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1.
Cryo Letters ; 44(5): 299-306, 2023.
Article in English | MEDLINE | ID: mdl-38032310

ABSTRACT

BACKGROUND: Semen cryopreservation is a complex process during which there is alteration in the expression of sperm and seminal plasma proteins, molecular weight of protein or loss of membrane proteins during the process. In order to compensate for these changes, different membrane stabilizers are used in freezing semen extenders. However, there is scarcity of such studies during cryopreservation of goat semen. OBJECTIVE: To investigate the effect of membrane stabilizers on sperm membrane protein expression during cryopreservation of goat semen. MATERIALS AND METHODS: A total of 36 semen ejaculates from nine Assam Hill Goat bucks aged 2 to 2.5 years was collected by artificial vagina method. Three membrane stabilizers, each at two different concentrations viz. 50 and 80 mM sucrose, 50 and 100 mM trehalose, and 100 and 150 ng per mL IGF-1 (insulin-like growth factor 1 protein) were added to Tris-citric acid fructose egg yolk glycerol (TCFEYG) extender and semen samples were cryopreserved. The sperm membrane protein profile was studied in fresh and cryopreserved semen by SDS-PAGE. RESULTS: SDS- PAGE of sperm membrane extract of fresh semen revealed the presence of 24 protein bands with molecular weights ranging from 10 kDa to 240 kDa. Samples supplemented with 50 mM sucrose and 80 mM sucrose revealed 21 protein bands with molecular weights ranging from 10 kDa to 240 kDa. All the 21 protein bands were same as those observed in the sperm membrane of fresh spermatozoa, except that the 23 kDa, 29 kDa and 42 kDa bands were absent in frozen semen. Similarly, frozen semen extended with 50 mM trehalose and 100 mM trehalose revealed 22 protein bands with molecular weights ranging from 10 kDa to 240 kDa, but lacking the 29 kDa and 42 kDa bands. Proteins with molecular weights of 29 kDa, 130 kDa and 240 kDa were absent in frozen semen supplemented with 100 ng per mL IGF-1 and 150 ng per mL IGF-1. CONCLUSION: The present study revealed that supplementation of tris basic extender with trehalose at 100 mM and or IGF-1 at 100 ng/mL or 150 ng per mL improves the post-thaw semen characteristics and protects certain fertility related sperm membrane proteins. Doi.org/10.54680/fr23510110612.


Subject(s)
Semen Analysis , Semen , Male , Female , Animals , Insulin-Like Growth Factor I/pharmacology , Goats , Trehalose/pharmacology , Cryopreservation/veterinary , Spermatozoa , Membrane Proteins , Sucrose/pharmacology
2.
Am J Trop Med Hyg ; 91(1): 165-172, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24778198

ABSTRACT

During April 2007-April 2010, surveillance physicians in adult and pediatric medicine wards of three tertiary public hospitals in Bangladesh identified patients who developed hospital-acquired diarrhea. We calculated incidence of hospital-acquired diarrhea. To identify risk factors, we compared these patients to randomly selected patients from the same wards who were admitted > 72 hours without having diarrhea. The incidence of hospital-acquired diarrhea was 4.8 cases per 1,000 patient-days. Children < 1 year of age were more likely to develop hospital-acquired diarrhea than older children. The risk of developing hospital-acquired diarrhea increased for each additional day of hospitalization beyond 72 hours, whereas exposure to antibiotics within 72 hours of admission decreased the risk. There were three deaths among case-patients; all were infants. Patients, particularly young children, are at risk for hospital-acquired diarrhea and associated deaths in Bangladeshi hospitals. Further research to identify the responsible organisms and transmission routes could inform prevention strategies.


