Cholesterol homeostasis is vital for proper cellular and systemic functions. Disturbed cholesterol balance underlies not only cardiovascular disease but also an increasing number of other diseases such as neurodegenerative diseases and cancers. The cellular cholesterol level reflects the dynamic balance between biosynthesis, uptake, export and esterification — a process in which cholesterol is converted to neutral cholesteryl esters either for storage in lipid droplets or for secretion as constituents of lipoproteins. In this Review, we discuss the latest advances regarding how each of the four parts of cholesterol metabolism is executed and regulated. The key factors governing these pathways and the major mechanisms by which they respond to varying sterol levels are described. Finally, we discuss how these pathways function in a concerted manner to maintain cholesterol homeostasis. Cholesterol is an important structural component of all animal cell membranes that functions in various processes, including membrane dynamics and cell signalling, and is also a precursor of other molecules. Deregulation of cholesterol metabolism — biosynthesis, dietary absorption and cellular uptake, storage and efflux — is linked to many diseases, including cardiovascular and genetic diseases, and cancer. A better understanding of cholesterol metabolism offers the possibility to control systemic cholesterol levels to improve human health.

Mechanisms and regulation of cholesterol homeostasis.

The biology and control of phlebotomine sand flies.

Plant-based repellents have been used for generations in traditional practice as a personal protection measure against host-seeking mosquitoes. Knowledge on traditional repellent plants obtained through ethnobotanical studies is a valuable resource for the development of new natural products. Recently, commercial repellent products containing plant-based ingredients have gained increasing popularity among consumers, as these are commonly perceived as “safe” in comparison to long-established synthetic repellents although this is sometimes a misconception. To date insufficient studies have followed standard WHO Pesticide Evaluation Scheme guidelines for repellent testing. There is a need for further standardized studies in order to better evaluate repellent compounds and develop new products that offer high repellency as well as good consumer safety. This paper presents a summary of recent information on testing, efficacy and safety of plant-based repellents as well as promising new developments in the field.

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Plant-based insect repellents: a review of their efficacy, development and testing

Five pyrethroid insecticides: cypermethrin, deltamethrin, fenpropathrin, fenvalerate and permethrin, were tested for their ability to induce micronuclei in both whole-blood (WB; three donors) and isolated human lymphocyte (IL, 2 donors) cultures, by using the cytokinesis-block method with 6 micrograms/ml cytochalasin B (Cyt-B). Fenvalerate and permethrin were tested with two different concentrations of Cyt-B (3 and 6 micrograms/ml). At the concentration ranges tested, all the five pyrethroids induced clear dose dependent cytotoxic effects, fenpropathrin being the most toxic. Nuclear division index (NDI) and the newly introduced index of cytotoxicity, the cytokinesis block proliferation index (CBPI), reflected the dose dependency more accurately than the percentage of binucleated cells did. CBPI is similar to NDI except that it estimates the average number of cell divisions that the cell population has gone through, and, therefore, classifies both trinucleate and tetranucleate cells into the same category. Cypermethrin and fenpropathrin slightly increased the number of MN and micronucleated cells in WB lymphocyte cultures from two out of the three donors. Deltamethrin produced a positive response only in WB cultures of one donor and in IL cultures of another donor. Permethrin gave mostly negative results, although it increased the MN frequency in WB cultures of one donor when 6 micrograms/ml Cyt-B was used. Fenvalerate did not significantly induce MN. With certain reservations to the purity and isomer composition of each pesticide, the existing information appears to support the idea that pyrethroid insecticides have a weak (cypermethrin, deltamethrin and fenpropathrin) or nule (fenvalerate and permethrin) genotoxic activity in vitro.

Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures.

Mosquito repellent activity of essential oils of aromatic plants growing in Argentina.

Repellents are an inexpensive and practical means of protection against nuisance and disease vector arthropods in conjunction with or when other control measures are not feasible. Appropriate selection of skin and/or clothing repellents along with proper wear of clothing can provide adequate protection from biting arthropods, and are available in a wide variety of forms including lotions, creams, foams, soaps, aerosols, sticks, and towellettes. A coordinated effort among different research groups associated with advances in the science of insect repellents such as mode of action information, doses of repellents to generate threshold level responses and controlled release delivery mechanisms, may help in understanding the mechanisms by which repellents work. This in turn may revolutionize the development of repellents for personal protection and their use in vector control.

