Can Kelp Extract (KELPAK®) be Useful in Seaweed Mariculture?

The addition of low concentrations of commercial kelp extract (Ecklonia maxima: Kelpak^®) in addition to fertiliser has proven to be beneficial in agriculture. It triggers rooting in field crops, increases yields and has other useful effects, such as parasite reduction. Its efficacy has been attributed to the fact that Kelpak^® is produced by a cold process, and is a high auxin/low cytokinin product. The aim of this study was to investigate if seaweeds (which do not have a root system) grown in culture systems, would benefit from the addition of Kelpak^® or a combination of Kelpak^® and fertilizer. A preliminary laboratory experiment was carried out by growing excised 15 mm tips of the red alga Gracilaria gracilis in culture dishes containing Provasoli Enriched Seawater medium to which various concentrations of Kelpak^® were added. Gracilaria tips in some of the Kelpak^® treatments (1:2500; 1:1000; 1:500) grew significantly better than the control. Further experiments were carried out on a pilot commercial scale at Jacobsbaai Sea Products Ltd. on the South African west coast. Ulva lactuca was grown in effluent from fish (turbot) culture, with additions of 1:5000, 1:2500 and 1:500 concentrations of Kelpak^® once a week. The intermediate Kelpak^® concentration (1:2500) produced the highest growth of Ulva in the turbot water, while the highest Kelpak^® concentration (1:500) inhibited Ulva growth. In another Ulva experiment, various combinations of aquaculture effluent water, commercial fertiliser and Kelpak^® at 1:2500 were used. Best growth of Ulva was obtained in turbot water containing both fertiliser and Kelpak^®. The results suggest that Kelpak^® could be useful in commercial seaweed mariculture operations.     

Fate of 3-Allyloxy-1,2-benzisothiazole 1,1-Dioxide (Oryzemate®) in Rice Plants

Studies on absorption, translocation and metabolism of 3-allyloxy-1,2-benzisothiazole 1,1-dioxide (Oryzemate), a new rice blast controlling agent, in rice plants were undertaken using the ³⁵S-labeled preparation. Oryzemate was administrated to the plants by liquid application. Uptake of labeled compound into rice plants was demonstrated by autoradiography and quantitative ³⁵S-analyses. Preferential accumulation of radioactive compounds in the leaves was observed. The metabolites in the plants were identified as allyl o-sulfamoylbenzoate, saccharin and N-d-glucopyranosylsaccharin by cochromatography and cocrystallization with synthesized authentic compounds. Most of ³⁵S-labeled compounds accumulated in the plants were saccharin and N-d-glucopyranosylsaccharin. A small amount of allyl o-sulfamoylbenzoate was detected and Oryzemate was detectable in trace quantities at all harvest.     

Genital lesions in male red fronted gazelles (Gazella rufifrons) experimentally infected with Trypanosoma brucei and the effect of melarsamine hydrochloride (Cymelarsan®) and diminazene aceturate (Berenil®) in its treatment

