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2.
Mar Pollut Bull ; 165: 112124, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33652256

ABSTRACT

Reduction in the impact of human-induced factors is capable of enhancing the environmental health. In view of COVID-19 pandemic, lockdowns were imposed in India. Travel, fishing, tourism and religious activities were halted, while domestic and industrial activities were restricted. Comparison of the pre- and post-lockdown data shows that water parameters such as turbidity, nutrient concentration and microbial levels have come down from pre- to post-lockdown period, and parameters such as dissolved oxygen levels, phytoplankton and fish densities have improved. The concentration of macroplastics has also dropped from the range of 138 ± 4.12 and 616 ± 12.48 items/100 m2 to 63 ± 3.92 and 347 ± 8.06 items/100 m2. Fish density in the reef areas has increased from 406 no. 250 m-2 to 510 no. 250 m-2. The study allows an insight into the benefits of effective enforcement of various eco-protection regulations and proper management of the marine ecosystems to revive their health for biodiversity conservation and sustainable utilization.


Subject(s)
COVID-19 , Pandemics , Animals , Communicable Disease Control , Ecosystem , Environmental Monitoring , Humans , India , SARS-CoV-2
3.
Sci Rep ; 10(1): 22133, 2020 12 17.
Article in English | MEDLINE | ID: mdl-33335160

ABSTRACT

Coral reefs around the world are undergoing severe decline in the past few decades. Mass coral mortalities have predominantly been reported to be caused by coral bleaching or disease outbreaks. Temporary hypoxic conditions caused by algal blooms can trigger mass coral mortalities though are reported rarely. In this study in Gulf of Mannar (GoM), southeast India, we report a significant coral mortality caused by a bloom of the ciguatoxic dinoflagellate Noctiluca scintillans during September-October 2019. Dissolved oxygen levels declined below 2 mg l-1 during the bloom causing temporary hypoxia and mortality (up to 71.23%) in the fast growing coral genera Acropora, Montipora and Pocillopora. Due to global climate change, more frequent and larger algal blooms are likely in the future. Hence, it is likely that shallow water coral reefs will be affected more frequently by episodic hypoxic conditions driven by algal blooms. More studies are, however, required to understand the mechanism of coral mortality due to algal blooms, impacts on community composition and the potential for subsequent recovery.


Subject(s)
Anthozoa , Antibiosis , Dinoflagellida/physiology , Harmful Algal Bloom , Oxygen/metabolism , Animals , Coral Reefs , Environment , Geography , India
4.
Mar Pollut Bull ; 151: 110793, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32056588

ABSTRACT

Underwater survey was conducted to assess the accumulation and impact of marine debris in the reef areas of Gulf of Mannar in southeast India. A combination of roving diver technique and belt transect method was applied for the assessment, which was conducted during the period between February 2018 and March 2019. An estimated total reef area of 1152 m2 has been affected by marine debris. Abandoned fishing nets were found to constitute the major portion of 43.17 ± 5.48% of the marine debris. Live corals were found to be dominant substrates for marine debris with 39.11%. The average prevalence of coral colonies in contact with marine debris was 3.28 ± 0.27%. Prevalence of corals in contact with debris was very high in genus Acropora with 8.23 ± 1.29% followed by Montipora with 4.63 ± 1.29% due to their complex growth form. Of the corals in contact with debris, 47.56% were fragmented and 34% were found with tissue loss.


Subject(s)
Anthozoa , Coral Reefs , Environmental Monitoring , Waste Products , Water Pollutants , Animals , India
5.
Environ Monit Assess ; 191(7): 430, 2019 Jun 12.
Article in English | MEDLINE | ID: mdl-31190173

ABSTRACT

Seagrass beds are important marine ecosystems that provide significant ecological services. The global decline of seagrass beds is becoming severe due to the increasing pressure of human-induced factors and changing climatic conditions. Restoration of seagrasses is an evolving science that started in 1939. In this study, we report a remarkably successful restoration activity carried out in the Gulf of Mannar (GoM), Southeast India. This is the first wide-scale effort in Indian waters. After the initial experimentation, manual transplantation of seagrass sprigs was carried out near Vaan and Koswari islands in GoM. Transplantation was performed with PVC quadrats and jute twines in areas of 800 m2 in both the islands during February to May 2014. An increase from 16.4 ± 0.3 to 32.3 ± 0.6% in Vaan and from 15.1 ± 0.2 to 35.1 ± 0.9% in Koswari was observed in seagrass percentage cover during the period from June 2014 to May 2016. Area cover, shoot density, macrofaunal density and fish density increased at the restoration sites after the transplantation. Bottom trawling was found to be the most serious threat to the seagrass beds in these islands. This method of transplantation can be replicated in other areas of degraded seagrass in India to carry out wide-scale restoration of seagrasses.