Subject(s)
Cross Infection , Diarrhea/epidemiology , Disease Outbreaks , Tertiary Healthcare/statistics & numerical data , Adolescent , Adult , Aged , Bangladesh/epidemiology , Child , Child, Preschool , Diarrhea/pathology , Female , Hospitals, Public , Humans , Incidence , Infant , Length of Stay , Male , Middle Aged , Risk Factors , Survival Analysis
3.
Drug Res (Stuttg) ; 63(4): 177-84, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23471702

ABSTRACT

BACKGROUND: This study was aimed to investigate the relative bioavailability of fixed-dose-combination (FDC) product of amlodipine, telmisartan and hydrochlorothiazide with individual marketed products in healthy male volunteers. Control of blood pressure with fixed dose combination of the above drugs acting through different mechanism have a benefit of convenient dosing in terms of compliance, lower the dose and subsequently reduce the side effects. METHODS: The authors investigated the relative bioavailability under a fasting state of the 3 drugs in a randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a washout period of 21 days. Plasma concentration of the analytes were assayed in timed samples with a simple, highly sensitive and rapid validated method using HPLC coupled to tandem mass spectrometry that had a lower limit of quantification of 1 ng/mL for all the 3 components. RESULTS: Test and reference formulations gave a mean Cmax of 5.234±0.914 ng/mL and 4.991±0.563 ng/mL, 108.839±13.601 ng/mL and 114.783±12.315 ng/mL and 97.814±10.779 ng/mL and 93.731±10.018 ng/mL for amlodipine, telmisartan and hydrochlorothiazide respectively. The AUC0-t of amlodipine, telmisartan and hydrochlorothiazide was 161.484 ng.h/mL, 1 917.644 ng.h/mL and 822.847 ng.h/mL for test formulation and 162.108 ng.h/mL, 2 014.764 ng.h/mL and 829.323 ng.h/mL for reference in the fasting state. CONCLUSION: The 90% confidence intervals for the test/reference ratio of the pharmacokinetic parameters in fasting state (mean Cmax, AUC0-t, and AUC0-∞) were within the acceptable range of 80.00-125.00. Thus, these findings clearly indicate that the FDC product is bioequivalent with the individual marketed products in terms of rate and extent of drug absorption and is well tolerated with no significant adverse reactions.


Subject(s)
Hypertension/drug therapy , Hypoglycemic Agents/pharmacokinetics , Adolescent , Adult , Amlodipine/administration & dosage , Amlodipine/pharmacokinetics , Benzimidazoles/administration & dosage , Benzimidazoles/pharmacokinetics , Benzoates/administration & dosage , Benzoates/pharmacokinetics , Cross-Over Studies , Drug Therapy, Combination , Humans , Hydrochlorothiazide/administration & dosage , Hydrochlorothiazide/pharmacokinetics , Hypoglycemic Agents/administration & dosage , Middle Aged , Telmisartan
4.
Cryo Letters ; 33(1): 58-68, 2012.
Article in English | MEDLINE | ID: mdl-22434123

ABSTRACT

The present investigation was aimed at developing a protocol for long-term preservation of germplasm of Pinus kesiya Royle ex. Gord. through vitrification. Some of the critical components affecting explant tolerance to cryopreservation, such as effects of preculture, vitrification solutions, exposure time to vitrification solutions, volume of vitrification solution and its toxicity, washing of vitrified tissues after thawing, were analysed. The results showed that shoot regrowth of P. kesiya shoot-tips was considerably affected when exposed to cryoprotectants for longer periods of time (longer than 10 min). Among different vitrification solutions studied, maximum survival (76 percent) of shoot-tips was achieved with mVSL (using 0.6 ml of the solution) in MS basal medium containing 4.0 mg l-1 N6-benzyladenine (BA).


Subject(s)
Cryopreservation/methods , Cryoprotective Agents , Germ Cells, Plant/cytology , Pinus/cytology , Vitrification , Benzyl Compounds , Cold Temperature , Culture Media , Dimethyl Sulfoxide , Ethylene Glycol , Germ Cells, Plant/physiology , Glycerol , Kinetin , Osmolar Concentration , Pinus/physiology , Plant Shoots/growth & development , Plant Somatic Embryogenesis Techniques , Purines , Regeneration , Sucrose
5.
Indian J Med Res ; 128(4): 462-83, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19106441