Thirty red fronted gazelles (Gazella rufifrons) were used to assess the genital lesions associated with trypanosomosis and the efficacy of melarsamine hydrochloride (Cymelarsan^®) and diminazene aceturate (Berenil^®) in the treatment of the condition. The animals were divided into 6 equal groups (A-F). Animals in groups A-E were infected with Trypanosoma brucei, and later treated on day 8 post infection (p.i.) with either melarsamine hydrochloride (Cymelarsan^®) at 0.3 mg/kg (Group A) and 0.6 mg/kg (Group B) or diminazene aceturate (Berenil^®) at 3.5 mg/kg (Group C) and 7.0 mg/kg (Group D). Animals in group E remained untreated while group F served as healthy controls. Parasitaemia was established by day 8 p.i. in all infected groups and eliminated by day 16 following treatment on day 8 p.i. with melarsamine hydrochloride (Cymelarsan^®) (Groups A and B) or diminazene aceturate (Berenil^®) (Group D). On the other hand, diminazene aceturate treatment (Berenil^®) on day 8 p.i. at 3.5 mg/kg (Group C) caused a temporary disappearance of parasites from the circulation by day 16 p.i. but there was a relapse parasitaemia on day 44 with a peak count of 500 ± 2.79 × 10³ parasites/μL of blood by day 52 p.i. In the infected/untreated group (E), parasitaemia fluctuated but attained the same peak as Group C by day 52 p.i. Increase in body temperatures (40.5 ± 3.16 - 42.8 ± 3.25 °C) occurred during the first wave of parasitaemia but declined to pre-infection values from day 28 p.i. in Groups A, B and D. In Groups C and E, there was a second wave of parasitaemia (P < 0.05) with peak counts of 42.4 ± 0.81 × 10³/μL and 41.8 ± 0.80 × 10³/μL respectively by day 52 p.i. A significant (P < 0.05) decline in packed cell volume was also noted by day 52 p.i. The major clinical signs observed in Groups C and E were pyrexia, inappetance, emaciation, anaemia, dullness, starry hair coat, pallor of buccal and ocular mucous membranes. Similarly, in Groups C and E, the testicles appeared oedematous and painful to touch with degenerative changes, morphological sperm abnormalities and oligospermia with 2.0% and 0% sperm reserves respectively. Sperm reserve was 100% in Groups A, B and D. It is therefore, concluded that trypanosomosis can cause serious infertility in male red fronted gazelles and that early treatments with melarsamine hydrochloride (Cymelarsan^®) at 0.3 and 0.6 mg/kg body weight or diminazene aceturate (Berenil^®) at 7.0 mg/kg body weight may prevent such effects.     

Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (orthene®)

Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5–2 ppm acephate. The regions exhibited cholinesterase recovery at 2–16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: 1) ChE resistance threshold, 2) ChE compensation threshold, and 3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.     

Absorption and Translocation of O-Ethyl S,S-Diphenyl Phosphorodithiolate (Hinosan®) in Rice Plants

Absorption and translocation of (O-ethyl S,S-diphenyl phosphorodithiolate (Hinosan) in rice plants were studied by means of techniques of gas-liquid chromatography, radioautograph and ³²P-radioactivity determination. ³²P-labeled Hinosan was used in the present study. Hinosan on the surface of a leaf and on a glass plate was dissipated in a much slower rate than the other phosphorus pesticides tested. Hinosan was chemically transformed to a small extent after taken up into the plant tissues and largely remained in the local region. Up- and downward translocation of Hinosan occurred slightly in the ride seedlings. Translocation and accumulation of Hinosan were also studied concerning with growth stage of rice plants, such as the seedling, the milk-ripening, and the ripening stage. Accumulation in grains was in most cases found to be less than the limit of determination. Translocation of Hinosan was discussed in relation to physiological conditions of rice plants.     

Toxicological implications of a commercial formulation of deltamethrin (Decis®) in developing chick embryo

A deltamethrin containing insecticide formulation (Decis®) was evaluated for its toxic potential in developing chick embryos. For the present study, three water emulsified concentrations of Decis® (12.5 mg L^?1, 25 mg L^?1, and 50 mg L^?1) were used. Fertilized eggs of Gallus domesticus were immersed in these three concentrations of the insecticide for 60 min at 37°C on day 0 of incubation and kept for incubation till embryonic day 7. Recovered embryos were evaluated for teratogenic and biochemical changes. The results revealed that administration of Decis® at its lower concentrations (12.5 mg L^?1 and 25 mg L^?1) did not show any significant teratological changes but the significant number of abnormal survivors was observed at 50 mg L^?1 of dose concentration when compared with vehicle-treated control. Among biochemical changes, total glycogen and RNA contents of embryos was significantly decreased at 25 mg L^?1 and 50 mg L^?1 of Decis® concentrations. Similarly, significant alteration (p ≤ .05) was observed in alanine transaminase activity at 50 mg L^?1 concentration of Decis®. Thus, the present study concluded that the no-effect-level for developmental toxicity for Decis® is below the concentration of 25 mg L^?1 under standard laboratory conditions.     