Role of repellents in vector control and disease prevention

Breeding populations of phlebotomine sandflies (Diptera, Psychodidae) on the floor of a rain forest in Panama were studied with soil emergence traps. The species Lutzomyia trapidoi (Fairchild and Hertig) was predominant. L. panamensis (Shannon), L. gomezi (Nitzulescu), L. pessoana (Barretto), L. rorotaensis (Floch and Abonnenc), and L. insolita (Fairchild and Hertig) were regularly collected. The overall mean emergence rate was estimated at 24 sandflies/100 m2 of forest soil per day. Data are given on the sex ratios, local and seasonal effects, and associated animal taxa. The ecology and medical importance of the species complement of the forest floor habitat and the implications of the study with regard to sand fly control are discussed. It was concluded that the availability of vector sandflies is probably not the primary limiting factor in the distribution of leishmaniasis in forested areas of Panama.

Production of phlebotomine sandflies on the open forest floor in Panama: the species complement

The mating behavior of the sand fly, Lutzomyia longipalpis, was studied under laboratory conditions. Male sand flies landed on the bodies of anesthetized mice, where they exhibited leklike displays such as wing fanning, parading, and aggression. Lek behavior was more frequent in older males, and dominance hierarchies were established. Male sand flies at leks copulated more frequently than male sand flies at other locations in the cage. Females mated by older males produced more eggs than did females mated by younger males; however, there was no difference in the number of larvae produced.

Laboratory observations on mating and leklike aggregations in Lutzomyia longipalpis (Diptera: Psychodidae).

Breeding populations of phlebotomine sandflies (Diptera, Psychodidae) on the floor of a rain forest in Panama were studied with soil emergence traps. Supporting studies were made of physiographic and hydrologic features of the breeding habitat. The pattern of distribution of the forest litter and the composition, texture and stability of local deposits are largely determined by physiographic and hydrologic features which are operative in soil transport. The forest litter tends to be removed from steep slopes and valleys and to cumulate on gentle slopes and prominences. On hilltops the forest litter tends to occur in stable, residual deposits, while on hillsides and stream banks relatively unstable, alluvial deposits are more common. Breeding populations of Lutzomyia pessoana (Barretto), L. panamensis (Shannon), L. gomezi (Nitzulescu), and L. insolita (Fairchild and Hertig) are greater in hilltop regions, while those of L. trapidoi (Fairchild and Hertig) are greater in hillside and streamside regions. No comparable effect was noted in the case of L. rorotaensis (Floch and Abonnenc). No effects of physiographic aspect or of non-destructive inundation on breeding populations of sandflies were detected.

Production of Phlebotomine Sandflies on the Open Forest Floor in Panama: Phytologic and Edaphic Relations

Abrasion of repellent-treated human skin affected the efficacy of a sustained-release insect repellent containing N,N-diethyl-3-methylbenzamide (deet) against bites of Aedes aegypti. Skin treated with repellent when abraded up to 30 times showed significantly lower protection than unabraded skin against mosquito bites for 10 h. The mean value of the kinetic coefficient of friction during skin abrasion by clothing (battle dress uniform fabric) for repellent-treated skin (0.159 +/- 0.003) was significantly higher than untreated skin (0.122 +/- 0.005). Repellent-treated skin appeared stickier than the untreated skin. An increase in the number of skin abrasions by clothing resulted in a reduced duration of protection against mosquito bites.

L. C. Rutledge

Papers

Role of repellents in vector control and disease prevention

Production of phlebotomine sandflies on the open forest floor in Panama: the species complement

Laboratory observations on mating and leklike aggregations in Lutzomyia longipalpis (Diptera: Psychodidae).

Production of Phlebotomine Sandflies on the Open Forest Floor in Panama: Phytologic and Edaphic Relations

Effect of skin abrasions on the efficacy of the repellent deet against Aedes aegypti.