 21 mo, respectively; Ptime = 0.017. This trial shows the capacity of helminths to up-regulate inhibitory molecules and to suppress proinflammatory immune responses in humans. This could help to explain the inferior immunological responses to vaccines and lower prevalence of inflammatory diseases in low- compared with high-income countries. PMID:27791067
It has been argued that the delivery of anthelmintics to school-children through existing education infrastructure can be one of the most cost-effective approaches to controlling parasitic worm infection. This paper examines the actual costs of a combination of mass and selective treatment for schistosomiasis using praziquantel and mass treatment for intestinal nematodes using albendazole, as an integral part of school health programmes reaching 80442 pupils in 577 schools in Volta Region, Ghana, and reaching 109099 pupils in 350 schools in Tanga Region, Tanzania. The analysis shows that financial delivery costs per child treated using praziquantel, which involved a dose related to body mass and a prior screening at the school level, were US$ 0.67 in Ghana and US$ 0.21 in Tanzania, while the delivery costs for albendazole, which was given as a fixed dose to all children, were US$ 0.04 in Ghana and US$ 0.03 in Tanzania. The higher unit costs in Ghana reflect the epidemiology of infection; overall, fixed costs were similar in both countries, but fewer children required treatment in Ghana. Analysis of economic costs-which includes the cost of unpaid days of labour--indicates that the financial costs are increased in Ghana by 78% and in Tanzania by 44%. It is these additional costs which are avoided by integration into an existing infrastructure. It is concluded that: the base cost of delivering a universal, standard, school-based health intervention can be as low as US$ 0.03 per child treated; that even a slight increase in the complexity of delivery can have a significant impact on the cost of intervention; and that the use of the education infrastructure does indeed offer significant savings in delivery costs.
Larrieu, E; Frider, B; del Carpio, M; Salvitti, J C; Mercapide, C; Pereyra, R; Costa, M; Odriozola, M; Pérez, A; Cantoni, G; Sustercic, J
Until a short time ago, hydatidosis was considered a pathology that could only be resolved surgically. However, in recent years progress has been made with the epidemiology, diagnosis, and treatment of the disease, and new information on the natural history of hydatidosis has helped define new criteria for its treatment. It is now known that as many as 67% of the carriers of liver cysts who are asymptomatic remain so throughout their lives. This situation produces special results in immunologic testing. Enzyme-linked immunosorbent assay (ELISA) has a sensitivity of 63% and a specificity of 97% with asymptomatic carriers, while the double diffusion arc 5 test (DD5) achieves a sensitivity of only 31% with the same population. On the other hand, imaging studies based on ultrasonography have become the method of choice to detect asymptomatic carriers. Ultrasonography studies are 49% to 73% more sensitive than serological tests, and they can even be used as a part of epidemiological surveillance systems and to monitor control programs. Treatment schemes have also been modernized. Treating asymptomatic carriers chemotherapeutically with albendazole produces favorable results in as many as 69% of cases, while such minimally invasive surgical treatments as puncture-aspiration-injection-reaspiration (PAIR) reduce average cyst volume by as much as 66%. These factors have made it possible for hospital services in the province of Río Negro, Argentina, to establish a treatment scheme for asymptomatic carriers. It is based on the monitoring of small cysts (type Ia on the modified Gharbi scale); initial treatment with albendazole, followed by PAIR if there is no response, in larger or more complex cysts (types Ib, II, and III); and follow-up of inviable or dead cysts (types IV and V).
Lemoine, Jean Frantz; Monestime, Franck; Fayette, Carl R.; Direny, Abdel N.; Desir, Luccene; Beau de Rochars, Valery E.; Streit, Thomas G.; Renneker, Kristen; Chu, Brian K.; Chang, Michelle A.; Mace, Kimberly E.; Won, Kimberly Y.; Lammie, Patrick J.
Background Since 2001, Haiti’s National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of lymphatic filariasis (LF) through annual mass drug administration (MDA) with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti’s NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. Methodology/Principle findings The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment with albendazole to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. Conclusions/Significance Haiti’s 2014–2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria. PMID:28207792
Boubaker Elandalousi, Ramzi; Akkari, Hafidh; B'chir, Fatma; Gharbi, Mohamed; Mhadhbi, Moez; Awadi, Soufia; Darghouth, Mohamed Aziz
The increasing prevalence of anthelmintic resistant strains of helminths, the drug residues in animal products and the high cost of conventional anthelmintics has created an interest in studying medicinal plants as an alternative source of anthelmintics. Thymus capitatus (Lamiales: Lamiaceae) is used traditionally by people as spices and reported to possess some biological effects. The objective of this study is to evaluate the anthelmintic efficacy of T. capitatus in comparison to albendazole against the gastrointestinal nematodes of sheep. To fulfil the objectives, in vitro anthelmintic activities of crude aqueous and crude ethanolic extracts of aerial parts of T. capitatus were investigated on the eggs and adults of the nematode parasite Haemonchus contortus. Both extract types of T. capitatus completely inhibited egg hatching at a concentration close to 2 mg/ml. LC₅₀ of ethanolic extract of T. capitatus was 0.368 mg/ml while that of aqueous extract was 6.344 mg/ml (p<0.05). The ethanolic extract showed higher in vitro activity against adult parasites than the aqueous one in terms of the paralysis and/or death of the worms at different hours post-treatment. Dose dependent effect was observed for both extracts. Chemical analyses revealed that the overall profile of both extracts was dominated by oxygenated constituents. In addition, ethanolic extract is mainly composed of phenols among which thymol (71.22%) and camphor (17.18%). As far as the literature could be ascertained, this is the first publication on anthelmintic activity of T. capitatus. The results of the present study suggest that T. capitatus extracts are a promising alternative to the commercially available anthelmintics like albendazole for the treatment of small ruminants' gastrointestinal nematodes.
Vecchio, Rosa Fontana Del; Pinzone, Marilia Rita; Nunnari, Giuseppe; Cacopardo, Bruno
Patient: Male, 23 Final Diagnosis: Neurocysticerosis Symptoms: Diplopia • fever • headache • insomnia • neck stiffness • vomiting Medication: Albendazole Clinical Procedure: — Specialty: Neurology Objective: Challenging differential diagnosis Background: Neurocysticercosis is a brain infection caused by the larval stage of the tapeworm Taenia (T.) solium. It is the most important parasitic disease of the human central nervous system and represents the most common cause of acquired epilepsy in developing countries. Case Report: Here, we report the case of a 23-year-old Chinese man who presented to the emergency department with a 7-day history of helmet headache radiating to the nuchal region and associated with vomiting, confusion, and fever. Cerebrospinal fluid (CSF) was clear, with increased pressure, lymphocytic pleocytosis, decreased glucose, and increased protein levels. Bacterial antigen detection test on CSF was negative, as were CSF bacterial and fungal cultures. Despite broad-spectrum antibiotic and antiviral therapy, the patient still complained of insomnia, diplopia, headache, neck stiffness, and pain in the sacral region. A second LP was performed and CSF had the same characteristics as the first LP. A brain and spinal cord MRI revealed widespread arachnoiditis and small septated cysts with CSF-like signal in the cisterna magna, within the fourth ventricle, and at the level of L3–L4. Cysticercus-specific immunoglobin G antibodies were detected by ELISA in the CSF. The patient received albendazole (15 mg/kg/day) and dexamethasone (5 mg/day) for 4 weeks, with progressive resolution of neurological symptoms. Conclusions: This case shows that, even if rare, neurocysticercosis may be responsible for meningeal symptoms and should be included in the differential diagnosis, especially in patients from endemic countries. PMID:24459541
Novobilský, Adam; Höglund, Johan
Control of Fasciola hepatica infection in livestock is based on annual treatment using flukicides such as triclabendazole, albendazole and closantel. However, triclabendazole resistant F. hepatica populations are emerging worldwide and resistance is emerging to albendazole, whereas it has until now never been described for closantel. In Sweden, a topical formulation containing a combination of closantel and ivermectin (Closamectin Pour On) has been registered for use in cattle only since 2011. This study evaluated the efficacy of closantel against F. hepatica in naturally infected beef cattle using both coproantigen and faecal egg count reduction tests. Faecal egg counts (FEC) and coproantigen ELISA examinations were conducted in February 2014 in three beef cattle herds (A, B, C) in south-western Sweden. On each farm, 10 F. hepatica coproantigen-positive and F. hepatica egg-positive animals were allocated after 12-16 weeks of housing into groups and treated topically with a minimum of 20 mg closantel per kg body weight. Faecal samples were collected from selected animals on 0, 7 and 21 day post-treatment (PT). Based on FEC, closantel efficacy 21 days PT was 72% (95% CI: 65-77%) and 97% (95% CI: 95-98%) on farms A and B, respectively. No FEC reduction at all was observed on farm C. In total, 4, 1 and 6 animals remained coproantigen-positive at 21 days PT on farms A, B and C, respectively. Closantel treatment failure was confirmed on two of the farms. As the animals were housed 12-16 weeks before treatment and thereafter during the entire study, failure due to the presence of juvenile flukes was excluded. Although the cause of closantel failure currently remains unclear, development of resistance or/and absorption failure of topical administration should be considered. To our knowledge, this is the first report of closantel treatment failure against F. hepatica in cattle.
