Proton-decoupled, 31P three-dimensional (3-D) chemical shift imaging (CSI) spectra have been acquired from the entire human brain using a new dual tuned resonator. The resonator operates in quadrature mode to provide improved sensitivity, excellent B1 homogeneity and reduced power deposition at both frequencies. Proton-decoupled and fully NOE enhanced, 31P spectra were acquired from normal volunteers using Waltz-4 proton decoupling with continuous wave bi-level excitation applied through a second radio frequency channel. Well resolved peaks in the phosphomonoester (PME) and phosphodiester regions were obtained from nonlocalized FIDs and spectra localized with 3-D CSI without processing for resolution enhancement. pH measurements made over large regions of the brain using the P(i) resonance show no significant variations (6.9 +/- 0.02) for a single individual. The improved spectral resolution and sensitivity of the PME resonances results in more well defined metabolite images of the PME peak region.

Brain↗

PubMedDate not supplied

Adult thymus expresses an embryonic nicotinic acetylcholine receptor-like protein.

The subunit composition of acetylcholine receptor-like protein(s) (AChR-LP) expressed by normal thymus was investigated. In skeletal muscle, the AChR exists in two forms, an embryonic form which contains the gamma-subunit and an adult form where the gamma-subunit is substituted by a different, homologous subunit called epsilon. Antibodies against unique sequence segments of the embryonic gamma-subunit and of the adult epsilon-subunit of bovine muscle AChR, in addition to antibodies specific for the alpha-, beta-, and delta-subunits of bovine muscle AChR, were used to probe immunoblots of AChR-LP(s) from bovine thymus. Subunits of approximate Mr 41 kDa, 48-54 kDa, 57 kDa and 67-72 kDa were recognized by anti-alpha, anti-beta, anti-gamma and anti-delta antibodies respectively. Anti-epsilon antibodies did not recognize any protein band from bovine thymus. AChR-LP similar or identical to the embryonic muscle AChR is therefore expressed in normal thymus.

Amino Acid Sequence↗

PubMedDate not supplied

Ethanol relaxes pulmonary artery by release of prostaglandin and nitric oxide.

Acute-intake of ethanol is associated with vasodilation of vascular smooth muscle (VSM). Relaxation of VSM is dependent, in part, on the actions of nitric oxide (NO) and prostaglandin (PG) produced by endothelial cells (EC) lining the VSM. We examined the effects of endothelium rubbing and inhibition of EC synthesis of NO and PG on ethanol-induced relaxation of bovine pulmonary artery (BPA) and pulmonary vein (BPV) in vitro. Rings of isolated BPA and BPV were mounted in muscle chambers for the isometric recording of force development. Blood vessels were precontracted with an EC50 concentration of the thromboxane receptor mimetic U46619. Ethanol (0.01, 0.02, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28% (w/v) produced concentration-dependent relaxation of BPA and BPV. Ethanol-induced relaxation was attenuated in BPA with rubbed EC and by the NO synthase inhibitors, L-NG monomethylarginine (LNMMA, 50 microM) and L-nitroarginine (NOLA, 10 microM), and the prostaglandin cyclooxygenase inhibitor, ibuprofen (10 microM). In contrast, ethanol-induced relaxation of BPV was not affected by endothelium rubbing or by NOLA or LNMMA, but was partially attenuated by ibuprofen. Nitric oxide was measured with the chemiluminescence technique. Ethanol increased the content of NO released under basal conditions by the BPA but did not effect basal NO release from BPV. However, ethanol enhanced bradykinin-induced release of NO from BPA and BPV and, at low concentrations, augmented bradykinin-induced relaxation of both BPA and BPV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Ethanol suppresses LPS-induced mRNA for nitric oxide synthase II in alveolar macrophages in vivo and in vitro.

