Bioavailability and pharmacokinetics of a praziquantel bolus in kingfish Seriola lalandi

Oral praziquantel (PZQ) preparations have recently been investigated for the treatment of monogeneans that infect the skin and gills of kingfish Seriola lalandi cultured in sea-cages. To evaluate an oral PZQ dosing strategy, the pharmacokinetics of a dissolved and in feed oral PZQ preparation (40 mg kg(-1) body weight) were compared with an intravenous bolus in kingfish plasma and skin using HPLC. Compared with intravenous administration, PZQ bioavailability (area under curve, AUC0-24h) was slightly improved when the drug was administered with food in both kingfish plasma (56.8% in feed vs. 50.8% in solution) and skin (55.5% in feed vs. 50.3% in solution). After oral dosing, maximum drug concentrations in skin were approximately one-third of those achieved in plasma and higher when the drug was administered in solution (5.26 microg ml(-1)) than in feed (3.96 microg ml(-1)); additionally, the time to achieve maximum PZQ concentration was similar in plasma and skin, although markedly reduced when the drug was administered in solution (1 h) than in feed (6 h). However, clearance of the drug was delayed in skin; administered as an oral formulation, PZQ concentrations in the systemic circulation fell below the limit of quantification after 24 h, but remained quantifiable (0.3 microg g(-1)) in skin at this time. These initial studies indicate that a daily treatment interval will lead to the exposure of parasites to highly variable anthelmintic concentrations, which may be sub-optimal for the treatment of monogeneans in this finfish species.     

Evaluation of the transformation of organic matter to humic substances in compost by coupling sec-page

Humic acids (HAs) from soil and compost at the beginning (S0) and at the end of the stabilization process after 130 days (S130) have been fractionated by coupling size exclusion chromatography (SEC) and polyacrylamide gel electrophoresis (PAGE). Preparative quantities of HA fractions (HAFs) with different molecular sizes (MSs) and exactly defined electrophoretic mobility (EMs) have been obtained from all samples and the HAFs weight content has been studied. A high degree of similarity in HAFs weight content between soil HA and a stabilized compost HAs130 has been observed. Such data seem to be reliable for monitoring the evolution of the compost organic matter to humic substances for their agricultural uses.     

Interactions of Zn(II) Ions with Humic Acids Isolated from Various Type of Soils. Effect of pH,Zn Concentrations and Humic Acids Chemical Properties

The main aim of this study was the analysis of the interaction between humic acids (HAs) from different soils and Zn(II) ions at wide concentration ranges and at two different pHs, 5 and 7, by using fluorescence and FTIR spectroscopy, as well as potentiometric measurements. The presence of a few areas of HAs structures responsible for Zn(II) complexing was revealed. Complexation at α-sites (low humified structures of low-molecular weight and aromatic polycondensation) and β-sites (weakly humified structures) was stronger at pH 7 than 5. This trend was not observed for γ-sites (structures with linearly-condensed aromatic rings, unsaturated bonds and large molecular weight). The amount of metal complexed at pH5 and 7 by α and γ-structures increased with a decrease in humification and aromaticity of HAs, contrary to β-areas where complexation increased with increasing content of carboxylic groups. The stability of complexes was higher at pH 7 and was the highest for γ-structures. At pH 5, stability decreased with C/N increase for α-areas and -COOH content increase for β-sites; stability increased with humification decrease for γ-structures. The stability of complexes at α and β-areas at pH 7 decreased with a drop in HAs humification. FTIR spectra at pH 5 revealed that the most-humified HAs tended to cause bidentate bridging coordination, while in the case of the least-humified HAs, Zn caused bidentate bridging coordination at low Zn additions and bidentate chelation at the highest Zn concentrations. Low Zn doses at pH 7 caused formation of unidentate complexes while higher Zn doses caused bidentate bridging. Such processes were noticed for HAs characterized by high oxidation degree and high oxygen functional group content; where these were low, HAs displayed bidentate bridging or even bidentate chelation. To summarize, the above studies have showed significant impact of Zn concentration, pH and some properties of HAs on complexation reactions of humic acids with zinc.     