Larki, Sara; Saharkhiz, Mohammad Jamal; Oryan, Ahmad; Ansary Lari, Maryam; Mootabi Alavi, Amir
Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were employed to determine the chemical composition of the essential oil (EO) from aromatic water (AW) of Zataria multiflora. Thymol (66.9%), carvacrol (15.2%), and carvone (7.3%) were found to be the major EO constituents. Eighty laboratory BALB/c mice were infected intraperitoneally by injection of 1,500 viable protoscolices and were divided into prevention (40 mice) and therapeutic (40 mice) groups. To prove the preventive effect of the Z. multiflora AW on development of hydatid cysts, the 40 infected mice were allocated into three treatment groups, including the albendazole group (10 mice that received 150 mg/kg body weight/day for 10 days), the Z. multiflora AW group (15 mice that received 20 ml/liter in drinking water for 8 months), and a control group (15 mice that received no treatment). To estimate the therapeutic effect of the Z. multiflora AW on the hydatid cyst, after 8 months of infection, the 15 remaining mice were allocated into three experimental treatment groups of five animals each, including the albendazole group (300 mg/kg/day for 20 days), Z. multiflora AW group (40 ml/liter in drinking water for 30 days), and control group (no treatment). All mice were then euthanized, and the sizes and weights of the cysts as well as their ultrastructural changes were investigated. The weights and sizes of the hydatid cysts significantly decreased upon treatment with the Z. multiflora AW in both the preventive and therapeutic groups (P < 0.05). The results of scanning electron microscopy also showed considerable damage in the germinal layer of the hydatid cysts recovered from the treated animals. PMID:25070113
Khan, S; Afshan, K; Mirza, B; Miller, J E; Manan, A; Irum, S; Rizvi, S S R; Qayyum, M
Artemisia plant genus, natural inhabitant of northern Punjab Pakistan, is well known for its anthelmintic properties; many Artemisia species have not been so far scientifically proved. The aim of this study was to assess in vitro anthelmintic activity of Artemisia indica and Artemisia roxburghiana against mixed infection of gastrointestinal nematodes in small ruminants. This study is first scientifically proven study on anthelmintic activity of A. indica and A. roxburghiana. Five different concentrations (50, 25, 12.5, 6.25 and 3.75 mg/mL) accompanied by negative control (PBS) and positive control (albendazole, 10%) were used to carry out the egg hatch inhibition assay, larval mortality assay and adult worm mortality assay. The Baermann technique was used first time in larval mortality assay and proved to be effective. The results revealed that methanolic extracts of both A. indica and A. roxburghiana, showed maximum anthelmintic activity at concentration of 50 mg/ml by egg hatch inhibition (85±21.2; 80±28.3), larvae mortality (18±2.8; 17±4.2) and adult worm mortality (8.5±2.1; 8±2.8) assays. However, at concentration of 50 mg/ml both plant extracts in comparison to albendazole showed statistically insignificant (p≤0.05) results. The A. indica showed higher anthelmintic activity at all concentrations as compared to A. roburghiana. It has been concluded both plants exhibit anthelmintic activity and further evaluation of these plants should be carried out to purify the active ingredients for anthelmintic activity. Moreover, the decoctions of these plants could be used to GINs after confirming anthelmintic properties through in vivo.
Weber, R; Bryan, R T; Schwartz, D A; Owen, R L
Microsporidia are obligate intracellular spore-forming protozoal parasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes of vertebrates. More than 100 microsporidial genera and almost 1,000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Among persons not infected with human immunodeficiency virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic-antiprotozoal drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured with albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing
Bazh, Eman K A; El-Bahy, Nasr M
Intestinal helmintic infection, continue to be a cause of major concern in several parts of the world, particularly in the developing nations. The use of plant extracts to control poultry helminths is increasing in different rearing systems. The anthelmintic activity of ginger and curcumin was studied on the nematode Ascaridia galli. In vitro and in vivo studies were allocated. Live parasites for in vitro studies were collected from the intestine of naturally infected chickens. Some living worms were incubated at 37 °C in media containing ginger at three concentration levels (25, 50, and 100 mg/ml), and others were incubated in media containing curcumin at the same concentration levels. Another living worm group was incubated in media containing albendazole at a dose of 7.5 mg/ml. The extracts' efficacy was exhibited in a concentration-time-dependent manner mainly at 100 mg/ml and after 48 h. The in vivo study takes place on experimentally infected chickens. Group of infected chickens was treated with ginger extract at dose of 100 mg, another group was treated with curcumin extract at dose of 100 mg, and a third group was treated with albendazole at dose of 7.5 mg. In vivo study of ginger and curcumin recorded lower mortality rates than the in vitro study. It is concluded that ginger and curcumin extracts have potential anthelmintic properties against A. galli. Ginger in all concentrations used exhibited a higher death rate observed than curcumin. Their wormicidal effect is concentration-time dependent.
Vermeire, Jon J.; Suzuki, Brian M.; Caffrey, Conor R.