Alcohol abuse increases the incidence and severity of opportunistic lung infections and pneumonias. Inducible nitric oxide (NO) synthase (iNOS II) and NO may be a pivotal system in the intracellular bactericidal activity of macrophages. We tested the hypothesis that acute administration of ethanol (ETOH) suppressed Escherichia coli endotoxin lipopolysaccharide (LPS) mediated upregulation of the iNOS II system in the lung of the rat, in vivo. We also tested the effect of ETOH on alveolar macrophage (AM) production of free NO using microelectrodes. Male Sprague-Dawley rats were given ETOH (5.5 g/kg, IP) 30 min. before giving intratracheal sterile phosphate buffered saline solution (PBS, 0.5 ml) or LPS (1 mg/kg in a total volume of 0.5 ml PBS). The isolated lungs were subjected to bronchoalveolar lavage (BAL) 3.5 hr. later. Aliquots of the BAL fluid were assayed for tumor necrosis factor alpha TNF alpha and reactive nitrogen intermediates (nitrate and nitrite) (RNI) with chemiluminescence. Aliquots of AM were incubated 1 hr ex vivo for spontaneous production of RNI or frozen and assayed for iNOS II mRNA with competitor exchange reverse transcriptase polymerase chain reaction (cERT-PCR). The lung was homogenized and assayed for RNI. LPS increased BAL fluid TNF alpha and RNI, lung RNI, and the spontaneous production of RNI by AM, ex vivo. These effects were inhibited by in vivo administration of inhibitors of iNOS II. LPS increased iNOS mRNA in AM. This was unaffected by iNOS inhibitors. ETOH suppressed LPS-induced BAL fluid TNF, iNOS mRNA and RNI production by AM and the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMedDate not supplied

Bioavailability of ethanol is reduced in several commonly used liquid diets.

Liquid diets are often used as a vehicle for chronically treating laboratory animals with ethanol. However, a recent report suggested that one or more components of these diets may bind ethanol which could result in a decrease in the bioavailability of ethanol. Consequently, we compared the blood ethanol concentration vs. time curves obtained following the intragastric (i.g.) administration of ethanol dissolved in water or in one of three liquid diets (Bioserv AIN-76, Sustacal, or Carnation Slender) using the long-sleep (LS) and short-sleep (SS) mouse lines. The initial rates of absorption were generally the same for the water-ethanol and diet-ethanol groups, but the diets generally produced lower peak levels and the areas under the ethanol concentration-time curves were less for all of the liquid diets than for the control, ethanol-water solution. In vitro dialysis experiments indicated that the Bioserv diet binds ethanol in a saturable manner. Therefore, it may be that the slower release of ethanol, which should occur as a result of binding, serves to increase the role of first pass metabolism in regulating ethanol concentrations following oral administration. Because the effects of the diets were seen even after pyrazole treatment, it may be that the lower blood ethanol levels arise because metabolism by gastric ADH, rather than hepatic ADH, is responsible for a major portion of ethanol metabolism as ethanol is slowly released by the diets. If so, the observation that the diet/water differences were uniformly greater in the LS mice may indicate that LS-SS differences in gastric ADH exist.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMedDate not supplied

Type A behavior in children: what a pediatric nurse practitioner needs to know.

Type A behavior has been shown in adults to be a predictor of heart disease equal in magnitude to cigarette smoking and cholesterol level. This article reviews current thinking on Type A behavior and its relationship to cardiovascular health. Particular emphasis is given to current literature about Type A behavior in adolescents, school-aged children, and preschoolers. Discussion covers the importance of the primary subcomponents of Type A behavior (i.e., competitiveness, hostility, and impatience). Clinical cautions and applications of this research are included.

Adolescent↗

PubMedDate not supplied

Toxocara canis infection in preschool age children: risk factors and the cognitive development of preschool children.

Risk factors for Toxocara canis (T. canis) infection were evaluated in a prospective study of disadvantaged preschool children. In addition, the hypothesis that T. canis exposure is associated with lower intelligence was tested. Seropositivity was tested at 2 years, 3 years, and at 4 years 10 months (4-10). Intelligence was measured at age 4-10 by the Full Scale IQ of the Wechsler Preschool and Primary Scales of Intelligence (WPPSI). Pica and ownership of a dog were unrelated to seropositivity. Seropositive children had lower scores on the Mental Development Index (MDI) of the Bayley Scales of Infant Development at age 1 year (prior to likely exposure). They also had less favorable scores on a measure of the quality of childrearing. These findings suggest that, for disadvantaged children, lower initial intelligence and less advantageous child rearing are risk factors for T. canis exposure. Seropositive children also had higher blood lead levels, probably as a result of the common pathway of hand to mouth transmittal. Seropositivity at 3 years, at age 4-10, or, cumulatively, at any of the age 2, 3, or 4-10 assessments was associated with the WPPSI IQ after adjustment for sociodemographic factors. Exposure at age 4-10-years was significantly associated with reduced IQ scores (p = 0.030). However, when the age 1 year MDI score was controlled, the estimate became nonsignificant. We, thus, can neither confirm nor deny a relationship of T. canis and intelligence, but the importance of considering prior developmental status is emphasized.

Animals↗

PubMedDate not supplied

Induction of mosquito hemolymph proteins in response to immune challenge and wounding.