Bioactivity of humic acids isolated from vermicomposts at different maturation stages

Background and aims

Vermicomposts are useful to improve environmental quality and sustainable agriculture. Moreover, it is enriched with highly bioactive humic acids (HAs)-like substances and can substitute no-renew source of humic substances to use as plant growth promoters in agriculture. The aim of this work was to evaluate the biological effects of HAs isolated at increasing vermicompost maturation stages.

Methods

Lateral root emergence, aqueous growth medium acidification and proton pumps of maize seedlings were used to monitor HAs bioactivity. Molecular conformation of the HAs was determined by size-exclusion and reverse-phase high performance liquid chromatography. We applied spectroscopy ¹³C-NMR on VC samples to follow the humification process.

Results

We observed a decrease of carbohydrate content and selective preservation of hydrophobic alkyl and aryl C components by ¹³C-NMR during vermicompost maturation. Apparent molecular weight distribution of HAs did not change with vermicompost maturation, but was possible observed increase on hydrophobic moieties.

Conclusion

After 60 days of vermicomposting, all HAs promotes lateral root emergence, acidification of growth aqueous medium and induction of proton pumps without changes on apparent molecular weight but with enhance on hydrophobic domains.     

Induction of drug-metabolizing enzymes and aryl hydrocarbon hydroxylase by microscope immersion oil

Microscope immersion oil when administered intraperitoneally or applied to skin in experimental animals substantially increased liver weight, microsomal protein, NADPH-cytochrome c reductase activity, cytochrome P-450 content and the metabolism of the model substrates, ethylmorphine and benzo(a)pyrene. Immersion oil caused the induction of the polycyclic hydrocarbon type of hemoprotein, cytochrome P-448. When applied to skin, the oil also caused an 11-fold increase in benzo(a)pyrene hydroxylase activity at the skin sites.     

Antigastrolesive, gastric antisecretory, diarrheagenic and mucus-stimulating effects in rats following topically applied rioprostil, a synthetic prostaglandin E1 analog

Prostaglandins may have many biological actions including hypotensive and antipeptic ulcer activity. The purpose of this investigation was to determine if the primary alcohol prostaglandin E1 analog rioprostil1 prevents ethanol-induced gastric lesions (antigastrolesive activity), inhibits gastric acid secretion (antisecretory activity), or causes diarrhea in rats when administered topically, and to compare these responses to the effect of rioprostil following enteral (oral or intraduodenal) administration. Rioprostil exhibited antigastrolesive activity in rats when administered either orally or when applied topically. The topical antigastrolesive potency of rioprostil against ethanol-induced lesions [ED50 = 3.7 (0.5-12) micrograms/kg] was similar to its oral potency [ED50 = 1.9 (1.7-2.2) micrograms/kg]. In 4 hr pylorus-ligated rats, topically administered rioprostil inhibited total gastric acid output with a potency [ED50 = 5.1 (2.6-24) mg/kg] similar to intraduodenal administration [ED50 = 3.7 (2.8-5.3) mg/kg]. In addition, in these rats rioprostil increased mucin levels and did not cause dermal irritation. Finally, the incidence of diarrhea was lower when rioprostil was applied topically than when given orally with a 16-fold difference in potency between these two routes of administration. These data show that when rioprostil is applied via the skin it has antigastrolesive, gastric antisecretory and mucus stimulatory effects in rats equal to enteral administration, and a diarrheagenic potency lower than following oral administration. This profile suggests that topical administration of rioprostil may be a useful means of delivery for clinical treatment of peptic ulcer disease.     

Description of characteristics of humic substances from different waste materials

Humic acids (HAs) extracted from different organic wastes have been characterised by chemical methods. The chemical properties of HAs showed differences depending on the source from which they were obtained. The C content in HAs from organic wastes (41.1-63.2%) fluctuated around the C value in soil HA with the exception of composted bark and tobacco dust. Compared with soil HA, the N contents of HAs from sewage sludge and brewery sludge were found much higher than the others. E4:E6 ratios for HAs in organic wastes were generally greater than that for soil HA, which indicated a low degree of condensation and humification. The carboxyl and phenolic-OH group contents ranged 0.51-2.23 and 11.1-20.7 meq g(-1), respectively. High values of carboxyl and phenolic-OH contents indicated that these materials were still within early stages of humification.     

