Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus.

OBJECTIVES: We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. METHODS: SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. RESULTS: S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with (n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement (n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. CONCLUSION: HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.

Preharvest Fungicide, Potassium Sorbate, or Chitosan Use on Quality and Storage Decay of Table Grapes.

Potassium sorbate, a program of four fungicides, or one of three chitosan formulations were applied to clusters of 'Thompson Seedless' grape berries at berry set, pre-bunch closure, veraison, and 2 or 3 weeks before harvest. After storage at 2°C for 6 weeks, the natural incidence of postharvest gray mold was reduced by potassium sorbate, the fungicide program, or both together in a tank mixture, in 2009 and 2010. In 2011, the experiment was repeated with three chitosan products (OII-YS, Chito Plant, and Armour-Zen) added. Chitosan or fungicide treatments significantly reduced the natural incidence of postharvest gray mold among grape berries. Berries harvested from vines treated by two of the chitosan treatments or the fungicide program had fewer infections after inoculation with Botrytis cinerea conidia. None harmed berry quality and all increased endochitinase activity. Chitosan decreased berry hydrogen peroxide content. One of the chitosan formulations increased quercetin, myricetin, and resveratrol content of the berry skin. In another experiment, 'Princess Seedless' grape treated with one of several fungicides before 4 or 6 weeks of cold storage had less decay than the control. Fenhexamid was markedly superior to the other fungicides for control of both the incidence and spread of gray mold during storage.

Control of Postharvest Gray Mold of Table Grapes in the San Joaquin Valley of California by Fungicides Applied During the Growing Season.

Fungicides applied before harvest were evaluated to control postharvest gray mold of table grapes, caused by Botrytis cinerea. The concentrations of thiophanate methyl (THM), iprodione (IPR), cyprodinil (CYP), pyraclostrobin + boscalid (PS+BO), pyrimethanil (PYR), or fenhexamid (FEN) that inhibited the growth of four isolates sensitive to these fungicides by 50% (EC50) were 12.4, 2.5, 0.61, 0.29/0.57, 0.26, or 0.17 mg liter-1, respectively. THM, IPR, CYP, PS+BO, PYR, or FEN were applied to detached 'Thompson Seedless' berries at the equivalent of the maximum approved rates of 600, 500, 270, 59/116, 370, or 290 mg liter-1, respectively, except PS+BO, which were used at 54.2% of their current registered maximum rates. The berries were inoculated with B. cinerea 48 or 24 h before treatment or 24 or 48 h after treatment. Gray mold 2 weeks after treatment and storage at 15°C was lowest after FEN application, followed by PYR, CYP, IPR, PS+BO, and THM. In commercial vineyards, one application of FEN, PYR, CYP, or PS+BO, all at their current maximum approved rates, 2 weeks before harvest reduced postharvest gray mold by approximately 50%. When fungicides were applied repeatedly after berry set either in mixtures or alternated with fungicides of different mode of action classes, postharvest gray mold was reduced by about 50% using a commercial air-blast sprayer and by 70 to 87% using a hand-held sprayer that was directed into the clusters. The fungicide sensitivity of isolates collected in numerous vineyards indicated those with reduced sensitivity to all of the tested fungicides, except FEN, were common. The efficacy of preharvest fungicide regimes was not sufficient to replace postharvest sulfur dioxide fumigation.

Influence of Temperature and Humidity on Survival of Penicillium digitatum and Geotrichum citri-aurantii.

Longevity of conidia of Penicillium digitatum (cause of citrus green mold) and arthroconidia of Geotrichum citri-aurantii (cause of sour rot of citrus) was determined under controlled temperature and relative humidity (RH) or ambient summer conditions in central California. Longevity at low RH was longer than at high RH. Hours to kill 99% of the conidia (LT99) of nine P. digitatum isolates were determined at 50°C and 75 or 95% RH. At 75 and 95% RH, the LT99 was 24.9 and 4.9 h, respectively. The LT99 was 30 and 42 days, respectively, for conidia of P. digitatum under ambient conditions at two outdoor locations. The LT99 of arthroconidia of G. citriaurantii from colonies cultured on potato dextrose agar was briefer than that of conidia of P. digitatum. At 45°C and 75 or 95% RH, the LT99 was about 4 and 2 h, respectively, whereas at 50°C, none was viable after 1 h at either humidity. Sanitation is an important practice for managing these diseases. Since there was little or no survival of either fungus after 1 day at 50°C and 75% RH or higher, we conclude that commercial sanitation could employ a similar regime.

Pre- and Postharvest Treatments to Control Green Mold of Citrus Fruit During Ethylene Degreening.

Two approaches, fungicide applications to trees before harvest and drenching fruit after harvest, were evaluated to minimize postharvest green mold, caused by Penicillium digitatum, particularly among fruit subjected to ethylene gas after harvest, a practice termed "degreening" that eliminates green rind color. Preharvest applications of thiophanate methyl (TM) controlled postharvest green mold consistently. In five tests, green mold among degreened orange fruit was 16% when TM was applied 1 week before harvest; whereas, among fruit not treated, the incidence was 89.5%. Thiabendazole (TBZ) applied to harvested fruit in bins before degreening also was very effective. TBZ effectiveness was enhanced by mild heating (41°C), adding sodium bicarbonate, and immersing fruit, rather than drenching them, with the solution. With these measures, an isolate of P. digitatum with a high level of TBZ resistance was significantly controlled. In semicommercial tests with naturally inoculated fruit, TBZ and sodium bicarbonate treatment reduced green mold incidence from 11% among untreated orange fruit to 2%. TBZ residues in lemon fruit at 41°C were about twice those treated at 24°C. Neither TM before harvest nor TBZ and sodium bicarbonate applied after harvest influenced green color removal during degreening of orange fruit. Sodium bicarbonate slightly reduced the rate of lemon color change.

