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This paper examines herbicide use in South African commercial plantations in 2017/18 across three climate zones (cool temperate − CT, warm temperate − WT and subtropical − ST) for three genera (euc...

Cardiac stroke volume (S(V)) is compromised in Atlantic cod and rainbow trout following acclimation to hypoxia (i.e., 40% air saturation; ~8 kPa O(2)) at 10–12°C, and this is not due to changes in heart morphometrics or maximum achievable in vitro end-diastolic volume. To examine if this diminished S(V) may be related to compromised myocardial contractility, we used the work-loop method to measure work and power in spongy myocardial strips from normoxic- and hypoxic-acclimated steelhead trout when exposed to decreasing Po(2) levels (21 to 1.5 kPa) at several frequencies (30–90 contractions/min) at 14°C (their acclimation temperature). Work required to lengthen the muscle, as during filling of the heart, was strongly frequency dependent (i.e., increased with contraction rate) but was not affected by hypoxic acclimation or test Po(2). In contrast, although shortening work was less frequency dependent, this parameter and network (and power) 1) were consistently lower (by ~30–50 and ~15%, respectively) in strips from hypoxic-acclimated fish and 2) fell by ~40–50% in both groups from 20 to 1.5 kPa Po(2), despite the already-reduced myocardial performance in the hypoxic-acclimated group. In addition, strips from hypoxic-acclimated trout showed a poorer recovery of net power (by ~15%) when returned to normoxia. These results strongly suggest that hypoxic acclimation reduces myocardial contractility, and in turn, may limit S(V) (possibly by increasing end-systolic volume), but that this diminished performance does not improve the capacity to maintain myocardial performance under oxygen limiting conditions.

OBJECTIVES: The purpose of this study was to validate the lower end of the putative therapeutic range of serum tacrine concentrations of 7-20 ng ml(-1) in the treatment of Alzheimer's disease. METHODS: The relationship between dose, steady-state serum tacrine concentrations and change in MMSE score (a measure of cognitive function) was examined in 106 Alzheimer's disease patients who had been treated with the drug for 12 weeks. RESULTS: In all, 72% of patients showed some response, but there was no relationship between dose and the chance of a favourable outcome. The proportion of patients with serum concentrations above 7 ng x ml(-1) who improved (79%) was significantly greater than that of those with serum concentrations below this level (47%) (P < 0.02). Also, a significantly greater proportion of patients with serum concentrations above both 5 ng x ml(-1) and 9 ng x ml(-1) showed improvement in comparison to those with concentrations below these levels. CONCLUSIONS: This study indicates that therapeutic monitoring of serum tacrine concentrations might increase the possibility of responding to tacrine by some 68%. This represents an important contribution to the management of Alzheimer's disease patients with this drug, and may also be relevant to the use of the newer generation of cholinesterase inhibitors.

Joints and other minor structural elements were recorded at 429 stations on the S. Gower coast. A systematic pattern exists comprised of up to 6 sets of joints which strike at 360°, 340°, 290°, 270°, 240° and 200°. Joint set maxima are frequently parallel to the strike of major and minor faults, but no simple geometric relationship exists between joint orientation and fold axis trend. Axial-trace-fracturing has been recognized, whilst en echelon gash arrays, mineralized joint sets and their cross-cutting relationships enable a tectonic sequence of events to be determined. The systematic joints are thought to have developed during the folding under the influence of a N–S compression, but variation in the strike of minor structures suggests a swing in orientation of o through time. Subsequent stress relaxation facilitated dilation and the production of mineralized vein suites.

Joints, minor faults and mineral veins were recorded at 334 stations between Kidwelly and Black Mountain, S. Wales. A systematic pattern occurs with joint sets striking at 360°, 340°, 290°, 250°, and 210°. Minor faults and shear planes exhibit both strike and dip-slip displacements. The jointing is considered to have formed quite early during folding, and both joints and faults can be attributed to a principal compression acting almost N-S and subparallel to bedding. Phases of dilation are recorded by sets of mineral veins. All the deformational structures are considered to be of Armorican age.

Joints and faults were studied in Mesozoic and Avonian strata along 35 km of coast between Ogmore-by-Sea and Lavernock Point, Glamorgan, South Wales. Observations on joint and fault planes were recorded at 22 localities (i.e. approx. 750 stations), an analysis of which suggests the following. In the Mesozoic strata systematic joint patterns of tectonic origin exist with principal azimuths at 340°, 200° and 280°, with the more complex patterns characteristic of Triassic sequences, whilst a System of orthogonal microjoints (striking at 280°–190°) representa perhaps the earliest formed fractures in the Mesozoic strata. The joints in general formed early in the deformation of the area, whilst joints and faults can both be ascribed to a general northsouth compressive force. A study of fracture patterns in Avonian basement reveals a close similarity of trend, but there is little visible evidence to indicate much basement influence on cover tectonics.

