Geranyl phenyl ethers from Illicium micranthum and their anti-HBV activity / 中国天然药物

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.

Four new diphenyl ether derivatives from a mangrove endophytic fungus Epicoccum sorghinum / 中国天然药物

Four new diphenyl ethers, named epicoccethers K-N (1-4), were purified from the fermentation medium of a fungus Epicoccum sorghinum derived from Myoporum bontioides, and identified through HR-ESI-MS and NMR spectral analysis. Except that compound 1 showed moderate antifungal activity against Penicillium italicum and Fusarium graminearum, the other three compounds showed stronger activity against them than triadimefon. All of them showed moderate or weak antibacterial activity towards Staphylococcus aureus and Escherichia coli with O6 and O78 serotypes except that 3 was inactive to E. coli O6.

Two natural molecules preferentially inhibit azole-resistant Candida albicans with MDR1 hyperactivation / 中国天然药物

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.

Aspectos institucionais, legais, políticos e técnicos para a implementação da Convenção de Estocolmo sobre Poluentes Orgânicos Persistentes: os éteres difenilícos polibromados / Institutional, legal, political and technical aspects for the Stockholm Convention on Persistent Organic Pollutants Implementation the polybrominated diphenyl ethers

Novos poluentes orgânicos persistentes (POPs) têm sido adicionados à lista da Convenção de Estocolmo, exemplificado nesta pesquisa pelos éteres difenílicos polibromados (polybrominated diphenyl ethers-PBDEs) aplicados como retardantes de chama em diversos artigos de consumo (eletrônicos, têxteis, móveis, automóveis e na construção civil). São substâncias semi voláteis, persistentes no ambiente, bioacumulativos nos tecidos adiposos e podem interferir no sistema endócrino humano e dos animais. Os países signatários devem cumprir as medidas estabelecidas e enfrentam desafios para a sua implementação, a julgar pelos poucos países que atualizaram os Planos Nacionais de Implementação (National Implementation Plans-NIPs). Esta pesquisa teve por objetivo identificar os aspectos institucionais, legais, políticos e técnicos para a implementação das exigências oriundas da Convenção de Estocolmo, no que diz respeito aos PBDEs, realizar revisão sistematizada da literatura sobre os artigos colocados no mercado e em unidades de reciclagem de resíduos contendo PBDE e apresentar as experiências de dois países na implementação das medidas. O método de pesquisa de estudo de casos comparados, com o delineamento de casos mais diferentes com o mesmo resultado, foi empregado para a República Tcheca e a Suécia, apoiado por análise de congruência. Entrevistas foram realizadas com profissionais envolvidos com as atividades para a elaboração e a implementação da Convenção de Estocolmo. A revisão sistematizada para PBDEs indicou o aumento da quantidade de artigos científicos a partir de 2008 e os estudos revelaram a presença de PBDEs na poeira e no ar em ambientes internos, como residências e escritórios e nos ambientes internos e externos às instalações de reciclagem de resíduos com avaliação da exposição humana aos PBDEs, e novos estudos devem ser desenvolvidos. A revisão mostrou também que na América Latina e Caribe as publicações ainda são em pequeno número, mas o Brasil tem posição de destaque. O estudo dos dois países revelou que é requerida uma complexa abordagem para a transposição das medidas em âmbito nacional, incluindo legislação sobre gestão de produtos químicos, arranjos institucionais nacionais para a implementação do NIP apoiados por instituições de pesquisas científicas, existência de programas de monitoramento ambiental e de controle de POP-BDEs em artigos de consumo colocados no mercado. Os principais desafios técnicos são a segregação de plásticos, contendo PBDEs em parceria com o setor industrial para identificar o conteúdo PBDEs em artigos em uso que se tornarão resíduos e a viabilização do uso das alternativas tecnológicas. Os benefícios gerados pela implementação da Convenção são a proteção da saúde humana e do meio ambiente, a melhoria da governança, a promoção de assistência técnica, a maior visibilidade sobre riscos de uso de produtos tóxicos, em especial os POPs, a maior interação entre a ciência e as políticas públicas e o aumento das pesquisas cientificas. A Convenção de Estocolmo é um acordo complexo porém contribui com o entendimento mais amplo dos riscos químicos e sobre gestão coordenada das substâncias químicas