Subject(s)
Environmental Monitoring/methods , Environmental Restoration and Remediation/methods , Seaweed/growth & development , Animals , Climate Change , Ecosystem , Fishes/growth & development , Humans , India , Indian Ocean , Indian Ocean Islands
6.
Dis Aquat Organ ; 126(1): 63-70, 2017 09 20.
Article in English | MEDLINE | ID: mdl-28930086

ABSTRACT

Acropora white syndrome (AWS) and Terpios sponge overgrowth (TSO) are serious threats to coral communities in various regions; however, information on these 2 lesions in the Indian Ocean is much more limited than in the Indo-Pacific. The present study revealed the impact of these lesions on the Palk Bay reef, India, and covered an area of 7 km2. In total, 1930 colonies were permanently monitored to assess incidences of AWS and TSO and consequent mortality for a period of 1 yr. TSO affected 5 coral genera and caused 20.7% mortality; overall prevalence increased from 1.3% (n = 25) to 25.5% (n = 492). In contrast, AWS only affected Acropora colonies and caused a mortality of 8%; overall prevalence increased from 0.9% (n = 17) to 12.9% (n = 249). Year-round monitoring revealed an increasing trend of both AWS and TSO, followed by temperature rise. These results add to the known geographic distribution of these coral diseases and reveal the impacts of AWS and TSO on coral reefs in the Indian Ocean.


Subject(s)
Anthozoa/microbiology , Porifera/physiology , Animals , Coral Reefs , Host-Pathogen Interactions , India , Indian Ocean
7.
Article in English | AIM (Africa) | ID: biblio-1260360

ABSTRACT

Background: Moderate exercise is associated with a lower risk for coronary heart disease (CHD). A suitable integrated model of the CHD pathogenetic pathways relevant to moderate exercise may help to elucidate this association. Such a model is currently not available in the literature.Methods: An integrated model of CHD was developed and used to investigate pathogenetic pathways of importance between exercise and CHD. Using biomarker relative-risk data, the pathogenetic effects are representable as measurable effects based on changes in biomarkers.Results: The integrated model provides insight into higherorder interactions underlying the associations between CHD and moderate exercise. A novel 'connection graph' was developed, which simplifies these interactions. It quantitatively illustrates the relationship between moderate exercise and various serological biomarkers of CHD. The connection graph of moderate exercise elucidates all the possible integrated actions through which risk reduction may occur.Conclusion: An integrated model of CHD provides a summary of the effects of moderate exercise on CHD. It also shows the importance of each CHD pathway that moderate exercise influences. The CHD risk-reducing effects of exercise appear to be primarily driven by decreased inflammation and altered metabolism


Subject(s)
Biomarkers , Coronary Artery Disease , Exercise , Risk Factors , South Africa
8.
Dis Aquat Organ ; 110(3): 227-34, 2014 Aug 11.
Article in English | MEDLINE | ID: mdl-25114046

ABSTRACT

Information on the progression of coral diseases and transmission to live corals is scarce despite the fact that coral disease poses one of the most lethal threats to the survival of coral reefs. In this study, in situ progression rates of lesions similar to black band disease (BBD) and white band disease (WBD) were measured in different species of corals from the Gulf of Mannar (GoM) and Palk Bay, southeastern India, during the period between January and December of 2009. Maximum progression rates of 3 and 1.6 cm mo-1 for BBD and WBD, respectively, were observed during May, when the temperature exceeded 30°C. The annual progression rate was 10.9 and 4.9 cm yr-1 for BBD at GoM and Palk Bay, respectively. Significant variation in the progression rate (p < 0.001) was observed between months in all the examined species. Significant correlation between temperature and disease progression rates for BBD (R2 = 0.875, p ≤ 0.001) and WBD (R2 = 0.776, p ≤ 0.001) was recorded. Rates of disease progression were higher in Palk Bay than in GoM. This could be attributed to the higher temperature coupled with higher anthropogenic activities in Palk Bay. Severe mortality was observed due to both BBD and WBD. No sign of recovery was noticed in the disease-affected colonies at either study site. Anthropogenic activities should be checked, and further research on both the transmission and progression rate and role of the diseases in reef dynamics should be carried out to understand the causal factors in reef degradation and generate a plan to manage the reef properly.


