Laboratory evaluation of controlled-release repellent formulations on human volunteers under three climatic regimens

Six controlled-release personal-use topical insect/arthropod repellent formulations of diethylmethylbenzamide (deet) were evaluated in an environmental chamber on volunteers for repellency against the mosquitoes Aedes aegypti and Ae. taeniorhynchus under three climatic regimens: basic variable high humidity (tropical environment), basic constant high humidity (forested and wet environment) and basic hot (hot-dry environment). The best protection under all the climatic regimens was provided by the Biotek formulation. In a tropical environment, some formulations induced more biting from mosquitoes than the concurrent untreated control in the late hours of the testing. Repellency was not directly related to the deet concentration in the various controlled-release repellent formulations.     

5种避蚊胺缓释制剂实验室驱蚊效果观察

目的实验观察5种避蚊胺缓释制剂的驱蚊效果。方法利用高分子化合物PVP、PVPP,制备PVPP-Ⅰ、PVPP-Ⅱ、PVPP-Ⅲ、PVP-Ⅰ、PVP-Ⅱ5种避蚊胺缓释制剂,在实验室对淡色库蚊进行驱避效果试验,并与避蚊胺普通制剂Ⅰ(凝胶剂)、Ⅱ(凝胶乳剂)、Ⅲ(霜剂)及2种市售驱避剂(六神驱蚊花露水、隆力奇驱蚊花露水)的驱避效果进行比较。结果SD大鼠腹部脱毛,按1.5 mg/cm2或1.5μl/cm2处理。5种避蚊胺缓释制剂的有效保护时间达10-13 h,使用11 h后的有效保护率依次为82.43%、97.09%、100%、92.32%和100%,明显优于3种避蚊胺普通制剂和2种市售驱避剂(有效保护时间4-8 h,使用11 h后的有效保护率依次为23.08%、45.62%、34.55%、43.96%和50.87%)。结论利用高分子聚合物研制成的避蚊胺缓释制剂缓释驱蚊效果较好。     

Controlled release microparticles for vaccine development.

The primary and secondary sera IgG antibody responses to ovalbumin (OVA) entrapped in biodegradable poly(lactide-co-glycolide) (PLGA) microparticles were compared with the responses obtained with soluble OVA. In addition, OVA in PLGA microparticles was also administered after dispersion in an immunostimulatory vehicle, Freund's incomplete adjuvant (FIA). The primary IgG responses to OVA in microparticles/FIA were significantly greater than the responses to soluble OVA from day 14 to day 42, when booster immunizations were administered. From day 49 to the end of the study at day 84, the responses to OVA, both in microparticles alone and in microparticles/FIA, were significantly greater than the responses to soluble OVA. Nevertheless, the responses obtained for OVA in microparticles or microparticles/FIA were, in general, not as high as those obtained with OVA in Freund's complete adjuvant.     

Controlled vitamin C restriction and physical performance in volunteers.

A double-blind study on the effects of vitamin C restriction on physical performance was executed with 12 healthy men. During seven weeks of low vitamin C intake six subjects were on a daily diet of regular food products, providing 20% of the Dutch Recommended Dietary Allowances (RDA) for vitamin C (Dutch RDA is 50 mg/day). Other vitamins were supplemented at twice the RDA level. After three weeks of low vitamin intake an additional vitamin C dose of 15 mg/day was provided, resulting in a total intake of 25 mg/day (50% of the Dutch RDA). Six control subjects consumed the same diet supplemented with twice the RDA for all vitamins. In the restriction group blood vitamin C levels decreased significantly (p less than 0.01). Vitamin C restriction had no harmful effects on health, aerobic power (VO2-max), and onset of blood lactate accumulation (OBLA). However, an increased heart rate at OBLA level was observed during the period of low vitamin C intake (p less than 0.05), possibly by interference with either catecholamine or carnitine metabolism. These results suggest that short-term marginal vitamin C deficiency does not affect physical performance in single bouts of intensive exercise.     

Response of Culicoides sonorensis (Diptera: Ceratopogonidae) to 1-octen-3-ol and three plant-derived repellent formulations in the field