Additional new Persistent Organic Pollutants (POPs) have been included to the list of Stockholm Convention, in the research exemplified by means of polybrominated diphenyl ethers (PBDEs) which resist degradation, are transported far from their place of release, where they accumulate in terrestrial and aquatic ecosystems and possess toxic properties, since they are classified as endocrine disruptive chemicals. They were used as brominated flame retardants and applied in many articles/consumer products such as electronics, textiles, vehicles, furniture and building materials. The signatories countries must comply with obligations and measures taken by Convention however they are facing many challenges in order to implement them, once few countries submitted the updated National Implementation Plans (NIPs) to the Convention. This research aims at identifying the institutional, legal, technical and politics aspects in order to transpose those measures to the national level, conducting a systematized research of literature on consumer products that may contain c-BDE put in the market besides recycling units of articles upon becoming wastes, consisting of, containing or contaminated with a chemical PBDEs and presenting the experience of two countries in implementing PBDEs actions plans of the NIPs. The comparative case studies was used as the research method, improved by the most different cases and most similar outcomes, designed for two countries as Czech Republic and Sweden, supported by the congruence analyses. Standardized interviews were applied to professionals involved in elaborating and implementing the Stockholm Convention in the countries. The systematized research indicated the increase from 2008 of the scientific number articles related to PBDEs which presented the occurrence of PBDEs in indoor house, office and recycling units dust and air internal and outdoor environments nearby waste electronic and electric equipment recycling units, with human exposure analyses related to and the researches must be continued, accordingly the conclusions. The comparative case studies of two countries revealed the requirement of a complex chemical substances management approach in order to transpose the PBDEs obligations to the national level, including the industrial chemical and environmental legislations, especially on POP-BDEs in products, a integrated institutional arrangement with the scientific institutional support, environmental monitoring programs and chemical control of the spread of POP-BDEs substances present in a number of consumer products put on the market; as the main challenges are the segregation of plastics containing PBDE in order to avoid recycled articles containing PBDEs and the importance of dialogue with the industrial sector in order to identify the PBDEs content in articles in use and to evaluate technology alternatives to PBDEs as well as promote technical capacities to raise awareness of chemicals to importers and private sector. The benefits generated by the Convention implementation are protection on healthy and environmental, the governance improvement, technical assistance promotion, POPs visibility, science and politics integration and the increase of scientific research

Efficacy and safety of a single dose pentamidine (7mg/kg) for patients with cutaneous leishmaniasis caused by L. guyanensis: a pilot study

Abstract: BACKGROUND: There have been few studies on pentamidine in the Americas; and there is no consensus regarding the dose that should be applied. OBJECTIVES: To evaluate the use of pentamidine in a single dose to treat cutaneous leishmaniasis. METHODS: Clinical trial of phase II pilot study with 20 patients. Pentamidine was used at a dose of 7 mg/kg, in a single dose. Safety and adverse effects were also assessed. Patients were reviewed one, two, and six months after the end of treatments. RESULTS: there was no difference between the treatment groups in relation to gender, age, number or location of the lesions. Pentamidine, applied in a single dose, obtained an effectiveness of 55%. Mild adverse events were reported by 17 (85%) patients, mainly transient pain at the site of applications (85%), while nausea (5%), malaise (5%) and dizziness (5%) were reported in one patient. No patient had sterile abscess after taking medication at a single dose of 7mg/kg. CONCLUSIONS: Clinical studies with larger samples of patients would enable a better clinical response of pent amidine at a single dose of 7mg, allowing the application of more powerful statistical tests, thus providing more evidences of the decrease in the effectiveness of that medication. Hence, it is important to have larger studies with new diagrams and/or new medications.

VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen

Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.

Design, synthesis and biological evaluation of fingolimod analogues containing diphenyl ether moiety / 药学学报

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.