ABSTRACT

The contaminants of concern for smelting and mining sites include arsenic (As), cadmium (Cd), lead (Pb) and zinc (Zn). Risk assessments for such sites need to consider whether toxicity values can be developed for this mixture, and if not, whether interactions among the individual components are significant and can be incorporated quantitatively into the assessment. No information is available for the risk characterization of the toxic interactions of AsCdPbZn mixtures. Studies of the AsCdPb and CdPbZn mixtures supported the assumption that a reasonable approximation to the toxicity of a mixture can be achieved by considering the binary submixtures. Data relevant to long-term simultaneous exposure to binary submixtures were not conclusive. For example, data from animal and human studies of Zn and Pb suggested that moderately elevated Zn intakes may slightly inhibit Pb absorption and haematological effects in children who have deficient or marginal Zn intakes, but were not adequate for adjusting absorption parameters in the Integrated Exposure Uptake Biokinetic (IEUBK) model for Pb. Thus the existing database calls for plausible approaches for risk characterization and considerations in the data usage for such characterization. This article is an attempt to identify such data gaps and the scientific considerations for such efforts.


Subject(s)
Metals/toxicity , Environmental Exposure , Humans , Metals/chemistry , Mining , Occupational Exposure , Risk Assessment
6.
Neuroradiol J ; 20(2): 228-31, 2007 Apr 30.
Article in English | MEDLINE | ID: mdl-24299650

ABSTRACT

Ossification of the posterior longitudinal ligament is an uncommon disorder mostly seen in the Japanese population and hence termed by some the "Japanese disease". Ossification of the posterior longitudinal ligament is more common in the cervical spine (2). Clinically it is usually asymptomatic, but serious neurological deficits have been seen in some patients (2). The ossified mass composed of lamellar bone and focal calcified cartilage expands in volume causing spinal canal stenosis and cord compression. Morphologically, four forms of ossification of the posterior longitudinal ligament have been described: continuous, segmental, mixed and rarely a focal retrodiscal form (4). CT scan is the method of choice for detecting the presence and extent of the ossified mass. MR imaging is helpful in depicting the nature of cord compression such as myelomalacia, edema, demyelination or cyst formation and root sleeve involvement.

7.
Reprod Domest Anim ; 41(2): 162-8, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16519723

ABSTRACT

The objective of the present study was to establish the changes in plasma concentrations of LH, FSH, estradiol 17-beta (E2) and progesterone (P4), as well as to understand their temporal relationships during oestrus in mithun (Bos frontalis). The experiment was conducted on 11 mithuns during third or fourth postpartum oestrous cycle. Since oestrus onset the jugular vein blood samples were collected every 2 h for 72 and 96 h, respectively from the animals without and with standing heat. The LH, FSH, E2 and P4 concentrations were estimated in plasma. The P4 concentration was fluctuated throughout the oestrus period and the average P4 concentration was found significantly (p<0.05) lower on the day of oestrus onset. The multiple rises in LH and FSH concentrations above the basal level in spike like fashion were observed throughout the oestrus period irrespective of the occurrence of standing heat. A significant (p<0.01) gradual increase in the average daily E2 concentration was observed till day 2 following oestrus onset irrespective of the occurrence of standing heat. A significant (p<0.05) simultaneous increase in LH, FSH and E2 concentrations and a transient increase in P4 concentration at approximately the time of standing heat onset were observed. During investigation a definite temporal coupling between LH and FSH rises was absent throughout the oestrus period. The results suggest that (1) the multiple short-duration low-amplitude LH and FSH surges during oestrus may be crucial for the final maturation of ovulatory follicle and subsequent ovulation in mithun; (2) a differential mechanism for controlling LH and FSH secretions probably exists in mithun.


Subject(s)
Cattle/physiology , Estradiol/blood , Estrus/blood , Follicle Stimulating Hormone/blood , Luteinizing Hormone/blood , Progesterone/blood , Animals , Cattle/blood , Estrus/physiology , Female , Time Factors
8.
J Pharmacol Exp Ther ; 316(3): 1335-45, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16326923