Hookworm infection is chief among soil-transmitted helminthiases (STHs) for the chronic morbidly inflicted. Deworming via mass drug administration (MDA) programs most often employs single doses of benzimidazole drugs to which resistance is a constant threat. To discover new drugs, we employ a hamster model of hookworm infection with Ancylostoma ceylanicum and use albendazole (ABZ; 10 mg/kg orally) as the gold standard therapy. We previously showed that a single oral 100 mg/kg dose of the cathepsin cysteine protease (CP) inhibitor, K11777, offers near cure of infection that is associated with a 95% reduction in the parasite’s resident CP activity. We confirm these findings here and demonstrate that odanacatib (ODN), Merck’s cathepsin K inhibitor and post-clinical Phase III drug candidate for treatment of osteoporosis, decreases worm burden by 73% at the same dose with a 51% reduction in the parasite’s CP activity. Unlike K11777, ODN is a modest inhibitor of both mammalian cathepsin B and the predominant cathepsin B-like activity measureable in hookworm extracts. ODN’s somewhat unexpected efficacy, therefore, may be due to its excellent pharmacokinetic (PK) profile which allows for sustained plasma exposure and, possibly, sufficient perturbation of hookworm cathepsin B activity to be detrimental to survival. Accordingly, identifying a CP inhibitor(s) that combines the inhibition potency of K11777 and the PK attributes of ODN could lead to a drug that is effective at a lower dose. Achieving this would potentially provide an alternative or back-up to the current anti-hookworm drug, albendazole. PMID:27384569
Flisser, A; Valdespino, J L; García-García, L; Guzman, C; Aguirre, M T; Manon, M L; González-González, G; Gyorkos, T W
Mexico established national health weeks (NHWs) in the early 1980s to promote childhood vaccinations. Because of the cumulative worldwide peer-reviewed scientific evidence, the recommendations of the World Health Organization and other international organisations, the political will of the Mexican government and the infrastructure provided by the NHWs, deworming was added to the NHWs in 1993. In addition to the Ministry of Health, several other government organisations participated in administering the deworming component. Tens of millions of school-age and preschool children between the ages of 2 years and 14 years now receive deworming (a single 400 mg dose of albendazole) approximately every 8 months. Between 1993 and 1998 evaluations were carried out in over 90,000 children to determine the effect of NHWs on the prevalence of geohelminth infections. In 1993, the overall prevalence of Ascaris was 20% and that of Trichuris was 15%. Prevalences decreased significantly over time (p <0.001). Treatment efficacy for Ascaris ranged from 91.6% to 85.3%, and for Trichuris, from 97.9% to 42.6%. In 1998, after conducting 12 NHWs with deworming, the respective prevalences were Ascaris 8% and Trichuris 11%. The experience of Mexico in integrating albendazole into its NHWs shows how deworming can be delivered to large numbers of at-risk children using an existing infrastructure. The NHW approach may be generalisable in other countries with successful national vaccination campaigns. The challenge remaining is to sustain the deworming programme until other longer-term behavioural, environmental and socioeconomic changes can be implemented.
Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission. From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 µg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole included in the combination chemotherapy produced “beyond-filariasis” benefits: clearance/reduction of intestinal helminths, and, additionally, in the case of ivermectin, skin-dwelling ectoparasites. The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started its worldwide activities in 2000, with the target of elimination by 2020. The basic strategy is to conduct annual single-dose MDAs for 4-6 years. In 2000-2007, a minimum of 570 million individuals were treated in 48 of 83 endemic countries. The drugs used are DEC 6 mg/kg plus albendazole 400 mg in most countries, or ivermectin 200-400 µg/kg plus albendazole 400 mg particularly in onchocerciasis endemic countries in Africa. (MDAs with DEC alone had been used in India.) The GPELF achieved impressive results in terms of parasitological cure/improvement, clinical benefits, social and economic impacts, etc. However, the most impressive result of all was
Chacon, L.; Gomez, M.C.; Jenkins, J.A.; Leibo, S.P.; Wirtu, G.; Dresser, B.L.; Pope, C.E.
Summary Usually, fibroblasts are frozen in dimethyl sulphoxide (DMSO, 10% v/v) at a cooling rate of 1 C/min in a low-temperature (80 C) freezer (LTF) before storage in liquid nitrogen (LN2); however, a LTF is not always available. The purpose of the present study was to evaluate apoptosis and viability of bovine fibroblasts frozen in a LTF or conventional freezer (CF; 20 C) and their subsequent ability for development to blastocyst stage after fusion with enucleated bovine oocytes. Percentages of live cells frozen in LTF (49.5%) and CF (50.6%) were similar, but significantly less than non-frozen control (88%). In both CF and LTF, percentages of live apoptotic cells exposed to LN2 after freezing were lower (4% and 5%, respectively) as compared with unexposed cells (10% and 18%, respectively). Cells frozen in a CF had fewer cell doublings/24 h (0.45) and required more days (9.1) to reach 100% confluence at the first passage (P) after thawing and plating as compared with cells frozen in a LTF (0.96 and 4.0 days, respectively). Hypoploidy at P12 was higher than at P4 in cells frozen in either a CF (37.5% vs. 19.2%) or in a LTF (30.0% vs. 15.4%). A second-generation cryo-solution reduced the incidence of necrosis (29.4%) at 0 h after thawing as compared with that of a first generation cryo-solution (DMEM + DMSO, 60.2%). The percentage of apoptosis in live cells was affected by cooling rate (CF = 1.9% vs. LFT = 0.7%). Development of bovine cloned embryos to the blastocyst stage was not affected by cooling rate or freezer type. ?? 2009 Cambridge University Press.
Chiu, Wing Sin; Belsey, Natalie A; Garrett, Natalie L; Moger, Julian; Delgado-Charro, M Begoña; Guy, Richard H
The effective treatment of diseases of the nail remains an important unmet medical need, primarily because of poor drug delivery. To address this challenge, the diffusion, in real time, of topically applied chemicals into the human nail has been visualized and characterized using stimulated Raman scattering (SRS) microscopy. Deuterated water (D2O), propylene glycol (PG-d8), and dimethyl sulphoxide (DMSO-d6) were separately applied to the dorsal surface of human nail samples. SRS microscopy was used to image D2O, PG-d8/DMSO-d6, and the nail through the O-D, -CD2, and -CH2 bond stretching Raman signals, respectively. Signal intensities obtained were measured as functions of time and of depth into the nail. It was observed that the diffusion of D2O was more than an order of magnitude faster than that of PG-d8 and DMSO-d6. Normalization of the Raman signals, to correct in part for scattering and absorption, permitted semiquantitative analysis of the permeation profiles and strongly suggested that solvent diffusion diverged from classical behavior and that derived diffusivities may be concentration dependent. It appeared that the uptake of solvent progressively undermined the integrity of the nail. This previously unreported application of SRS has permitted, therefore, direct visualization and semiquantitation of solvent penetration into the human nail. The kinetics of uptake of the three chemicals studied demonstrated that each altered its own diffusion in the nail in an apparently concentration-dependent fashion. The scale of the unexpected behavior observed may prove beneficial in the design and optimization of drug formulations to treat recalcitrant nail disease.
