Developing public health management training capacity in Nicaragua.

The Cooperative for Assistance and Relief Everywhere (CARE) and Centers for Disease Control and Prevention (CDC) Health Initiative in Nicaragua is distinctive in its focus on developing a cadre of in-country trainers whose aim is to equip frontline public health managers with widely applicable tools and techniques to assist them in identifying and solving implementation problems. Since 1999, 137 trainees--37% more than originally planned--have demonstrated competence by completing and presenting applied management projects. Nineteen professors from the preventive medicine faculty at the Autonomous University of Nicaragua also have been trained. The country office now has a cadre of seasoned trainers who can meet the ongoing management training needs of CARE staff and their counterparts in the Ministry of Health and in other nongovernmental organizations.

A verified case of recovered memories of sexual abuse.

A case is presented that shows verifiable evidence of repression at work. Rachel, a 40-year-old woman with no history of mental illness and ten years of exemplary professional work, recovers memories of childhood sexual abuse by her father through a call from her youth pastor in whom she had confided as an adolescent. This reminder triggered a severe depression, suicidal action, and the need for hospitalization. Rachel's older sister, herself an abuse victim, had witnessed the abuse, yet Rachel had no memory of the events. No apparent causes of false memories are present, so a different mechanism than forgetting must have been at work.

Effects of exposure to cypermethrin on saxitoxin binding in susceptible and pyrethroid-resistant houseflies.

Saxitoxin (STX) binding was measured in susceptible (SBO) and pyrethroid-resistant (KDR) female houseflies having only target site insensitivity as a resistance mechanism. In KDR flies, there was a quantitative decrease in STX binding capacity (Bmax) relative to SBO flies coupled with an increase in binding affinity (Kd). Treatment of SBO flies with sublethal doses of cypermethrin resulted in a large decrease in the number of STX binding sites and an increase in STX binding affinity. In KDR flies, identical treatments had the opposite effects. Treatment of both strains with higher doses of cypermethrin resulted in smaller decreases in Bmax values coupled with decreases in binding affinities. The results show that physiological changes in STX binding occur upon exposure to extremely low doses of cypermethrin. The data suggest that the kdr resistant gene may be expressed as changes in STX binding kinetics and that measurements of STX binding in pyrethroid-treated insects may be a useful approach for studying pyrethroid's mode of action and resistance.

Operational problems of an iron supplementation programme for pregnant women: an assessment of UNRWA experience.

Assessed is a large-scale iron supplementation programme for the 70 000 pregnant refugee women cared for by the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA). For this purpose, a retrospective survey of 1267 antenatal records was conducted in health centres located in the West Bank, Gaza, Syrian Arab Republic, Jordan, and Lebanon. The following operational problems were identified: late entry to antenatal care; high drop-out rate from antenatal care; low compliance in follow-up haemoglobin examinations; and misdirected continued testing of women who were not anaemic at registration. Routine iron supplementation of all pregnant women should be considered only in those countries where severe anaemia is prevalent and should always be coupled with additional interventions that are effective at improving iron deficiency anaemia in a given population. In most countries attention should be directed towards changing dietary habits to enhance the availability of local foodstuffs that are rich in iron. One initial haemoglobin test may help in focusing on the relatively few initially anaemic subjects who need further attention. Repeated testing during pregnancy is unwarranted.

PIP: The authors identified the following operational problems in their assessment of an iron supplementation program for the 70,000 pregnant refugee women cared for by the UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA): late entry to antenatal care, high drop-out rate from antenatal care, low compliance in follow-up hemoglobin examinations, and misdirected continued testing of women who were not anemic at registration. These findings are based upon data obtained through the retrospective survey of 1267 antenatal records in health centers located in the West Bank, Gaza, Syrian Arab Republic, Jordan, and Lebanon. The authors stress that routine iron supplementation of all pregnant women should be considered only in countries where severe anemia is prevalent and should always be coupled with additional interventions which are effective at improving iron deficiency anemia in a given population. In most countries, attention should be directed toward changing dietary habits to enhance the availability of local foodstuffs which are rich in iron. An initial hemoglobin test may help to identify the relatively few initially anemic subjects who need further attention. Repeated testing during pregnancy is not warranted.

Interactions of carbaryl with susceptible and multiresistant house flies (Diptera: Muscidae).