ABSTRACT

Alpha5IA is a compound that binds with equivalent subnanomolar affinity to the benzodiazepine (BZ) site of GABA(A) receptors containing an alpha1, alpha2, alpha3, or alpha5 subunit but has inverse agonist efficacy selective for the alpha5 subtype. As a consequence, the in vitro and in vivo effects of this compound are mediated primarily via GABA(A) receptors containing an alpha5 subunit. In a mouse hippocampal slice model, alpha5IA significantly enhanced the burst-induced long-term potentiation of the excitatory postsynaptic potential in the CA1 region but did not cause an increase in the paroxysmal burst discharges that are characteristic of convulsant and proconvulsant drugs. These in vitro data suggesting that alpha5IA may enhance cognition without being proconvulsant were confirmed in in vivo rodent models. Hence, alpha5IA significantly enhanced performance in a rat hippocampal-dependent test of learning and memory, the delayed-matching-to-position version of the Morris water maze, with a minimum effective oral dose of 0.3 mg/kg, which corresponded to a BZ site occupancy of 25%. However, in mice alpha5IA was not convulsant in its own right nor did it potentiate the effects of pentylenetetrazole acutely or produce kindling upon chronic dosing even at doses producing greater than 90% occupancy. Finally, alpha5IA was not anxiogenic-like in the rat elevated plus maze nor did it impair performance in the mouse rotarod assay. Together, these data suggest that the GABA(A) alpha5-subtype provides a novel target for the development of selective inverse agonists with utility in the treatment of disorders associated with a cognitive deficit.


Subject(s)
Cognition/drug effects , GABA Agonists/pharmacology , GABA-A Receptor Agonists , Animals , Dose-Response Relationship, Drug , Hippocampus/drug effects , Hippocampus/physiology , Humans , Kindling, Neurologic/drug effects , Long-Term Potentiation/drug effects , Male , Maze Learning/drug effects , Mice , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/metabolism , Xenopus laevis
9.
J Neurosci Methods ; 132(2): 137-48, 2004 Jan 30.
Article in English | MEDLINE | ID: mdl-14706711

ABSTRACT

We describe a novel brain slice system 'SliceMaster' that allows electrophysiological recordings from eight brain slices independently. The system consists of two autonomous units each supporting four modular brain slice chambers enabling high signal-to-noise ratio recordings, each chamber has one stimulation electrode, one recording electrode, a twin camera system and a solution application system. The positioning of both electrodes and cameras are controlled from a remote user console. The software both acquires and performs on-line analysis of the data. We have demonstrated utility of this system in obtaining recordings of spontaneous firing activity and evoked synaptic activity from mouse hippocampal slices, with reduced variability within and between experiments. Furthermore, we show recordings of population spikes from the perirhinal cortex, indicating applicability of this system for further brain regions. In addition, stable recordings could be maintained until recording was terminated after 3 h, permitting investigation of the induction and maintenance of synaptic plasticity. Recordings of spontaneous and synaptic activity, and effects of pharmacological and electrophysiological manipulation, were consistent with reports using conventional methods. However, the described system permits concurrent and independent recordings from eight brain slices, thus improving throughput, statistical design, and reducing animal use.


Subject(s)
Action Potentials/physiology , Brain/physiology , Diffusion Chambers, Culture/instrumentation , Electrophysiology/instrumentation , Microelectrodes/standards , Presynaptic Terminals/physiology , Animals , Brain/cytology , Diffusion Chambers, Culture/methods , Electric Stimulation/instrumentation , Electric Stimulation/methods , Electrophysiology/methods , Excitatory Postsynaptic Potentials/physiology , Hippocampus/cytology , Hippocampus/physiology , In Vitro Techniques , Long-Term Potentiation/physiology , Mice , Mice, Inbred C57BL , Microtomy/methods , Perfusion/methods , Presynaptic Terminals/ultrastructure , Rats , Rats, Sprague-Dawley , Signal Processing, Computer-Assisted , Software , Synaptic Transmission/physiology
10.
Environ Sci Technol ; 37(22): 5228-35, 2003 Nov 15.
Article in English | MEDLINE | ID: mdl-14655712

