Use of different coloured ovitraps in the surveillance of Aedes mosquitoes in an arid-urban area of western Rajasthan, India.

BACKGROUND & OBJECTIVES: In the absence of any commercially available dengue vaccine or antiviral therapy, controlling the primary mosquito vector, Aedes aegypti, is currently the only means to prevent dengue outbreaks. Ovitraps are being employed as a sensitive method for detecting the presence of Ae. aegypti. Size, colour, material, paddle and use of oviposition attractant have been reported as important factors influencing the efficacy of ovitraps. METHODS: For the study of coloured ovitraps baited with grass infusion, 24 households were randomly selected in a locality and five ovitraps/premises were installed. Weekly ovitrap surveys were conducted during the study for four times. Ovitrap data were analyzed on the basis of its location, day-wise percent positivity, presence of eggs laid and inference of different ovitrap parameters were drawn. RESULTS: Grass infusion, used in the ovitraps has highest attractiveness on Day 6 in comparison to other days. Percent positivity of different coloured ovitraps revealed that red coloured ovitraps have highest positivity (92.7%), followed by black and orange (91.7% each), green (76.3%) and transparent (45.8%). The individual colour-wise ovitrap positivity revealed that the highest ovitrap positivity on Day 1 was recorded for black colour (21.8%), which on D2 and D3, in case of red colour (37.5 and 26%). However, on D4, D5 and D6 highest number of positive ovitraps was recorded in orange coloured (12.5, 21.9 and 31.3%, respectively) and on D7 highest number of positive ovitraps were recorded in transparent (21.9%), followed by green coloured ovitrap (20.8%). The overall location-wise ovitraps positivity revealed that highest positivity was recorded among the ovitraps installed inside bathrooms (92.0%), followed by bedrooms (85.0%), lobby (66.7%) and stores (48.3%). INTERPRETATION & CONCLUSION: The study revealed that for immediate detection of the presence of gravid females in a particular locality during epidemics, the black coloured ovitraps may be useful, however, in normal situations for surveillance of the vector species, the orange coloured ovitraps might be more suitable. Bathrooms were found to be the highest positive location for pitching ovitraps.

Larvicidal potential of wild mustard (Cleome viscosa) and gokhru (Tribulus terrestris) against mosquito vectors in the semi-arid region of Western Rajasthan.

Cleome viscosa L. (Family: Capparaceae) commonly known as Tickweed or wild mustard and Tribulus terrestris L. (Family: Zygophyllaceae) commonly known as Gokhru, growing wildly in the desert areas in the monsoon and post monsoon season, are of great medicinal importance. Comparative larvicidal efficacy of the extracts from seeds of C. viscosa and fruits and leaves of T. terrestris was evaluated against 3rd or early 4th stage larvae of Anopheles stephensi (Liston), Aedes aegypti (Linnaeus) and Culex quinquefasciatus (Say) in different organic solvents. 24 and 48 hr LC50 and LC90 values along with their 95% fiducial limits, regression equation, chi-square (chi2)/ heterogeneity of the response was determined by log probit regression analysis. The 24 hr LC50 values as determined for seeds of C. viscosa were 144.1, 99.5 and 127.1 (methanol); 106.3, 138.9 and 118.5 (acetone) and 166.4, 162.5 and 301.9 mg l(-1) (petroleum ether extracts) for all the three mosquito species respectively showing that methanol and acetone extracts were a little bit more effective than the petroleum ether extracts. Experiments were carried out with fruits and leaves of T. terrestris with all the solvents and mosquito species. The 24 hr LC50 values, as determined for fruits of T. terrestris were 70.8, 103.4 and 268.2 (methanol); 74.0,120.5 and 132.0 (acetone) and 73.8,113.5 and 137.4 mg l(-1) (petroleum ether extracts) while the 24 hr LC50 values for leaves were 124.3, 196.8 and 246.5 (methanol); 163.4, 196.9 and 224.3 (acetone) and 135.8, 176.8 and 185.9 mg l(-1) (petroleum ether extracts) for all the three mosquito species respectively. The results clearly indicate that fruit extracts of T. terrestris were more effective as compared to leaves extracts in the three solvents tested. Larvae of An. stephensi were found more sensitive to both fruit and leaves extracts of T. terrestris followed by larvae of Ae. aegypti and Cx. quinquefasciatus. Extracts from the seeds of C. viscosa were found less effective as compared to the fruit extracts of T. terrestris indicating that active larvicidal principle may be present in the fruits of this plant species. The studywould be of great importance while formulating the control strategy, for vectors of malaria, dengue and lymphatic filariasis, based on alternative plant based insecticides in this semi-arid region.

