Insecticide-treated clothes for the control of vector-borne diseases: a review on effectiveness and safety.

Insecticide-treated clothing has been used for many years by the military and in recreational activities as personal protection against bites from a variety of arthropods including ticks, chigger mites, sandflies and mosquitoes. Permethrin is the most commonly used active ingredient, but others, including bifenthrin, deltamethrin, cyfluthrin, DEET (N,N-diethyl-3-methylbenz-amide) and KBR3023, have also been trialled. Treatment is usually carried out by home or factory dipping. However, new microencapsulation technologies which may prolong the activity of insecticides on clothing are now available and may help to overcome the inevitable reduction in efficacy over time that occurs as a result of washing, ultraviolet light exposure, and the normal wear and tear of the fabric. The aim of this article is to review the evidence base for the use of insecticide-treated clothing for protection against bites from arthropods and its effect on arthropod-borne pathogen transmission. Although some studies do demonstrate protection against pathogen transmission, there are surprisingly few, and the level of protection provided varies according to the disease and the type of study conducted. For example, insecticide-treated clothing has been reported to give between 0% and 75% protection against malaria and between 0% and 79% protection against leishmaniasis. Studies vary in the type of treatment used, the age group of participants, the geographical location of the study, and the pathogen transmission potential. This makes it difficult to compare and assess intervention trials. Overall, there is substantial evidence that insecticide-treated clothing can provide protection against arthropod bites. Bite protection evidence suggests that insecticide-treated clothing may be useful in the prevention of pathogen transmission, but further investigations are required to accurately demonstrate transmission reduction.

Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations.

The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr human colon carcinoma multicellular tumor spheroids was investigated. Continuous exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid disruption, whereas 100 nM methotrexate (MTX) was required for similar effects. Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM 1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to 10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast, treatment with 10 or 100 nM 1843U89 for 6-48 h or treatment with 1 nM 1843U89 for up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM 1843U89 in the presence of 0.05-0.3 microM thymidine was as effective in causing spheroid disruption as treatment in the absence of thymidine, but treatment in the presence of 0.7-3.0 microM thymidine caused partial reversal of spheroid disruption. The results of these experiments suggest that 1843U89 should have potent solid tumor activity in humans but should be less effective in mice due to differences in circulating thymidine levels (0.1 vs 1 microM, respectively).

Seasonal variations in hepatic and ovarian zinc concentrations during the annual reproductive cycle in female channel catfish (Ictalurus punctatus).

Seasonal variations in hepatic and ovarian zinc concentrations were studied during the reproductive cycle in female channel catfish (Ictalurus punctatus). The gonadal somatic index (GSI) increased dramatically in April and peaked in June prior to spawning. Exogenous vitellogenesis was initiated in the fall as noted by increases in serum estradiol and testosterone and liver somatic index (LSI). Total hepatic zinc and zinc in the cytosolic high-molecular weight (HMW) and metallothionein-like (MT) fractions were elevated in March but decreased during rapid vitellogenic oocyte growth in April and May. Following spawning in July, total hepatic zinc and zinc in the HMW and MT-like fractions were again elevated. Total ovarian zinc and zinc associated with HMW and MT-like fractions increased with GSI, then decreased to a low after spawning. However, on a per g tissue basis, ovarian zinc concentrations in both cytosolic pools declined during rapid oocyte growth, indicating a different intracellular localization of the zinc binding proteins. Hepatic MT-like proteins exhibit UV absorption profiles similar to mammalian MT while the ovarian proteins appear to be different. Results give evidence for the homeostatic regulation of hepatic zinc by MT during exogenous vitellogenesis and a similar function for the ovarian MT-like protein during oocyte development.

The use of spinographic parameters in the differential diagnosis of lumbar facet and disc syndromes.

Biomechanical parameters measured on lateral postural x-rays were correlated with the clinical syndromes of lumbar extension facet subluxation and herniations of the disc nucleus pulposes to determine their value as a differential diagnostic tool. Statistically significant differences in the disc angle of the involved spinal segment were found between the two test groups. Both groups also contrasted significantly with asymptomatic controls. There also appears to be distinct postural complexes associated with these syndromes, although it is not clear if these postural changes were secondary processes such as antalgia, or primary and possibly predisposing.

Lumbar facet syndrome: spinographic assessment of treatment by spinal manipulative therapy.

Spinographic parameters of a group of patients with extension facet subluxations and a group with herniated disc nucleus pulposus of the lumbar spine were evaluated pre- and post-manipulative treatment. A statistically significant decrease in the mean disc angle at the involved level in the extension facet subluxation group was seen with the mean post-treatment disc angle more closely resembling that of the controls. Likewise, a statistically significant increase occurred in the mean disc angle at the involved level in the disc herniation group post-treatment to one more closely resembling that of the controls. Distinct postural configurations were identified in the two test groups. That of the disc group normalized post-treatment, suggesting it to be a secondary pathomechanical process such as antalgia. The postural complex of the facet group was significantly different than that of the control group, but did not change significantly after correction of the acute lesion by manipulation, suggesting it to possibly be an antecedent etiological factor to these lesions.