The in vivo and in vitro fate of [14C]carbaryl was compared in adult male and female house flies from an insecticide-susceptible (S) strain and a resistant (R) strain with multiple resistance to different classes of insecticides. Cuticular penetration of topically applied carbaryl (0.01 microgram/insect) was very rapid and rates were essentially the same among males and females of both strains. Rates of penetration were dramatically reduced as the concentration of applied carbaryl was increased over a range of 0.01-5.0 micrograms/insect. In vivo and in vitro tests demonstrated that the R strain had an enhanced capability for the metabolic degradation of carbaryl. In evaluations of topical toxicity and in vitro metabolic degradation, coadministration of the metabolic synergists piperonyl butoxide (a microsomal oxidase inhibitor) and S,S,S-tributyl phosphorothioate (DEF, an esterase inhibitor) with carbaryl provided conclusive evidence that microsomal oxidases were the major factor in enhanced metabolism and that hydrolytic enzymes had only a minor effect. Studies of the in vitro inhibition of acetylcholinesterase (AChE) activity by carbaryl demonstrated that there was no difference between males and females of a given strain and that the R strain AChE was considerably less sensitive to inhibition. These tests also indicated that homogenates of brains from the R strain contained more than one form of AChE with different sensitivities to the inhibitor. This information and results of toxicity tests with other insecticides suggest that the R strain is not homozygous in its resistance to carbaryl.

Plasmid-associated sensitivity of Bacillus thuringiensis to UV light.

Spores and vegetative cells of Bacillus thuringiensis were more sensitive to UV light than were spores or cells of plasmid-cured B. thuringiensis strains or of the closely related Bacillus cereus. Introduction of B. thuringiensis plasmids into B. cereus by cell mating increased the UV sensitivity of the cells and spores. Protoxins encoded by one or more B. thuringiensis plasmids were not involved in spore sensitivity, since a B. thuringiensis strain conditional for protoxin accumulation was equally sensitive at the permissive and nonpermissive temperatures. In addition, introduction of either a cloned protoxin gene, the cloning vector, or another plasmid not containing a protoxin gene into a plasmid-cured strain of B. thuringiensis all increased the UV sensitivity of the spores. Although the variety of small, acid-soluble proteins was the same in the spores of all strains examined, the quantity of dipicolinic acid was about twice as high in the plasmid-containing strains, and this may account for the differences in UV sensitivity of the spores. The cells of some strains harboring only B. thuringiensis plasmids were much more sensitive than cells of any of the other strains, and the differences were much greater than observed with spores.

Hydrolysis of sphingomyelin and phosphatidylcholine by midgut homogenates of the stable fly.

Qualitative and quantitative analyses were made to characterize the enzymatic degradation of sphingomyelin and phosphatidylcholine by midgut homogenates of the adult stable fly, Stomoxys calcitrans (L.). The results indicated that sphingomyelin was hydrolyzed by an enzyme with sphingomyelinase-like properties, and that phosphatidylcholine was hydrolyzed by an enzyme with properties similar to phospholipase C. The optimum pH for the sphingomyelinase was 7.6, and the rate of hydrolysis of sphingomyelin at that pH was linear from 1 to 4 nmol of substrate and 5 to 25 micrograms of enzyme preparation. Dialysis of the homogenates against Tris-HCl and imidazole buffers resulted in a decrease of sphingomyelinase activity by 59% and 98%, respectively, and the original activity was not restored with the addition of Ca++, Mg++, or Mn++.

Pharmacodynamics of malathion and carbaryl in susceptible and multiresistant German cockroaches (Dictyoptera: Blattellidae).

Studies with malathion and carbaryl were done to compare toxicity; absorption, metabolism, internal accumulation, and excretion; and in vivo inhibition of acetylcholinesterase (AChE) after topical applications to adult male susceptible (S, Orlando normal) or multiresistant (R, HRDC) German cockroaches, Blattella germanica (L.). Compared with the S strain, R cockroaches were highly resistant to malathion (about 33-fold) and only moderately resistant or tolerant to carbaryl (about 5-fold). Tests with topically applied 14C-labeled malathion and carbaryl indicated that both compounds penetrated rapidly and radioactive products were readily excreted. Rates of absorption or excretion in S and R strains did not differ significantly. Both insecticides were extensively metabolized; each yielded the same array and similar concentrations of metabolites in insects from either strain. In contrast, metabolic detoxification of malathion and carbaryl was significantly greater in R cockroaches when the insects were treated by injection. Strains did not differ significantly in the in vitro inhibition of brain AChE by either malaoxon or carbaryl. However, dramatic differences were observed between strains in the in vivo inhibition of AChE during a 6-h test period after topical treatment with malathion, and moderate but significant differences occurred between strains in the in vivo inhibition of AChE by carbaryl. These data suggest that the strong resistance to malathion and moderate resistance or tolerance to carbaryl in R cockroaches is probably a result of enhanced capability for metabolic detoxification.

Fate of [14C]xanthotoxin (8-methoxypsoralen) in a goat and in bovine ruminal fluid.