Hydration state of goats transported by road for 12 hours during the hot-dry conditions and the modulating role of ascorbic acid

This study investigated the effects of 12 hr of road transportation during the hot-dry conditions and the modulating role of ascorbic acid (AA) on the hydration state of goats. Twenty goats who served as treatment goats received oral administration of 100 mg/kg body weight of AA, whereas another 20 control goats received sterile water; thereafter, the goats were loaded and transported. The study determined changes in skin thickness; albumin (Alb); total protein (TP); elimination of the gut content; fecal water; urine specific gravity (SG); and pH before, during, and after the transportation. The result obtained in the control goats showed significant (p < .05) increases in the values of TP, Alb, urine SG, and pH; elimination; and drinking behavior, whereas skin thickness decreased over transportation. In the treatment goats who were administered AA, the changes observed in the values were insignificant (p > .05). In conclusion, 12-hr road transportation of goats induced dehydration, which may affect the welfare and health status of the goats. The administration of AA ameliorated the risk of adverse effects of handling, loading, transportation, and hot-dry conditions on hydration state of goats.     

A quantitative histochemical study of three oxidative enzymes in solar keratoses and Bowen's disease

Synopsis Succinate dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH) activities have been studied using quantitative enzyme histochemical techniques in the epidermis of five patients with solar keratoses and Bowen's disease. Non sun-exposed buttock skin was compared with the skin from the actual lesion and adjacent, clinically normal paralesional skin. SDH activity was significantly increased in the basal layer and decreased in the granular layer in the epidermis of both lesion and paralesional skin, although the total epidermal activities were unchanged when compared to non-exposed buttock skin. G6PDH activity was increased in the granular layer of paralesional epidermis and of lesions. No change in LDH activity was detected. Inclusion of phenazine methosulphate in the reaction mixtures resulted in a three-fold increase in formazan deposition without altering the localization.It is concluded that the quantitative changes and alteration in localization of SDH and G6PDH reported in solar keratoses are accompanied by similar changes in adjacent, clinically normal sun-exposed skin and differ from normal non-exposed skin. It is suggested that these changes may precede the development of the solar keratoses and that these findings may indicate a significant metabolic alteration in the events that lead to neoplasia.     

Effects of leptin and cholecystokinin in rats with a null mutation of the leptin receptor Lepr(fak)

The Koletsky ("corpulent) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor (Lepr) that results in hyperphagia, obesity, and hyperlipidemia. Unlike the Lepr mutation that characterizes the fatty Zucker rat (Lepr(fa)), the Koletsky mutation (Lepr(fak)) is null. Because the Lepr(fak) mutation is null, exogenous leptin should have no effect on body weight or food intake in fa(k)/fa(k) rats. We confirmed that prediction: murine leptin, administered into the third ventricle for 5 consecutive days, did not affect daily food intake or body weight in fa(k)/fa(k) rats but produced dose-related inhibitions of food intake and body weight in +/+ and +/fa(k) rats. Although fa(k)/fa(k) rats did not respond to leptin, their response to CCK-8 (4 microg/kg ip) injected before 30-min test meals of 10% sucrose was not different from that of +/+ or +/fa(k) rats. These results demonstrate that the fa(k)/fa(k) rat is a good model in which to analyze the controls of food intake, energy expenditure, and energy storage in the absence of leptin effects.     

Lack of carcinogenicity of agaritine by subcutaneous administration in mice

Agaritine (A), an ingredient of the cultivated mushroom of commerce Agaricus bisporus, was administered by subcutaneous injection to two groups of randomly bred Swiss mice. In the first group the animals of both sexes were treated at a 100 g/g body weight basis five times at weekly intervals, while in the second group the mice received a single A treatment of 100 g/g body weight for females and 50 g/g body weight for males. The administration of the compound resulted in no detectable carcinogenic effect in the animals. Since some of the breakdown products of A were shown to be carcinogenic in mice and the mushroom itself was found to be mutagenic, the field is discussed in the light of the obtained results.     