Subject(s)
Anthozoa/microbiology , Animals , Coral Reefs , India , Indian Ocean , Oceans and Seas
9.
Dis Aquat Organ ; 106(1): 69-77, 2013 Sep 24.
Article in English | MEDLINE | ID: mdl-24062554

ABSTRACT

The present study reports coral mortality, driven primarily by coral diseases, around Shingle Island, Gulf of Mannar (GOM), Indian Ocean. In total, 2910 colonies were permanently monitored to assess the incidence of coral diseases and consequent mortality for 2 yr. Four types of lesions consistent with white band disease (WBD), black disease (BD), white plaque disease (WPD), and pink spot disease (PSD) were recorded from 4 coral genera: Montipora, Pocillopora, Acropora, and Porites. Porites were affected by 2 disease types, while the other 3 genera were affected by only 1 disease type. Overall disease prevalence increased from 8% (n = 233 colonies) to 41.9% (n = 1219) over the 2 yr study period. BD caused an unprecedented 100% mortality in Pocillopora, followed by 20.4 and 13.1% mortality from WBD in Montipora and Acropora, respectively. Mean disease progression rates of 0.8 ± 1.0 and 0.6 ± 0.5 cm mo-1 over live coral colonies were observed for BD and WBD. Significant correlations between temperature and disease progression were observed for BD (r = 0.86, R2 = 0.75, p < 0.001) and WBD (R2 = 0.76, p < 0.001). This study revealed the increasing trend of disease prevalence and progression of disease over live coral in a relatively limited study area; further study should investigate the status of the entire coral reef in the GOM and the role of diseases in reef dynamics.


Subject(s)
Anthozoa/microbiology , Animals , Coral Reefs , Ecosystem , India , Indian Ocean , Islands , Time Factors
10.
Vet Pathol ; 50(2): 234-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22700850

ABSTRACT

Epitheliotropism is an important diagnostic feature of cutaneous epitheliotropic lymphoma and canine cutaneous histiocytoma; however, although noted in certain feline mastocytic diseases, it has not been considered a feature of canine cutaneous mast cell tumor. In this study, 3 canine cutaneous mast cell tumors had epitheliotropic invasion of neoplastic mast cells into the epidermis and follicular epithelium. This unusual histologic finding was characterized by infiltrates of individual and clusters of neoplastic mast cells in the stratum basale and stratum spinosum. The mast cell origin of these cells was documented by demonstration of metachromasia with Giemsa stain and positive immunoreactivity to KIT protein. On the basis of these findings, mast cell tumors should be included in the differential diagnosis for canine cutaneous round cell neoplasms that infiltrate the epidermis.


Subject(s)
Dog Diseases/diagnosis , Dog Diseases/pathology , Dog Diseases/therapy , Epidermis/pathology , Mastocytosis/veterinary , Skin Neoplasms/veterinary , Animals , Azure Stains , Diagnosis, Differential , Dogs , Female , Male , Mastocytosis/diagnosis , Mastocytosis/pathology , Mastocytosis/therapy , Proto-Oncogene Proteins c-kit , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/therapy
11.
Anaesthesia ; 68(1): 111-2, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23231615

Subject(s)
Oximetry/standards , Humans
12.
Anaesthesia ; 67(4): 396-401, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22324874

ABSTRACT

Peripheral pulse oximetry has become a core monitoring modality in most fields of medicine. Pulse oximeters are used ubiquitously in operating theatres, hospital wards, outpatient clinics and general practice surgeries. This study used a portable spectrometer (Lightman(®), The Electrode Co. Ltd., Monmouthshire, UK) to measure the emission spectra of the two light emitting diodes within the pulse oximeter sensor and to determine the accuracy of 847 pulse oximeters currently in use in 29 NHS hospitals in the UK. The standard manufacturing claim of accuracy for pulse oximeters is ± 2-3% over the range of 70-100% S(p)O(2). Eighty-nine sensors (10.5%) were found to have a functional error of their electrical circuitry that could cause inaccuracy of measurement. Of the remaining 758 sensors, 169 (22.3%) were found to have emission spectra different from the manufacturers' specification that would cause an inaccuracy in saturation estimation of > 4% in the range of 70-100% saturation. This study has demonstrated that a significant proportion of pulse oximeter sensors may be inaccurate.