A lactating Nubian goat was treated with [14C]xanthotoxin, a photosensitizing psoralen that occurs naturally in some phototoxic range plants, as a single oral dose equivalent to 10.0 mg of xanthotoxin/kg of body weight. The radiochemical was rapidly absorbed, metabolized, and excreted. Although expired air was not monitored for the presence of volatile radiocarbon, the data indicated that greater than 50% of the administered [14C]xanthotoxin was metabolized by cleavage of the O-[14C]methyl moiety, with subsequent loss of the label as, presumably, [14C]CO2. Studies with bovine ruminal fluid in vitro indicated that cleavage of the O-methyl moiety of xanthotoxin could occur rapidly in the rumen. In the goat, nonmetabolized xanthotoxin was not excreted in urine, and of several metabolites in urine extracts, 3 were identified as resulting from opening of the furan or lactone ring. Only about 2% of the dose was recovered in the feces, and this consisted mainly of unmetabolized xanthotoxin. Although appreciable amounts of radiocarbon were secreted into milk, this radiocarbon was not in the form of xanthotoxin or any identifiable metabolites. The radiocarbon in milk likely resulted from the biosynthetic incorporation of [14C]CO2 into normal milk components.

Comparative metabolism of [(3)H]psoralen and [ (3)H]isopsoralen by black swallowtail (Papilio polyxenes Fabr.) caterpillars.

The comparative fate of tritiated preparations of a linear furanocoumarin (psoralen) and an angular furanocoumarin (isopsoralen) was determined in last-instar caterpillars of the black swallowtail butterfly (Papilio polyxenes Fabr.). Oral administration of either furanocoumarin at 5 µg/g is followed by rapid metabolism, primarily through oxidative cleavage of the furan ring, and the metabolites are rapidly excreted. Isopsoralen is, however, metabolized at a somewhat slower rate than is psoralen, and levels of unmetabolized isopsoralen in body tissues of the treated caterpillars are about three-fold higher. These data are compatible with the hypothesis that a reduced detoxification rate accounts at least in part for the susceptibility ofP. polyxenes caterpillars to the deleterious effect of isopsoralens.

In vitro metabolism of a linear furanocoumarin (8-methoxypsoralen, xanthotoxin) by mixed-function oxidases of larvae of black swallowtail butterfly and fall armyworm.

Studies were made of the comparative in vitro metabolism of [(14)C]xanthotoxin and [(14)C]aldrin by homogenate preparations of midguts and bodies (carcass minus digestive tract and head) of last-stage larvae of the black swallowtail butterfly (Papilio polyxenes Fabr.) and the fall armyworm [Spodoptera frugiperda (J. E. Smith)]. The two substrates were metabolized by 10,000g supernatant microsomal preparations from both species. Evidence gained through the use of a specific inhibitor and cofactor indicated that mixed-function microsomal oxidases were major factors in the metabolism and that the specific activity of this enzyme system was considerably higher in midgut preparations fromP. polyxenes than in similar preparations fromS. frugiperda. Aldrin was metabolized 3-4 times faster byP. polyxenes, and xanthotoxin 6-6.5 times faster.

Fate of photosensitizing furanocoumarins in tolerant and sensitive insects.

The fate of [(14)C]xanthotoxin (8-methoxypsoralen) was studied in larvae of insect species that are tolerant (Papilio polyxenes Stoll) or sensitive (Spodoptera frugiperda J.E. Smith) to the phototoxic effects of photosensitizing psoralens. Both insects metabolize xanthotoxin by oxidative cleavage of the furan ring, but the detoxification occurs at a much more rapid rate inP. polyxenes in which >95% of an oral 5 µg/g xanthotoxin dose is metabolized within 1.5 hr after treatment. The detoxification of psoralens byP. polyxenes appears to occur primarily in the midgut tissue prior to absorption, with the result that the intact phototoxin does not reach appreciable levels in body tissues. Studies with an angular furanocoumarin indicated that isopsoralens are metabolized byP. polyxenes at a somewhat slower rate than observed for psoralens; however, a reduced rate of metabolic detoxification of isopsoralens probably does not explain the fact that psoralen tolerance inP. polyxenes does not extend to the isopsoralen series.

Metabolic detoxification: mechanism of insect resistance to plant psoralens.

Larvae of the black swallowtail butterfly, Papilio polyxenes Stoll, forage successfully on plants that contain high levels of photosensitizing psoralens. These insects rapidly detoxify psoralens, particularly in the midgut tissue prior to absorption, with the result that appreciable levels of unmetabolized phototoxin do not enter the body circulation where deleterious light-induced interactions with dermal or subdermal tissues would occur.