The rapid induction of proteins in the hemolymph of the mosquito, Anopheles gambiae, was examined after wounding or injection of immune elicitors (Escherichia coli, lipopolysaccharide, laminarin, zymosan). One-dimensional gel electrophoresis revealed at least six hemolymph polypeptides >25 kDa that consistently appeared after any breech of the cuticle. All of these polypeptides appeared in the hemolymph within 30 min and reached a maximum concentration after approx. 6 h. No proteins were specifically induced by bacteria or bacterial or fungal cell wall products, however two constitutively expressed proteins were repressed by these injections. Patterns of hemolymph proteins were further analyzed by two-dimensional electrophoresis. Seven spots were enhanced or induced 2 h after injection in four replicate experiments. An additional two spots demonstrated some variability between replicates, but were generally responsive to injection. These rapidly induced polypeptides are candidates for regulating and initiating the mosquito's responses to pathogens and wounding.

Animals↗

PubMedDate not supplied

Feasibility of paramedic treatment and referral of minor illnesses and injuries.

BACKGROUND: Approximately 40% of Hennepin County Medical Center's (HCMC's) ambulance runs are for minor medical conditions as defined by billing criteria ["ALS minor," i.e., no advanced life support (ALS) procedures done in the field]. Current metropolitan guidelines mandate that all such patients must be transported to a hospital unless they refuse this service. It has been proposed that some patients with minor medical conditions could be better served by treatment in the field by paramedics and referred to a clinic or hospital for early follow-up care. It is proposed that this approach would save costs and improve paramedic availability for patients with more serious conditions. OBJECTIVE: To evaluate the feasibility and safety of implementing such a program by identifying high-volume, low-complexity groupings of cases. Such high-volume, low-complexity cases would serve as the topics for curriculum development for paramedic training in field treatment and referral. METHODS: Data were obtained from ambulance run sheets and emergency department (ED) records for all patients transported by the HCMC ambulance service in 1996 who were covered by the Metropolitan Health Plan (MHP) and who were categorized for billing purposes as "ALS minor" transports. The data included demographic information, vital signs, presenting problem, diagnoses in the ED, and procedures, laboratory studies, or x-rays done in the ED. Patients were classified as "potentially treatable" in the field if they were treated and discharged from the ED without undergoing any procedures or diagnostic studies. Patients who required more extensive evaluation in the ED, or who were admitted, were classified as likely too "complex" to be treated at the scene and then referred for early follow-up. The data were analyzed to find the most common presenting problems and the numbers, characteristics, and dispositions of "potentially treatable" and "complex" patients in each group. This information was used to determine what, if any, types of patients could potentially be treated safely and effectively according to this scheme. RESULTS: The study group comprised 1,103 patients, representing 127 different presenting medical problems. There were 523 (47%) "potentially treatable" patients and 580 (53%) "complex" patients. The 127 medical problems were grouped and the 15 most common presenting problem groups were identified. Within these groups there was no single medical problem with high volume. Each of these 15 most common problem groups contained a substantial proportion of "complex" patients, ranging from 24% to 100%. CONCLUSIONS: None of the 15 most frequently encountered problem groups consisted of a high enough proportion of "potentially treatable" cases to serve as a high-volume, low-complexity category for paramedic treatment in the field with early follow-up. Without any identified high-volume, low-complexity categories, a treatment and referral program as proposed in this article would require a substantial investment in development of appropriate criteria and in training paramedics to apply the criteria for numerous clinical entities. This would limit any cost saving, and require great care to avoid compromising patient safety accompanied by substantial professional liability exposure.

Ambulances↗

PubMedDate not supplied

Studies on the mechanism of the acute antihypertensive and vasodilator actions of several beta-adrenoceptor antagonists.