Laboratory observations on the larvicidal efficacy of three plant species against mosquito vectors of malaria, dengue/dengue hemorrhagic fever (DF/DHF) and lymphatic filariasis in the semi-arid desert.

Comparative larvicidal efficacy of aqueous and organic solvent extracts from seeds, leaves and flowers of three desert plants viz. Calotropis procera (Aiton), Tephrosia purpurea (L.) Pers. and Prosopis juliflora (Sw.) DC. was evaluated against Anopheles stephensi (Liston), Aedes aegypti (Linnaeus) and Culex quinquefasciatus (Say). For this purpose larvae of all the three mosquito species were reared in the laboratory and studies carried out on late 3rd or early 4th instars using standard WHO technique. Based on concentration mortality data 24 and 48 hr LC50and LC90 values along with their 95% fiducial limits, regression equation, chi-square (chi2)/ heterogeneity of the response were determined by log probit regression analysis. Experiments were carried out with different solvent extracts of seeds of C. procera which revealed that methanol (24 hr LC50: 127.2, 194.8, 361.0) and acetone (229.9, 368.1,193.0 mg l(-1)) extracts were more effective with the three mosquito species, respectively. Petroleum ether extract was effective only on An. stephensi while aqueous extracts were not effective at all with any of the mosquito species (mortality < 10-30%). Tests carried out with methanol extracts of fresh leaves (24 hr LC50: 89.2, 171.2, 369.7) and flowers (24 hr LC50: 94.7,617.3, 1384.0 mg l-(-1)) of Calotropis showed that preparations from fresh parts were 2-3 times more effective as compared to the stored plant parts. Efficacy was less than 10-30% with both An. aegypti and Cx. quinquefasciatus while An. stephensi was still susceptible to extracts from both leaves and flowers even after two years of storage. The 24 hr LC50 values as observed for methanol extracts of seeds of T. purpurea and leaves of P. juliflora were 74.9, 63.2 and 47.0 and 96.2,128.1 and 118.8 mg l(-1) for the above three mosquito species, respectively. Experiments carried out up to 500 mg l-(1) with leaves (T. purpurea) and seeds (P. juliflora) extracts show only up to 10-30% mortality indicating that active larvicidal principle may be present only in the seeds of Tephrosia and leaves of Prosopis. In general, anophelines were found more susceptible than the culicines to the plant derived derivatives. More studies are being carried outon some other desert plants found in this arid region. The study would be of great importance while formulating vector control strategy based on alternative plant based insecticides in this semi-arid region.

Comparative larvicidal potential of different plant parts of Withania somnifera against vector mosquitoes in the semi-arid region of Rajasthan.

Larvicidal potential of the extracts from different parts viz. green and red fruits, seeds, fruit without seeds, leaves and roots of Withania somnifera in different solvents was evaluated against larvae of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, the important disease vectors prevalent in the semi-arid region. Experiments were carried out on late 3rd or early 4th instar larvae of these mosquitoes using standard WHO technique. 24 and 48 hr LC50 values along with their 95% confidence limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined by log probit regression analysis. The 24 hr LC50 values as observed for whole green fruits in water, methanol and petroleum ether were 350.9, 372.4, 576.9; 115.0, 197.1, 554.6; 154.9, 312.0, 1085.0 while corresponding values for red fruits were 473.5, 406.4,445.2; 94.7, 94.5, 1013.0; 241.8, 535.0, 893.3 mg l(-1) for An. stephensi, Ae. aegypti and Cx. quinquefasciatus respectively showing that methanol extracts were more effective against anophelines as compared to culicines when whole fruits were taken. The 24 hr LC50 values as observed for seeds in acetone, methanol and petroleum ether were 188.1, 777.5, 822.5; 245.5, 769.0, 1169.0; 140.3, 822.9, 778.4 and for fruit without seeds were 80.2, 97.6, 146.6; 88.4, 404.4, 1030.0; 30.0, 44.5, 54.2 mg l(-1) for the above mosquito species respectively showing that extract of fruit without seeds were most effective in petroleum ether followed by acetone and methanol extracts. However, experiments conducted with methanol extracts of leaves and roots of this plant species did not show any appreciable larvicidal activity and a 20-40% mortality was observed up to 500 mg l(-1) of the extracts. Overall larvae of anophelines were found more susceptible as compared to culicines to all the extracts tested. Petroleum ether extract of fruit without seeds was found most effective against all the mosquito species showing that active ingredient might be present in this part of the plant species. The study would be of great importance while planning vector control strategy based on alternative plant derived insecticides.