Cal, S; Aparicio, J F; de los Reyes-Gavilan, C G; Nicieza, R G; Sanchez, J
A new exocytoplasmic, nutritionally controlled endodeoxyribonuclease (EC 3.1.21.-) was purified to homogeneity from Streptomyces antibioticus. The enzyme showed an apparent molecular mass of 29 kDa (being active in the monomeric form) and a pI of approximately 7.8. The nuclease hydrolysed endonucleolytically double-stranded circular and linear DNA. The enzyme makes nicks in one strand of the DNA in G-rich regions, leaving either 5' or 3' short, single-stranded overhangs with 3'-hydroxy and 5'-phosphate termini. Breaks in the DNA occur when two nicks in opposite strands are close together. The enzyme had an optimum pH of 7.5 and an absolute requirement for bivalent cations and > or = 100 mM NaCl in the reaction buffer. Activity was greatly diminished in the presence of phosphate, Hg2+ or iodoacetate and was stimulated by dimethyl sulphoxide. Single-stranded DNA was a much poorer substrate than double-stranded DNA. The nuclease hydrolyses sequences of three or preferably more (dG).(dC) tracts in the DNA. The initial specificity shifts to other sequences (including sequences shorter than those initially hydrolysed) during the course of the reaction, giving the changing pattern of bands observed in agarose gels. 5-Methylcytosine-hemimethylated DNA is not hydrolysed by the nuclease. The properties of this novel enzyme suggest a relationship with class II restriction endonucleases and also with some eukaryotic nucleases. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7864833
Farag, Mayada Ragab; Alagawany, Mahmoud; Tufarelli, Vincenzo
This study was conducted to explore the potential benefits of using cinnamaldehyde (CIN), resveratrol (RES) separately or in combination on cyadox (CYA)-induced alterations in isolated rabbit erythrocytes. Erythrocytes suspensions were partitioned into 7 groups (5 replicates/group), 1st kept as control treated with phosphate buffered saline (PBS) with dimethyl sulphoxide (DMSO); 2nd group was subjected to CYA (40 μg/ml), 3rd group was incubated with CIN (40 μM), 4th group was subjected to RES (40 μM), 5th group was co-exposed to CYA (40 μg/ml) and CIN (40 μM), 6th group was co exposed to CYA (40 μg/ml) and RES (40 μM), and 7th group was exposed to CYA in combination with both CIN and RES at the same indicated concentrations. The reaction mixtures of different groups were incubated at 37 °C for 3 h with gentle shaking every 15 minutes. Our results revealed that exposure to CYA caused a significant decrease (linear and quadratic) in superoxide dismutase (SOD) and catalase (CAT) activities and the contents of reduced glutathione (GSH) and glutathione transferase (GST). Incubation of erythrocytes with CYA increased GSSG content, GSSG/GSH ratio, malonaldehyde (MDA) and protein carbonyl (PrC) concentrations while it decreased the total protein (TP). CYA also lead to hemolysis and energy depletion of erythrocytes beside activation of caspase cascades, suggesting the pro-oxidant effect CYA that could be implicated in eryptosis. CIN and RES were able to inverse these hazardous effects of CYA. However, CIN was more effective than RES, their combination showed a positive synergistic effect in protecting the cells against oxidative injury caused by CYA.
Chiu, Wing Sin; Belsey, Natalie A.; Garrett, Natalie L.; Moger, Julian; Delgado-Charro, M. Begoña; Guy, Richard H.
The effective treatment of diseases of the nail remains an important unmet medical need, primarily because of poor drug delivery. To address this challenge, the diffusion, in real time, of topically applied chemicals into the human nail has been visualized and characterized using stimulated Raman scattering (SRS) microscopy. Deuterated water (D2O), propylene glycol (PG-d8), and dimethyl sulphoxide (DMSO-d6) were separately applied to the dorsal surface of human nail samples. SRS microscopy was used to image D2O, PG-d8/DMSO-d6, and the nail through the O-D, -CD2, and -CH2 bond stretching Raman signals, respectively. Signal intensities obtained were measured as functions of time and of depth into the nail. It was observed that the diffusion of D2O was more than an order of magnitude faster than that of PG-d8 and DMSO-d6. Normalization of the Raman signals, to correct in part for scattering and absorption, permitted semiquantitative analysis of the permeation profiles and strongly suggested that solvent diffusion diverged from classical behavior and that derived diffusivities may be concentration dependent. It appeared that the uptake of solvent progressively undermined the integrity of the nail. This previously unreported application of SRS has permitted, therefore, direct visualization and semiquantitation of solvent penetration into the human nail. The kinetics of uptake of the three chemicals studied demonstrated that each altered its own diffusion in the nail in an apparently concentration-dependent fashion. The scale of the unexpected behavior observed may prove beneficial in the design and optimization of drug formulations to treat recalcitrant nail disease. PMID:26056283
Freag, May S; Elnaggar, Yosra SR; Abdallah, Ossama Y
Diosmin (DSN) is an outstanding phlebotonic flavonoid with a tolerable potential for the treatment of colon and hepatocellular carcinoma. Being highly insoluble, DSN bioavailability suffers from high inter-subject variation due to variable degrees of permeation. This work endeavored to develop novel DSN loaded phytosomes in order to improve drug dissolution and intestinal permeability. Three preparation methods (solvent evaporation, salting out, and lyophilization) were compared. Nanocarrier optimization encompassed different soybean phospholipid (SPC) types, different solvents, and different DSN:SPC molar ratios (1:1, 1:2, and 1:4). In vitro appraisal encompassed differential scanning calorimetry, infrared spectroscopy, particle size, zeta potential, polydispersity index, transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed under sink versus non-sink conditions. Ex vivo intestinal permeation studies were performed on rats utilizing noneverted sac technique and high-performance liquid chromatography analysis. The results revealed lyophilization as the optimum preparation technique using SPC and solvent mixture (Dimethyl sulphoxide:t-butylalchol) in a 1:2 ratio. Complex formation was contended by differential scanning calorimetry and infrared data. Optimal lyophilized phytosomal nanocarriers (LPNs) exhibited the lowest particle size (316 nm), adequate zeta-potential (−27 mV), and good in vitro stability. Well formed, discrete vesicles were revealed by transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed. LPNs demonstrated significant enhancement in DSN dissolution compared to crude drug, physical mixture, and generic and brand DSN products. Permeation studies revealed 80% DSN permeated from LPNs via oxygenated rat intestine compared to non-detectable amounts from suspension. In this study, LPNs (99% drug loading) could be successfully
Griffiths, Gareth; Trueman, Laurence; Crowther, Timothy; Thomas, Brian; Smith, Brian
Onion (Allium cepa L.) is botanically included in the Liliaceae and species are found across a wide range of latitudes and altitudes in Europe, Asia, N. America and Africa. World onion production has increased by at least 25% over the past 10 years with current production being around 44 million tonnes making it the second most important horticultural crop after tomatoes. Because of their storage characteristics and durability for shipping, onions have always been traded more widely than most vegetables. Onions are versatile and are often used as an ingredient in many dishes and are accepted by almost all traditions and cultures. Onion consumption is increasing significantly, particularly in the USA and this is partly because of heavy promotion that links flavour and health. Onions are rich in two chemical groups that have perceived benefits to human health. These are the flavonoids and the alk(en)yl cysteine sulphoxides (ACSOs). Two flavonoid subgroups are found in onion, the anthocyanins, which impart a red/purple colour to some varieties and flavanols such as quercetin and its derivatives responsible for the yellow and brown skins of many other varieties. The ACSOs are the flavour precursors, which, when cleaved by the enzyme alliinase, generate the characteristic odour and taste of onion. The downstream products are a complex mixture of compounds which include thiosulphinates, thiosulphonates, mono-, di- and tri-sulphides. Compounds from onion have been reported to have a range of health benefits which include anticarcinogenic properties, antiplatelet activity, antithrombotic activity, antiasthmatic and antibiotic effects. Here we review the agronomy of the onion crop, the biochemistry of the health compounds and report on recent clinical data obtained using extracts from this species. Where appropriate we have compared the data with that obtained from garlic (Allium sativum L.) for which more information is widely available.
Kuliková, Barbora; Di Iorio, Michele; Kubovicova, Elena; Kuzelova, Lenka; Iaffaldano, Nicolaia; Chrenek, Peter
The aim of this study was to evaluate the effect of the addition of Ficoll 70 into the cryopreservation medium containing sucrose and dimethyl sulfoxide (DMSO) on rabbit spermatozoa characteristics following freezing/thawing. This large molecular weight polymer elevates the viscosity of medium and, therefore, could better protect spermatozoa during the freezing process. Only ejaculates of good initial motility (>80%) were used in the experiments. Heterospermic pools were diluted in a freezing medium composed of commercial diluent, 16% dimethyl sulphoxide (DMSO) and 2% sucrose (control) or in the same medium enriched with 4% Ficoll 70 (Ficoll) and frozen in liquid nitrogen vapours for 10 min before being plunged in liquid nitrogen. The quality of fresh and frozen/thawed spermatozoa samples was evaluated in vitro using the Computer Assisted Semen Analysis (CASA) system, fluorescent probes (peanut agglutinin (PNA)-Alexa Fluor®; annexin V-FLOUS) and by electron microscopy. Better cryoprotective effect was observed when Ficoll 70 was added, compared with the semen cryopreserved with sucrose and DMSO only. The higher values (P < 0.05) of motile and progressively moving spermatozoa immediately after thawing and at 30 min following incubation at 37°C were obtained in the Ficoll group. Moreover, the higher number (P < 0.05) of acrosome intact sperm was found in the Ficoll compared with the control group. Furthermore, no significant differences in kindling rates and number of pups born between frozen/thawed and fresh semen group were found. In conclusion, our study showed that the addition of Ficoll 70 might improve several characteristics of rabbit spermatozoa measured in vitro following freezing/thawing.