Influence of pH and NaHCO3 on Effectiveness of Imazalil to Inhibit Germination of Penicillium digitatum and to Control Postharvest Green Mold on Citrus Fruit.

In vitro, spores of Penicillium digitatum germinated without inhibition between pH 4 and 7, but were inhibited at higher pH. Estimated concentrations of imazalil (IMZ) in potato-dextrose broth-Tris that caused 50% reduction in the germination of spores (ED50) of an IMZ-sensitive isolate M6R at pH 4, 5, 6, and 7 were 0.16, 0.11, 0.015, and 0.006 µg/ml, respectively. ED50 IMZ concentrations of an IMZ-resistant isolate D201 at pH 4, 5, 6, and 7 were 5.9, 1.4, 0.26, and 0.07 µg/ml, respectively. The natural pH within 2-mm-deep wounds on lemon was 5.6 to 5.1 and decreased with fruit age. IMZ effectiveness to control green mold and its residues increased with pH. The pH in wounds on lemon fruit 24 h after immersion in 1, 2, or 3% NaHCO3 increased from pH 5.3 to 6.0, 6.3, and 6.7, respectively. NaHCO3 dramatically improved IMZ performance. Green mold incidence among lemon fruit inoculated with M6R and treated 24 h later with IMZ at 10 µg/ml, 1% NaHCO3, or their combination was 92, 55, and 22%, respectively. Green mold among lemon fruit inoculated with D201 and treated 24 h later with water, IMZ at 500 µg/ml, 3% NaHCO3, or their combination was 96.3, 63.0, 44.4, and 6.5%, respectively. NaHCO3 did not influence IMZ fruit residue levels.

Survival of spores of Rhizopus stolonifer, Aspergillus niger, Botrytis cinerea and Alternaria alternata after exposure to ethanol solutions at various temperatures.

AIMS: To quantify and model the toxicity of brief exposures of spores of Rhizopus stolonifer, Aspergillus niger, Botrytis cinerea and Alternaria alternata to heated, aqueous ethanol solutions. These fungi are common postharvest decay pathogens of fresh grapes and other produce. Sanitation of produce reduces postharvest losses caused by these and other pathogens. METHODS AND RESULTS: Spores of the fungi were exposed to solutions containing up to 30% (v/v) ethanol at 25-50 degrees C for 30 s, then their survival was determined by germination on semisolid media. Logistical, second-order surface-response models were prepared for each fungus. Subinhibitory ethanol concentrations at ambient temperatures became inhibitory when heated at temperatures much lower than those that cause thermal destruction of the spores by water alone. At 40 degrees C, the estimated ethanol concentrations that inhibited the germination of 50% (LD(50)) of the spores of B. cinerea, A. alternata, A. niger and R. stolonifer were 9.7, 13.5, 19.6 and 20.6%, respectively. CONCLUSIONS: Ethanol and heat combinations were synergistic. Control of spores of these fungi could be accomplished with much lower temperatures and ethanol concentrations when combined compared with either used alone. Botrytis cinerea and A. alternata were less resistant to the combination than A. niger or R. stolonifer.

Improved Control of Green Mold of Citrus with Imazalil in Warm Water Compared with Its Use in Wax.

The effectiveness of imazalil for the control of citrus green mold (caused by Penicillium digitatum) improved significantly when fruit were treated with heated aqueous solutions of the fungicide as compared with the current commercial practice of spraying wax containing imazalil on fruit. When applied at less than 500 µg·ml-1 in solutions heated to 37.8°C, control of postharvest green mold of citrus was significantly superior to applications of 4,200 µg·ml-1 imazalil in wax sprayed on fruit at ambient temperatures. The improvement in imazalil efficacy was obtained with a decrease in fungicide residues on the fruit. Residues of about 3.5 µg·g-1 imazalil deposited by the application of imazalil in wax reduced the incidence of green mold on lemons from 94.4% among untreated controls to 15.1%, whereas an equal residue deposited by passing fruit through heated aqueous imazalil reduced green mold incidence to 1.3%. Similar differences were found in tests with oranges. Residues of 2 and 3.5 µg·g-1 imazalil were needed to control the sporulation of P. digitatum on oranges and lemons, respectively. The mode of application of imazalil did not influence control of sporulation. The influence of immersion time, imazalil concentration, and solution temperature on imazalil residues on oranges and lemons was determined in tests using commercial packing equipment, and a model that describes residue deposition was developed. Residues after a 30- or 60-s treatment in heated aqueous imazalil were sufficient to control sporulation, but residues after 15-s treatments were too low and required an additional application of 1,070 µg·ml-1 imazalil in wax to deposit an amount of imazalil sufficient to control sporulation. An imazalil-resistant isolate of P. digitatum was significantly controlled by heated aqueous imazalil. The incidence of green mold of navel oranges was reduced from 98.8 to 17.4% by treatment in 410 µg·ml-1 imazalil at 40.6°C for 90 s. However, control of the resistant isolate required imazalil residues on the fruit of 7.9 µg·g-1, which is within the U.S. tolerance of 10 µg·g-1 but above the 5 µg·g-1 tolerance of some countries that import citrus fruit from the United States.