A new diphenyl ether from the endophytic fungus Verticillium sp. isolated from Rehmannia glutinosa / 中国天然药物

AIM@#To investigate the chemical constituents of the endophytic fungus Verticillium sp. isolated from Rehmannia glutinosa.@*METHODS@#The compounds were isolated and purified by repeated column chromatography, and their structures were determined on the basis of physicochemical properties and spectral analysis. Their cytotoxic and antifungal activities were evaluated.@*RESULTS@#Ten compounds were obtained and their structures were identified as 2, 4-dihydroxy-2', 6-diacetoxy-3'-methoxy-5'-methyl-diphenyl ether (1), paecilospirone (2), α-acetylorcinol (3), 2-methoxy-1,8-dimethyl-xanthen-9-one (4), 4-hydroxy-α-lapachone (5), enalin A (6), 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (7), 4-hydroxyethyl-phenol (8), 2,4-dihydroxy-3,5,6-trimethyl- methylbenzoate (9), and 3-isopropenyl-(Z)-monomethyl maleate (10).@*CONCLUSIONS@#Compound 1 is a new diphenyl ether, and showed cytotoxic activity against HL-60 cells (IC50 2.24 μg · mL(-1)), and antifungal activities against Candida albicans (MIC 8 μg · mL(-1)) and Aspergillus fumigatus (MIC 16 μg · mL(-1)).

Effect of nitrofen in the final stages of development of the diaphragm muscle in rats / Efeito do nitrofen na fase final do desenvolvimento da musculatura do diafragma em ratos

PURPOSE: To evaluate the expression of myosin in muscle fibers of the diaphragm in experimental congenital diaphragmatic hernia (CDH). METHODS: Fetuses of pregnant rats were divided into four groups: External Control (EC), composed of non-manipulated rats; Nitrofen, composed of pregnant rats that received 100 mg of nitrofen (2,4-dichloro-4'nitrodiphenyl ether) diluted in olive oil on gestational day (GD) 9.5, whose fetuses developed CDH (N+) or not (N-), and Olive Oil Placebo (OO), composed of pregnant rats that received the oil on the same GD. The fetuses were collected on GD 18.5, 19.5, 20.5 and 21.5 (term = 22 days). We obtained body weight (BW) and photographed the diaphragm area (DA), hernia area (HA) and subsequent calculated the HA/DA ratio in N+ group. Samples of Diaphragm muscle were processed for histological staining with H/E and immunohistochemistry (IHQ) for myosin.} RESULTS: The fetuses of N- and N+ groups had decreased BW and DA compared to EC and OO groups (p <0.001). HA was decreased on GD 18.5 compared to 21.5 (p <0.001) and the HA/DA ratio showed no difference. IHQ showed decreased expression of myosin in nitrofen groups. CONCLUSION: CDH induced by nitrofen model contributes to the understanding of muscularization in the formation of the diaphragm where the myosin expression is decreased.

OBJETIVO: Avaliar a expressão da miosina na muscularização do diafragma na hérnia diafragmática congênita (CDH) experimental. MÉTODOS: Fetos de ratas foram divididos em quatro grupos: Controle Externo (EC), composto de ratas não manipuladas; Nitrofen, composto de ratas que receberam 100 mg de nitrofen (2,4-dicloro-4'nitrodifenil éter) diluído no azeite no dia de gestação (GD) 9.5, cujos fetos desenvolveram CDH (N+) ou não (N-) e Placebo óleo de oliva (OO), composto de ratas que ingeriram apenas óleo no mesmo GD. Os fetos foram coletados com 18,5, 19,5, 20,5 e 21,5 GD (termo = 22 dias). Foi obtido o peso corporal (BW) e tiradas fotografias da área do diafragma (DA), da hérnia (HA) e calculada a relação HA/DA no grupo N+. Amostras de diafragmas foram processadas histologicamente para coloração com H/E e imunohistoquímica. RESULTADOS: Os fetos dos grupos N- e N+ tiveram BW e DA diminuídos em relação aos grupos EC e OO (p<0.001). Só houve diferença na HA entre os GD 18.5 e 21.5 (p<0.001) e a relação HA/DA não mostrou diferença entre os grupos. A imunohistoquímica mostrou menor expressão de miosina nos grupos que receberam nitrofen. CONCLUSÃO: O modelo de CDH induzida por nitrofen contribui para entender a muscularização na formação do diafragma onde a expressão da miosina está diminuída.

Development of a controlled release formulation of an indigenous insect growth regulator, DPE-28, a substituted diphenylether, for controlling the breeding of Culex quinquefasciatus.