Johannesen, Asa; Arge, Regin
This study has established a successful protocol to cryopreserve lumpfish Cyclopterus lumpus (Linnaeus, 1758) milt. Three cryosolutions were tested based on Mounib’s medium; the original medium including reduced l-glutathione (GSH), the basic sucrose and potassium bicarbonate medium without GSH, or with hen’s egg yolk (EY). Dimethyl sulphoxide (DMSO) was used as the cryoprotectant along with all three diluents in a 1–2 dilution. Cryopreservation was performed with the mentioned cryosolutions at two freezing rates. Motility percentages of spermatozoa were evaluated using ImageJ with a computer assisted sperm analyzer (CASA) plug-in. Findings revealed that spermatozoa cryopreserved in Mounib’s medium without GSH had a post-thaw motility score of 6.4 percentage points (pp) higher than those in the original Mounib’s medium, and an addition of EY to the modified Mounib’s medium lowered the post-thaw motility score by 19.3 pp. The difference in motility between both freezing rates was 13.0 pp, and samples cryopreserved on a 4.8 cm high tray resulted in a better post-thaw motility score. On average, cryopreserved milt had a 24.1 pp lower post-thaw motility score than fresh milt. There was no significant difference in fertilisation success between cryopreserved and fresh milt. Cryopreservation of lumpfish milt has, to our knowledge, never been successfully carried out before. The established protocol will be a main contributing factor in a stable production of lumpfish juveniles in future. PMID:26056612
Tutolo, Manuela; Ammirati, Enrico; Castagna, Giulia; Klockaerts, Katrien; Plancke, Hendrik; Ost, Dieter; der Aa, Frank Van; Ridder, Dirk De
ABSTRACT Objective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed. PMID:28124536
Pereira, D A; Williams, J A
This article reviews the origin and evolution of high throughput screening (HTS) through the experience of an individual pharmaceutical company, revealing some of the mysteries of the early stages of drug discovery to the wider pharmacology audience. HTS in this company (Pfizer, Groton, USA) had its origin in natural products screening in 1986, by substituting fermentation broths with dimethyl sulphoxide solutions of synthetic compounds, using 96-well plates and reduced assay volumes of 50-100μl. A nominal 30mM source compound concentration provided high μM assay concentrations. Starting at 800 compounds each week, the process reached a steady state of 7200 compounds per week by 1989. Screening in the Applied Biotechnology and Screening Group was centralized with screens operating in lock-step to maximize efficiency. Initial screens were full files run in triplicate. Autoradiography and image analysis were introduced for 125I receptor ligand screens. Reverse transcriptase (RT) coupled with quantitative PCR and multiplexing addressed several targets in a single assay. By 1992 HTS produced ‘hits' as starting matter for approximately 40% of the Discovery portfolio. In 1995, the HTS methodology was expanded to include ADMET targets. ADME targets required each compound to be physically detected leading to the development of automated high throughput LC-MS. In 1996, 90 compounds/week were screened in microsomal, protein binding and serum stability assays. Subsequently, the mutagenic Ames assay was adapted to a 96-well plate liquid assay and novel algorithms permitted automated image analysis of the micronucleus assay. By 1999 ADME HTS was fully integrated into the discovery cycle. PMID:17603542
Avberšek, Miha; Žegura, Bojana; Filipič, Metka; Heath, Ester
There are many published studies that use either chemical or biological methods to investigate steroid estrogens in the aquatic environment, but rarer are those that combine both. In this study, gas chromatography with mass selective detection (GC-MSD) and the ER-Calux(®) estrogenicity assay were integrated into a single protocol for simultaneous determination of natural (estrone--E1, 17β-estradiol--E2, estriol--E3) and synthetic (17α-ethinylestradiol--EE2) steroid estrogens concentrations and the total estrogenic potential of environmental samples. For integration purposes, several solvents were investigated and the commonly used dimethyl sulphoxide (DMSO) in the ER-Calux(®) assay was replaced by ethyl acetate, which is more compatible with gas chromatography and enables the same sample to be analysed by both GC-MSD and the ER-Calux(®) assay. The integrated protocol was initially tested using a standard mixture of estrogens. The results for pure standards showed that the estrogenicity calculated on the basis of GC-MSD and the ER-Calux(®) assay exhibited good correlation (r(2)=0.96; α=0.94). The result remained the same when spiked waste water extracts were tested (r(2)=0.92, α=1.02). When applied to real waste water influent and effluent samples the results proved (r(2)=0.93; α=0.99) the applicability of the protocol. The main advantages of this newly developed protocol are simple sample handling for both methods, and reduced material consumption and labour. In addition, it can be applied as either a complete or sequential analysis where the ER-Calux(®) assay is used as a pre-screening method prior to the chemical analysis.
Cerqueira, Marcos Rodrigues Facchini; Grasseschi, Daniel; Matos, Renato Camargo; Angnes, Lucio
Different materials like glass, silicon and poly(methyl methacrylate) (PMMA) are being used to immobilise enzymes in microchannels. PMMA shows advantages such as its low price, biocompatibility and attractive mechanical and chemical properties. Despite this, the introduction of reactive functional groups on PMMA is still problematic, either because of the complex chemistry or extended reaction time involved. In this paper, a new methodology was developed to immobilise glucose oxidase (GOx) in PMMA microchannels, with the benefit of a rapid immobilisation process and a very simple route. The new procedure involves only two steps, based on the reaction of 5.0% (w/w) polyethyleneimine (PEI) with PMMA in a dimethyl sulphoxide medium, followed by the immobilisation of glucose oxidase using a solution containing 100U enzymes and 1.0% (v/v) glutaraldehyde. The reactors prepared in this way were evaluated by a flowing system with amperometric detection (+0.60V) based on the oxidation of the H2O2 produced by the reactor. The microreactor proposed here was able to work with high bioconversion and a frequency of 60 samples h(-1), with detection and quantification limits of 0.50 and 1.66µmol L(-1), respectively. Michaelis-Menten parameters (Vmax and KM) were calculated as 449±47.7nmol min(-1) and 7.79±0.98mmol. Statistical evaluations were done to validate the proposed methodology. The content of glucose in natural and commercial coconut water samples was evaluated using the developed method. Comparison with spectrophotometric measurements showed that both methodologies have a very good correlation (tcalculated, 0.05, 4=1.35
Ottakam Thotiyl, Muhammed M; Freunberger, Stefan A; Peng, Zhangquan; Chen, Yuhui; Liu, Zheng; Bruce, Peter G
Rechargeable lithium-air (O2) batteries are receiving intense interest because their high theoretical specific energy exceeds that of lithium-ion batteries. If the Li-O2 battery is ever to succeed, highly reversible formation/decomposition of Li2O2 must take place at the cathode on cycling. However, carbon, used ubiquitously as the basis of the cathode, decomposes during Li2O2 oxidation on charge and actively promotes electrolyte decomposition on cycling. Replacing carbon with a nanoporous gold cathode, when in contact with a dimethyl sulphoxide-based electrolyte, does seem to demonstrate better stability. However, nanoporous gold is not a suitable cathode; its high mass destroys the key advantage of Li-O2 over Li ion (specific energy), it is too expensive and too difficult to fabricate. Identifying a suitable cathode material for the Li-O2 cell is one of the greatest challenges at present. Here we show that a TiC-based cathode reduces greatly side reactions (arising from the electrolyte and electrode degradation) compared with carbon and exhibits better reversible formation/decomposition of Li2O2 even than nanoporous gold (>98% capacity retention after 100 cycles, compared with 95% for nanoporous gold); it is also four times lighter, of lower cost and easier to fabricate. The stability may originate from the presence of TiO2 (along with some TiOC) on the surface of TiC. In contrast to carbon or nanoporous gold, TiC seems to represent a more viable, stable, cathode for aprotic Li-O2 cells.