Low dose Oral Interferon Alpha 2a in HIV-1 Seropositive Patients: A Double-blind, Placebo-controlled Trial

Low dose oral interferon alpha has been shown to be of benefit in viral disease in animals. In a double-blind, placebo-controlled trial, 177 patients seropositive for HIV-1 were randomly assigned to receive placebo or recombinant human interferon alpha 2a (rIFN). Endpoints were survival, alteration of disease classification, performance, and changes in CD4+ T cell numbers. There was a trend for improved survival in the group receiving rIFN at the dose of 1.0 IU/lb. The changes in disease classification or in weight were not significantly different. Performance was improved to a greater extent (p=0.1) in the patients who received the two higher rIFN dosages (1.0 IU/lb and 10.0 IU/lb) at 6 months. In addition, the CD4+ T cell count was improved only in the 1.0 IU/lb dose treatment group at 6 months. Treatment with low dose oral interferon at 1.0 IU/lb was associated with improved CD4+ T cell count, performance and a trend toward enhanced survival in HIV seropositive patients. These differences were, however, not statistically significant. A larger study, with better return rate, will be needed to determine whether low dose, oral interferon alpha is actually beneficial for these patients.     

Role of humic acid fraction with higher aromaticity in enhancing the activity of a biomimetic catalyst, tetra(p-sulfonatophenyl)porphineiron(III)

To elucidate the structural features of humic acids (HAs) that potentially contribute to enhancing the activity of a tetra(p-sulfonatophenyl)porphineiron(III) (Fe(III)-TPPS) catalyst, the effects of the chemical properties of molecular weight fractionated HAs on the catalytic activity of Fe(III)-TPPS were investigated. Three fractions were obtained as the following order of molecular size: F3 < F2 < F1. The deactivation of Fe(III)-TPPS, which can be attributed to the self-degradation of Fe(III)-TPPS, was retarded in the presence of HAs, and the pseudo-first-order rate constant in the presence of F3 was the smallest of the three fractions. In addition, the highest catalytic activity, determined as the percent degradation of an organic substrate, was observed in the presence of F3. The enhanced catalytic activity of Fe(III)-TPPS was due to the formation of supramolecular complexes with HAs, and the formation constant for F3 was the largest. Thus, the F3 fraction was the most effective fraction. Solid-state CPMS 13C NMR spectra indicated that the aromaticity of F3 was the highest of all of the fractions. Thus, it can be concluded that aromatic moieties in HAs play an important role in the formation of supramolecular complexes with Fe(III)-TPPS, leading to an enhancement in catalytic activity.     

Increasing effect of an oral intake of L-hydroxyproline on the soluble collagen content of skin and collagen fragments in rat serum

We examined the effects of oral L-hydroxyproline (Hyp) on collagen in the body. After 2 weeks' administration of Hyp (0.5 or 1 g/kg) to F344 male rats, the soluble collagen content of the skin had increased, and the serum concentration of collagen peptides was correlated with the skin content of soluble collagen. This result suggests that oral Hyp augmented collagen metabolism.     

Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-α-lipoic acid

The present study investigated the protective effect of DL--lipoic acid on the tissue peroxidative damage and abnormal antioxidant levels in cyclophosphamide (CP) induced hepatotoxicity. Male Wistar rats of 140± 20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce hepatotoxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to the CP administration). A vehicle (saline) treated control group and a lipoic acid drug control group were also included. The extent of liver damage in CP-induced rats was evident from the increased activities of serum aminotransferases, alkaline phosphatase and lactate dehydrogenase; whereas lipoic acid pretreatment prevented the rise in these marker enzymes. We evaluated the changes in activities/levels of tissue enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) and non-enzymic (reduced glutathione, ascorbate and -tocopherol) antioxidants along with malondialdehyde levels in the experimental groups. In CP-administered rats the antioxidant enzymes showed significantly depressed activities (p < 0.001, p < 0.01) and the antioxidant molecules also showed depleted levels (p < 0.001, p < 0.01), in comparison with the control group. However the extent of lipid peroxidation and the abnormal antioxidant status were normalized in lipoic acid pretreated rats. The present work highlights the efficacy of lipoic acid as a cytoprotectant in CP-induced hepatic oxidative injury.     