Background & objectives: DPE-28, a substituted diphenyl ether (2,6-ditertiarybutyl phenyl-2’,4’-dinitro phenyl ether) was reported to exhibit promising insect growth regulating activity against Culex quinquefasciatus, the vector of lymphatic filariasis. A controlled release formulation (CRF) of DPE-28 has been developed to control Cx. quinquefasciatus in its breeding habitats. Toxicity of DPE-28, safety to non-target mosquito predators and the release profile of the CRF of DPE-28 are studied and discussed. Methods: The acute oral and dermal toxicity was tested in male and female Wistar rats as per the Organization for Economic Cooperation and Development (OECD) guidelines 425 and 402 respectively. The toxicity of DPE-28 to non-target predators was tested as per the reported procedure from this laboratory. The CRF of DPE-28 was prepared by following the reported procedure developed at this laboratory earlier. The concentration of DPE-28 released from the CRF was monitored by HPLC by constructing a calibration graph by plotting the peak area in the Y-axis and the concentration of DPE-28 in the X-axis. Results: DPE-28 has been tested for acute oral toxicity and found to be moderately toxic with LD50 value of 1098 mg/kg body weight (b.w). The results of the acute dermal toxicity and skin irritation studies reveal that DPE-28 is safe and non-irritant. DPE-28 when tested at 0.4 mg/litre against non-target mosquito predators did not produce any mortality. The release profile of the active ingredient DPE-28 from the CRF by HPLC technique showed that the average daily release (ADR) of DPE-28 ranged from 0.07 to 5.0 mg/litre during first four weeks. Thereafter the matrix started eroding and the ADR ranged from 5 to 11 mg/litre during the remaining 5 wk. The cumulative release of active ingredient showed that > 90 per cent of the active ingredient was released from the matrix. Interpretation & conclusions: The controlled release matrix of DPE-28 was thus found to inhibit the adult emergence (>80%) of Cx. quinquefasciatus for a period of nine weeks. The CRF of DPE-28 may play a useful role in field and may be recommended for mosquito control programme after evaluating the same under field conditions.

Polybrominated Diphenyl Ethers Orally Administration to Mice Were Tansferred to Offspring during Gestation and Lactation with Disruptions on the Immune System

BACKGROUND: The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings. METHODS: In this study, mated female C57BL/6J mice were orally administered penta-BDE, deca-BDE or corn oil for 5 weeks, from gestational day 6 to lactational day 21. RESULTS: The body weight of PND21 exposed to penta-BDE was significantly decreased relative to control mice, but that of post-natal day 63 (PND63) were recovered. Orally dosed dams with penta-BDE had significantly smaller absolute and relative spleen masses than control mice. Absolute and relative spleen and thymus masses of PND21 exposed to penta-BDE were significantly decreased over control. The exposure of dams and PND21 with penta-BDE reduced the number of splenocytes and thymocytes. As results of hematologic analysis, percentage WBC and percentage neutrophils increased in dams with deca-BDE. Splenic T cell proliferation in dams and PND21 exposed to penta-BDE was increased, and there were no significant difference in splenic B cell proliferation in all treatment groups. As results of flow cytometric analysis of splenocyte, percentage total T cell, Th cell and Tc cell in PND21 exposed to penta-BDE was slightly increased, and percentage macrophage in dams and PND21 exposed to deca-BDE was decreased. The ELISA results of antibody production show no significant difference in all treatment groups relative to controls. CONCLUSION: These results imply that PBDEs given to the dam were transferred to the offspring during gestation and lactation, and PBDEs transferred from the dam affect immune system of offspring.

Impact of PBDE-209 exposure during pregnancy and lactation on immune function of offspring rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the potential hazard of environmental deca-brominated diphenyl ether (PBDE-209) exposure to the immune function of the offspring rats.</p><p><b>METHODS</b>The parental Wistar rats were exposed to PBDE-209 administered intragastrically during pregnancy and lactation, and the development of the immune organs and changes in T lymphocyte subset and their proliferation, NK cell surface markers CD161 and serum immunoglobulins (IgM and IgG) were observed.</p><p><b>RESULTS</b>Significant differences in the weight of the immune organs were noted between the exposure group and control group. In the exposure group, the percentage of T lymphocyte subset CD3(+), CD4(+), CD8(+), CD4(+)CD8(+), the percentage of NK cell surface markers CD16 1 and CD4(+)/CD8(+) ratio were lowered, while the percentage of CD4(-)CD8(-) cells increased. T lymphocyte subset proliferation in the exposure group did not show obviously changes, but compared with the control group, the IgM level in the exposure group was significantly lowered. No significant differences were observed in IgG levels between the exposure and control groups.</p><p><b>CONCLUSION</b>Continuous exposure to high-dose PBDE-209 in female rats during pregnancy and lactation results in possible adverse effect on the immune function of the offspring rats.</p>

