Osmotic repulsion force due to adsorbed surfactants.

When considering interaction forces in surfactant-stabilized colloidal dispersions a factor that has been rarely discussed is the possible effect of osmotic force due to overlapping adsorbed surfactant monolayers. In the present work, the osmotic repulsion force is built-in on the basis of DLVO mechanics and based on Fischer's consideration of the analogous situation for adsorbed polymer layers on solid surfaces [E.W. Fischer, Kolloid Zeitschrift 160 (1958) 120-141] and on Langmuir's earlier concept of osmotic pressure excess due to overlapping adsorption layers [I. Langmuir, J. Chem. Phys. 6 (1938) 873-896]. The advanced method for calculation of the net repulsion force in overlapping surfactant monolayers is developed and applied to real adsorbed surfactant systems. We show that the value of disjoining pressure can reach values as high as 8 MPa for the condition of fully overlapping surfactant adsorption layers, based on the calculation of the first virial term of the general expression for osmotic pressure. Thus, we have shown that osmotic forces can be substantial at distances of close interfacial approach, and that they can easily be of the same or greater order of magnitude than the forces that have been more conventionally considered.

[Issues of France's "Leonetti Act": Involvement of amyotrophic lateral sclerosis patients in prior discussions concerning respiratory support and end-of-life care]. / Les enjeux de la loi Leonetti: participation des patients atteints de sclérose latérale amyotrophique à une discussion anticipée sur la réanimation respiratoire et les soins de fin de vie.

In accordance with the principle of personal autonomy, expert consensus statements on amyotrophic lateral sclerosis (ALS) recommend early engagement with terminal-phase patients on the type of symptomatic treatment to be administered in the event of respiratory failure, since decompensation progresses too rapidly to allow time for a discussion. The French Parliamentary Act on Patients' Rights and End-of-Life Care (dated 22 April 2005) grants individuals the right to refuse unreasonable treatment and obliges physicians to take account of any prior instructions given by a person before he/she became incapable of communicating. The provision of prior instructions is a very reassuring situation for the physician: the autonomous patient indicates his or her choice of end-of-life care. However, there are two pitfalls which must be avoided: (i) holding a discussion for the sole purpose of obtaining prior instructions and (ii) not acknowledging the patient's vulnerability. The present study dealt with 35 ALS patients for whom the question of either intensive care or palliative end-of-life care remained open. Even though the great majority of these individuals were keen to know their exact state of health, 48% refused to consider this circumstance and only 20% expressed prior instructions. These results prompted us to question the ethical dimension of the concept of autonomy beyond its founding formulation: can one envisage an incapacity to confront oneself with the existential question of possible death? In 80% of cases, the physician will have to take a care decision in the absence of any prior instructions from the patient. This amounts to more than respecting a person's autonomy and involves exercising medical responsibility.

Achievements of the Belgian Antibiotic Policy Coordination Committee (BAPCOC).

A Belgian Antibiotic Policy Coordination Committee (BAPCOC) was officially established in 1999 by Royal Decree. The overall objective of BAPCOC is to promote judicious use of antibiotics in humans and animals and to promote infection control and hospital hygiene, with the overall aim to reduce antibiotic resistance. BAPCOC fostered strong and interdisciplinary public health, scientific and political leadership, which led to many evidence-based interventions such as multimedia campaigns to promote the prudent use of antibiotics in the community, national campaigns to promote hand hygiene in hospitals, publication of clinical practice guidelines, staffing and technical support for establishment of antibiotic management teams in all Belgian hospitals, surveillance programmes on antibiotic use and resistance in humans and animals and the promotion of research. These activities and interventions resulted in a measurable decrease in antibiotic use and resistance in the community and hospitals.

On the nature of Athabasca Oil Sands.

The existence of a thin aqueous film, separating bitumen (a form of heavy oil) from inorganic solids in Athabasca Oil Sands, is analysed based on "first principles". There is a general consensus in the literature on the hydrophilic character of the solids in oil sands. However, a review of the references cited in support of the solids being encapsulated in thin water envelopes produced a surprising lack of evidence. A theoretical analysis indicates that a water film separating clean, hydrophilic quartz and bitumen is stable under most conditions, and unstable for acidic oil sand ores. The existence of water-wet solids in the Athabasca Oil Sands remains a reasonable yet unproven postulate. It could therefore be dangerous to accept the water-wet solids postulate and then use it to interpret other phenomena.