Evaluation of the diagnostic potential and DIVA capability of recombinant LigBCon1-5 protein of Leptospira interrogans serovar Pomona in canine leptospirosis.

BACKGROUND: Canine leptospirosis is a serious public health concern. AIMS: This study aims to investigate the feasibility of conserved first to fifth domains of recombinant Leptospira immunoglobulin like protein B antigen (rLigBCon1-5) as a serodiagnostic marker for detecting canine leptospirosis. METHODS: A total of 340 unvaccinated canine serum samples were screened using microscopic agglutination test (MAT) and rLigBCon1-5 based immunoglobulin G (IgG) indirect-enzyme-linked immunosorbent assay (I-ELISA). Further, 60 vaccinated canine sera were screened using MAT and rLigBCon1-5 based latex agglutination test (LAT). RESULTS: Microscopic agglutination test results revealed seropositivity of 28.6%. The relative sensitivity, specificity, and accuracy of IgG I-ELISA in comparison to MAT were 100%, 96.0%, and 97.2%, respectively. Out of 60 vaccinated sera, 46 sera reacted with MAT alone, and eight sera reacted by both tests, while six sera were non-reactive with both tests. Anti-LigB antibodies were detected in eight canine sera by rLigBCon1-5 based LAT. In five LAT reactive sera, agglutinins of locally circulating Leptospira serovars Grippotyphosa (n=4) and Australis (n=1) were detected. In three LAT reactive sera, agglutinins against Icterohaemorrhagiae (n=3) produced due to natural infection were present. CONCLUSION: Immunoglobulin G based indirect ELISA assay (IgG I-ELISA) can be employed as an alternative test instead of MAT. rLigBCon1-5 based LAT detected anti-LigB antibodies in eight vaccinated sera where the vaccine failure occurred partially or totally due to the limited efficacy spectrum of Nobivac® RL and cold chain breakage. This vaccine could not provide cross-protection against locally circulating Leptospira serovars. The recombinant LigBCon1-5 antigen based LAT possesses capability of differentiating infected from vaccinated individuals (DIVA capability) when employed as a pen-side test for detecting canine leptospirosis.

Larvicidal activity of the extracts from different parts of the plant Solanum xanthocarpum against important mosquito vectors in the arid region.

Larvicidal efficacy of the aqueous and methanol extracts from green unripe and yellow ripe fruits, seeds, leaves and roots of the plant Solanum xanthocarpum was evaluated against Anopheles culicifacies, Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, the important mosquito vectors prevalent in the arid region. Studies were carried out on late 3rd orearly 4th instarlarvae of these species using standard WHO technique. Based on concentration mortality data LC50 and LC90 values along with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined bylog probit regression analysis. The 24 hr LC50 values as observed for aqueous extracts for green unripe and yellow ripe fruits were 112.7, 498.2 and 846.3 mg l(-1) and 104.7, 267.7and 832.2 mg l(-1) for Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus respectively. However, the 24 hr LC50 values formethanol extracts of yellow ripe fruits and seeds were 51.6, 52.2, 118.3 and 157.1 mg l(-1) and 66.9, 73.7, 123.8 and 154.9 mg l(-1) for the above four vector species respectively. The results showed that larvae of anophelines were much more susceptible as compared to culicines to both the aqueous and methanol extracts from fruits and seeds of the plant tested. The methanol extracts were found 2-5 times more effective as compared to the aqueous extracts. The chi-square values calculated during the analysis did not show any heterogeneity of the response. Experiments conducted with aqueous and methanol extracts from leaves and roots of this plant species didn't show any larvicidal activity against any of the mosquito species tested. The study would be of great importance while formulating vector control strategy based on alternative plant based insecticides.

Evaluation of larvicidal efficacy of Solanum xanthocarpum storage against vector mosquitoes in north - western Rajasthan.