The potential attractant 1-octen-3-ol and 3 potential repellents were assayed for activity for Culicoides sonorensis, the primary vector of bluetongue virus in North America. Collections using octenol were low, but numbers in suction traps were greater in the high-octenol treatment (11.5 mg/h) than in the low-octenol treatment (1.2 mg/h) or unbaited control for both sexes. Collections using high octenol, CO2 (approximately 1,000 ml/min), or both showed octenol alone to be significantly less attractive than either of the CO2 treatments and that octenol did not act synergistically with this level of CO2. A plant-derived (Meliaceae) extract with 4.5% of active ingredient (AI) (Ag1000), heptanone solvent, Lice free (2% AI from plant extracts in water), Mosi-guard with 50% Eucalyptus maculata var. citriodora Hook extract, and N,N-diethyl-m-toluamide (deet) were applied to polyester-cotton coarse mesh nets and deployed in conjunction with suction light traps plus CO2. Collections in the trap with deet were 66% lower (P < 0.05) than the heptanone and 56% (P > 0.05) less than the untreated (negative) control. Relative to deet, collections in the traps with the lice repellent, Ag1000, and Mosi-guard were reduced by 15, 34, and 39%, respectively (P > 0.05). The method has promise for field screening of potential repellents before on-animal testing.     

Oviposition deterrence and larvicidal activity of three formulations of piperidine repellent (AI3-37220) against field populations of Stegomyia albopicta

Two proprietary controlled-release (CR) formulations (CR55 and CR56) of 20% AI337220 (1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine) in an aqueous dispersion, and the same repellent formulated in water (W220), were compared with a repellent-free control for oviposition deterrent and larvicidal activity against natural populations of Stegomyia albopicta. A single application of each formulation (final concentration: 0.1%) prevented oviposition by St. albopicta for 4 wk, with highest deterrence (46%) observed for CR55 at 8 wk posttreatment. At the same application rate, each repellent formulation reduced larval activity in experimental containers by 100% through week 4 posttreatment and, for CR55, by 92-100% through week 8. In a municipal cemetery (Gainesville, Florida, USA), 1 application of CR55 or CR56 (final concentration: 0.1%) in concrete flower vases eliminated St. albopicta larvae for 10 wk. With formulation improvements to enhance efficacy at low repellent concentrations, AI3-37220 may have potential for use in the control of container-inhabiting mosquitoes.     

Enterobacteriaceae suppression by three different oral doses of polymyxin E in human volunteers

Polymyxin E is frequently used as an oral drug for flora suppression of the gastrointestinal canal. The suppression effect is dose dependent because polymyxin E is moderately inactivated by faecal and food compounds. Three oral polymyxin E doses (150, 300, 600 mg daily) were given to six volunteers for 6 days. The Enterobacteriaceae suppression effect was compared by means of the suppression index i.e. ratio of total number of faecal samples free of Enterobacteriaceae to the total number of faecal samples. The impact on the indigenous (mostly anaerobic) flora was measured in four ways: (i) beta-aspartylglycine content; (ii) volatile fatty acid pattern; (iii) yeast overgrowth and (iv) Streptococcus faecalis decrease. Enterobacteriaceae suppression was most successful during 600 mg oral polymyxin E (suppression indices during 150, 300 and 600 mg were 0.32, 0.55 and 0.89 respectively). None of the four markers of indigenous flora alterations were positive. However, using this dosage half of the volunteers suffered rather severe gastrointestinal side-effects. Oral polymyxin E in a dosage of minimum 600 mg daily seems to possess the ideal properties of a flora suppression agent, if the gastrointestinal side-effects could be mitigated.     

A new Pseudomonas vaccine: preliminary trial on human volunteers.

Fifteen healthy volunteers were given three weekly subcutaneous injections of a new polyvalent Pseudomonas aeruginosa vaccine (PEV-01). Four doses - 1-0 RHD (manufacturer''s recommended human dose), 0-75 RHD, 0-5 RHD and 0-1 RHD - were used in separate groups of volunteers. Blood samples taken before each of the injections and one taken 7 days after the last injection were examined for immune response to the vaccine and for possible adverse clinical, biochemical and haematological effects. Raised titres of antibody in serum of volunteers given 0-5-1-0 RHD vaccine were shown, often by the seventh day, in passive haemagglutination tests against all of the 16 serotypes of Ps. aeruginosa represented in the vaccine; serum from volunteers who received 0-1 RHD usually showed a reduced antibody titre. Tests of mouse protection by serum against intraperitoneal challenge with Ps. aeruginosa P14 showed increased titres of mouse protective antibody in the blood of volunteers given 1-0, 0-75 or 0-5 RHD of vaccine but a reduced mouse-protective titre in two out of three sera from volunteers given 0-1 RHD vaccine. There was a suggestion of enhanced phagocytic ingestion and intracellular killing of two strains of Ps. aeruginosa by the blood of vaccinated volunteers, and more definite enhancement of ingestion of inert latex particles, which were less well ingested than were the bacterial cells by phagocytes from unvaccinated volunteers. Apart from slight or moderate local reactions and a transient rise of temperature in some volunteers, there were no clinical, biochemical or haematological abnormalities in the vaccinated volunteers.     

