The Plasmodium falciparum eIK1 kinase (PfeIK1) is central for melatonin synchronization in the human malaria parasite. Melatotosil blocks melatonin action on parasite cell cycle

Melatonin and its indoles derivatives are central in the synchronization of malaria parasites. In this research, we discovered that melatonin is unable to increase the parasitemia in the human malaria Plasmodium falciparum that lacks the kinase PfeIK1. The PfeIK1 knockout strain is a valuable tool in the screening of indol-related compound that blocks the melatonin effect in wild-type (WT) parasite development. The assays were performed by using flow cytometry with simultaneous labeling for mitochondria viability with MitoTracker Deep Red and nucleus staining with SYBR Green. We found that Melatotosil leads to an increase in parasitemia in P. falciparum and blocks melatonin effect in the WT parasite. Using microscopy imaging system, we found that Melatotosil at 500 nM is able to induce cytosolic calcium rise in transgenic PfGCaMP3 parasites. On the contrary, the compound Triptiofen blocks P. falciparum cell cycle with IC₅₀ 9.76 µM ± 0.6, inhibits melatonin action, and does not lead to a cytosolic calcium rise in PfGCaMP3 parasites. We also found that the synthetic indol-related compounds arrested parasite cycle for PfeIK1 knockout and (WT) P. falciparum (3D7) in 72 hours culture assays with the IC₅₀ values slighting lower for the WT strain. We concluded that the kinase PfeIK1 is central for melatonin downstream signaling pathways involved in parasite cell cycle progression. More importantly, the indol-related compounds block its cycle as an upstream essential mechanism for parasite survival. Our data clearly show that this class of compounds emerge as an alternative for the problem of resistance with the classical antimalarials.     

Nutritional status of middle-aged and elderly females in Kentucky in two seasons: Part 1. Body weight and related factors

Middle-aged and elderly females aged between 51 and 86 years volunteered for this study. In June and July, 147 females were studied; data collected through interview included general socioeconomic information, health history, use of medication, and a 7-day food intake. During the same 7-day period, physical activity level was measured for each person by use of a pedometer. On the 8th day, anthropometric measurements were conducted and fasting blood was analyzed for certain hormones and related metabolites. In the following January and February, the same group was surveyed again and the same measurements were repeated. Of the initial 147 subjects, 130 persons completed the winter survey. A comparison of the summer and winter data indicated some significant differences: mean body weight increased in winter from 70.4 +/- 12.7 to 71.1 +/- 13.5 kg (p less than or equal to 0.05); energy intake was raised from 1450 +/- 384 to 1549 +/- 372 kcal (p less than or equal to 0.01); physical activity decreased from 10.9 +/- 8.2 to 8.5 +/- 5.4 miles/week (p less than or equal to 0.01); and serum free thyroxine (T4) fell from 1.72 +/- 0.27 to 1.64 +/- 0.27 ng/dl. These results together with other data suggest that more attention should be addressed to seasonal fluctuations involved in body weight maintenance.     

Occupational exposure to agricultural chemicals: effect on the activities of some enzymes in the blood of farm workers

Objective: To determine the effect of different durations of exposure to agricultural chemicals on the activities of the blood enzymes δ-aminolevulinic acid dehydratase (ALAD), superoxide dismutase (SOD), and cholinesterase (ChE) in tobacco field workers. Methods: For this preliminary investigation, 8 volunteers (all smoked tobacco) who were working on a small tobacco farm were monitored over a period of 2 years along with a comparable urban unexposed group (n = 4). During the growing season between 1994 and 1996, dermal and respiratory exposure were determined and blood samples were drawn after the following durations of field work: (1) preexposure (0 DAY); (2) after 1 day of field work (1 DAY) – workers reentered fields at 24 h after spraying of acephate and maleic hydrazide; (3) after 30 days of field work (postspraying; 30 DAYS); and (4) Postexposure – no tobacco production. Standard analytical methods were used. Results: Activity of ALAD was depressed by 30% after 1 DAY and there was no further decrease in ALAD activity after 30 DAYS of field work. SOD activity, in contrast, declined by 29% and 50% after 1 DAY and 30 DAYS, respectively, as compared with 0-DAY activity and that of the urban control, which was similar to 0-DAY activity (P ≤ 0.05). Plasma ChE activity declined by 19% after both 1 and 30 DAYS of exposure/field work. The activities of all three enzymes were restored to urban control or preexposure levels during postexposure. Plasma Cd levels were high in the samples taken after 30 DAYS as compared with the preexposure levels. Respiratory nicotine exposure was highest after 30 DAYS of field work. Conclusion: This preliminary study suggests that erythrocyte SOD is a sensitive indicator of exposure to agricultural chemicals in tobacco field workers. Received: 18 May 1998 / Accepted: 31 October 1998     