Subject(s)
Oximetry/standards , Humans , Oximetry/methods , Reproducibility of Results , United Kingdom
13.
J Clin Monit Comput ; 25(3): 211, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21874564

Subject(s)
Oximetry/standards , Humans
14.
Psychoneuroendocrinology ; 28(8): 1010-26, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14529705

ABSTRACT

In most mammals, behaviors that show sex differences are influenced by androgen during early life. In the current study, the hypothesis that androgen influences the development of human spatial abilities was investigated. Participants included 40 females and 29 males with congenital adrenal hyperplasia (CAH), a genetic disorder that causes overproduction of adrenal androgens beginning prenatally, and 29 unaffected female and 30 unaffected male relatives of individuals with CAH. Participants ranged in age from 12-45 years. Measures of spatial abilities included two mental rotations tasks and two targeting tasks, all of which showed large sex differences favoring males in the unaffected relative controls. Females with CAH (exposed to higher than normal levels of androgen prenatally) performed better than unaffected females on the targeting tasks, and resembled unaffected males and males with CAH in this respect. However, females with CAH did not perform better than unaffected females on the measures of mental rotations abilities. Males with CAH showed unaltered performance on the targeting tasks, and impaired performance on the mental rotations tasks. Results are discussed in terms of differences in experiential and hormonal contributions to different spatial abilities, as well as in terms of possible differences in critical periods for hormonal influences on targeting versus mental rotations abilities. Specifically, we speculate that, although androgen may influence targeting abilities prenatally, if hormones influence the development of mental rotations ability, they do so at some other time, perhaps during the first six months of postnatal life.


Subject(s)
Adrenal Hyperplasia, Congenital/physiopathology , Adrenal Hyperplasia, Congenital/psychology , Androgens/physiology , Mental Processes/physiology , Prenatal Exposure Delayed Effects , Space Perception/physiology , Adolescent , Adult , Analysis of Variance , Child , Female , Humans , Male , Middle Aged , Pregnancy , Rotation , Sex Characteristics
15.
JAMA ; 283(5): 639-45, 2000 Feb 02.
Article in English | MEDLINE | ID: mdl-10665704

ABSTRACT

CONTEXT: In laboratory trials, nucleic acid amplification tests for the diagnosis of tuberculosis (TB) are more accurate than acid-fast bacilli (AFB) smear microscopy and are faster than culture. The impact of these tests on clinical diagnosis is not known. OBJECTIVE: To assess the performance of a nucleic acid amplification test, the enhanced Mycobacterium tuberculosis Direct (E-MTD) test, against a uniform clinical standard stratified by level of clinical suspicion. DESIGN: Prospective multicenter trial conducted between February and December 1996, documenting the clinical suspicion of TB at enrollment and using final comprehensive diagnosis as the criterion standard. SETTING: Six urban medical centers and 1 public health TB clinic. PATIENTS: A total of 338 patients with symptoms and signs consistent with active pulmonary TB and complete clinical diagnosis were stratified by the clinical investigators to be at low (< or =25%), intermediate (26%-75%), or high (>75%) relative risk of having TB. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of the E-MTD test in clinical suspicion of groups with low (n = 224); intermediate (n = 68); and high (n = 46) clinical suspicion of TB. RESULTS: Based on comprehensive clinical diagnosis, sensitivity of the E-MTD test was 83%, 75%, and 87% for low, intermediate, and high clinical suspicion of TB, respectively, and corresponding specificity was 97%, 100%, and 100% (P = .25). Positive predictive value of the E-MTD test was 59% (low), 100% (intermediate), and 100% (high) compared with 36% (low), 30% (intermediate), and 94% (high) for AFB smear. Corresponding negative predictive values were 99%, 91%, and 55% [corrected] (E-MTD test) vs 96%, 71%, and 37% (AFB smear). CONCLUSIONS: For complex diagnostic problems like TB, clinical risk assessments can provide important information regarding predictive values more likely to be experienced in clinical practice. For this series, a clinical suspicion of TB was helpful in targeting areas of the clinical spectrum in which nucleic acid amplification tests can make an important contribution.