Observations on joints, minor faults and mineral veins at 47 localities along the south and south east crop of the S. Wales Coalfield indicate the presence of a joint system comprised of up to 6 sets of fractures striking at 350°, 330°, 290°, 270°, 250° and 210°. The joint sets are parallel to minor faults of strike and dip-slip types, whilst minor thrust faults indicate an early phase of sub-horizontal compression. The joint system is thought to be of tectonic origin and developed early in the deformational history of the area in response to a N-S compression. Later, dilational episodes facilitated the infilling of mineral veins, with the W.N.W. trending set probably indicating the latest phase of dilation in the area. All structures are considered to be of Armorican age, whilst the marked similarity in the orientation of the joint system to that of the North Crop of the Coalfield suggests that the brittle deformation was relatively homogeneous on both flanks of the Coalfield.

Small-scale thrust faults are described from the North Crop of the South Wales Coalfield in strata of Avonian age. Two main sets occur which strike at east-west and north-south respectively, and show apparent stratigraphic zonation. It is suggested that the sets were initiated during the early stage of deformation of the area in response to primary and secondary resolved compressional forces.

The photochemistry of the title compound 1 in methanol and 2,2,2-trifluoroethanol has been examined. In both solvents two ether products were obtained: one (18) resulting from trapping of the carbocation 2 (expected from photosolvolysis of 1), and the other (19) from the carbocation 3 (expected after rearrangement by hydride migration of cation 2). The substituted trans- and cis-stilbene derivatives 20 and 21 were also primary photoproducts. Analysis of product yields as a function of time revealed that the ether product 19 was formed by secondary photolysis of the stilbene derivatives, presumably by a pathway involving excited state protonation. Nanosecond laser flash photolysis results demonstrated that substituted trans-stilbene 20 was produced on the same time scale as the laser pulse.Key words: ester photochemistry, stilbene photoadditions, carbocation rearrangements.

Solid unstiffened, sandwich, and hat-stiffened rectangular orthotropic fiber-reinforced plastic (FRP) plates were tested in uniaxial in-plane compression and out-of-plane uniform pressure. The two short edges of all plates were clamped, whereas the two long edges of the unstiffened and sandwich plates were simply supported and the same edges of the hat-stiffened plate were left free. Unstiffened plates reached global buckling at about 688 kN (155 klb); however, the plates did not collapse up to the machine load limit of 1334 kN (300 klb). Sandwich plates never reached the overall elastic buckling load; they collapsed in local buckling by face sheet delamination and core shear failure at loads of about 939 kN (211 klb). Hat-stiffened plates exhibited local buckling of the outer unsupported flanges at a load of about 356 kN (80 klb). All hat-stiffened plates collapsed under uniaxial compression due to a combination of face sheet to stiffener delamination followed by hat-stiffener local buckling at loads of about 939 kN (211 klb). The stresses and deflections due to out-of-plane uniform pressure were compared between the unstiffened, sandwich, and hat-stiffened plates from pressures of 6.895 kPa (1 psi) to 34 kPa (5 psi). With the plates under uniaxial compression and out-of-plane uniform pressure simultaneously, there was a general decrease in buckling and collapse with an increase in out-of-plane uniform pressure.

An experiment was designed to determine the critical design parameters for a metal/composite joint in a composite electronic enclosure where both thermal and mechanical performance are important. A combination bolted and bonded single-lap joint that simulates the interface between the thermal wall and the card guide was studied under static loading with power supplied through a surface-mounted chip resistor. The following parameters were varied: fiber orientation, type of thermally conductive pitch fiber, type of adhesive, adhesive thickness, bolt spacing, bolt size, and input power. Load, strain, and temperature from five thermocouples were collected during a tensile test with a 0.02 in/ min. strain rate. A fractional factorial experimental design was used. A dual failure mechanism was consistently recorded: failure of the adhesive bond followed by bolt shear failure. Initial screening results indicated that a configuration can be achieved that significantly enhances both mechanical and thermal performance.

Velnacrine is a centrally acting anticholinesterase which has been considered for use in the treatment of Alzheimer's disease. If proven to be of value, it will be used concurrently with other medications. Its potential to cause interaction is, therefore, important to study. The aim of this work was to investigate velnacrine as an inhibitor of hepatic oxidative enzymes. The effects of velnacrine on antipyrine metabolism in isolated rat hepatic microsomes were compared to those of cimetidine. Aliquots of 200, 250 and 300 micrograms/ml antipyrine were incubated alone, with 20 micrograms/ml cimetidine and with each of 20, 50 and 100 micrograms/ml velnacrine. The concentrations of antipyrine and of its metabolites, 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine were assayed by reverse phase high performance liquid chromatography. Cimetidine inhibited production of all three metabolites. Velnacrine did not affect 3-hydroxymethylantipyrine production. Mean inhibition of 4-hydroxyantipyrine production of 15%, 30% and 25% (P0.01), and of 14%, 25% and 12% of norantipyrine production (P0.01) occurred. These results indicate that velnacrine may inhibit the enzymes responsible for the metabolism of antipyrine to norantipyrine and 4-hydroxyantipyrine. The clearance rate of drugs that are metabolised through the hepatic oxidase system may, therefore, be reduced in the presence of concurrent treatment with velnacrine.