Kim, Dong Wuk; Kim, Young Hun; Yousaf, Abid Mehmood; Kim, Dong Shik; Kwon, Taek Kwan; Park, Jung Hee; Kim, Yong Il; Park, Jae-Hyun; Jin, Sung Giu; Kim, Kyung Soo; Cho, Kwan Hyung; Li, Dong Xun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon
To develop a montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats, several montelukast sodium-loaded suspensions were prepared with a suspending agent, stabilizers and anti-aggregation agents, and their stabilities were investigated by visually observing the sedimentation phenomenon and determining the concentration of the degradation product. Moreover, dissolution and pharmacokinetic studies of the optimized formulation were examined in rats compared to commercial montelukast sodium-loaded granules. Avicel RC-591 (Avicel), a suspending agent, prevented the sedimentation of these suspensions at >2.496 (w/v) per cent composition. Amongst the stabilizers tested, fumaric acid provided the lowest concentration of montelukast sulphoxide (a degradation product) in these suspensions at 40 °C, demonstrating its excellent stabilizing activity. Furthermore, as an anti-aggregation agent, glycerin gave lower amounts of degradation product than those with poloxamer 407 and Tween 80. In particular, montelukast-loaded oral suspension, an aqueous suspension containing montelukast sodium/Avicel/fumaric acid/glycerin at a concentration of 312/2496/15.6/62.4 (mg/100 ml), and the commercial granules exhibited similar dissolution profiles in 0.5% (w/v) aqueous solution of sodium lauryl sulphate. Moreover, the pharmacokinetics in rats provided by this suspension was comparable to that of the commercial granules, suggesting that they were bioequivalent. In addition, it was physically and chemically stable at 40 °C for at least 6 months. Thus, this montelukast sodium-loaded oral suspension, with bioequivalence to the commercial granules and excellent stability, could be a prospective dosage form for the treatment of asthma.
Orabueze, Celestina Ifeoma; Adesegun, Sunday Adeleke; Coker, Herbert Alexander
Background: Petersianthus macrocarpus (Lecythidaceae) is widely used in the folk medicine in Nigeria to relieve pain and fever associated with malaria. This study evaluated the analgesic and antioxidant activities of the methanol extract and fractions of the stem bark of the plant. Materials and Methods: The analgesic activity was determined in mice using hotplate and acetic acid-induced writhing models. Morphine sulphate (5 mg/kg, i.p.) and aspirin (100 mg/ml, p.o.) were used as reference analgesic agents. The antioxidant potential was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical; reducing power, iron chelating properties and determination of total phenolic content. Results: The extract at 200 and 500 mg/kg, produced an insignificant (P > 0.05) increase in pain threshold in hotplate but a significant (P < 0.05) increase at 1000 mg/kg. The extract significantly (P < 0.05) reduced the writhing induced by acetic acid in mice in a dose dependent manner. Fractionation increased the analgesic activities significantly (P < 0.05) in ethyl acetate and aqueous fractions (200 mg/kg). The extract demonstrated strong DPPH radical scavenging activity with IC50 0.05 mg/ml, good reducing power and weak iron chelating activities. The total phenol content was 142.32 mg/gin term of gallic acid. The antioxidant effects were more pronounced in ethyl acetate and aqueous fractions. Conclusion: The findings of the study suggested that the extract has strong analgesic and antioxidant activities which reside mainly in the polar fractions thus confirming the traditional use of the plant to alleviate pains. SUMMARY Analgesic and antioxidant activities of extract and solvent fractions of Petersianthus macrocarpus investigated indicated that extract has analgesic and antioxidant properties that reside mainly in the polar fractions. Abbreviations Used: DMSO: Dimethyl sulphoxide, ANOVA: analysis of variance, EDTA: ethylene diamne tetraacetic acid, SDM: standard deviation of mean
Hennessy, DB; Curry, D; Cartwright, C; Downey, P; Pahuja, A
Introduction Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory condition of the bladder. Bladder instillation is one avenue of treatment but evidence for its effectiveness is limited. Chondroitin sulphate solution 2.0% (Urocyst) is a glycosaminoglycan (GAG) replenishment therapy instilled for patients with IC/PBS. We assessed its effectiveness for treating IC/PBS in Northern Ireland. Methods Patients with IC/PBS were assessed with the O'Leary-Sant interstitial cystitis index score and global response assessment questionnaire prior to commencing treatment. Assessment with these questionnaires was performed after 6 treatments (10 weeks) and again after 10 treatments (24 weeks). Assessment end points were pain, urgency, symptom score and problem score. Results Data was collected on 10 patients, 9 female and 1 male. 6 patients had failed RIMSO-50 dimethyl sulphoxide (DMSO) 50% treatment prior. At baseline the mean pain score was 6.6, urgency score 7.00, symptom score 13.5 and problem score 12.5. After 24 weeks the mean pain score fell to 2.0, urgency score to 1.80, symptom score to 6.89 and problem score to 5.67. At 10 weeks the global response to treatment was 100%. Nocturia was the first symptom to improve with urgency and pain following. No side effects were noted during instillation and all patients tolerated the treatments. Conclusion IC/PBS is a difficult disease to treat. It requires a multimodal approach. We found that intravesical chondroitin sulphate reduced pain, urgency and O'Leary-Sant symptom and problem scores in patients with IC/PBS. All patients tolerated the treatment and no side effects were reported. PMID:26668417
Sahu, Mahesh Chandra; Padhy, Rabindra Nath
Objective To investigate the antibacterial activity, using cold and hot extraction procedures with five solvents, petroleum ether, acetone, ethanol, methanol and water to validate medicinal uses of Butea monosperma Lam (B. monosperma) in controlling infections; and to qualitatively estimate phytochemical constituents of leaf-extracts of the plant. Methods The antibacterial activity of leaf-extracts was evaluated by the agar-well diffusion method against clinically isolated 12 Gram-positive and -negative multidrug resistant (MDR) pathogenic bacteria in vitro. Values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of leaf-extracts against each bacterium were obtained in a 96-well micro-titre plate, by broth dilution micro-titre plate technique. Results The presence of tannins, flavonoids, starch, glycosides and carbohydrates in different leaf extracts was established. Pathogenic bacteria used were, Acinetobacter sp., Chromobacterium violaceum, Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella sp., Enterococcus sp., Staphylococcus aureus (S. aureus), methicillin resistant S. aureus and vancomycin resistant S. aureus, along with standard bacterial strains. These MDR bacteria had been recorded to have significant inhibitions by leaf extracts, obtained by cold and hot extraction procedures with five solvents. In addition, the hot aqueous extract against Enterococcus sp. had the highest inhibition zone-size (21 mm). Ciprofloxacin 30 µg/disc was the positive/reference control and the diluting solvent, 10% dimethyl sulphoxide was the negative control. Recorded MIC values of different extracts ranged between 0.23 and 13.30 mg/mL, and MBC values were 0.52 to 30.00 mg/mL, for these bacteria. Conclusions Leaf-extracts with hot water and ethanol had shown significant antibacterial activity against all bacteria. B. monosperma leaf-extract could be used in treating infectious