Pharmacokinetics,Biodistribution and Therapeutic Efficacy of Doxorubicin Encapsulated in Stealth® Liposomes (Doxil®)

Abstract

Doxil® (Stealth® liposomal doxorubicin HCl) Injection is doxorubicin HCl incorporated into long circulating liposomes that contain surface-grafted polyoxyethylene chains. These surface-grafted polymer chains reduce the interaction of the liposomes with the mononuclear phagocytic system, accounting for the long circulation and altered biodistribution of Stealth liposomes. They also reduce adhesion of the liposomes to cells, blood vessel walls and other surfaces and result in increased vascular permeability of Stealth liposomes compared to conventional liposomes of equal size. Efficacy studies in several tumor models, including human xenograft models, have demonstrated that Doxil is more effective than unencapsulated doxorubicin (Adriamycin) or doxorubicin encapsulated in non-coated conventional liposomes. Doxil exhibits altered plasma pharmacokinetics, with a longer plasma half-life, large AUC and markedly smaller volume of distribution than Adriamycin. Tissue levels of doxorubicin are generally lower in Doxil-treated animals than in animals that receive an equivalent dose of Adriamycin, and Doxil is less cardiotoxic, myelotoxic and nephrotoxic than Adriamycin. Phase I and II studies evaluating the efficacy of Doxil in AIDS-related Kaposi sarcoma have been encouraging, with evidence of increased delivery of drug to the lesions and an overall good response to therapy. The increased efficacy of Doxil is believed to be related to its increased extravasation through the leaky tumor vasculature and its accumulation in tumor tissue.     

First detection of chlorfenapyr (Secure®) resistance in two-spotted spider mite (Acari: Tetranychidae) from nectarines in an Australian orchard

Chlorfenapyr resistance (2.9- and 19.9-fold respectively at LC50 and LC99 level) was detected in Tetranychus urticae Koch causing control failure following a single application of product to nectarines.     

Metabolic Transformation and Accumulation of O-Ethyl S,S-Diphenyl Phosphorodithiolate (Hinosan®) in Rice Plants

³²P-labeled organophosphorus fungicide Hinosan was sprayed on rice plants at various growth stages, and metabolic fate of the pesticide in the rice plants was studied. Identification of Hinosan and its metabolites in the n-hexane and water extracts was conducted by TLC and GLC (FPD).

The rate of hydrolysis of Hinosan in rice plants seemed to be slower than that of other organophosphorus pesticides. Hexane-soluble components, which were detected throughout the experimental period, consisted mainly of Hinosan. Among the water-soluble metabolites identified were O-ethyl S-phenyl phosphorothioic acid and S,S-diphenyl phosphoro- dithioic acid, which were detected one to four days after the application, and ethyl phosphate and phosphoric acid which increased with the lapse of time.

Upon examination of the radioactivity of Hinosan and its metabolites in rice grains, a certain level was detected in husk, but very little in hulled rice and polished rice.     

Gas Chromatographic Determination of a New Fungicide,Procymidone (Sumilex®) in Technical Preparation and Formulation

Monoclonal antibodies (MoAbs) reacting with human G-CSF and /or its muteins were established by cell fusion between P3.X63/Ag8.U1 myeloma cells and spleen cells from BALB/C mice immunized with recombinant human intact G-CSF or its mutein, designated ND28. Two MoAbs reacted with intact G-CSF and all kinds of muteins tested, designated KM341 and KM342, and two MoAbs specific for intact G-CSF, designated KM340 and KM343, were obtained from the mice immunized with recombinant human intact G-CSF.

The sera from the mice immunized with a mutein of G-CSF, ND28, reacted with intact G-CSF and all muteins tested. Two MoAbs specific for ND28, designated KM498 and KM511, were obtained from these mice. These MoAbs seem to recognize the sequence of a few amino acids that is peculiar for ND28. However, the epitopes recognized by KM498 and KM511 were maybe subtly different, because KM498 and KM511 could not completely inhibit each other.

Human G-CSF and/or its muteins could be measured by sandwich ELISA using these MoAbs with suitable combinations. The immuno-affinity column using KM342 or KM498 adsorbed G-CSFs or specifically ND28, previously. By elution with 0.15m NH₄OH, the G-CSFs or ND28 were eluted with a high recovery.     

Genetic mapping of non-target-site resistance to a sulfonylurea herbicide (Envoke®) in Upland cotton (Gossypium hirsutum L.)