Efficacy of the methanol extracts from fruits without seeds, whole yellow ripe fruits and seeds of the plant Solanum xanthocarpum was evaluated against larvae of Anopheles culicifacies, Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, the important vector mosquitoes prevalent in the arid region. Experiments were carried out on late 3rd or early 4th instar larvae of these mosquitoes using standard WHO technique. 24 and 48 hr LC50 and LC90 values along with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined by log probit regression analysis. The 24 hr LC50 values as observed for fruit without seeds, whole fruits and seeds after six months were 79.6, 91.7 and 131.7; 131.4, 186.9 and 195.6; 273.4, 290.9 and 377.6 and 384.9, 450.6 and 520.0 mg l(-1) for An. culicifacies, An. stephensi, Ae. aegypti and Cx. quinquefasciatus respectively. However, the 24 hr LC50 values for fresh yellow ripe fruits and seeds determined previously were 51.6 and 66.9; 52.2 and 73.7; 118.3 and 123.8 and 157.1 and 154.9 mg l(-1) for the above four vector species respectively showing that the efficacy was decreased two to three times more after six months of storage. The 24 hr LC50 values were also determined after one year of storage for fruit without seeds, whole fruits and seeds. The values were 103.3, 120.1 and 195.7; 146.3, 224.3 and 251.2; 316.9, 336.5 and 426.2 and 393.0, 500.3 and 656.7 mg l(-1) as compared to the 24 hr LC50 values of 47.4, 51.6 and 66.9; 52.3, 52.2 and 73.7; 108.0, 118.3 and 123.8 and 141.1, 157.1 and 154.9 mg l(-1) of all the three fresh preparations for the above four vector species respectively showing that the efficacy was further decreased after one year of storage. Further the extracts should be used when they have been prepared from the fresh plant parts instead of the old stored parts. Larvae of anophelines were found more susceptible as compared to culicine. HPLC and IR studies showed that active component might be present in the fruits and seeds of this plant species. The study would be of great importance while planning vector control strategy based on alternative plant derived insecticides.

Relative susceptibility of some common mosquito vector larvae to synthetic insecticidal compounds in north-western Rajasthan.

Relative susceptibility of three important mosquito vector larvae viz., Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, prevalent in the arid region was determined against four organophosphates (malathion, fenitrothion, fenthion, temephos) and three synthetic pyrethroid (alphamethrin, deltamethrin and fanvalerate) compounds. Studies were carried out on late 3rd or early 4th instar larvae of these species using standard WHO technique. Based on concentration mortality data LC50 and LC90 values along with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined by log probit regression analysis. LC50 values as observed for the above seven insecticides were 0.8097, 0.0398. 0.0432, 0.0035, 0.0025, 0.0092, 0.1006; 1.2370, 0.0531, 0.0655, 0.0076, 0.00004, 0.00004, 0.0046 and 1.4980, 0.0719, 0.0817, 0.0056, 0.00021, 0.00073, 0.0112 mg/l for the above three mosquito species respectively Among the four organophosphates tested temephos was the most effective followed by fenitrothion, fenthion and malathion. In general, Anopheles was found more susceptible as compared to the other two culicines to the above four compounds. The results also showed that larvae of Ae. aegypti were most susceptible followed by Cx. quinquefasciatus and An. stephensi to all the three pyrethroids tested. Among the three compounds tested alphamethrin was found to be the most toxic followed by deltamethrin while fanvalerate was the least toxic. The study would be of great importance while planning use of these insecticides for the control of different vector species in this area.

Combinations of mesna with cyclophosphamide or adriamycin in the treatment of mice with tumors.

Following therapeutic administration, cyclophosphamide and Adriamycin are biotransformed to reactive metabolites, some of which are responsible for undesirable systemic toxicities of these chemicals, whereas others are responsible for their chemotherapeutic effectiveness. Microsomal mixed function oxidases activate cyclophosphamide to produce phosphoramide mustard and acrolein, while cytochrome reductase and xanthine oxidase are capable of transforming Adriamycin and forming free radicals. These reactive metabolites produce unwanted toxic side effects; however, their action may be partially ameliorated by the concomitant administration of thiols. In this study we evaluated the therapeutic activity of combinations of mesna (2-mercaptoethanesulfonate) with cyclophosphamide or Adriamycin in mice with a variety of transplantable tumors (L1210 and P-388 leukemia, Lewis lung and colon 26 carcinoma, B16 melanoma, and M5076 sarcoma). In all cases the administration of mesna prior to cyclophosphamide or Adriamycin treatment did not reduce the antitumor effectiveness of these agents and in some instances (C57BL/6 mice with B16 melanoma or M5076 sarcoma) small improvements were observed. Therefore, the addition of thiols, to reduce effectively the buildup of toxic metabolites of cyclophosphamide or Adriamycin may result in the improved therapeutic effectiveness for these agents in the treatment of cancer.