van Dalen, C J; Kettle, A J
Eosinophil peroxidase has been implicated in promoting oxidative tissue damage in a variety of inflammatory conditions, including asthma. It uses H(2)O(2) to oxidize chloride, bromide and thiocyanate to their respective hypohalous acids. The aim of this study was to establish which oxidants eosinophil peroxidase produces under physiological conditions. By measuring rates of H(2)O(2) utilization by the enzyme at neutral pH, we determined the catalytic rate constants for bromide and thiocyanate as 248 and 223 s(-1) and the Michaelis constants as 0.5 and 0.15 mM respectively. On the basis of these values thiocyanate is preferred 2.8-fold over bromide as a substrate for eosinophil peroxidase. Eosinophil peroxidase catalysed substantive oxidation of chloride only below pH 6.5. We found that when eosinophil peroxidase or myeloperoxidase oxidized thiocyanate, another product besides hypothiocyanite was formed; it also converted methionine into methionine sulphoxide. During the oxidation of thiocyanate, the peroxidases were present as their compound II forms. Compound II did not form when GSH was included to scavenge hypothiocyanite. We propose that the unidentified oxidant was derived from a radical species produced by the one-electron oxidation of hypothiocyanite. We conclude that at plasma concentrations of bromide (20-120 microM) and thiocyanate (20-100 microM), hypobromous acid and oxidation products of thiocyanate are produced by eosinophil peroxidase. Hypochlorous acid is likely to be produced only when substrates preferred over chloride are depleted. Thiocyanate should be considered to augment peroxidase-mediated toxicity because these enzymes can convert relatively benign hypothiocyanite into a stronger oxidant. PMID:11485572
Lawson, Bianca; Clulow, Simon; Mahony, Michael J; Clulow, John
Gene banking is arguably the best method available to prevent the loss of genetic diversity caused by declines in wild populations, when the causes of decline cannot be halted or reversed. For one of the most impacted vertebrate groups, the amphibians, gene banking technologies have advanced considerably, and gametes from the male line can be banked successfully for many species. However, cryopreserving the female germ line remains challenging, with attempts at cryopreserving oocytes unsuccessful due to their large size and yolk content. One possible solution is to target cryopreservation of early embryos that contain the maternal germ line, but consist of smaller cells. Here, we investigate the short term incubation, cryoprotectant tolerance, and cryopreservation of dissociated early embryonic cells from gastrulae and neurulae of the Striped Marsh Frog, Limnodynastes peronii. Embryos were dissociated and cells were incubated for up to 24 hours in various media. Viability of both gastrula and neurula cells remained high (means up to 40-60%) over 24 hours of incubation in all media, although viability was maintained at a higher level in Ca(2+)-free Simplified Amphibian Ringer; low speed centrifugation did not reduce cell viability. Tolerance of dissociated embryonic cells was tested for two cryoprotectants, glycerol and dimethyl sulphoxide; dissociated cells of both gastrulae and neurulae were highly tolerant to both-indeed, cell viability over 24 hours was higher in media containing low-to-medium concentrations than in equivalent cryoprotectant-free media. Viability over 24 hours was lower in concentrations of cryoprotectant higher than 10%. Live cells were recovered following cryopreservation of both gastrula and neurula cells, but only at low rates. Optimal cryodiluents were identified for gastrula and neurula cells. This is the first report of a slow cooling protocol for cryopreservation of amphibian embryonic cells, and sets future research directions for
Islam, Marivil D; Haberhauer, Georg; Kist, Alla; Rathor, M Nasir; Gerzabek, Martin; Cannavan, Andrew
The translocation of antiparasitic drugs from animal excrement through soil and water to crops and forages and their recycling to food-producing animals is a potential concern with respect to the contamination of the food chain. To facilitate the investigation of this problem, an LC-MS/MS method for selected anthelmintics in soil and water was developed. The soil sample preparation involved a simple solvent extraction and dispersive clean-up technique. The method was validated at 10, 20 and 40 µg kg(-1) for levamisole, fenbendazole, fenbendazole sulphoxide and fenbendazole sulphone and at 20, 40 and 80 µg kg(-1) for eprinomectin. LOQs were 10 µg kg(-1) for the first four compounds and 20 µg kg(-1) for eprinomectin. The overall mean recoveries ranged from 76.1% to 89% for loamy soils and from 79.9% to 96.9% for sandy soils. Analysis of water samples was performed by extraction/concentration on an Oasis-HLB (Aschaffenburg, Germany) cartridge. Validation was performed at 0.25, 0.5 and 1.0 µg l(-1). The LOQ for all compounds was 0.25 µg l(-1). Method recovery (and RSD) varied between 35.4% (28) for eprinomectin and 125.1% (16) for fenbendazole sulphone. The validated methods were applied to soil and water samples in a study on the behaviour of anthelmintic drugs in a soil-plant-water system (manuscript on "transport investigation of antiparasitic drugs based on a lysimeter experiment" in preparation).
Allahtavakoli, Mohammad; Shabanzadeh, Alireza P; Sadr, Seyed Shahabeddin; Parviz, Mohsen; Djahanguiri, Bijan
1. Stroke is accompanied by a robust inflammatory response, glutamate-mediated excitotoxicity, release of reactive oxygen species and apoptosis. Thiazolidinediones, which target the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-g, have been reported recently to exhibit potent anti-inflammatory and anti-oxidant actions and inhibit both neural excitotoxicity and apoptosis. 2. The present study was conducted to determine whether rosiglitazone, a potent thiazolidinedione for PPAR-g, would show efficacy against the cerebral infarction and neurological dysfunctions induced by embolic middle cerebral artery (MCA) occlusion in the rat. 3. Focal ischaemic injury was induced by embolizing a preformed clot into the MCA. Rosiglitazone was dissolved in dimethyl sulphoxide and injected i.p. 1 h before MCA occlusion at doses of 0.33, 0.1, 0.3 or 1 mg/kg. In addition, 1 mg/kg rosiglitazone was used immediately or 4 h after embolization. Forty-eight hours after MCA occlusion, brains were removed, sectioned and stained with a 2% solution of 2,3,5-triphenyltetrazolum chloride and analysed using a commercial image-processing software program. 4. When rosiglitazone was administered 1 h before embolization, it significantly reduced infarct volume by 48.2, 68.4% and 70.3% at doses of 0.1, 0.3 and 1 mg/kg, respectively (P < 0.001). Administration of rosiglitazone (1 mg/kg) immediately or 4 h after stroke also reduced infarct volume by 67 and 50.8%, respectively (P < 0.001). Rosiglitazone-treated rats also demonstrated improved neurological functions. However, there were no statistically significant differences between control and treated groups in terms of brain oedema at 48 h after ischaemic injury. 5. The findings of the present study may support the idea of a potential benefit of thiazolidinediones in the management of ischaemic stroke.