Pharmacological and molecular characterization of muscarinic receptor subtypes in human esophageal smooth muscle.

Esophageal peristalsis is dependent on activation of muscarinic receptors, but little is known about the roles of specific receptor subtypes in the human esophagus. We examined muscarinic receptor expression and function in human esophageal smooth muscle obtained from patients undergoing resection for cancer. [(3)H]Quinuclidinyl benzylate (QNB)-specific binding was similar in longitudinal muscle (B(max) = 106 +/- 22 fmol/mg of protein, K(d) = 68 +/- 9 pM) and circular muscle (B(max) = 81 +/- 16 fmol/mg of protein, K(d) = 79 +/- 15 pM). Subtype-selective antagonists inhibited [(3)H]QNB similarly in muscle from both layers. Further analysis of antagonist inhibition of [(3)H]QNB binding showed a major site (60-70%) with antagonist affinity profile consistent with the M2 subtype and a second site that could not be classified. Reverse transcription-polymerase chain reaction and immunoblotting demonstrated the presence of all five known muscarinic receptor subtypes, and immunocytochemistry on acutely isolated smooth muscle cells confirmed the expression of each subtype on the muscle cells. Subtype-selective antagonists had similar inhibitory effects on carbachol-evoked contractions in longitudinal muscle and circular muscle strips with pA(2) values of 9.5 +/- 0.1 and 9.6 +/- 0.2 for 4-diphenylacetoxy-N-methylpiperidine methiodide, 7.1 +/- 0.1 and 7.0 +/- 0.2 for pirenzepine, and 6.2 +/- 0.2 and 6.4 +/- 0.2 for methoctramine, respectively. We conclude that human esophageal smooth muscle expresses muscarinic receptor subtypes M1 through M5. The antagonist sensitivity profile for muscle contraction is consistent with activation of the M3 subtype.

Human esophageal smooth muscle cells express muscarinic receptor subtypes M(1) through M(5).

Receptor characterization in human esophageal smooth muscle is limited by tissue availability. We used human esophageal smooth muscle cells in culture to examine the expression and function of muscarinic receptors. Primary cultures were established using cells isolated by enzymatic digestion of longitudinal muscle (LM) and circular muscle (CM) obtained from patients undergoing esophagectomy for cancer. Cultured cells grew to confluence after 10-14 days in medium containing 10% fetal bovine serum and stained positively for anti-smooth muscle specific alpha-actin. mRNA encoding muscarinic receptor subtypes M(1)-M(5) was identified by RT-PCR. The expression of corresponding protein for all five subtypes was confirmed by immunoblotting and immunocytochemistry. Functional responses were assessed by measuring free intracellular Ca(2+) concentration ([Ca(2+)](i)) using fura 2 fluorescence. Basal [Ca(2+)](i), which was 135 +/- 22 nM, increased transiently to 543 +/- 29 nM in response to 10 microM ACh in CM cells (n = 8). This response was decreased <95% by 0.01 microM 4-diphenylacetoxy-N-methylpiperidine, a M(1)/M(3)-selective antagonist, whereas 0.1 microM methoctramine, a M(2)/M(4)-selective antagonist, and 0.1 microM pirenzepine, a M(1)-selective antagonist, had more modest effects. LM and CM cells showed similar results. We conclude that human smooth muscle cells in primary culture express five muscarinic receptor subtypes and respond to ACh with a rise in [Ca(2+)](i) mediated primarily by the M(3) receptor and involving release of Ca(2+) from intracellular stores. This culture model provides a useful tool for further study of esophageal physiology.

Effects of continuous conjugated estrogen and micronized progesterone therapy upon lipoprotein metabolism in postmenopausal women.

The effects of continuously administering both conjugated equine estrogens (CEE) and micronized progesterone (MP) on the concentration, composition, production and catabolism of very low density (VLDL) and low density lipoproteins (LDL) have not previously been reported. The mechanism of the hormonally induced reductions of plasma LDL cholesterol of S(f) 0;-20 (mean 16%, P < 0.005) and LDL apoB (mean 6%, P < 0.025) were investigated by studying the kinetics of VLDL and LDL apolipoprotein (apo) B turnover after injecting autologous (131)I-labeled VLDL and (125)I-labeled LDL into each of the 6 moderately hypercholesterolemic postmenopausal subjects under control conditions and again in the fourth week of a 7-week course of therapy (0.625 mg/d of CEE + 200 mg/d of MP). The combined hormones significantly lowered plasma LDL apoB by increasing the mean fractional catabolic rate of LDL apoB by 20% (0. 32 vs. 0.27 pools/d, P < 0.03). Treatment also induced a significant increase in IDL production (6.3 vs. 3.7 mg/kg/d, P = 0.028). However, this did not result in an increase in LDL production because of an increase in IDL apoB direct catabolism (mean 102%, P = 0.033). VLDL kinetic parameters were unchanged and the concentrations of plasma total triglycerides (TG), VLDL-TG, VLDL-apoB did not rise as often seen with estrogen alone. Plasma HDL-cholesterol rose significantly (P < 0.02). Our major conclusion is that increased fractional catabolism of LDL underlies the LDL-lowering effect of the combined hormones.

