scholarly journals Biological Safety Evaluation of 99mTc-DTPA-Ketoconazole for Diagnosis of Fungal Infection

2017 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Maula Eka Sriyani ◽  
Hendris Wongso ◽  
Eva Maria Widyasari ◽  
Rizky Juwita Sugiharti ◽  
Iim Halimah ◽  
...  

Infectious diseases have become one of the leading cause of mortality around the world, including in the Southeast Asia. One of the microbial that cause infection is fungi. Occasionally, deep-seated fungal infection is difficult to detect using conventional diagnosis methods and therefore leads to inaccurate detection. Our previous research was conducted in order to obtain the labeled compound of <sup>99m</sup>Tc-DTPA-Ketoconazole with a high radiochemical purity (98.40 ± 0.86%). Moreover, the in-vitro assays showed that <sup>99m</sup>Tc-DTPA-Ketoconazole can potentially bind to Candida albicans. On the other hand, in clinical routine use, diagnostic kit should be safe for the patients. Consequently, this research was conducted to determine the biological safety parameters of <sup>99m</sup>Tc-DTPA-Ketoconazole on the animal study, including single dose and acute toxicity test, sterility, and apirogenicity test. The results showed that both the single dose at 34.6 μCi and dose until 149 times of the single dose did not stimulate the toxic response to the animals. In addition, the sterility data revealed that there was no microbial growth after 7 days of incubation at 37°C as well as fungal growth after 14 days of incubation at 25°C. Furthermore, the apirogenicity test using rabbits revealed that there was no increase in temperature more than 0.6°C for each animal and not more than 1.5°C of total increase of temperature for all the animals. It is concluded that the <sup>99m</sup>Tc-DTPA-Ketoconazole is satisfy the requirements of biological safety of a radiopharmaceutical and therefore was acceptable for fungal detection in nuclear medicine.

2016 ◽  
Vol 1 (3) ◽  
pp. 138
Author(s):  
Maula Eka Sriyani ◽  
Hendris Wongso ◽  
Eva Maria Widyasari ◽  
Rizky Juwita Sugiharti ◽  
Iim Halimah ◽  
...  

Infectious diseases have become one of the leading cause of mortality around the world, including in the Southeast Asia. One of the microbial that cause infection is fungi. Occasionally, deep-seated fungal infection is difficult to detect using conventional diagnosis methods and therefore leads to inaccurate detection. Our previous research was conducted in order to obtain the labeled compound of <sup>99m</sup>Tc-DTPA-Ketoconazole with a high radiochemical purity (98.40 ± 0.86%). Moreover, the in-vitro assays showed that <sup>99m</sup>Tc-DTPA-Ketoconazole can potentially bind to Candida albicans. On the other hand, in clinical routine use, diagnostic kit should be safe for the patients. Consequently, this research was conducted to determine the biological safety parameters of <sup>99m</sup>Tc-DTPA-Ketoconazole on the animal study, including single dose and acute toxicity test, sterility, and apirogenicity test. The results showed that both the single dose at 34.6 μCi and dose until 149 times of the single dose did not stimulate the toxic response to the animals. In addition, the sterility data revealed that there was no microbial growth after 7 days of incubation at 37°C as well as fungal growth after 14 days of incubation at 25°C. Furthermore, the apirogenicity test using rabbits revealed that there was no increase in temperature more than 0.6°C for each animal and not more than 1.5°C of total increase of temperature for all the animals. It is concluded that the <sup>99m</sup>Tc-DTPA-Ketoconazole is satisfy the requirements of biological safety of a radiopharmaceutical and therefore was acceptable for fungal detection in nuclear medicine.


2017 ◽  
Vol 41 (6) ◽  
pp. e12421 ◽  
Author(s):  
Huihai Yang ◽  
Lulu Wang ◽  
Hang Sun ◽  
Xiaofeng He ◽  
Jing Zhang ◽  
...  

2017 ◽  
Vol 12 (6) ◽  
pp. 209
Author(s):  
Yadi Suryadi ◽  
Tri Puji Priyatno ◽  
I Made Samudra ◽  
Dwi Ningsih Susilowati ◽  
Hermawati Nurzulaika ◽  
...  