Optimization of technological conditions for one-pot synthesis of (S)-alpha-cyano-3-phenoxybenzyl acetate in organic media / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Optically active form of alpha-cyano-3-phenoxybenzyl (CPB) alcohol, building block of pyrethroid insecticides, was synthesized as its acetate by the combination of anion-exchange resin (D301)-catalyzed transcyanation between m-phenoxybenzaldehyde (m-PBA) and acetone cyanohydrin (AC), and lipase (from Alcaligenes sp.)-catalyzed enantioselective transesterification of the resulting cyanohydrin with vinyl acetate. Through optimizing technological conditions, the catalyzing efficiency was improved considerably compared to methods previously reported. Concentrations of CPB acetate were determined by gas chromatograph. The enantio excess (e.e.) values of CPB acetate were measured by NMR (nuclear magnetic resonance) method. Effects of solvents and temperatures on this reaction were studied. Cyclohexane was shown to be the best solvent among the three tested solvents. 55 degrees C was the optimal temperature for higher degree of conversion. External diffusion limitation was excluded by raising the rotational speed to 220 r/min. However, internal diffusion could not be ignored, since the catalyst (lipase) was an immobilized enzyme and its particle dimension was not made small enough. The reaction rate was substantially accelerated when the reactant (m-PBA) concentration was as high as 249 mmol/L, but decreased when the initial concentration of m-PBA reached to 277 mmol/L. It was also found that the catalyzing capability of recovered lipase was high enough to use several batches. Study of the mole ratio of AC to m-PBA showed that 2:1 was the best choice. The strategy of adding base catalyst D301 was found to be an important factor in improving the degree of conversion of the reaction from 20% to 80%. The highest degree of conversion of the reaction has reached up to 80%.

Efeito da radiação ionizante sobre a oxidação do colesterol em hambúrgueres de frango e bovino congelados / Effect of the ionizing radiation about the oxidation of the cholesterol in chicken and bovine hamburgers frozen

Várias tecnologias vêm sendo desenvolvidas com o intuito de assegurar a qualidade dos alimentos. Dentre estes processos tecnológicos, a radiação ionizante vem sendo apontada como uma alternativa viável na conservação de alimentos, principalmente produtos cárneos, por manter inalterado seu estado natural. A utilização da irradiação em hambúrgueres tem sido enfocada devido ao freqüente envolvimento deste produto em surtos de toxinfecção alimentar, geralmente provocados pela E. coli O157:H7, muitas vezes com registro de óbitos. Entretanto, a utilização de radiação ionizante neste produto pode gerar radicais livres capazes de desencadear a oxidação lipídica no tecido muscular...