Metabolism and binding of cyclophosphamide and its metabolite acrolein to rat hepatic microsomal cytochrome P-450.

The hepatic cytochrome P-450-mediated metabolism and metabolic activation of [chloroethyl-3H]cyclophosphamide [( chloroethyl-3H]CP) and [4-14C]cyclophosphamide [( 4-14C]CP) were investigated in vitro in the reconstituted system containing cytochrome P-450 isolated from phenobarbital-treated rats. In addition, hepatic microsomal binding and the hepatic microsome-mediated metabolism of [14C]acrolein, a metabolite of [4-14C]CP, were also investigated. The metabolism of [chloroethyl-3H]CP and [4-14C]CP to polar metabolites was found to depend on the presence of NADPH and showed concentration dependence with respect to cytochrome P-450 and NADPH:cytochrome P-450 reductase. Km and Vmax values were essentially similar (Km, 0.44 and 0.42 mM; Vmax, 4.8 and 7.0 nmol of polar metabolites formed/min/nmol of cytochrome P-450 for [4-14C]CP and [chloroethyl-3H]CP, respectively). The patterns of inhibition by microsomal mixed-function oxidase inhibitors, anti-cytochrome P-450 antibody, and heat denaturation of the cytochrome P-450 were essentially similar, with subtle differences between [4-14C]CP and [chloroethyl-3H]CP metabolism. The order of inhibition by various mixed-function oxidase inhibitors was SKF greater than alpha- and beta-naphthoflavones greater than metyrapone. The in vitro metabolic activation of CP in the reconstituted system demonstrated predominant binding of [chloroethyl-3H]CP to nucleic acids and almost exclusive binding of [4-14C]CP to proteins. Gel electrophoresis-fluorography of the proteins in the reconstituted system treated with [4-14C]CP demonstrated localization of the 14C label in the cytochrome P-450 region. To examine this association further, hepatic microsomes were modified with [14C]acrolein in the presence and the absence of NADPH. The results confirmed covalent association between [14C]acrolein and cytochrome P-450 in the microsomes and also demonstrated further metabolism of [14C]acrolein, apparently to an epoxide, which is capable of binding covalently to proteins. The results of these investigations not only confirm the significance of primary metabolism but also emphasize the potential role of the secondary metabolism of cyclophosphamide in some of its toxic manifestations.

Bioanalytical method development and validation for a large peptide HIV fusion inhibitor (Enfuvirtide, T-20) and its metabolite in human plasma using LC-MS/MS.

A method for measuring a human immunodeficiency virus (HIV) cell membrane fusion inhibitor (T-20/Ro 29-9800) and its metabolite (M-20/Ro 50-6343) in human plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. The relatively large peptide analytes and their corresponding deuterated (d(10)) peptides used as internal standard were isolated from plasma by protein precipitation with two volumes of acetonitrile to plasma. A large pore size reversed-phase C(18) column was employed to elute the peptides. A triple quadrupole mass spectrometer with electrospray interface operating in positive ion and multiple reaction monitoring modes with transitions m/z 1124-->1343 for both T-20 and M-20 was utilized for peak detection. The advantages of the method were a simple sample preparation, specific and sensitive MS/MS detection, and a wide dynamic range of 10-2000 ng/ml for T-20. The method was validated and used for analyzing samples from clinical studies to provide pharmacokinetic profiles of the HIV fusion inhibitor peptide drug and its metabolite.

Selective beta(1)-adrenoreceptor blocking activity of newly synthesized acyl amino-substituted aryloxypropanolamine derivatives, DPJ 955 and DPJ 890, in rats.