联苯菊酯3种剂型对台湾乳白蚁的药效研究

目的研究联苯菊酯水乳剂、悬浮剂和乳油对白蚁的药效。方法采用药膜法、木材试块法和土壤法测定3种剂型联苯菊酯对乳白蚁的毒杀和驱避效果。结果联苯菊酯乳油24h对台湾乳白蚁的接触毒性LC50为204．941mg／L,水乳剂为257．849mg／L,悬浮剂为277．699mg/L,差异不显著;浓度为125mg／L乳油有较好的木材抗蛀效果,1000mg／L悬浮剂和水乳剂也有较好的防蛀效果;联苯菊酯乳油浓度为250mg／L时可完全阻止白蚁穿透5cm长土壤柱,悬浮剂和水乳剂浓度为500mg／L时也具有同样效果。结论在实际应用中,应综合考虑药效、持效性和环保等各方面因素,选择合适的药剂。     

Studies on trachoma: 5. Complement fixation tests in human volunteers

Complement-fixation tests carried out on serial serum samples from human volunteers indicate that group-specific antibodies develop after experimental inoculation of trachoma virus and inclusion conjunctivitis virus. The results obtained with antigens prepared from four trachoma virus strains isolated in Tunisia and one strain from Japan and with an ornithosis antigen suggest that there may be antigenic differences among trachoma virus strains and that the use of homologous antigens will therefore give the best results.     

Preliminary observations on clotting under three hydrocolloid dressings.

Four patients with five wounds were randomly assigned to treatment with three occlusive dressings: DuoDERM, Restore and Comfeel Ulcus; the dressings were left intact for 24-48 h. When the dressings were removed, it was found that wounds that had been covered with Restore and Comfeel contained coagulated sanguinous material. Two wounds that had been covered with Comfeel and Restore, respectively, were then covered with DuoDERM, while one wound previously covered with DuoDERM was covered with Restore. Either no clotting occurred under DuoDERM or clots may have resolved. Although these preliminary data suggest that DuoDERM gel may have fibrinolytic properties, more extensive and controlled studies are needed to assess the characteristics of this dressing.     

Effectiveness of hand-cleansing formulations containing tea tree oil assessed ex vivo on human skin and in vivo with volunteers using European standard EN 1499

The efficacy of formulations containing tea tree oil (TTO) has been assessed in vitro in previous studies. Products that passed the European suspension test guidelines were investigated further in this study, in vivo with volunteers using the European handwashing method (EN 1499) and ex vivo using freshly excised human skin samples. The activity of 5% TTO in 0.001% Tween 80, in a hygienic skin wash (HSW) and in an alcoholic hygienic skin wash (AHSW) was investigated and compared with that of a non-medicated soft soap (SS, control). These formulations were assessed against Escherichia coli K12 as recommended by the European standard. In-vivo results showed that 5% TTO in Tween 80 and the AHSW were significantly more active than the SS after 1 min of handwashing. When assessed ex vivo, these two products were also significantly more active than the reference soap after 1 min of rubbing. Both methods showed that 5% TTO in Tween 80 was generally, although not always, more active than a handwash formulation, and that the AHSW was generally more active than the HSW, although this difference was not significant. The formulations tested, as well as the SS, were more active when assessed in vivo than ex-vivo against E. coli, although only the SS and the HSW were significantly more active in vivo. There appeared to be a pattern in the comparison between ex vivo and in vivo results. The antiseptics tested were, on average, 1.28+/-0.06 times more active when assessed in-vivo than when assessed ex vivo. Nevertheless, the main outcome of the European handwashing method is for the formulation tested to be significantly more active than the SS; both 5% TTO in Tween 80 and the AHSW achieved this both in-vivo and ex-vivo. TTO in Tween 80 and in formulations met the European in-vivo method requirements.     

三种方案治疗重度宫颈炎症的疗效观察

目的:探讨微波联合保妇康栓治疗重度宫颈炎症的临床疗效。方法:将诊断为重度宫颈炎症并规范治疗的患者120例按治疗方案不同随机分为3组,A组44例,微波联合保妇康栓外用治疗;B组36例,微波治疗;C组40例,保妇康栓外用治疗。治疗后随访患者临床症状有无改善、宫颈创面修复时间长短、宫颈液基细胞学(TCT)检测有无改善和随访术后不良反应发生情况。结果:A、B、C组治愈率分别为90.9%、61.1%、12.5%,A组与B、C组比较差异有统计学意义(P<0.05),B组和C组组间比较差异有统计学意义(P<0.05)。4周内创面愈合A组优于B组(P<0.05),3周内阴道排液消失A组优于B组(P<0.05),结痂出血发生率A、B组分别为22.7%、41.7%,差异无统计学意义(P>0.05)。结论:微波联合保妇康栓治疗重度宫颈炎症可以优势互补,缩短治疗时间,提高治愈率,同时缓解微波术后不良反应,值得临床广泛推广。     

Evaluation of three candidate cypermethrin-piperonyl butoxide formulations compared with Scourge against adult Culex quinquefasciatus.