Food type, food preparation, and competitive food purchases impact school lunch plate waste by sixth-grade students

Because plate waste reduces nutritional benefits of school lunches, the objective of this study was to determine the factors that influence waste. Lunches of 743 sixth graders in three middle schools were photographed after students made food selections and after eating. Sample items were purchased to determine initial portion weights. The Statistical Package for Social Sciences software (Base 10.0, 1995, SPSS Inc, Chicago, IL) was used for statistical analysis. Preparation method influenced acceptance rates and plate waste: Whole apples had lower acceptance (23%) and greater waste (62%) compared with applesauce (37% acceptance, 23% waste). Mashed potatoes and heated fries had similar acceptance (approximately 69%), but mashed potatoes were wasted less (19% vs 33%, respectively). Students who purchased competitive food items with lunch (n=250) had significantly greater waste of fruits (52% vs 36%, respectively, P=.0001), grain products (26% vs 14%, respectively, P=.009), meats (25% vs 16%, respectively, P=.015), and mixed dishes (30% vs 18%, respectively, P=.0001). Changing preparation methods and limiting availability of competitive food items may reduce plate waste.     

Competitive foods increase the intake of energy and decrease the intake of certain nutrients by adolescents consuming school lunch

OBJECTIVE: To determine the influence of competitive foods on energy and nutrient intakes of adolescents participating in a school lunch program. DESIGN: Weighed plate waste data were used to assess the energy and nutrient consumption from school lunch menus items and competitive food items chosen and consumed by adolescents. The two test groups were students choosing competitive foods and those choosing no competitive foods. SUBJECTS/SETTING: Participants were sixth-grade students aged 11 to 13 years purchasing lunch in three public middle school cafeterias in Franklin County, KY (n=493 for no competitive foods and n=250 for competitive foods). The data were collected over 24 days in 2 school years. STATISTICAL ANALYSES PERFORMED: Significant differences between the competitive foods and no competitive foods groups were determined using frequency and analysis of variance procedures. RESULTS: The data indicate that sixth-grade adolescents consumed energy and other nutrients (except iron) at significantly lower than recommended levels; one third of students purchasing school lunch also purchased competitive food items; competitive foods purchasers reduced their school lunch servings, portion weight and/or item selection and increased school lunch item plate waste, resulting in lower intakes of energy (400 kcal vs 530 kcal for no competitive foods), calcium (300 mg vs 362 mg for no competitive foods), and vitamin A (77 retinol equivalents vs 113 retinol equivalents for no competitive foods) from the school lunch; and competitive foods supplied more than one third of total energy for the meal. CONCLUSIONS: These data will enable school cafeteria planners to develop menus that include more nutritious foods, snacks, and drinks instead of the currently available competitive foods.     

Evaluation of the indices of retinol and alpha-tocopherol status in free-living elderly.

The relationship between plasma vitamins and lipids was determined in volunteers (N = 131; age = 73.1 +/- 6.1 y). The 24-hour food intake data and fasting plasma retinol and alpha-tocopherol (HPLC), cholesterol, and triglycerides were determined three times in one year; 30 and 37% of elderly subjects had retinol and tocopherol intakes below two-thirds RDA, respectively; 35% used vitamin supplements. Plasma levels were: retinol = 1.76 +/- 0.41 mumol/L and tocopherol = 22.61 +/- 0.68 mumol/L; cholesterol = 5.15 +/- 0.77 mmol/L; triglycerides = 1.63 +/- 0.87 mmol/L. Plasma vitamin levels were adjusted to average plasma cholesterol (5.6 mmol/L) and triglyceride (1.24 mmol/L). Diet plus supplemental tocopherol intake correlated with plasma tocopherol (p less than .003). Using plasma vitamin levels, retinol status was normal, whereas 70% had low tocopherol status. Ratio of plasma alpha-tocopherol to lipids indicated that only 1-2% had low tocopherol status, while that of lipid-adjusted alpha-tocopherol to plasma lipids showed that 12% had low status. The latter ratio may be a better index of status.     

The role of melatonin in parasite biology

Regarded as the circadian hormone in mammals, melatonin is a highly conserved molecule, present in nearly all species. In this review, we discuss the role of this indolamine and its precursors in the cell biology of parasites and the role of the molecule in the physiology of the host. In Plasmodium, melatonin can modulate intracellular concentrations of calcium and cAMP, which in turn can regulate kinase activity and cell cycle. In Trypanosoma infections, modulation of the immune system by melatonin is extremely important in controlling the parasite population. Melatonin also contributes to the inflammatory response to Toxoplasma gondii infection. Thus, there are a number of unique adaptations involving intricate connections between melatonin and the biology of the parasite-host relationship.