ABSTRACT

As part of the EPA's mission to protect the environment, chemicals of concern (CoCs) at Superfund or other hazardous waste sites are cleaned up based on their potential toxicity to humans and the surrounding ecosystem. Oftentimes, there is a lack of experimental toxicity data to assess the health effects for a CoC in the literature. This research describes a method using Quantitative Structure Toxicity Relationships (QSTRs) for identifying a surrogate chemical for any given CoC. The toxicity data of the surrogate chemical can then be used to rank hazardous waste-site chemicals prior to cleanup decisions. A commercial QSTR model, TOPKAT, was used to establish structural and descriptor similarity between the CoC and the compounds in the QSTR model database using the Oral Rat Chronic LOAEL model. All database chemicals within a similarity distance of < or = 0.200 from the CoC are considered as potential surrogates. If the CoC fails to satisfy model considerations for the LOAEL model, no surrogate is suggested. Potential surrogates that have toxicity data on Integrated Risk Information System (IRIS), Health Effects Assessment Summary Tables (HEAST), or National Center for Environmental Assessment (NCEA) provisional toxicity value list become candidate surrogates. If more than one candidate surrogate is identified, the chemical with the most conservative RfD is suggested as the surrogate. The procedure was applied to determine an appropriate surrogate for dichlorobenzophenone (DCBP), a metabolite of chlorobenzilate, dichlorodiphenyltrichloroethane, and dicofol. Forty-seven potential surrogates were identified that were within the similarity distance of < or = 0.200, of which only five chemicals had an RfD on IRIS, HEAST, or on the NCEA provisional toxicity value list. Among the five potential surrogates, chlorobenzilate with an RfD of 2 x 10(-2) mg/kg-day was chosen as a surrogate for DCBP as it had the most conservative toxicity value. This compared well with surrogate selection using available metabolic information for DCBP and its metabolites or parent compounds in the literature and the provisional toxicity value of 3 x 10(-2) mg/kg-day that NCEA developed using a subchronic study.


Subject(s)
Environmental Pollutants/toxicity , Models, Theoretical , Toxicity Tests/methods , Algorithms , Animals , Benzophenones/toxicity , Computer Simulation , Databases, Factual , Quantitative Structure-Activity Relationship
11.
J Toxicol Environ Health A ; 63(5): 321-50, 2001 Jul 06.
Article in English | MEDLINE | ID: mdl-11471865

ABSTRACT

The Cadmium Dietary Exposure Model (CDEM) utilizes national survey data on food cadmium concentrations and food consumption patterns to estimate dietary intakes in the U.S. population. The CDEM has been linked to a modification of the cadmium biokinetic model of Kjellström and Nordlberg (KNM) to derive predictions of kidney and urinary cadmium that reflect U.S. dietary cadmium intake and related variability. Variability in dietary cadmium intake was propagated through the KNM using a Monte Carlo approach. The model predicts a mean peak kidney cadmium burden of approximately 3.5 mg and a 5th-95th percentile range of 2.2-5.1 mg in males. The corresponding peak renal cortex cadmium concentration in males is 15 microg/g wet cortex (10-22, 5th-95th percentile). Predicted kidney cadmium levels in females were higher than males: 5.1 (3.3-7.6) mg total kidney, 29 (19-43) microg/g wet cortex. Predicted urinary cadmium in males and females agreed with empirical estimates based on the NHANES III, with females predicted and observed to excrete approximately twice the amount of cadmium in urine than males. An explanation for the higher urinary cadmium excretion in females is proposed that is consistent with the NHANES III data as well as experimental studies in humans and animals. Females may absorb a larger fraction of ingested dietary cadmium than males, and this difference may be the result of lower iron body stores in females compared to males. This would suggest that females may be at greater risk of developing cadmium toxicity than males. The predicted 5th-95th percentile values for peak kidney cadmium burden are approximately 60% of the peak kidney burden (8-11 mg) predicted for a chronic intake at the U.S. Environmental Protection Agency (EPA) chronic reference dose of 1 microg/kg-d.