Acetolactate synthase (ALS) is responsible for a rate-limiting step in the synthesis of essential branched-chain amino acids. Resistance to ALS-inhibiting herbicides, such as trifloxysulfuron sodium (Envoke^®), can be due to mutations in the target gene itself. Alternatively, plants may exhibit herbicide tolerance through reduced uptake and translocation or increased metabolism of the herbicide. The diverse family of cytochrome P450 proteins has been suggested to be a source of novel herbicide metabolism in both weed and crop plants. In this study we generated a mapping population between resistant and susceptible cotton (Gossypium hirsutum L.) cultivars. We found that both cultivars possess identical and sensitive ALS sequences; however, the segregation of resistance in the F2 progeny was consistent with a single dominant gene. Here we report the closely linked genetic markers and approximate physical location on chromosome 20 of the source of Envoke herbicide susceptibility in the cotton cultivar Paymaster HS26. There are no P450 proteins in the corresponding region of the G. raimondii Ulbr. genome, suggesting that an uncharacterized molecular mechanism is responsible for Envoke herbicide tolerance in G. hirsutum. Identification of this genetic mechanism will provide new opportunities for exploiting sulfonylurea herbicides for management of both weeds and crop plants.     

Suppressive effect on food intake of a potato extract (Potein®) involving cholecystokinin release in rats

We have recently reported that oral gavage of a potato extract (Potein?) suppressed the food intake in rats. The satiating effect of the potato extract was compared in the present study to other protein sources, and the involvement of endogenous cholecystokinin (CCK) secretion was examined. Food consumption was measured in 18-h fasted rats after oral gavage of the potato extract or other protein sources. The CCK-releasing activity of the potato extract was then examined in anesthetized rats with a portal cannula. Oral gavage of the potato extract reduced the food intake in the rats, the effect being greater than with casein and a soybean β-conglycinin hydrolysate. The suppressive effect on appetite of the potato extract was attenuated by treating with a CCK-receptor antagonist (devazepide). The portal CCK concentration was increased after a duodenal administration of the potato extract to anesthetized rats. These results indicate that the potato extract suppressed the food intake in rats through CCK secretion.     

Region-specific effects of STW 5 (Iberogast®) and its components in gastric fundus,corpus and antrum

Functional dyspepsia (FD) is a disorder that involves impaired gastric accommodation, antral hypomotility, and upper abdominal pain. The herbal drug STW 5 (Iberogast^®) is used to successfully treat FD patients. Here, we report in vitro data revealing the mode of action of STW 5 and its individual herbal extracts on gastric motility. STW 5 evoked a relaxation of the proximal stomach but increased antral motility. Both effects are myogenic. The extracts of Angelica root, chamomile flower and liquorice root mimicked the inhibitory effects in the proximal stomach whereas the extracts of greater celandine herb, Melissa leaf, caraway fruit and bitter candy tuft increased motility of the proximal stomach. All extracts increased motility in the antrum comparable to the effects of STW 5. We conclude that the differential effects of STW 5 on proximal and distal stomach motor activity are not caused by solely spasmolytic or anti-spasmolytic effects of the individual components. It is suggested that the individual extracts target transduction mechanisms that are specifically expressed in the proximal vs. distal stomach. We present a rationale for the differential effect of STW 5 which is a result of the combined actions of its individual components and reason that the inhibitory effects in the proximal and the excitatory effects in the distal stomach may contribute to symptom relief in FD patients treated with STW 5 (Iberogast^®).     

Absorption,Translocation and Metabolism of O,O-Diisopropyl S-Benzyl Phosphorothiolate (Kitazin P®) in Rice Plant

Behavior and metabolism of O,O-diisopropyl S-benzyl phosphorothiolate (Kitazin P©) in rice plant were examined using ³²P, ³⁵S-double labeled compound. Uptake of Kitazin P by the plant was different with the growth stages of the plant, and the rate of uptake was rapid in early growth stage. Kitazin P penetrated into plant tissues was gradually hydrolyzed to produce O,O-diisopropyl hydrogen phosphorothioate which was converted to diisopropyl hydrogen phosphate, isopropyl dihydrogen phosphate and phosphoric acid. As toluene soluble metabolites, eight spots were detected by thin-layer chromatography, but their percentages in toluene soluble fraction were extremely low as compared with that of Kitazin P. Only two metabolites, dibenzyl disulfide and O,O-diisopropyl O-benzyl phosphorothionate were identified by a gas-liquid chromatography with a flame thermionic detector or a flame photometric detector. Diisopropyl hydrogen phosphorothioate was detected as a persistent metabolite even in rice grains.     