Subject(s)
Mycobacterium tuberculosis/isolation & purification , Nucleic Acid Amplification Techniques , Tuberculosis, Pulmonary/diagnosis , Adult , Bacteriological Techniques , Clinical Laboratory Techniques , Female , Humans , Male , Middle Aged , Mycobacterium tuberculosis/genetics , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity
16.
J Res Natl Inst Stand Technol ; 105(1): 97-100, 2000.
Article in English | MEDLINE | ID: mdl-27551592

ABSTRACT

This paper reports on recent progress toward unraveling the origin of gamma-ray bursts. It is concluded that neutron-star binaries are one of the few remaining candidates. A model is proposed based upon general relativistic hydrodynamic studies which indicate a new physical process by which to power a gamma-ray burst. Relativistically driven compression, heating, and collapse of the individual neutron stars can occur many seconds before inspiral and merger. This compression may produce a neutrino burst of ∼10(53) ergs lasting several seconds. The associated thermal neutrino emission produces an e (+)-e (-) pair plasma by [Formula: see text] annihilation. We show first results of a simulated burst which produces ∼10(51) erg in γ rays of the correct spectral and temporal properties.

17.
Arch Pathol Lab Med ; 123(11): 1101-3, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10539916

ABSTRACT

OBJECTIVE: To evaluate the performance of the enhanced Mycobacterium Tuberculosis Direct Test (E-MTD), for the direct detection of M tuberculosis complex (MTBC) in respiratory specimens. DESIGN: Two hundred seventy-four respiratory specimens from 151 patients in respiratory isolation were tested with the E-MTD, and the results were compared with the results of mycobacterial smear, culture, and the earlier form of the test, MTD-1. RESULTS: Forty-one specimens were culture positive for mycobacteria (20 MTBC and 21 nontuberculous mycobacteria), 23 of which were smear positive (16 MTBC, 7 nontuberculous mycobacteria). Twenty-four specimens were positive by E-MTD, and 21 were positive by MTD-1. Of the 20 MTBC culture-positive specimens, 19 were positive by the E-MTD and 19 were positive by the MTD-1. The remaining specimens were MTBC negative by all methods. After resolution of discrepancies, the sensitivity, specificity, and positive and negative predictive values were 95.2%, 100%, 100%, 99.6% for the MTD-1 and 95.2%, 98.8%, 87.0%, and 99.6%, for the E-MTD. For the E-MTD smear-positive and smear-negative specimens, these same values were 93.8%, 100%, 100%, and 87.5% and 100%, 98.8%, 62.5%, and 100%, respectively. CONCLUSION: The results suggest that the E-MTD is a reliable method for the direct detection of MTBC in smear-positive respiratory specimens.


Subject(s)
Bacteriological Techniques , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Nucleic Acid Amplification Techniques , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Bacteriological Techniques/statistics & numerical data , Bronchoalveolar Lavage Fluid/microbiology , Diagnostic Errors , Evaluation Studies as Topic , Humans , Sensitivity and Specificity , Sputum/microbiology
18.
J Parasitol ; 83(4): 686-91, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9267412

ABSTRACT

Anopheles mosquitoes frequently respond to invading malaria parasites with a rejection mechanism consisting of phenoloxidase-mediated melanization of ookinetes in the mosquito midgut epithelium. The relative roles of hemolymph vs. midgut phenoloxidase in this rejection mechanism is unclear. We have separated and identified phenoloxidase isozymes from midgut and hemolymph of Anopheles stephensi by native gel electrophoresis followed by zymography. The isozymes from the 2 sites had distinctively different electrophoretic characteristics. Hemolymph possessed 2 phenoloxidase-positive bands, both of which were bifunctional molecules that oxidized monophenol as well as o-diphenol substrates. Midgut extract possessed 3 bands that migrated more rapidly than those of the hemolymph. None of these midgut bands had detectable monophenoloxidase activity; they possessed, however, a broad spectrum of diphenoloxidase activity in their ability to oxidize both o- and p-diphenol substrates, as well as the laccase substrate syringaldazine. The 2 most rapidly migrating midgut PO bands could be distinguished from the more slowly migrating band through their insensitivity to inhibition by the chelating agent tropolone. A question to be resolved in the future relates to the relative roles of hemolymph vs. midgut phenoloxidase in mosquito defense against invasive parasites.