The in-vivo beta-adrenoreceptor antagonistic activity of test compounds DPJ 955 and DPJ 890 was assessed against beta-adrenoreceptor agonist (isoprenaline) induced tachycardia in anaesthetized rats. The selectivity to block isoprenaline responses on different &beta-adrenoreceptor subtypes (beta(1), beta(2) and beta(3)) of the test compounds was carried out on isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively. Intravenous injection of isoprenaline alone in anaesthetized rats caused hypotension and tachycardia. DPJ 955 or DPJ 890 alone produced a fall in mean arterial pressure and bradycardia in a dose-dependent manner. Administration of isoprenaline to anaesthetized rats pre-treated with test compounds significantly blocked both the tachycardial and hypotensive responses induced by isoprenaline. The test compounds shifted the concentration response curves of isoprenaline towards the right for isolated rat right atrial preparations, rat uterus and rat colon, indicating beta(1), beta(2) and beta(3) adrenoreceptor blockade, respectively. The selectivity ratio for beta(1)/beta-adrenoreceptors to DPJ 955 and DPJ 890 was 64.6 and 83.2, respectively. DPJ 890 was more potent in blocking beta(1)-adrenoreceptors and was more selective towards beta(1) receptors than to other beta-adrenoreceptor subtypes. In conclusion, DPJ 955 and DPJ890 have beta-adrenoreceptor blocking activity with high selectivity for the beta(1)-adrenoreceptor subtype.

Study on serum and urinary cortisol levels of asthmatic patients after treatment with high dose inhaled beclomethasone dipropionate or budesonide.

BACKGROUND: The potential for long-term adverse effects from inhaled corticosteroids relates to their systemic absorption. With increasing use of high dose inhaled corticosteroids, there is need to establish whether similar doses of beclomethasone dipropionate (BDP) and budesonide (BUD) produce clinically important differences in untoward side effects specially hypothalamo-pituitary-adrenal (HPA) axis suppression. METHODS: Fifteen asthmatic patients were started on BDP or BUD (2000 microg/day) through spacer for six weeks. Serum cortisol (9 AM and 4 PM), 24-hour urinary steroid and pulmonary function testing parameters were performed. RESULTS: The serum cortisol levels were not found to be suppressed with either BDP or BUD. Similarly no significant changes were found in 24 hours urinary excretion of steroids with either of the drugs. Significant improvement was found in values of forced expiratory volume in the first second (FEV1) with BDP. With BUD the changes in forced vital capacity (FVC) and FEV1 were found to be significant. CONCLUSION: BDP or BUD in high doses of 2000 microg/day given upto six weeks through spacer are equally effective for treatment of bronchial asthma and do not cause any significant change in serum and urinary cortisol levels, and adrenal function/HPA axis.

Phrenic neuropathy in arsenic poisoning.

A patient presented with acute arsenic neuropathy with asymmetric bilateral phrenic nerve involvement. The clinical and roentgenographic observations of phrenic nerve dysfunction were confirmed by prolonged phrenic nerve conduction time. The patient made a significant recovery with d-penicillamine therapy.

In vitro disruption of ATP dependent active transport following treatment with aldrin and its epoxy analog dieldrin in a fresh water teleost, Labeo rohita.

Tissue homogenates of brain, gill, liver and kidney of Labeo rohita were subjected in vitro to the various concentrations as 5.00, 1.66, 0.55, 0.18 and 0.06 mu M of 2 organochlorine pesticides aldrin and dieldrin and the disruption of ATP dependent active transport (involving ATPase) was studied. The inhibition of total ATPase, Mg2+ and Na+, K+-dependent ATPase by both the pesticides was quite similar and there was an increased inhibition with increased concentration of the toxicant, however, at the lowest concentrations of both the pesticides stimulation was observed in all tissues except gill Mg2+ ATPase where insignificant inhibition was observed after dieldrin treatment. Inhibition of ATPase system was noted maximum in brain followed by gill, kidney and liver of the experimental fish, however in each tissue maximum inhibition of ATPase was noted after dieldrin treatment than that of th e aldrin treatment. Therefore, the observed action of these pesticides might be related to the ability of the compounds to alter the cellular membrane configuration by binding with the lipid portion of the membrane and this blocking the movement of substances by active transport.

Chlordecone toxicity: effect of withdrawal of treatment on ATPase inhibition.