Delayed rectifier and Ca(2+)-dependent K(+) currents in human esophagus: roles in regulating muscle contraction.

We have examined K(+) channels and their function in human esophageal smooth muscle using perforated patch recording, RT-PCR to identify channel mRNA, and muscle contraction to study the effects of channel blockers. Depolarization revealed at least two types of currents: a 4-aminopyridine (4-AP)-sensitive transient delayed rectifier K(+) (K(V)) and a Ca(2+)-dependent K(+) (K(Ca)) current. K(Ca) current was active at positive potentials and was blocked by tetraethylammonium (TEA), iberiotoxin, and charybdotoxin but was insensitive to 4-AP. The mRNA encoding the gene products of Kv1.2 and Kv1.5 was identified in muscle and dissociated cells, consistent with these channel types contributing to K(V) current. 4-AP increased resting tension of muscle strips, suggesting a role for K(V) in setting the membrane potential. TEA, but not 4-AP, augmented the amplitude and duration of electrically evoked contraction, effects that were abolished by nifedipine. Here we provide the first description of macroscopic K(+) currents in human esophagus. K(V) channels participate in regulation of resting tension, whereas the K(Ca) channel limits depolarization and contraction during excitation.

Pharmacological and molecular characterization of muscarinic receptors in cat esophageal smooth muscle.

The muscarinic receptor subtypes that mediate cholinergic responses in cat esophageal smooth muscle were examined. Antagonist effects on carbachol-induced and nerve-evoked contractions were studied in vitro using muscle strips from the distal esophagus. Antagonists displayed similar relative selectivities in suppressing carbachol and nerve-mediated responses as follows: 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) > zamifenacin > para-fluoro-hexahydrosiladiphenidol > pirenzepine > AF-DX 116 > methoctramine, indicating that these responses are mediated by the same receptor subtype. 4-DAMP, pirenzepine and methoctramine effects on carbachol responses gave pA2 values characteristic of the M3 receptor in both the circular muscle (9.25 +/- 0.12, 6.79 +/- 0.09 and 6.04 +/- 0.11, respectively) and longitudinal muscle (9.46 +/- 0.14, 7.25 +/- 0.07 and 6.10 +/- 0.06, respectively). Reverse transcription-polymerase chain reaction analysis was done using primer sequences based on the cloned human muscarinic receptor subtypes. Messenger RNA for the m3 receptor was readily identified, whereas m2 was not detected in esophageal muscle, but was present in cardiac muscle. Sequence homology between the amplified products from cat tissue and the corresponding human m2 and m3 receptors genes were 93% and 89%, respectively. In the cat esophagus, the M3 receptor mediates functional responses and messenger RNA for the corresponding molecular form of this receptor is abundant in this tissue.

Left displaced abomasum: considerations of treatment method and a case report of mesenteric torsion after rolling.

Treatment of left displaced abomasum by rolling a cow led to mesenteric torsion. In order to pre-empt possible veterinary surgeon liability claims following such an outcome of treatment, it is necessary to inform the owner of the poor prognosis and risks of this treatment.

Effects of intrastriatal infusion of D2 receptor antisense oligonucleotide on apomorphine-induced behaviors in the rat.

