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Biomedical subjects

C A Martin

Publications and source records attributed to C A Martin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Production of intoxication states by actors: perception by lay listeners.

The effects of ingesting ethanol have been shown to be somewhat variable in humans; there appear to be but few universals. Yet, questions about intoxication often are asked by law enforcement personnel (especially relative to DUI), clinicians and various individuals in social settings. A key question: Is it possible to determine if a person is intoxicated by observing them in some manner? A closely associated one: Can speech be used for that purpose? Two of the many issues related to the second of these questions involve the possibility that (1) speakers, especially actors, can effectively mimic the speech of intoxicated individuals, and (2) they may be able to volitionally reduce any speech degradation which results from intoxication. The approach used to test these two questions tasked auditors to determine if these simulations were possible. To this end, young, healthy actors chosen on the basis of a large number of selection criteria were asked to produce several types of controlled utterances (1) during a learning phase, (2) when sober, (3) at three simulated levels of intoxication (mildly, legally and severely drunk), (4) during actual, and parallel, levels of intoxication, and (5) at the highest intoxication level attained but when attempting to sound completely sober. Two aural-perceptual studies were conducted; both involved counterbalanced ABX procedures where each subject was paired with him/herself. Listeners were normally hearing university students drawn from undergraduate phonetics and linguistics courses. In the first study, they rated the actors as being more intoxicated--when they actually were sober but simulating drunkenness--88% more often than when they actually were intoxicated. In the second study, they were judged as sounding less inebriated when attempting to sound sober (than they actually were) 61% of the time. These relationships would appear to impact a number of situations; one of special importance would be the detection of intoxication in motorists.

Adult↗
PubMed1997

Discriminative stimulus effects of alcohol in humans.

The discriminative stimulus effects of alcohol were examined in 11 healthy moderate alcohol users. Study days occurred 5 days per week for 12-25 total days. Each day, participants completed visual-analog reports of drug effect and drug-discrimination tasks at 30-min intervals for 2.5 h following oral alcohol administration. Participants completed three phases. During the training phase, which occurred on the first 4 study days, participants were trained to discriminate color-coded placebo and alcohol doses (0 vs. 0.45 g per liter of body water (g/lbw)). Participants then completed a control phase, during which accurate drug-discrimination performance was verified. Finally, participants completed a testing phase, during which both training and intermediate doses (0.15 and 0.30 g/lbw) were administered. During the testing phase, 25 and 100% of responses occurred on the alcohol key at the 0- and 0.45-g/lbw doses, respectively, indicating that discrimination responding remained intact. At the low dose (0.15 g/lbw), 25% of the subjects responded on the alcohol key, whereas 75% of the subjects responded on the alcohol key at the moderate dose (0.30 g/lbw), indicating dose-related generalization to the training doses. These results confirm cross-species generality in the discriminative stimulus effects of alcohol, and further establishes the utility of human laboratory drug-discrimination procedures for analysis of the functional effects of alcohol.

Adult↗
PubMed1997

Gender differences in adolescent psychiatric outpatient substance use: associated behaviors and feelings.

OBJECTIVE: To investigate gender differences in substance use and associated high-risk behaviors and feeling states in 220 adolescent psychiatric outpatients. METHOD: One hundred seven females and 113 males with a mean age of 15.6 (SD +/- 1.4), seen in a tertiary care center adolescent psychiatry clinic, completed scales tapping substance use and associated feelings and behaviors. Approximately half had used nicotine and alcohol, one third had used marijuana, and 10% reported narcotic use. RESULTS: Conduct disorder behavior, suicidality, and impulsivity scale scores decreased with age in females while marijuana use, conduct disorder behavior, and Hypophoria scale scores increased with age in males. Alcohol use in males, as contrasted with females, correlated more significantly with other substance use and high-risk behaviors. Suicidality tended to correlate more with polysubstance use in females and with sexual behaviors in females only. Substance use correlated with the Impulsivity and Need scale scores in males and scores on the Sociopathy scale in females. CONCLUSIONS: Substance use in males correlates with high-risk behaviors and is associated with feelings of impulsivity and need. Substance use correlates with self-destructive behaviors and sociopathic feelings in females. There is evidence of more persistent high-risk behaviors, including substance use, in males than in females.