Zheng, Yan-Zhen; Zhou, Yu; Deng, Geng; Yu, Zhi-Wu
Task-specific ionic liquids (TSILs) have been introduced by incorporating additional functional groups in the cation or anion to impart specific properties or reactivates. In this work, the hydrogen-bonding interactions between a nitrile-functional TSIL 1-propylnitrile-3-methylimidazolium tetrafluoroborate ([PCNMIM][BF4]) and dimethyl sulphoxide (DMSO) were investigated in detail by attenuated total reflection infrared spectroscopy (ATR-IR), combined with hydrogen nuclear magnetic resonance (1H NMR) and density functional theory calculations (DFT). It was found that, first, introducing a nitrile group into the alkyl chain does not change the main interaction site in the cation. It is still the C2 hydrogen. So the v(C2-H) is more sensitive to the environmental change and can be used as an indicator of the environments change of IL. Second, the wavenumber shift changes of v(C2-H) have two turning points (xDMSO ≈ 0.6 and 0.9), dividing the dilution process into three stages. Combined with the calculation results, the dilution process is identified as: From larger ion clusters to smaller ion clusters (xDMSO < 0.6), then to ion pairs (0.6
Asgari, Fatemeh; Valojerdi, Mojtaba Rezazadeh; Ebrahimi, Bita; Fatehi, Roya
To evaluate the effects slow-freezing and vitrification on three dimensional in vitro culture of preantral follicles, ovaries of 12-14 days old female NMRI mice were isolated and randomly assigned to fresh control, slow-freezing and vitrification groups. Slow-freezing was performed using programmable freezer. Vitrification was carried out in a medium consisting of ethylene glycol (EG) and dimethyl sulphoxide (Me2SO) by needle immersion method. middle sized preantral follicles were mechanically isolated and cultured for 12 days in 0.7% sodium alginate gel. The follicles development and quantitative expression of oocyte specific genes (Bmp15, Gdf9, Fgf8) and the growth related genes (Igf1, Kit, Kit-l) were assessed after 1, 8 and 12 days of culture. Both cryopreserved groups showed reduction of follicular survival rates compared to the control group on days 8 and 12 of culture (P < 0.05). Antrum formation rates reduced in slow-freezing after 12 days of culture (P < 0.05). Evaluation of gene expression showed reduction of Bmp15, Gdf9, Fgf8, Kit and Kit-l during 12 days of culture (P < 0.05). Kit and Kit-l expression in slow-freezing group significantly reduced on day 8 of culture (p < 0.05). Igf1 expression was lower in slow-freezing group on 1st day of culture than vitrification and control groups (P < 0.05). Finally, intergroup comparison showed same expression pattern of genes after 12 days of culture. Thus, cryopreservation of mouse ovaries by both methods can preserve most developmental parameters and expression of maturation genes. However, vitrification is a better method for cryopreservation of mouse ovaries due to greater antrum formation and expression of growth related markers.
Rose, J G; Heath, D F
The effects of stress (diethyl ether anaesthesia for 4-8 min, or intravenous injection of 0.05 ml of a dimethyl sulphoxide/water mixture) and of a scald injury given under ether anaesthesia on hepatic PEPCK (phosphoenolpyruvate carboxykinase, EC 22.214.171.124) were studied in the post-absorptive rat. Injury raised PEPCK activity by about 70% in 2 h and by over 100% in 4 h, over three times as fast as in animals that had only been handled (controls). The two stresses, both of types commonly imposed in animal experiments, had almost as much effect as injury for the first 2 h, although much less thereafter. The roles of sympathetic stimulation and corticosterone in mediating these rises were studied by using alpha beta-blockers and trilostane respectively as inhibitors. (Trilostane only decreased corticosterone concentrations to a little above control values.) The ether-induced increase was somewhat decreased by alpha beta-blockade, but was only eliminated by combined alpha beta-blockade and trilostane. After injury, however, PEPCK synthesis was unaffected by either alpha beta-blockade or trilostane, although it was decreased by their combined action; and it seems that either corticosterone or sympathetic stimulation was sufficient to stimulate PEPCK synthesis maximally. Stimulation by corticosterone was much greater than reported previously by others, for reasons that are discussed. Sympathetic stimulation may have been mediated by glucagon and cyclic AMP, since injury raised portal glucagon concentrations, and stress and injury raised those of hepatic cyclic AMP. PEPCK synthesis was, however, stimulated despite increases in portal insulin concentration, and was not related to the [insulin]/[glucagon] ratio. Thus stress and injury over-rode normal control mechanisms. PMID:3006659
Gounaris, A D; Slater, E E
Cysteine-proteinase activity was observed in homogenates of human-cadaver renal cortex. This activity co-purified with renin enzymic activity until separation by aminohexyl-Sepharose--pepstatin affinity chromatography. The cysteine proteinase was purified 1780-fold after the following successive chromatographic procedures: Sephadex G-75, DEAE-cellulose DE-52, and an organomercurial affinity resin. The proteinase activity was dependent upon activation by thiol-containing compounds such as dithiothreitol, as well as by EDTA, and was inhibited by the thiol-group-specific alkylating reagents iodoacetic acid and N-ethylmaleimide. DE-52 cellulose chromatography resolved the cysteine proteinase into two components. On the basis of molecular size (26 000 daltons), activity as a function of pH, stability as a function of pH, substrate specificity and thermal lability, the major component (95%) has been identified as cathepsin B. The DE-52 cellulose elution pattern of the minor component (5%) is suggestive of cathepsin H [Schwartz & Barrett (1980) Biochem. J. 191, 487-497] Enzymic activity was determined with synthetic substrates, in particular alpha-N-benzoyl-DL-arginine 2-naphthylamide (Bz-Arg-NNap), thus precluding the detection of cathepsin L [Kirschke, Langner, Wiederanders, Ansorge, Bohley & Broghammer (1976) Acta Biol. Med. Germ. 35, 285-299]. Inhibition by dimethyl sulphoxide was observed in the determination of Km = 7.0 +/- 0.4 mM for the substrate Bz-Arg-NNap, and care must therefore be taken in the preparation of substrate solutions. Images Fig. 4. PMID:7138503
Shalaby, Mona Fattouh Mohamed; El-din, Asmaa Nasr; El-Hamd, Mohammed Abu
Aim The objective of this study was to isolate, identify, and explore the in-vitro antifungal susceptibility pattern of dermatophytes isolated from clinically suspected cases of dermatophytosis (tinea infections) attending the Dermatology Outpatient Clinic. Methods This study was conducted at Sohag University Hospital from December 2014 to December 2015. Clinical samples (e.g., skin scrapings and hair stumps) were collected under aseptic precautions. The identification of dermatophytes was performed through microscopic examination using 10% potassium hydroxide (KOH) with 40% dimethyl sulphoxide (DMSO) mounts and culture on Sabouraud dextrose agar (SDA) and on Dermasel agar base media, both supplemented with chloramphenicol and cycloheximide. All dermatophytes isolates were subjected to antifungal susceptibility testing using the agar-based disk diffusion (ABDD) method against Clotrimazole, Miconazole, Fluconazole, and Griseofulvin. Data were analyzed via SPSS 16, using Chi square and a screening test (cross-tabulation method). Results A total of 110 patients of dermatophytosis were studied. The patients were clinically diagnosed and mycologically confirmed as having tinea capitis (49), tinea corporis (30), tinea pedis (16), tinea cruris (9), or tinea barbae (6). The dermatophytes isolates belonged to 4 species: Microsporum canis 58 (52.7%), Microsporum gypseum 23 (20.9%), Trichophyton mentagrophytes 18 (16.4%), and Microsporum audouinii 11 (10%). The most effective antifungal drugs tested were Clotrimazole, followed by Miconazole (95.5% and 84.5% of isolates were susceptible, respectively). Conclusion Every patient with a tinea infection should be properly studied for a mycological examination and should be treated accordingly. Dermasel agar is more useful as an identification medium in the isolation of dermatophytes. The ABDD m