Subject(s)
Anopheles/enzymology , Hemolymph/enzymology , Insect Vectors/enzymology , Isoenzymes/analysis , Monophenol Monooxygenase/analysis , Animals , Centrifugation , Electrophoresis, Polyacrylamide Gel , Female , Isoenzymes/blood , Isoenzymes/isolation & purification , Molecular Weight , Monophenol Monooxygenase/blood , Monophenol Monooxygenase/isolation & purification
19.
Am J Trop Med Hyg ; 55(4): 417-23, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8916799

ABSTRACT

Mice (BALB/c) were immunized to mosquito saliva by repeated bites of Anopheles stephensi mosquitoes. Studies were conducted on the ability of these mice to develop antibodies against the apyrase component of the saliva. By means of immunoprecipitation procedures and Western blot analysis, we demonstrated the presence of antiapyrase antibodies to the mosquito saliva. Furthermore, these antibodies were able to inhibit apyrase activity. Serum titers of 1:20 were able to inhibit approximately 90% of salivary gland apyrase activity, while titers of 1:160 retained the ability to inhibit more than 50% of apyrase activity. Parallel inhibition assays with immunoglobulin G (IgG) from immunized versus nonimmunized mice showed that the inhibitory activity of serum from immunized mice could be accounted for by its IgG component. Mosquito salivary gland apyrase has previously been shown to facilitate mosquito feeding by inhibiting aggregation of platelets at the mosquito bite site. However, our studies have shown that mosquitoes feeding on immunized mice had no deficiency in probing these mice for a blood meal, even in the face of high titers of anti-apyrase antibodies.


Subject(s)
Anopheles/enzymology , Antibodies/immunology , Apyrase/antagonists & inhibitors , Insect Bites and Stings/immunology , Animals , Anopheles/immunology , Aorta , Apyrase/analysis , Apyrase/immunology , Blotting, Western , Cattle , Cell Line , Electrophoresis, Polyacrylamide Gel , Endothelium, Vascular/cytology , Endothelium, Vascular/enzymology , Enzyme-Linked Immunosorbent Assay , Female , Isoelectric Focusing , Mice , Mice, Inbred BALB C , Precipitin Tests , Salivary Glands/enzymology , Salivary Glands/immunology
20.
Neuropharmacology ; 35(2): 123-36, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8734480

ABSTRACT

The GABAA receptor/chloride ionophore (GABAR) is allosterically modulated by several classes of anticonvulsant agents, including benzodiazepines and barbiturates, and some alkyl-substituted butyrolactones. To test the hypothesis that the anticonvulsant butyrolactones act at a distinct positive-modulatory site on the GABAR, we examined the physiological effects of a butyrolactone, a benzodiazepine and a barbiturate on GABA-mediated currents in voltage-clamped neurons and cells transfected with various subunit combinations. The butyrolactone, alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone (alpha EMTBL), altered the EC50 for GABA and changed the apparent cooperativity of GABA responses. In contrast, the benzodiazepine chlordiazepoxide altered the EC50 for GABA with no effect on apparent cooperativity. The barbiturate phenobarbital altered both the EC50 and the amplitude of the maximal GABA response without altering apparent cooperativity. The GABA-mediated effect of the barbiturate, but not the benzodiazepine, added to the maximal effect of the butyrolactone, supporting the hypothesis that butyrolactones do not exert their effect at the barbiturate effector site. Both alpha EMTBL and phenobarbital potentiated GABA currents in transfected cells containing the alpha 1 beta 2 and alpha 1 gamma 2 subunit combinations, as well as alpha 1 subunits alone. Chlordiazepoxide had the minimum requirement of an alpha subunit and a gamma subunit. Specific GABARs lacking benzodiazepine or barbiturate modulation were tested for modulation by alpha EMTBL. The alpha 6 beta 2 gamma 2 combination was modulated by the butyrolactone but not chlordiazepoxide. However, GABARs comprising rho1 subunits were sensitive to both phenobarbital and alpha EMTBL. Although the molecular determinants for alpha EMTBL action appear similar to the barbiturates, our data support the conclusion that alpha EMTBL interacts with GABARs in a distinct manner from barbiturates and benzodiazepines.


Subject(s)
4-Butyrolactone/analogs & derivatives , Anticonvulsants/pharmacology , Chlordiazepoxide/pharmacology , Chlorine/metabolism , GABA Modulators/pharmacology , Hippocampus/drug effects , Phenobarbital/pharmacology , Receptors, GABA-A/drug effects , 4-Butyrolactone/pharmacology , Animals , Binding Sites , Cells, Cultured , Dose-Response Relationship, Drug , Hippocampus/metabolism , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/metabolism , Transfection , gamma-Aminobutyric Acid/metabolism , gamma-Aminobutyric Acid/pharmacology
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