Adolescent↗
PubMed1997

Ganglioside hydration study by 2H-NMR: dependence on temperature and water/lipid ratio.

Dynamic properties of 2H2O in samples of ganglioside aggregates hydrated at water/lipid ratios ranging from 25:1 to 8000:1 mole/mole were studied by using deuterium nuclear magnetic resonance (2H-NMR). We present a physical model for the interpretation of the measured spin-spin relaxation times (T2). For all the concentrations studied the model provides evidence for the existence of at least two kinds of water environments: one in which the rotational correlation time is in the range of 10(-9) to 10(-8) s, and a second in which it lies between 10(-11) to 10(-10) s. A detailed study on the temperature dependence was performed for two of the concentrations, one corresponding to the hexagonal phase (100:1 mole/mole) and the other involving a micellar phase (200:1 mole/mole). In the 100:1 2H2O/ganglioside molar ratio sample, most of the water is tightly bound to long cylindrical structures. For the 200: 1 sample, there are on average approximately 30 water molecules tightly bound to the polar head group of each ganglioside molecule. The relative number and dynamics of molecules in this environment are essentially insensitive to temperature variations in the range 220-300K The rest of water molecules are also influenced by the aggregate, having a different mobility from that observed in the free liquid state.

Animals↗
PubMed1996

Regulation of epidermal growth factor receptor activity by crotoxin, a snake venom phospholipase A2 toxin. A novel growth inhibitory mechanism.

Crotoxin (CT), a phospholipase A2 (PLA2) derived from the venom of Crotalus durissus terrificus, is a heterodimeric protein composed of subunit B with enzymatic activity and a binding regulatory subunit (A) without enzyme activity. Although the PLA2 activity of CT may be important in its anti-proliferative activity, its cytostatic mechanism is unknown. In this study, we examined the cytostatic effect of PLA2-associated CT activity on squamous carcinoma cells expressing distinct levels of epidermal growth factor receptor (EGFr). CT was most effective in suppressing growth on cells expressing high intrinsic levels of EGFr. Cardiotoxin, another membrane active toxin with no intrinsic PLA2 activity, had no differential anti-proliferative activity on cells expressing high EGFr levels, suggesting a correlation between EGFr expression and CT-directed anti-proliferative activity. Both chemically modified CT (MCT) devoid of PLA2 activity and covalently cross-linked CT (CCT), which is functionally unable to utilize cellular membranes as PLA2 substrate, were also without growth inhibitory activity. No evidence for direct binding of CT to EGFr was found, although pretreatment with EGF was able to partially suppress the anti-proliferative activity of CT. Tyrosine phosphorylation of EGFr, however, was stimulated by CT in intact A431 cells. Tyrosine phosphorylation of EGFr was concentration-dependently stimulated (3- to 8-fold) in cellular membranes of A431 cells treated in vitro with CT but not with anti-proliferatively inactive MCT or CCT. The data provide evidence for transmembrane receptors involved in growth signaling (namely EGFr) as cellular targets and potential effectors of PLA2-mediated anti-proliferative activity of snake venom.

Animals↗
PubMed1996

Stimulation of Rb+ influx by bradykinin through Na+/K+/Cl- cotransport and Na+/K(+)-ATPase in NIH-3T3 fibroblasts.