Subject(s)
Cadmium/urine , Diet , Adolescent , Adult , Aging/metabolism , Algorithms , Biomarkers/urine , Cadmium/pharmacokinetics , Child , Child, Preschool , Databases, Factual , Female , Humans , Infant , Kidney/metabolism , Male , Middle Aged , Models, Biological , Monte Carlo Method , Risk Assessment , Sex Factors , United States
12.
Toxicol Ind Health ; 17(5-10): 163-75, 2001 Jun.
Article in English | MEDLINE | ID: mdl-12539861

ABSTRACT

In 1988, Travis and Arms reviewed the literature and collected data to develop a relationship between the octanol-water partition coefficient (Kow) and the uptake of organic compounds into milk and beef (Travis and Arms, 1988). These equations have been utilized for predicting biotransfer factors for organic chemicals when empirical data are lacking. During the external peer review of the draft US Environmental Protection Agency (EPA) guidance entitled Human Health Risk Assessment Protocol for Hazardous Waste Combustion Facilities (US EPA, 1998) and the development of Superfund's Ecological Soil Screening Levels (US EPA, 2000b), questions challenging the derivation and use of these equations were raised. The primary questions raised were: 1) Are the equations presented in Travis and Arms (1988) for the estimation of transfer of organic compounds from contaminated feed to beef and milk technically valid and reproducible? If so, (2) are the equations appropriate across the entire log Kow range? For these reasons, this study was undertaken to validate the original Travis and Arms equations, to review more recent literature, and. if appropriate, to add to the original Travis and Arms data set to obtain updated equations. This paper presents an evaluation of the original Travis and Arms equations, limitations to their use, and steps to reduce uncertainties associated with their use by updating with more current literature.


Subject(s)
Algorithms , Environmental Pollutants/pharmacokinetics , Food Contamination , Models, Theoretical , Animals , Forecasting , Humans , Meat , Milk/chemistry , Reproducibility of Results , Risk Assessment , Solubility , Tissue Distribution
13.
Infect Immun ; 68(11): 6127-32, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11035715

ABSTRACT

The early role of natural killer cells and gamma delta T cells in the development of protective immunity to the blood stage of nonlethal Plasmodium yoelii infection was studied. Splenic cytokine levels were measured 24 h after infection of natural killer cell-depleted immunodeficient and littermate mice or transiently T-cell-depleted normal mice. Splenic gamma interferon levels were significantly increased above background in immunodeficient and littermate mice 24 h after infection. Depletion of natural killer cells resulted in markedly depressed gamma interferon levels and poor control of parasitemia, particularly in severe combined immunodeficient mice. In the littermates, gamma interferon levels were partially reduced, but parasitemias were resolved normally. However, in athymic mice, natural killer cell depletion had no effect on gamma interferon production. Levels of tumor necrosis factor alpha were increased in all animals 24 h after infection, and responses were not affected by natural killer cell depletion. However, in T-cell-depleted animals, both gamma interferon and tumor necrosis factor alpha levels were decreased 24 h after infection, and depleted mice were unable to control their parasitemia. These results suggest that the early production of both cytokines is important in the early control of parasitemia and that both natural killer and gamma delta T cells contribute equally towards their production. The data also suggest that the subsequent resolution of infection requires early production of gamma interferon, which might act by switching on the appropriate T-helper-cell subsets and other essential parasitotoxic effector mechanisms.


Subject(s)
Malaria/immunology , Plasmodium yoelii/immunology , T-Lymphocytes/immunology , Animals , Immunity, Innate , Interferon-gamma/biosynthesis , Killer Cells, Natural/physiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, SCID , Receptors, Antigen, T-Cell, gamma-delta/analysis , Thy-1 Antigens/physiology , Tumor Necrosis Factor-alpha/biosynthesis
14.
J Neurosci Methods ; 99(1-2): 91-100, 2000 Jun 30.
Article in English | MEDLINE | ID: mdl-10936648