An antisense oligonucleotide strategy was employed to specifically deplete postsynaptic striatal D2 receptors in order to determine the possible role of presynaptic D2 autoreceptors in mediating behavioral responses induced by low doses of apomorphine. A phosphorothioate-modified antisense oligonucleotide complementary to the first 19 bases of the coding region of D2 receptor mRNA, a scrambled sequence comprising the same bases, or saline was infused bilaterally into the striatum of adult rats, twice daily for 2 days via indwelling cannulae. After an interval of 8-12 h, rats were habituated and challenged with high (300 micrograms/kg; subcutaneous) or low (50 micrograms/kg; s.c.) doses of apomorphine or its vehicle (0.1% ascorbic acid). Yawning, vacuous chewing mouth movements, hypoexploration, and penile grooming induced by low-dose apomorphine were unaffected by antisense infusion into the striatum, whereas stereotypic sniffing following high-dose apomorphine was markedly suppressed. Intrastriatal infusion of antisense resulted in significantly diminished [3H]-raclopride binding, while binding of [3H]-SCH 23390 (D1 receptors) and [3H]-WIN 35428 (dopamine transporter) was unchanged. D2 mRNA levels determined by quantitative in situ hybridization were normal in the striatum and the substantia nigra. Our results confirm that stereotypic sniffing is mediated via postsynaptic D2 receptors in the striatum, and favor the notion that behavioral responses induced by low doses of apomorphine are mediated by presynaptic D2 autoreceptors.

Heterogeneous tissue-specific transcription of dopamine receptor subtype messenger RNA in rat brain.

The recent identification through molecular cloning techniques of multiple dopamine receptor subtypes has raised interest in the functional interactions between some of the newly described receptors and their classic counterparts. The dopamine D5 (D1B) receptor gene is of particular interest since there is some evidence that its transcriptional tissue distribution is different than that of the D1 and D2 receptor genes, possibly implying a unique role for the receptor that this gene encodes. This study compares the relative anatomical distribution of dopamine D1, D2, and D5 receptor mRNAs in the rat brain using Northern blot analysis. The results demonstrate that the patterns of expression for these three genes are quite different and tissue specific. Although levels of D1 and D2 mRNA are highest in the striatum, levels of D5 mRNA are proportionately much higher in the midbrain, hippocampus and hypothalamus. In addition two D5 mRNA transcripts were detected in the hippocampus, but not in other brain areas. There were tissue-specific differences in the size of D5 mRNA transcripts in human brain tissue as well. These data may suggest a more specialized role for the dopamine D5 receptor within the mammalian brain.

Dopamine receptor density, sensitivity and mRNA levels are altered following self-administration of cocaine in the rat.

The effects of cocaine administration and withdrawal on D1 and D2 dopamine receptor number, affinity, and mRNA levels were examined in rats trained to self-administer cocaine for four weeks on a continuous reinforcement schedule. Two hours after the last infusion of cocaine there was a decrease in the number and agonist sensitivity of dopamine D1 receptors in the anterior forebrain as well as in the limbic region. In contrast, there were no discernible changes in dopamine D2 receptors in any of the brain regions examined. Examination of dopamine receptor gene expression using Northern blot analysis revealed that there was an increase in D1 receptor mRNA levels in the forebrain, whereas D1 and D2 receptor mRNA levels both were increased in the limbic region. One week following the last infusion of cocaine, D1 and D2 receptor mRNA levels had returned to baseline. In the limbic region, D1 receptor numbers also had normalized by this time, whereas in the forebrain, changes in D1 receptors persisted. These data indicate that repeated exposure to cocaine induces regional changes in D1 receptor sensitivity and gene expression, suggesting that the D1 dopamine system plays an important role in mediating the reinforcing effects of cocaine.

Enterococcal and streptococcal species isolated from faeces of calves, young cattle and dairy cows.

Faeces from non-ruminating calves were found to contain several species of enterococci: Enterococcus avium, Ent. cecorum, Ent. durans, Ent. faecalis, Ent. faecium and Ent. hirae. Enterococcus faecalis was the most frequent. Few of these animals carried streptococci. Streptococcus bovis largely predominated in ruminating calves, young cattle and dairy cows. Other streptococci as well as enterococci were infrequent in dairy cows, but a variety of other streptococci and enterococci were found in the faeces of young ruminating animals.

Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.

Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.

Fluoride treatment of postmenopausal osteoporosis: age, renal function, and other clinical factors in the osteogenic response.

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation by dopamine of protein phosphorylation in rat striatal slices.

Incubation of rat striatal slices with dopamine enhanced the phosphorylation of two proteins with mol. wts. of 64,000 and 43,000. Although dopamine did increase cAMP levels in striatal slices, the addition of cAMP to striatal slices did not mimic the effects of dopamine on protein phosphorylation. The present results suggest that cAMP-independent protein kinases may mediate some of the effects of dopamine within the corpus striatum.