Bradykinin receptor stimulation results in G-protein-coupled phospholipase activation, initiating protein kinase C (PKC) stimulation and cytosolic free Ca2+ concentration ([Ca2+]i) rises as signalling pathways. Using Rb+ as a tracer for K+, we have studied the mechanisms involved in bradykinin-stimulated Rb+ influx in NIH-3T3 fibroblasts. The furosemide-sensitive Na+/K+/Cl- cotransport and the ouabain-sensitive Na+/K(+)-ATPase were both involved in Rb+ influx under resting conditions with a ratio Na+/K+/Cl- cotransport/Na+/K(+)-ATPase (r) = 0.73. Bradykinin stimulated Rb+ influx (+82.6%) through both systems without changing their ratio (r = 0.72). PKC stimulation by a 15-min-treatment with phorbol 12-myristate 13-acetate (PMA) (2x10(-7) M) increased Rb+ influx in resting cells by 75.7% without affecting r (0.75). PKC inhibition by H-7, and PKC down-regulation by 24-h PMA (10(-6) M) treatment decreased the bradykinin-induced stimulation of Rb+ influx (+31% and +14.9% above control, respectively). Both down-regulation and inhibition of PKC dramatically reduced the furosemide-sensitive Na+/K+/Cl- cotransport, as r fell to 0.239 and 0.032 in bradykinin-stimulated cells after H-7 and 24-h PMA treatments, respectively. BAPTA/AM pretreatment (10(-4) M, 60 min), which complexed with [Ca2+]i, not only prevented the bradykinin-induced [Ca2+]i raise, but also partially inhibited bradykinin-induced Rb+ influx stimulation (+39% above control), without modifying r (0.76). We conclude that stimulation of PKC is a major pathway involved in bradykinin stimulation of Rb+ influx in NIH-3T3 fibroblasts, and that rises in [Ca2+]i participate in bradykinin signalling, possibly through PKC activation. Our data also suggest that active PKC is required for basal and bradykinin-stimulated Na+/K+/Cl- cotransport activity in these cells.

3T3 Cells↗
PubMed1996

In vitro pharmacological effects of S 12370 (2-[4-benzhydryloxypiperidinoethyl]isoxindole; an antibronchoconstrictor agent) in normal and sensitized tissue.

The effects of S 12370 (2-[4-benzhydryloxypiperidinoethyl]isoxindole), were studied in vitro. In guinea pig isolated tracheal rings, S 12370 induced a similar competitive inhibition of the contractile responses produced by acetylcholine, histamine and serotonin. However, it did not affect the contractions induced by leukotriene D4 (LTD4), substance P and U 46619, a stable analogue of thromboxane A2. S 12370 induced a concentration dependent inhibition of the cholinergic component of the contraction induced by electrical field stimulation, whereas it did not influence the sustained nonadrenergic noncholinergic (NANC) excitatory response observed in guinea pig isolated bronchi. S 12370 did not influence the relaxations induced by prostaglandin E2, isoprenaline and salbutamol, and did not modify the nonadrenergic noncholinergic inhibitory response induced by electrical field stimulation. In isolated left atria, the negative inotropic effect of acetylcholine was competitively inhibited by S 12370. In binding experiments, S 12370 exhibited similar affinity for M1, M2, M3, M4 muscarinic receptors and also recognized 5-HT2 serotonin and H1 histamine receptor subtypes. In ovalbumin-sensitized animals, the contractile response of isolated tracheal rings produced by exposure to the allergen was not influenced by S 12370. Tracheal rings from sensitized animals preexposed in vitro to the allergen developed a hyporesponsiveness to beta-adrenoceptor stimulation. S 12370 prevented the inhibitory effect caused by ovalbumin immune sensitization in the relaxation to isoprenaline. In rat polymorphonuclear neutrophil (PMN) cells, S 12370 up to 10(-5) M did not inhibit the arachidonic acid metabolism. These results suggest that in guinea pig tracheal smooth muscle, S 12370 is a competitive inhibitor of muscarinic, serotonin and histamine receptors and can modulate the beta-adrenergic dysfunction induced by immune sensitization. S 12370 may present some therapeutic interest in inflammatory airway diseases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Substance use among adolescents: fulfilling a need state.