Recent studies show that mononuclear cells release a small peptide (molecular weight < 3,000) that stimulates chromaffin cell epinephrine secretion (1). The present study demonstrates that endotoxin (ETX) enhances this mononuclear cell-mediated epinephrine secretion and examines the potential mechanism for regulation of this peptide. Mononuclear cells from bovine spleen were cultured 24 h in serum-free media after which the supernatant (conditioned media, CM) was harvested and filtered to remove molecules with a molecular weight greater than 3,000. In vitro epinephrine secretion from bovine chromaffin cells was used as a test system and CM-secretion expressed as a percentage of total cell content. ETX challenge (1 microgram/mL) of mononuclear cell cultures significantly enhanced bioactivity of CM (control-CM = 11.8 +/- .7, ETX-CM = 17.7 +/- 2.8). Separation of cell populations by adherence to plastic revealed that T cell and/or B cell populations were the main source of the bioactive peptide(s) in unstimulated cell cultures (T/B cell = 12.9 +/- .7, M phi = 6.2 +/- .8). In contrast, ETX induced significant bioactive peptide release from the macrophage population (M phi = 6.2 +/- .8, ETX-M phi = 15.9 +/- 2.8). Polyacrylamide gel analysis revealed a small peptide in nonadherent cell CM that was present only in ETX-challenged macrophage cultures. Additionally, data are presented that demonstrate a correlation between CM bioactivity and protease activity in CM. Proteases secreted from mononuclear cells in response to ETX is hypothesized to cleave the bioactive peptide from a larger "parent" protein. This peptide may play a role in the elevation of plasma catecholamines observed in the setting of critical injury and illness and contribute to development of the systemic inflammatory response syndrome (SIRS) and subsequent shock states.

Exposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) induced apoptosis in the mouse TB8-3 hybridoma after 60-minute (LD(sub50) = 4.5mM) or during a 20-hour (LD(sub50) = 0.15 mM) exposure. In contrast, a 20-hour exposure to 17 mM L-cysteine or 10 mM cysteamine was required to induce 50 percent apoptosis within 20 hours. Apoptosis was not induced by either a 60-minute or 20-hour exposure to 10 mM of the thiazolidime prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). Thiolamine-induced apoptosis appeared to be a p53-independent process since it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4mM for 15 minutes) or cysteine (10mM for 60 minutes) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM for 3 hours) did not. Treatment with either WR-1065, cysteine, RibCys or RibCyst for 60 minutes beginning 60 minutes after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with either cysteine, cysteamine or RibCys for 20 hours beginning 60 minutes after irradiation enhanced radiation-induced apoptosis. Similar experiments could not be conducted with WR-1065 because of its extreme toxicity. Our results indicate that thiolamine enhancement of radiation-induced apoptosis is not involved in their previously reported capacity to reduce radiation-induced mutations.

The skull-brain complex is typically modeled as an integrated structure, similar to a fluid-filled shell. Under dynamic loads, the interaction of the skull and the underlying brain, cerebrospinal fluid, and other tissue produces the pressure and strain histories that are the basis for many theories meant to describe the genesis of traumatic brain injury. In addition, local bone strains are of interest for predicting skull fracture in blunt trauma. However, the role of skull flexure in the intracranial pressure response to blunt trauma is complex. Since the relative time scales for pressure and flexural wave transmission across the skull are not easily separated, it is difficult to separate out the relative roles of the mechanical components in this system. This study uses a finite element model of the head, which is validated for pressure transmission to the brain, to assess the influence of skull table flexural stiffness on pressure in the brain and on strain within the skull. In a Human Head Finite Element Model, the skull component was modified by attaching shell elements to the inner and outer surfaces of the existing solid elements that modeled the skull. The shell elements were given the properties of bone, and the existing solid elements were decreased so that the overall stiffness along the surface of the skull was unchanged, but the skull table bending stiffness increased by a factor of 2.4. Blunt impact loads were applied to the frontal bone centrally, using LS-Dyna. The intracranial pressure predictions and the strain predictions in the skull were compared for models with and without surface shell elements, showing that the pressures in the mid-anterior and mid-posterior of the brain were very similar, but the strains in the skull under the loads and adjacent to the loads were decreased 15% with stiffer flexural properties. Pressure equilibration to nearly hydrostatic distributions occurred, indicating that the important frequency components for typical impact loading are lower than frequencies based on pressure wave propagation across the skull. This indicates that skull flexure has a local effect on intracranial pressures but that the integrated effect of a dome-like structure under load is a significant part of load transfer in the skull in blunt trauma.