ABSTRACT

To facilitate the discovery of novel compounds that modulate human GABA(A) receptor function, we have developed a high throughput functional assay using a fluorescence imaging system. L(tk-) cells expressing combinations of human GABA(A) receptor subunits were incubated with the pH-sensitive dye 2',7'bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein, then washed and placed in a 96-well real-time fluorescence plate reader. In buffer adjusted to pH 6.9 there was a robust and persisting acidification response to addition of GABA, which was antagonised by the GABA(A) receptor antagonist bicuculline. The concentration-response relationship for GABA was modulated by allosteric ligands, including benzodiazepine (BZ) site agonists and inverse agonists. The effects of BZ site ligands on the pH response to GABA for receptors containing alpha1beta3gamma2, alpha3beta3gamma2 or alpha5beta3gamma2 subunits were well correlated with results from electrophysiological studies on the same receptor subunit combinations expressed in Xenopus oocytes. Most modulatory compounds tested were found to be relatively unselective across the three subunit combinations tested; however, some showed subtype-dependent efficacy, such as diazepam, which had highest agonist effects on the alpha3beta3gamma2 subtype, substantial but lesser agonism on alpha1beta3gamma2 and still substantial but the least agonism on alpha5beta3gamma2. This indicates that the alpha subunit within the recombinant receptor expressed in L(tk-) cells can affect the efficacy of the response to some BZ compounds. Inhibitors of Na(+)/Cl(-) cotransport, anion/anion exchange and the gastric type of H(+)/K(+) ATPase potently inhibited GABA-evoked acidification, indicating that multiple transporters are involved in the GABA-evoked pH change. This novel fluorescence-based high throughput functional assay allows the rapid characterization of allosteric ligands acting on human GABA(A) receptors.


Subject(s)
Biological Assay/methods , Fluorescent Dyes , Receptors, GABA-A/analysis , Receptors, GABA-A/drug effects , Animals , Cells, Cultured/drug effects , Cells, Cultured/metabolism , Humans , Hydrogen-Ion Concentration , Oocytes , Xenopus laevis , gamma-Aminobutyric Acid/metabolism , gamma-Aminobutyric Acid/pharmacology
15.
J Toxicol Environ Health ; 52(5): 447-60, 1997 Dec 12.
Article in English | MEDLINE | ID: mdl-9388535

ABSTRACT

The remedial investigation/feasibility studies conducted at certain Army installations showed a need to clean up contaminated sites, where high levels of ammunition chemicals such as 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitrobenzene (TNB), 1,3-dinitrobenzene (DNB), and their degradation products/metabolites were detected in surface soil and groundwater. TNB is a photodegradation product of TNT; it is not easily degraded, and persists in the environment. The toxicity data on TNB are scanty. Hence the U.S. Environmental Protection Agency in 1988 (U.S. EPA, 1997) developed a reference dose (RfD) for TNB (0.00005 mg/kg/d for chronic toxicity) based on the toxicity of DNB, which is structurally similar to TNB. Since then we have completed acute, subacute, subchronic, chronic, reproductive, and developmental toxicity studies and toxicokinetics studies. We have reviewed the mammalian toxicity data for TNB and have determined the no observed adverse effect levels (NOAEL) and low observed adverse effect levels (LOAEL) for subchronic, chronic, reproductive, and developmental toxicity. Based on the newly determined NOAEL and LOAEL values, we have now developed a new RfD for TNB (0.03 mg/kg/d), based on the chronic toxic effects on hematology and histopathological changes in testes and kidney.


Subject(s)
Environmental Pollutants/toxicity , Trinitrobenzenes/toxicity , Administration, Oral , Animals , Environmental Pollutants/pharmacokinetics , Female , Intestinal Absorption , Male , Mice , Mutagenicity Tests , No-Observed-Adverse-Effect Level , Rats , Rats, Inbred F344 , Risk Assessment , Structure-Activity Relationship , Tissue Distribution , Trinitrobenzenes/pharmacokinetics
17.
s.l; s.n; 1995. 2 p.
Non-conventional in English | Sec. Est. Saúde SP, HANSEN, Hanseníase Leprosy, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1236978
18.
J Assam Science Society ; 35(3): 188-94, 1993 Sep.
Article in English | MEDLINE | ID: mdl-12318461

ABSTRACT

"The present paper is aimed at investigating the ethnic differentials in respect of the effects of different socio-economic and demographic characteristics upon fertility among four major ethnic groups of people [in the Barpeta district of Assam, India]."