A factor that has received little investigation concerns the feeling state of need fulfillment and how this may relate to the significant public health problem of adolescent substance use. A survey of 823 students was conducted at a suburban public high school in the Southeastern United States. The questionnaire contained a scale focusing on fulfillment of adolescent needs, the Children's Depression Inventory, and items on current substance use. The results of t-tests indicated that the higher the adolescent is on the Need scale, the greater the likelihood of engaging in substance use (p < .05). Further, results indicated that cigarette smoking, drinking alcohol, and smoking marijuana are associated with significantly higher scores on the Need scale for both males and females. Although the Need scale was significantly positively correlated with the Children's Depression Inventory (r = .45, p = .0001), the two feeling states were not collinear. However, the Need scale was not significantly correlated with age, indicating that the need state is not simply a developmental process (r = .04, p = .11). The results suggest that a feeling state of unfulfilled needs may propel adolescents into the destructive behavior of substance use. A state of high wants and needs that cannot be gratified simply in a complex society may be a precursor of substance use.

Adolescent↗
PubMed1995

Role of thromboxane A2 in bradykinin-induced human isolated small bronchi contraction.

We previously demonstrated that the bradykinin-induced contraction of human isolated small bronchi is inhibited by indomethacin, capsaicin (N-methyl-N-6-nonenamide) and ruthenium red but not by tachykinin receptor antagonists. The thromboxane A2 receptor (TP receptor) antagonist GR32191 ((1R-(1 alpha(Z),2 beta,3 beta,5 alpha))-(+)-7-(5-(((1,1'-biphenyl)-4-yl)- methoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl)-4-heptenoic acid, hydrochloride) (10(-10) to 10(-8) M) dose dependently inhibited the effect of bradykinin, suggesting the mediation of the TP receptor in the action of bradykinin. With higher concentrations of GR32191 (10(-7) and 10(-6) M) bradykinin induced a relaxation which was inhibited by indomethacin and by the bradykinin B2 receptor antagonist Hoe 140 (D-Arg0[Hyp3,Thi-5,D-Tic7,Oic8]bradykinin). The thromboxane A2 synthase inhibitor dazoxiben (4-(-2-(1H-imidazol-1-yl)ethoxy) benzoic acid hydrochloride) 10(-6) M inhibited the bradykinin-induced contraction, suggesting that thromboxane A2 was involved in TP receptor stimulation. The thromboxane A2 mimetic U-46619 (9,11-dideoxy-11 alpha,9 alpha-epoxy-methano-prostaglandin F2 alpha)-induced contraction of human distal bronchi was not inhibited by capsaicin and ruthenium red. Our data suggest that bradykinin contracts human isolated small bronchi through thromboxane A2 release. The inhibitory effect of ruthenium red and capsaicin on the bradykinin response may be due to inhibition of thromboxane A2 release or arachidonic mobilisation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

In vitro effects of HOE 140 in human bronchial and vascular tissue.

Bradykinin is a potent inflammatory mediator which may be involved in various airway diseases. A selective and potent antagonist of the bradykinin B2 receptor has recently been discovered (HOE 140: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin). The purpose of this study was to evaluate the potency of this compound in isolated human tissue (bronchus, pulmonary artery endothelium, umbilical artery and vein smooth muscle). Bradykinin induced contractions of the isolated human bronchus and umbilical artery and vein (the umbilical vessels were pretreated with indomethacin and L-nitro-arginine to inhibit prostaglandin and nitric oxide synthesis). It provoked an endothelium-dependent relaxation in the human pulmonary artery. HOE 140 was a non-competitive antagonist in human bronchial tissue (pKB: 8.19 +/- 0.30) and a competitive one in vascular tissue (pA2: 7.97 +/- 0.12, 8.16 +/- 0.16 and 8.00 +/- 0.11 in human pulmonary artery, umbilical artery and vein respectively). The effect of HOE 140 was selective as it did not influence the umbilical vein contractile response to serotonin and histamine. HOE 140 up to 3 x 10(-6) M was devoid of residual agonistic activity in the various human preparations studied. Furthermore, although the effects of HOE 140 were fully reversible, in isolated bronchial airways and umbilical veins, HOE 140 (10(-6) M) still possessed activity 1 h after being washed out in both tissues. Our results indicate that HOE 140 is a potent and potentially long-acting antagonist of the human bradykinin B2 receptor.