Adult male Sprague-Dawley rats were treated P.O with 10 mg/kg/day chlordecone for 10 days. Five rats from control group receiving corn oil and five rats from chlordecone group were sacrificed for tissue preparations. The remaining rats in chlordecone group were withdrawn from treatment and left in cages for 45 days. At 15, 30 and 45 days after withdrawal, 5 rats from each group with equal number of controls were sacrificed. Brain, liver and kidney were removed and subcellular fractions were prepared. Na+-K+, oligomycin-sensitive and oligomycin-insensitive Mg2+ ATPases were determined. Rats treated with chlordecone for 10 days showed a significant reduction of Na+-K+ ATPase activity in brain and kidney. The decreased enzyme activity in kidney but not in brain returned to normal within 15 days of treatment withdrawal. In brain the enzyme activity stayed at reduced level throughout the experimental period. Oligomycin-sensitive Mg2+ ATPase activity in all the tissues was decreased significantly in chlordecone treated rats. The enzyme activity returned to normal levels in all tissues gradually by 30 days of treatment withdrawal. Oligomycin-insensitive Mg2+ ATPase activity was not decreased in any tissue by chlordecone treatment. These results suggest that chlordecone effects on ATPase system are reversible except for Na+-K+ ATPase in brain.

Asthma in the elderly: underperceived, underdiagnosed and undertreated; a community survey.

Bronchial asthma is now increasingly recognized in the elderly and is associated with significant morbidity and mortality. The aims of this study were two-fold: first, to assess the prevalence and, second, to evaluate diagnostic awareness, therapeutic management and patient perception of bronchial asthma among elderly patients in the community. From the age-sex register of an urban general practice in NE England, 2004 patients aged > 65 years were eligible for inclusion. Response to an initial screening questionnaire on respiratory symptomatology was 68% (n = 1362). Of these, 869 patients had respiratory symptoms: 390 voluntarily agreed to be evaluated further including assessment of airway physiology. In this group 369/390 had obstructive spirometry and, of these, 95 patients fulfilled clinical and physiological criteria of bronchial asthma. Prevalence of asthma within this age cohort was minimally and rather crudely assigned at 4.5% (95/2004). Among the 95 patients so-defined patients with asthma [age 70 +/- 8 years (mean +/- SD), FEV1 = 0.96 +/- 0.41, 33 male, 75 life-long non-smokers], subjective awareness, perception and attribution of pulmonary symptoms were poor. Further, despite tangible evidence of reversible and significant airflow limitation, only 21 were receiving inhaled glucocorticoid therapy (median daily dose 400 micrograms). Asthma in the elderly remains poorly perceived, poorly recognized and suboptimally treated. These findings are particularly apposite in the light of current epidemiological trends in asthma mortality and morbidity in elderly age cohorts.

Effects of chlordecone and its structural analogs on p-nitrophenyl phosphatase.

The effects of chlordecone, mirex, and four photoderivatives of mirex on K+-stimulated p-nitrophenyl phosphatase (KPNPPase) in rat brain synaptosomes were determined. Additionally, the effect of chlordecone on the substrate and K+ activation kinetics and the inhibition of KPNPPase at 17, 27, and 37 degrees C were determined. The sensitivity of KPNPPase to various chemicals was highly variable. Chlordecone was the most effective inhibitor with an IC50 of 6.2 X 10(-6)M. All other chemicals showed a maximum inhibition of 20% at 20 muM concentration. The order of inhibition at 20 muM concentration was chlordecone (100%) greater than 8-monohydro mirex (20%) greater than 2,8-dihydromirex (10%) greater than mirex (10%) greater than 10-monohydro mirex (9%) greater than 5,10-dihydro mirex (2%). Double reciprocal plots of the data obtained on the effect of chlordecone on the substrate and K+ activation kinetics showed that the Vmax and Km were decreased with respect to paranitrophenyl phosphate, while it was competitive inhibition with respect to K+ activation. Chlordecone inhibited KPNPPase more at 37 degrees C than at 27 degrees C and 17 degrees C suggesting a positive temperature effect. These results suggest that chlordecone is the most effective inhibitor among its structural analogs tested on KPNPPase in rat brain synaptosomes.

Lactate dehydrogenase isoenzymes in macrophages and serum during the development of pulmonary silicosis in the rat.

The lactate dehydrogenase (LDH) isoenzyme pattern in macrophages (peritoneal and alveolar) in the rat was studied on polyacrylamide gel electrophoresis. Further, the release of LDH isoenzymes from cultured macrophages exposed to silica dust and also the pattern of serum LDH isoenzymes in silica exposed animals were investigated. The isoenzyme pattern of the alveolar macrophages showed all the five bands, contrary to peritoneal macrophages in which two bands, viz. LDH1 and LDH2, were missing. Silica-exposed macrophages liberated LDH5 in the supernatant culture medium. This LDH isoenzyme also increased in the serum of silicotic rats during the early stages of the development of the disease.