Cypermethrin-piperonyl butoxide formulations (1:1, 1:5, 1:10) were evaluated in a laboratory wind tunnel against colony reared, susceptible adult Culex quinquefasciatus mosquitoes. Scourge (4% resmethrin:12% piperonyl butoxide) was used as the standard for comparison. Based on the LC90 data, the 3 cypermethrin-piperonyl butoxide formulations were 2.6-3.7x more toxic than Scourge 24-h posttreatment.     

Residual concentration and efficacy of three temephos formulations for control of larval Aedes aegypti.

The residual concentration and efficacy of Abate 5CG (impregnated in celatom granules) and plaster pellets impregnated with either Abate 4E or technical temephos were compared against late 3rd-instar Aedes aegypti larvae. Both plaster pellet formulations resulted in 100% larval mortality during the 6-wk test, compared with 2 wk for a similar level of mortality for the celatom formulation. The maximum temephos concentration in water treated with the celatom formulation occurred 30 min after treatment at 0.071 ppm. Temephos concentration of water treated with the 4E plaster formulation peaked at 12 h at 0.148 ppm while the concentration of the technical plaster formulation peaked at 48 h at 0.30 ppm.     

The influence of rice bran on plasma lipids and lipoproteins in human volunteers.

Eighteen healthy male normocholesterolaemic men consumed diets supplemented with 15 g wheat bran, 15 g and 30 g rice bran for 3-week treatment periods. Plasma lipoprotein concentrations were determined on the last 3 days of each treatment period. Nutrient intakes estimated by analysis of duplicate diets were similar during all treatments. Plasma triglyceride concentrations were statistically significantly (P less than 0.05) lowered by 15 g/day rice bran compared with 15 g/day wheat bran. Plasma total cholesterol, low density lipoprotein and high density lipoprotein cholesterol, apoprotein AI and B concentrations and body weight were unaffected by the supplements. It is concluded that the consumption of realistic amounts of rice bran does not contribute to a reduction in plasma cholesterol concentrations in man.     

Propylene glycol monomethyl ether occupational exposure. 3. Exposure of human volunteers

OBJECTIVE: Propylene glycol monomethyl ether (PGME) is a widely used additive in industrial and consumer products (paints, inks, diluents, cleaning products, cosmetics.). The aim of the present study was to determine uptake and disposition of PGME alpha-isomer in humans. METHOD: Six healthy male volunteers were exposed to PGME-alpha vapour (15, 50 and 95 ppm) with and without respiratory protection for 6 h including a 30-min break. Free PGME and total PGME (free and conjugated) were analysed in urine. The analytical method involved hydrolysis with HCl (only for the analysis of total PGME in urine), a solid phase extraction on LC-18 columns and a gas chromatograph-flame ionisation detector (GC/FID) analysis after derivatisation with trimethylsilylimidazole. RESULTS: End-exposure levels of free PGME in urine were found to reach 1.3 (+/-0.3), 4.4 (+/-1.6) and 7.9 (+/-2.5) mg/l for 15, 50 and 95-ppm exposure, respectively, without respiratory protection. End-exposure levels of total PGME in urine were found to reach 2.5 (+/-0.8), 6.2 (+/-1.6) and 10.3 (+/-2.3) mg/l for 15, 50 and 95-ppm exposure respectively. Levels of free PGME were also monitored in exhaled air (0.4 (+/-0.1), 1.4 (+/-0.4) and 2.9 (+/-0.9) ppm at the end of 15, 50 and 95-ppm exposure, respectively) and in blood (2.0 (+/-0.9), 4.9 (+/-2.3) and 11.8 (+/-2.4) mg/l at the end of 15, 50 and 95-ppm exposure, respectively). PGME is rapidly excreted in urine and in exhaled air; the half-lives were calculated to be approximately 3.5 h in urine and 10 min in exhaled air. PGME was below detection limits in breath (<0.1 ppm), in blood (<1 mg/l) and in urine (<1 mg/l) after dermal-only exposure to vapour. CONCLUSIONS: This study has demonstrated the relatively high pulmonary uptake compared with the dermal uptake. It has also shown the rapid excretion in urine (3.5 h) and in expired air (10 min). With regard to metabolism, this study has established the presence of conjugated PGME in urine.