Subject(s)
Ethnicity , Fertility , Socioeconomic Factors , Asia , Culture , Demography , Developing Countries , Economics , India , Population , Population Characteristics , Population Dynamics
19.
Toxicol Ind Health ; 7(4): 231-48, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1776155

ABSTRACT

A problem in evaluating the hazard represented by an environmental toxicant is that exposures can occur via multiple media such as water, land, and air. Lead is one of the toxicants of concern that has been associated with adverse effects on heme metabolism, serum vitamin D levels, and the mental and physical development of infants and children exposed at very low environmental levels. Effects of lead on development are particularly disturbing in that the consequences of early delays or deficits in physical or mental development may have long-term consequences over the lifetime of affected individuals. Experimental and epidemiologic studies have indicated that blood lead levels in the range of 10-15 micrograms/dl, or possibly lower, are likely to produce subclinical toxicity. Since a discernible threshold has not been demonstrated, it is prudent to preclude development of a Reference Dose (RfD) for lead. As an alternate, the U.S. Environmental Protection Agency (U.S. EPA) has developed the uptake/biokinetic lead model that provides a means for evaluating the relative contribution of various media to establishing blood lead levels in children. This approach will allow for the identification of site- and situation-specific abatement strategies based on projected blood lead levels in vulnerable human populations exposed to lead in air, diet, water, soil/dust, and paint; thus making it possible to evaluate regulatory decisions concerning each medium on blood levels and potential health effects.


Subject(s)
Environmental Exposure , Lead/pharmacokinetics , Humans , Lead/blood , Lead Poisoning/prevention & control , Maximum Allowable Concentration , Models, Biological , Reference Standards , Risk Factors
20.
Toxicol Ind Health ; 3(1): 5-69, 1987 Mar.
Article in English | MEDLINE | ID: mdl-3590208

ABSTRACT

Pure pentachloronitrobenzene (PCNB) is a colorless crystalline solid (Worthing, 1983). The commercial product may have a light-yellow to cream color with a musty odor (Hartley and Kidd, 1983). It is practically insoluble in a number of organic solvents. The compound is reasonably stable but may undergo hydrolysis in a strong alkaline medium (Hartley and Kidd, 1983). In 1983, Olin Corp., Leland, MS, was the only manufacturer of PCNB in the United States (SRI, 1984; Hartley and Kidd, 1983). No data for U.S. production volume for this chemical are available, but recent production source data (USITC, 1985; SRI, 1985) suggest that this chemical is no longer commercially produced in the United States. The primary usage of PCNB is as a soil fungicide for a wide variety of crops and in seed treatment (Worthing, 1983; Hartley and Kidd, 1983). The fate of PCNB in water has not been comprehensively studied. Only qualitative data regarding fate and transport in water are available. The half-life of PCNB in the water phase was estimated to be 1.8 days. The two processes reported to be most responsible for the rapid decrease in PCNB concentration in water were volatilization and sorption to seston and biota, followed by sedimentation as detritus (Schauerte et al., 1982). Neither biodegradation nor photolysis appears to be a significant process for the loss of PCNB from water (Crosby and Hamadmad, 1971; Schauerte et al., 1982). The BCFs for PCNB in the golden orfe, Leucisens idus melanotus, and in rainbow trout, Salmo gairdneri, were reported to be 950-1130 and 260-590, respectively (Korte et al., 1978; Oliver and Niimi, 1985). It therefore appears that PCNB will moderately bioaccumulate in aquatic organisms. Pertinent data regarding the fate and transport of PCNB in air could not be located in the available literature as cited in the Appendix. Based on its physical properties and its behavior in other media, it would appear that PCNB will persist in the atmosphere because no known chemical/photochemical processes significantly degrade this chemical. Precipitation of particulate PCNB, especially of larger particle size and higher particle density, may remove some PCNB from the atmosphere. PCNB is persistent in soils. The two processes that are important in the loss of PCNB from soils are volatilization and biodegradation; biodegradation is more rapid in soils under anaerobic conditions than under aerobic conditions (Ko and Farley, 1969; Casley, 1968; Gile and Gillett, 1979; Cole and Metcalf, 1977).(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Fungicides, Industrial/toxicity , Nitrobenzenes/toxicity , Animals , Carcinogens , Environmental Pollution , Mice , Neoplasms, Experimental/pathology , Nitrobenzenes/metabolism , Rats
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