Virulence, immunity, and vaccine related to Streptococcus pneumoniae.

The pathogenesis of bacterial infection involves a series of interactions between the virulence determinants of the microorganisms and the immunity of the host. Studies on the molecular structure and immunological properties of pneumococcal virulence factors have provided general knowledge for the chemical basis of immunogenicity and prevention of bacterial infection. Antibody responses to PS and protein antigens can be greatly affected by their physicochemical properties, e.g., molecular size, specific determinants, conformation, etc. Characterization of group 19 pneumolysins and cloning of their ply genes were studied to examine the relationship of ply to virulence. Group 19 pneumococci all contained ply; the disease-isolated types of 19F and 19A appeared to show a higher specific hemolytic activity and yield than the nonpathogenic types, 19B and 19C. Genomic DNA that contained the ply gene from group 19 strains were analyzed by the polymerase chain reaction (PCR). Type 2 oligonucleotide primers recognized and initiated synthesis of an identical 1.5 kb DNA fragment in types 2, 19F, 19A, 19B, and 19C. Their sizes of restriction DNA fragments were also found to be homologous. Thus, group 19 ply genes showed remarkably similar characteristics. A difficult problem in the development of vaccines against bacterial diseases is the poor immune response of young children to purified PSs. The efficacy of pneumococcal vaccine might be improved by supplementation with inactivated pneumolysin in the form of a PS-protein conjugate.

On the substrate specificity of bovine liver dihydrofolate reductase: new unconjugated dihydropterin substrates.

The substrate specificity of dihydrofolate reductase from cells of different origin has been thought to be quite narrow, and unconjugated dihydropterins such as 6-methyl-dihydropterin are known to be very poor substrates. We have reinvestigated the substrate specificity of several dihydropterins and, in addition, have observed that in a new series of unconjugated dihydropterins of the general structure 6-CH2O(CH2)nCH3 several compounds are excellent substrates for the bovine liver enzyme, but none of them bind as well as dihydrofolate. The substrate activity (apparent Vmax) of these compounds increases from 17 to 110% that of the natural substrate, dihydrofolate, as n is increased from 0 to 3. In contrast, these unconjugated dihydropterins are very poor substrates for the Escherichia coli enzyme.

Analysis of Neisseria meningitidis class 3 outer membrane protein gene variable regions and type identification using genetic techniques.

The class 3 porin proteins of Neisseria meningitidis stimulate bactericidal antibodies and express serotype-specific antigenic epitopes. Sequence analysis of porB genes for the class 3 proteins revealed regions of variability that map to surface-exposed loops. To evaluate the relationship between serotype and variable-region (VR) genotype, sequences from the 11 class 3-expressing serotype strains and 3 additional serotype 4 strains were analyzed by molecular techniques. Multiple-sequence alignment revealed a limited number of unique sequences at each of four VRs (VR1 to VR4), ranging from four unique sequences at VR1 to seven sequence patterns at VR2 and VR4. Serotype-specific VR sequences were found in each of the four VRs, suggesting that each VR has immunologic importance. Five serotypes had at least one VR sequence that was unique. Three serotypes which had sequences in common with other serotypes at each VR were distinguished by examining multiple VRs. Serotype 3 was identical to serotype 19 at each VR, and serotype 8 was identical to serotype 18 at each VR. Serotypes 4 and 21 were identical at VR1 and significantly different at VR3 and VR4. A subpopulation of serotype 4 strains with a unique VR2 sequence was identified. The serotypes which were grouped with closely related or identical sequences at one VR were grouped with different serotypes at other VRs consistent with the pattern of genetic mosaicism described for the porA (class 1 protein) gene. Hybridization assays demonstrated the ability to identify VR genotypes and distinguish serotypes using biotin-labelled oligonucleotide probes. This information may be useful in strain selection for vaccine development, in epidemiologic studies to determine the prevalence of the individual VR genotype (especially among nonserotypeable strains) and, combined with PCR, in the identification of culture-negative suspected meningococcal cases.

Activity of an NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase in normal tissue, neoplastic cells, and oncogene-transformed cells.

As an extension of the previously reported observation concerning the existence of NAD-dependent 5,10-methylenetrahydrofolate dehydrogenase in transformed cells a variety of tissues and cell lines have been assayed for this activity. This activity was found in all assayed transformed cells. Results with rat liver derived epithelial (RLE) cells transformed with a series of oncogenes (v-raf, v-raf/v-myc (J2), v-myc (J5), and v-Ha-ras (pRNR16)) indicated that expression of activity correlates with the extent of transformation and was independent of the oncogene used for transformation. Compared to previously reported values for normal tissue, surprisingly high levels of the NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase were found in the rat adrenal cortex. This activity was not seen in mouse or bovine adrenal. Enzymatic activity was also detected in mouse bone marrow and was strain dependent. The levels of activity in mouse bone marrow were lower than previously reported. The NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase activity in rat adrenal and RLE cells may represent tools for studying the regulation of expression of this activity.