Yttrium 90 ibritumomab tiuxetan (Zevalin®): A new bullet in the fight against malignant lymphoma?

Targeted immunotherapy utilizing monoclonal antibodies has improved survival in both indolent and aggressive lymphoma significantly. Since malignant lymphomas are also responsive to radiation, the combination of targeted immunotherapy and radiation with radionuclide coupled to monoclonal antibodies is an attractive option to further improve treatment results. Zevalin is a commercially available variation of the murine anti-CD20 antibody ibritumomab coupled to Yttrium 90 via the tiuxetan chelator. The development of this novel drug as well as the results of the pivotal studies and clinical strategies to implement this treatment into the routine practice of lymphoma oncology are presented in this review.     

Case report: intoxication with high dose of long-acting methylphenidate (Concerta®) in a suicidal 14-year-old girl

A 14-year-old girl with suicidal ideation was presented to the paediatric hospital about 2 h after ingestion of 21 long-acting methylphenidate (MPH) 54-mg tablets (1,134 mg Concerta(?)). At admission signs of sympathomimetic syndrome were observed like agitation, visual hallucinations, slight hypertension, and sinus tachycardia. Treatment included prevention of absorption (30 g activated charcoal orally) and careful observation related to the overstimulation of the sympathic system. Despite the intake of charcoal, the serum concentrations of MPH were 107 and 93 ng/ml 2.5 and 22 h after ingestion of MPH tablets. No support of vital functions was necessary. The girl made a full recovery and was discharged after 3 days of care at the paediatric clinic and referred to the child and adolescent psychiatric department. Exposure to a huge overdose of long-acting MPH exhibited acute sympathomimetic toxicity but no life-threatening symptoms in this patient. Thus this case report suggests that patients intoxicated with high dose long-acting MPH formulations can recover without sequelae when managed properly.     

SPL7013 Gel (VivaGel®) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans

SPL7013 Gel (VivaGel(?)) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with ≥5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup? pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p≤0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p?=?0.9]; HSV-2 [94% (91,97), p?=?0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov under identifier: NCT00740584.     

Heme Oxygenase 1-Mediated Neurogenesis Is Enhanced by Ginkgo biloba (EGb 761®) After Permanent Ischemic Stroke in Mice

Stroke is the fourth leading cause of death and a major cause of disability in stroke survivors. Studies have underlined the importance of repair mechanisms in the recovery phase of stroke. Neurogenesis in response to brain injury is one of the regeneration processes that, if enhanced, may offer better stroke treatment alternatives. Previously, we have demonstrated antioxidant, neuritogenic, and angiogenic properties of Ginkgo biloba/EGb 761® (EGb 761) in different mouse models of stroke. In the present study, we were interested to study whether EGb 761 could protect mice from permanent middle cerebral artery occlusion (pMCAO) and enhance neurogenesis. EGb 761 pre- and posttreated mice had lower infarct volume and improved motor skills with enhanced proliferation of neuronal stem/progenitor cells (NSPCs) at 24 h and 7 days posttreatment. Netrin-1 and its receptors (DCC and UNC5B) that mediate axonal attraction and repulsion were observed to be overexpressed in NSPCs only, implying that netrin-1 and its receptors might have partly played a role in enhanced neurogenesis. Interestingly, in heme oxygenase 1 knockout mice (HO1^?/?), neurogenesis was significantly lower than in vehicle-treated mice at day 8. Furthermore, EGb 761 posttreated mice also demonstrated heme oxygenase 1 (HO1)-activated pathway of phosphorylated glycogen synthase kinase 3 α/β (p-GSK-3 α/β), collapsin response mediator protein 2 (CRMP-2), semaphorin3A (SEMA3A), and Wnt, suggesting probable signaling pathways involved in proliferation, differentiation, and migration of NSPCs. Together, these results propose that EGb 761 not only has antioxidant, neuritogenic, and angiogenic properties, but can also augment the repair and regeneration mechanisms following stroke.