Investigation on injury of liver and kidney among the workers exposed to terephthalic acid, ethylene glycol and(or) dowtherm A / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study injury of liver and kidney among the workers exposed to terephthalic acid(TPA), ethylene glycol(EG) and(or) dowtherm A(DOW), and research for early biological monitoring indexes.</p><p><b>METHODS</b>By using the method of occupational epidemiology, an investigation of industrial hygiene in a chemical fibre corporation was carried out and the changes of the liver and kidney functions were analyzed among the workers who had been exposed to TPA, EG, DOW.</p><p><b>RESULTS</b>The values of serum gamma-glutamyl traspetidase(GGT) and total bile acid(TBA) in TPA + EG + DOW group men were (35.45 +/- 16.09) U/L, (10.29 +/- 6.76) mumol/L respectively and the values of serum alanine transaminase(ALT) and TBA in TPA + EG + DOW group women were(30.68 +/- 8.58) U/L, (9.53 +/- 6.63) mumol/L respectively, significantly higher than those in TPA, DOW and control groups(P < 0.05, P < 0.01). Compared with TPA, DOW and control groups, the values of urine N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-2-microglobulim (beta 2-MG) in TPA + EG + DOW group of both men and women increased significantly(P < 0.05, P < 0.01), with(5.68 +/- 4.01) U/mmol Cr and (23.49 +/- 13.44) mg/mol Cr, and(6.68 +/- 4.68) U/mmol Cr and (22.80 +/- 13.00) mg/mol Cr, respectively. Analysis of regression indicated that both liver and renal injuries of the workers were evidently correlated with their exposure to TPA, EG and DOW after adjustment for the confounding factors such as sex, smoking, drinking, etc(P < 0.001).</p><p><b>CONCLUSION</b>Based on available knowledge, it is reasonable to assume that the joint actions should be considered on the injury of liver and kidney caused by TPA, EG and(or) DOW among the workers. Serum ALT, GGT, TBA, urine NAG and beta 2-MG should be suggested as biomarkers for liver and kidney damage.</p>

Effects of a juvenoid, DPE-28, on biology and behaviour of Culex quinquefasciatus, the human filariasis vector.

Studies on the effect of a juvenoid, DPE-28 (2,4-dinitrophenyl-2',6'-di-tertiarybutyl phenyl ether) on biology and behaviour of Cx. quinquefasciatus showed that the developmental duration, sex ratio, mating success and blood feeding were considerably affected by the exposure of larvae and pupae to the compound. Exposure of fourth instar larvae to 0.007 (EI90) and 0.0019 (EI50) ppm of DPE-28 prolonged the duration of pupation by 58.6 and 52.4 hr and delayed the adult emergence by 35.4 and 17.7 hr in males and 36.8 and 21.1 hr in females respectively. Exposure of freshly ecdysed pupae to 10 and 5 ppm delayed the adult emergence with respect to the control by 54.3 and 32.4 hr in males and 55.2 and 33.2 hr in females respectively. The sex ratio of the adults emerged from treated larvae and pupae was also affected. The female mosquitoes that survived from the exposed fourth instar larvae and pupae exhibited a low blood engorgement ratio. This depression in blood feeding was more pronounced in adults emerged from treated pupae than that of treated fourth instar larvae. A significant proportion of adults emerged from treated larvae and pupae were able to feed only partially. Mating success of the treated populations declined considerably when crosses were made between the males and females emerged from treated fourth instar larvae and pupae. The adults emerged from treated larvae and pupae showed a significant reduction in the oviposition.

Action of some new insect growth regulators on mosquito vectors. Part II: Geraniol based diethers.

Biological activity of saturated diethers viz. 1-benzyloxy/phenoxy-8-alkoxy and 1-alkoxy-8-benzyloxy-3,7-dimethyl-1, 8-octanes (IIa-IIq) prepared from Geraniol, were studied on three mosquito species and the bug Dysdercus koenigii. These diethers exhibited oviposition deterrent and developmental inhibition activities of greater magnitudes than the compounds based on citronellol reported in Part I of this paper. Some of these new compounds inhibit development of mosquitoes at 0.05 ppm and deter oviposition at 0.05 per cent doses. Tests were extended to field simulated conditions in selected cases.

Structure-activity relationships in diphenyl ethers for insect growth regulating activity against mosquitoes.

Out of the 30 substituted diphenyl ethers synthesized and tested for insect growth regulating (IGR) activity against mosquitoes, three compounds viz., DPE-16, 19 and 28 showed promising IGR activity. While DPE-16 and 19 were found to be effective against all three vector species tested viz., Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi, with the respective EI50 values of 0.1485, 0.3650, 0.2225 mg/l and 0.1474, 0.1392, 0.1145 mg/l, DPE-28 was found to be highly effective against C. quinquefasciatus with an EI50 value of 0.0022 mg/l. The structure-activity relationship in the diphenyl ethers with respect to their octanol-water partition coefficients showed an increase of lipophilicity when both the ortho positions of the phenolic moiety are substituted by tertiary butyl group. The simulated field trial carried out with DPE-16, 19 and 28 showed that these compounds were effective for 7, 7 and 9 days respectively at 0.1 mg/l against C. quinquefasciatus.