The use of chitosan as a coating agent of harvested fruits is an alternative method in controlling anthracnose disease (Colletotrichum sp.). This study aimed to obtain an optimal enzymatic chitosan (EC) that hydrolyzed using chitinase from Burkholderia cepacia isolate E76. The optimal incubation condition to produce EC was 2 h with the yield of 3.52 ± 0.38 g. The degree of deacetylation (DD) chitosan and  EC was 66.91% and 80.91%, respectively. Based on in vitro assays, EC 2% was the most effective in inhibiting the growth of Colletotrichum sp. (94.22%)  than chitosan, while the highest inhibition for chitosan 3% was 55.26%. Moreover, the EC 2% showed the highest inhibition of spore germination (74.12%). The in vivo assay revealed that EC 2% showed the highest inhibition on the fungal growth (88.88%), compared to the other concentrations. On the other hand, the EC 2% and 3% gave similar results on inhibition of Colletotrichum sp.of chili (55.55%). 


2015 ◽  
Vol 34 (12) ◽  
pp. 1222-1230 ◽  
Author(s):  
DA Basketter ◽  
IR White ◽  
JP McFadden ◽  
I Kimber

Skin sensitization associated with allergic contact dermatitis is a common health problem and is an important consideration for toxicologists in safety assessment. Historically, in vivo predictive tests have been used with good success to identify substances that have the potential to induce skin sensitization, and these tests formed the basis of safety evaluation. These original tests are now being replaced gradually either by in vitro assays or by further refinements of in vivo methods such as the local lymph node assay. Human data have also been available to inform classification decisions for some substances and have been used by risk managers to introduce measures for exposure reduction. However, humans encounter hazards in the context of exposure rather than in the form of intrinsic hazards per se, and so in this article, we have examined critically the extent to which human data have been used to refine classification decisions and safety evaluations. We have also evaluated information on the burden of human allergic skin disease and used this to address the question of whether, and to what extent, the identification and evaluation of skin sensitization hazards has led to an improvement of public and/or occupational health.


Plant Disease ◽  
2015 ◽  
Vol 99 (9) ◽  
pp. 1254-1260 ◽  
Author(s):  
Erin Lonergan ◽  
Julie Pasche ◽  
Linnea Skoglund ◽  
Mary Burrows

Management of Ascochyta blight in pea, lentil, and chickpea relies on repeated fungicide applications, which has led to development of fungicide resistance and disease control failures in some systems. In vitro assays were conducted to determine baseline fungicide sensitivity in Mycosphaerella pinodes (Ascochyta pinodes), A. lentis, and A. rabiei populations to the demethylation-inhibiting fungicide prothioconazole and the succinate dehydrogenase-inhibiting fungicides boscalid and fluxapyroxad by determining the effective concentration at which 50% of germination or fungal growth was inhibited (EC50). Mean boscalid EC50 values from conidial germination assays were 0.669, 0.639, and 0.171 μg/ml and from mycelial growth assays were 0.258, 0.791, and 0.443 μg/ml for M. pinodes, A. lentis, and A. rabiei, respectively. Mean fluxapyroxad EC50 values were 0.050, 0.763, and 0.057 μg/ml for M. pinodes, A. lentis, and A. rabiei, respectively. Mean baseline EC50 values for prothioconazole with mycelial growth were 0.541, 0.604, and 0.283 μg/ml for M. pinodes, A. lentis, and A. rabiei, respectively. A single discriminatory fungicide concentration of 1 μg/ml was selected for all species. Established sensitivity profiles and discriminatory concentrations will be used to monitor sensitivity shifts in populations of Ascochyta spp. and to make effective disease management recommendations.


2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Nathan Stasko ◽  
Kimberly McHale ◽  
Stanley J. Hollenbach ◽  
Megan Martin ◽  
Ryan Doxey

ABSTRACTCutaneous and superficial fungal infections affecting the skin, nails, and hair of humans are caused primarily by dermatophytes of the generaTrichophytonandEpidermophytonor by yeasts of the generaCandidaandMalassezia.Onychomycosis is a common fungal infection of the nail that frequently coexists with tinea pedis, the most prevalent mycotic skin infection. Efficacy rates for current topical onychomycosis therapies are hampered by low drug penetration across the nail plate, which is theoretically obviated with nitric oxide (NO)-based topical therapies. The Nitricil technology platform is comprised of polysiloxane-based macromolecules that stably release therapeutic levels of NO. In the reported studies, NVN1000, the lead candidate of the platform, was assessed for its spectrum ofin vitroactivity against a broad range of filamentous fungi and yeast species commonly associated with cutaneous fungal infections. Time-kill assays demonstrated that NVN1000 exhibited fungicidal activity as early as 4 h. Additionally, the penetration of several unique NVN1000 NO-releasing drug product formulations (gel, cream, and lacquer) was evaluated following a single topical application in anin vitroinfected human nail assay, with all formulations showing similar inhibition of fungal growth. Repeated topical application in this model demonstrated that a lower-strength dose of NO could achieve the same efficacy as a higher-strength dose after 7 days. Together, thesein vitroresults demonstrate that NO-releasing treatments rapidly penetrate the nail plate and eradicate the fungal infection, representing promising novel topical therapies for the treatment of onychomycosis and other cutaneous fungal infections.