Binding Sites↗
PubMed1995

Beta 3-adrenoceptors and airways.

beta 3-adrenoceptors have been identified in a variety of tissues from humans and animals: adipose tissue, gastrointestinal smooth muscle, rat skeletal muscle, bovine skeletal muscle, and human and canine heart. In the airways, the investigation of the beta 3-adrenoceptors came from studies with a series of novel selective agonists. Stimulation of the "atypical" beta-adrenoceptor increases the active transport of albumin across the ferret tracheal epithelium and the ciliary beat frequency of canine bronchial epithelium. Furthermore, it has been demonstrated that beta 3-adrenoceptors agonists selectively inhibited nonadrenergic noncholinergic contractions of guinea-pig bronchi induced by electrical field stimulation or capsaicin. The presence of functional beta 3-adrenoceptors in the bronchial smooth muscle is disputed and seems to be species-related. In isolated canine bronchi, selective agonists induced a relaxation whereas they had no or slight effect in isolated human, guinea-pig and sheep bronchi. Likewise in man, a fall in airway resistance measured by plethysmography, was mediated by beta 2-adrenoceptors, but not beta 3-adrenoceptors. To conclude, an "atypical" or beta 3-adrenoceptor-mediated modulation of bronchomotricity exists, nevertheless strong species specific differences have been reported.

Animals↗
PubMed1994

Depression, suicidal ideation, and substance use among adolescents. Are athletes at less risk?

OBJECTIVES: To determine the relationship between participation in high school athletic programs and depression, suicidal ideation, and substance use, and to study the high-risk behaviors of suicidal ideation and substance use. DESIGN: Survey. SETTING: A suburban public high school in Kentucky. PARTICIPANTS: We received 823 (80%) responses from 1030 potential respondents. Athletes (ie, participation on a high school athletic team) were compared with non-athletes. MEASURES: Depression was measured by the Children's Depression Inventory by an index of suicidal ideation by an indicator of a past suicide attempt, and by current use of tobacco, alcohol, marijuana, and cocaine. RESULTS: Thirty percent of the sample participate in school athletic teams. Athletes are less depressed, have less suicidal ideation and attempts, and are less likely to currently smoke cigarettes or marijuana. The use of smokeless tobacco and cocaine was not related to athletic participation. After controlling for demographic characteristics, no difference in alcohol use was found between athletes and nonathletes. CONCLUSIONS: Athletic participation is a marker for a decreased likelihood of depression and some high-risk behaviors in adolescents. Future research could help in creating alternative interventions beyond participation in varsity and junior varsity athletic teams.

Adolescent↗
PubMed1994

Neurotensin modulates cholinergic and noncholinergic neurotransmission in guinea-pig main bronchi in vitro.

Guinea-pig main bronchi were stimulated transmurally in vitro by electrical field stimulation in the presence of indomethacin 10(-6) M, propranolol 10(-6) M and phosphoramidon 10(-5) M. Two contractile neurogenic responses were successively observed. The second noncholinergic contraction was concentration dependently inhibited or abolished by neurotensin whereas the first cholinergic contraction was only partially inhibited. SR 48692, a novel antagonist of neurotensin receptors, reduced the inhibition induced by neurotensin (pKB = 9.75) whereas levocabastine, an antagonist of low-affinity neurotensin receptors, did not significantly modify the inhibitory effects of neurotensin on both neurally-mediated contractions. These results demonstrate that neurotensin exerts an inhibitory effect on neurotransmission in guinea-pig airways. Furthermore, the present study shows that the newly developed neurotensin receptors antagonist, SR 48692, is a potent inhibitor of the neurotensin inhibitory effects on cholinergic and noncholinergic contractions induced by electrical field stimulation of the guinea-pig isolated main bronchus.

Acetylcholine↗
PubMed1994

Contractile effects of bradykinin on the isolated human small bronchus.

Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.

Acetylcholine↗