Several new beta-adrenoceptor antagonists (sulfinalol, MK 761, and prizidilol) have been reported to possess direct vasodilator activity in addition to blocking beta-receptors. The mechanism of the hypotensive and vasodilator actions of these agents was examined and compared to that of pindolol and hydralazine. Intraarterial injection of each agent increased blood flow in the sympathetically denervated hindlimb of anesthetized dogs. Doses increasing flow by 50 ml/min (ED50) were 0.48, 0.24, 331, 0.3, and 51 micrograms for sulfinalol, MK 761, prizidilol, pindolol, and hydralazine, respectively, Intravenous injection of each agent reduced blood pressure of anesthetized, ganglion-blocked dogs. Vasodilation and hypotension to sulfinalol, MK 761, and pindolol, but not prizidilol or hydralazine were attenuated by propranolol pretreatment. Oral administration of sulfinalol (2.5 mg/kg), MK 761 (2.5 mg/kg), prizidilol (10 mg/kg), pindolol (0.1 mg/kg), and hydralazine (2.5 mg/kg) reduced pressure of conscious spontaneously hypertensive rats. Antihypertensive actions of sulfinalol and pindolol, but not MK 761, prizidilol, and hydralazine were inhibited by propranolol pretreatment (25 mg/kg, p.o.). With the exception of hydralazine, each agent demonstrated effective beta-adrenergic blockade at the antihypertensive dose tested as judged by inhibition of the chronotropic responses to sympathetic stimulation and isoproterenol in pithed rats. These data suggest that the acute vasodilator and blood pressure lowering effects of sulfinalol, MK 761, and pindolol, but not prizidilol and hydralazine, are mediated, at least in part, through activation of vascular beta-receptors.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Angiotensin-converting enzyme inhibitory activity of SCH 31846, a new non-sulfhydryl inhibitor.

SCH 31846, 1-(N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanyl)-cis, syn-octahydro-(H-indole-2-S)-carboxylic acid; CI-907; PD 109, 763-2, is a new non-sulfhydryl-containing, angiotensin-converting enzyme (ACE) inhibitor. The present investigation describes its ACE inhibitory properties and compares them to those of MK 421. The diacid of SCH 31846 inhibited rabbit pulmonary ACE with an IC50 of 2.2 nM (MK 421 diacid 2.5 nM). The drug behaved as a competitive and specific inhibitor in vitro. SCH 31846 and its diacid effectively inhibited pressor actions of intravenous injection of angiotensin I (AI) in anesthetized rats. ID50 values were 27 and 11 micrograms/kg for SCH 31846 and SCH 31846 diacid, respectively (MK 421 and MK 421 diacid 57 and 15 micrograms/kg, respectively). Oral administration of SCH 31846 (0.03-1 mg/kg) inhibited pressor actions of AI in conscious rats with a duration of over 16 h at 0.3 and 1 mg/kg. SCH 31846 was 2.2 times as potent as MK 421 in this regard. The diacid of SCH 31846 was considerably less potent than the ester, implying poor oral absorption of the former. Effective ACE inhibition, as judged by attenuation of pressor actions of AI, was noted in dogs after both intravenous and oral administrations of SCH 31846. Onset of action was more rapid than that of MK 421. Intravenous administration of SCH 31846 inhibited the renal vascular actions of intrarenal injection of AI, indicating effective blockade of the renal enzyme. Intracerebroventricular administration of SCH 31846 diacid blocked pressor responses to intracerebroventricular AI, whereas oral administration of SCH 31846 (10 mg/kg) did not, implying that SCH 31846 inhibits brain ACE but does not gain access to the cerebral enzyme when administered orally. These data indicate that SCH 31846 is a potent and specific non-sulfhydryl ACE inhibitor. As such, it should be useful in the treatment of hypertension and heart failure.

Administration, Oral↗

PubMedDate not supplied

Antihypertensive activity of SCH 31846, a non-sulfhydryl angiotensin-converting enzyme inhibitor.

The antihypertensive, hemodynamic, and autonomic actions of SCH 31846, a new, potent and long-acting non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, were evaluated in several experimental preparations. Oral administration of 0.3-3 mg/kg caused dose-related decreases in blood pressure in spontaneously hypertensive rats (SHRs). Pretreatment with a diuretic augmented the maximum hypotensive response attainable. Single doses (3 mg/kg) of SCH 31846 reduced pressure for over 24 h. Five-day treatment lowered pressure progressively. Single oral doses of 3.2 and 10 mg/kg reduced blood pressure of conscious normotensive dogs. Diuretic pretreatment also enhanced the response. The antihypertensive action of SCH 31846 in SHRs was eliminated by nephrectomy, but not attenuated by indomethacin, indicating its dependency on renal renin but not on prostaglandin synthesis. Other studies using SHRs pointed to an absence of a central effect. SCH 31846 (1 mg/kg i.v.) decreased blood pressure and peripheral resistance of anesthetized dogs but did not alter cardiac output. Autonomic interactions were examined in normal and diuretic-pretreated SHRs and anesthetized dogs. SCH 31846 affected the response to sympathetic nerve stimulation and cardiovascular reflexes only minimally. It is concluded that SCH 31846 is a potent and long-lasting antihypertensive agent, the action of which is mediated, in all probability, by ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