Plant Disease ◽  
2014 ◽  
Vol 98 (1) ◽  
pp. 99-102 ◽  
Author(s):  
J. A. LaMondia

Calonectria pseudonaviculata causes leaf spot and stem lesions resulting in defoliation and dieback of boxwood. Fungicides representing 20 different active ingredients from 13 different Fungicide Resistance Action Committee groups were evaluated for their effects on conidial germination and mycelial growth using in vitro assays, and the concentration that suppressed fungal growth to 15% of that on unamended media (EC85) values were determined. A number of fungicides strongly inhibited mycelial growth of C. pseudonaviculata. Four demethylation inhibitor fungicides had EC85 values of 1.2 μg a.i./ml or less. Thiophanate-methyl, fludioxonil, pyraclostrobin, trifloxystrobin, kresoxim-methyl, mancozeb, and chlorothalonil also had activity against mycelial growth. Fludioxonil + cyprodinil had a lower EC85 than the same rate of fludioxonil alone, suggesting that cyprodinil had activity against mycelial growth. Fungicides that inhibited C. pseudonaviculata conidial germination include pyraclostrobin, trifloxystrobin, and kresoxim-methyl as well as fludioxonil, mancozeb, chlorothalonil, and boscalid. Quinoxyfen, etridiazole, fenhexamid, hymexazol, famoxadone, and cymoxanil did not inhibit either C. pseudonaviculata conidial germination or mycelial growth. In comparison with values found in the literature, EC50 values for kresoxim-methyl were up to 10 times higher than reported previously, suggesting that fungicide insensitivity may have developed. Protectant fungicides with activity against conidial germination and systemic fungicides with activity against mycelial growth, such as those identified here, may be complementary to achieve the high levels of pathogen management required for control of this disease. In addition, multiple fungicide active ingredients from different mode-of-action groups used in mixtures or over time may also act to slow selection for fungicide insensitivity.


Plant Disease ◽  
2016 ◽  
Vol 100 (9) ◽  
pp. 1848-1857 ◽  
Author(s):  
D. L. Fonseka ◽  
N. C. Gudmestad

Early blight and brown spot, caused by Alternaria solani and Alternaria alternata, respectively, are important foliar diseases of potato, affecting both tuber yield and quality. Most of the commercial cultivars lack resistance; therefore, the application of foliar fungicides remains a primary disease management strategy. Baseline sensitivities of A. solani to difenoconazole and metconazole (demethylation inhibitors) using mycelial growth assay exhibited similar intrinsic activity against the pathogen with mean EC50 (the effective concentration at which the fungal growth is inhibited by 50%) values of 0.09 μg/ml. However, the sensitivity of individual baseline A. solani isolates to each fungicide varied substantially, resulting in very low and nonsignificant correlation coefficients among fungicides. Mean EC50 values for baseline A. alternata isolates in response to difenoconazole and metconazole were 0.14 and 0.26 μg/ml, respectively. The sensitivity of the majority of A. solani and A. alternata isolates collected from 2010 to 2014 from various potato production states was consistent with baseline isolates, therefore, these potato pathogens remain sensitive to the two demethylation inhibitor chemistries used to manage it. Baseline sensitivity assays of pyrimethanil (anilino-pyrimidine) also indicated great intrinsic activity against both foliar pathogens with mean EC50 values of 0.44 and 0.35 μg/ml for A. solani and A. alternata, respectively. Although A. alternata remains largely sensitive to pyrimethanil, 6 out of 245 A. solani isolates collected from 2010 to 2014 exhibited reduced-sensitivity to the fungicide in in vitro assays. Reduced-sensitive isolates were not controlled at most pyrimethanil doses except at 100 μg/ml in greenhouse in vivo efficacy tests. These chemistries remain valuable options for fungicide rotation programs in areas of high disease pressure.


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