A Randomized Double-Blind Crossover Study of the Antiobesity Effects of Etiocholanedione

Etiocholanedione (ED), a natural metabolite of dehy-droepiandrosterone, has antiobesity effects in animals when given orally and is nontoxic. We carried out a trial of oral ED in obese humans. In a 20-week randomized double-blind crossover study, 14 subjects lost significantly more weight and body fat during treatment with oral ED, 4 gm daily, than during placebo administration. Mean weight loss during ED administration was 2.8 ± 5.5 kilograms, which was equivalent to 0.53 k 0.91 kilograms per week per 100 kilograms of body fat; mean weight change during placebo administration was essentially zero: M.21 ± 4.2 kg, or 4.04 ± 0.74 kg/wk/100 kg body fat. The difference between the weight changes in the two periods was significant: for A kg, P<0.05; for Δ kg/wk/100 kg body fat, P<0.03. Densitometric measurement of body fat content showed that the mean weight loss coincided almost exactly with the mean decrease in fat content; thus, over the 10-week period of ED administration, the mean fat loss was about 5% of the initial body fat content. Three of the obese subjects had strikingly greater fat loss, about 18%, 19%, and 25% of the initial body fat content. There were no significant subjective or objective side effects of ED administration .     

Hydration State of Goats Transported by Road for 12 Hours During the Hot-Dry Conditions and the Modulating Role of Ascorbic Acid

This study investigated the effects of 12 hr of road transportation during the hot-dry conditions and the modulating role of ascorbic acid (AA) on the hydration state of goats. Twenty goats who served as treatment goats received oral administration of 100 mg/kg body weight of AA, whereas another 20 control goats received sterile water; thereafter, the goats were loaded and transported. The study determined changes in skin thickness; albumin (Alb); total protein (TP); elimination of the gut content; fecal water; urine specific gravity (SG); and pH before, during, and after the transportation. The result obtained in the control goats showed significant (p < .05) increases in the values of TP, Alb, urine SG, and pH; elimination; and drinking behavior, whereas skin thickness decreased over transportation. In the treatment goats who were administered AA, the changes observed in the values were insignificant (p > .05). In conclusion, 12-hr road transportation of goats induced dehydration, which may affect the welfare and health status of the goats. The administration of AA ameliorated the risk of adverse effects of handling, loading, transportation, and hot-dry conditions on hydration state of goats.     

Vaccine design of hemagglutinin glycoprotein against influenza

Influenza viruses continue to cause annual epidemics and pose the threat of a deadly global pandemic. Vaccination has remained the best approach for prevention and control of influenza infection. However, current influenza vaccines are only effective against closely-matched circulating strains, and therefore must be updated and administered every year. In this review, we discuss recent developments in the search for better influenza vaccines, especially using the major virus surface glycoprotein hemagglutinins (HAs). Understanding how glycans on HAs affect the immune response and knowledge of how broadly neutralizing antibodies are induced will pave the way for a cross-protective influenza vaccine that does not require frequent updates or annual immunizations.     

Humic acids reduce the genotoxicity of mitomycin C in the human lymphoblastoid cell line TK6

The antimutagenic/desmutagenic activity of a leonardite humic acid (LHA) and a soil humic acid (SHA) was studied in the cultured human lymphoblastoid cell line TK6 treated with mitomycin C (MMC) as reference mutagen by evaluating the induction of micronuclei (MN). Two different concentrations of HA were used, 2.5 and 10 microg/ml, in three different treatments: (1) HA alone (genotoxic test); (2) HA after 2-h pre-incubation with 0.3 microM of MMC (desmutagenic test) and (3) combinations of HA and MMC at 0.3 microM without pre-incubation (antimutagenic test). Neither of the HA used alone did produce genotoxic effects, but both HAs reduced significantly the frequencies of MN induced by MMC, especially in the desmutagenic test. A slight cell-protective effect against the cytotoxicity of MMC was also exhibited by the two HAs in the desmutagenic test. The LHA showed a desmutagenic/antimutagenic activity that was more pronounced than that of SHA, which is possibly related to the higher carboxylic group content and lower phenolic group content of LHA. These results confirm the antigenotoxic action exerted by HAs in human cells, similarly to what has been previously observed in various plant species.     

Increasing Effect of an Oral Intake of L-Hydroxyproline on the Soluble Collagen Content of Skin and Collagen Fragments in Rat Serum

We examined the effects of oral L-hydroxyproline (Hyp) on collagen in the body. After 2 weeks' administration of Hyp (0.5 or 1 g/kg) to F344 male rats, the soluble collagen content of the skin had increased, and the serum concentration of collagen peptides was correlated with the skin content of soluble collagen. This result suggests that oral Hyp augmented collagen metabolism.