Since 2000, the Department of Defense has documented more than 253,000 cases of Traumatic Brain Injury (TBI). A significant portion of these injuries were attributed to explosive events, yet ninety-eight percent were non-penetrating. Understanding the response of the brain to blast events is critical, yet the mechanisms of brain injury from explosive trauma are poorly understood. This knowledge gap has led to an increased research focus on devices capable of investigating human brain response to non-penetrating, blast-induced loading. Furthermore, traumatic brain injury is a major issue for the civilian population as well with over 1.7 million cases of TBI per year in the US, primarily from falls and motor vehicle accidents. Current head surrogates and instrumentation are incapable of directly measuring critical parameters associated with TBI, such as brain motion, during dynamic loading. To this end, a novel sensor system for measuring brain motion inside of a human head surrogate was conceptualized and developed. The positioning system is comprised of a set of three fixed “generator” coils and a plurality of mobile, miniaturized “receiver” coil triads. Each generator coil transmits a sinusoidal electromagnetic signal at a unique frequency, and groups of three orthogonally arranged “receiver” coils detect these signals. Because of the oscillatory nature of these signals, the magnetic flux through the coil is always changing, allowing the application of Faraday’s Law of Induction and the point dipole model of an electric field to model the strength and direction of the field vector at any given point. Thus, the strength of the signal measured by a particular receiver coil depends on its position and orientation relative to the fixed position of the generators. These predictable changes are used to determine the six degrees of freedom (6-DOF) motion of the receiver. To calibrate and validate the system, a receiver coil was moved about in a controlled manner, and its actual position recorded by optical methods. Comparing the known position to the computed position at each time instance, a set of calibration constants were developed for each receiver triad. These constants were then utilized to convert receiver signal data into actual receiver position and orientation. Comparing this test case and several others like it, mean error was determined to be almost always less than 1.0 mm, and less than 0.5 mm85% of the time. Additionally, high rate validation was conducted to confirm operation of the system in the impact domain. A coil was accelerated to approximately 15 m/sec along a fixed axis by ballistic impact and tracked by high speed video. The computed position was within 1 mm of the actual position 93% of the time and within 0.5 mm 83% of the time. The successful development and calibration of this sensing system now enables the direct measurements of brain displacement due to mechanical insults applied to a human head surrogate.

The behaviour of juvenile European lobsters (Homarus gammarus (L.)) in artificial burrows was observed in the laboratory to determine features of within‐burrow behaviour likely to be important in their survival and well‐being during the early benthic phase of life. Burrow construction methods and within‐burrow behaviour of individually held, hatchery reared, juvenile lobsters (12 to 20 mm CL) in mid‐intermoult were observed in clear plastic aquaria half filled with cohesive mud taken from Newcastle Bay. Eleven separate behaviour categories were identified although it was found that most activities did not occur on their own or, necessarily, in one particular location. Behaviour categories included pleopod fanning, cleaning, food burying and retrieval, feeding, substrate probing and picking, sieving and moving substrate and resting. Factors affecting burrow occupancy and the durations of selected activities inside the burrow were burrow chamber size, number of entrances, water flow, moulting and hunger. Hu...

Objectives: To quantify the protein binding of velnacrine in healthy individuals and investigate potential sources of variability. Setting: Medical School Unit, Southmead Hospital, Bristol. Subjects: Plasma samples were obtained from the following groups: a) 11 healthy volunteers aged 18 to 30 years; b) 10 healthy volunteers aged 73 to 87 years; c) 10 patients aged 65 to 85 years hospitalised for a variety of acute illnesses. Methods: Aliquots of plasma from the above subjects were incubated with various concentrations of velnacrine, in the presence and absence of tacrine hydrochloride. Standard solutions of human serum albumin and α1 acid glycoprotein were incubated with velnacrine. The degree of protein binding was determined using the Amicon centrifree micropartition system. Results:Over the range of concentrations from 10 to 320 ng ⋅ml−1, there was a decrease in protein binding from 59.1 to 46.7%. 2) At 40 ng⋅ml−1 the plasma protein binding of velnacrine was 54.8% in the group a subjects, 51.9% in the group b subjects and 53.0% in the group c subjects (NS). 3) The mean total plasma protein concentration was significantly lower in the samples from elderly subjects. The mean albumin and α1 acid glycoprotein concentrations were lower and higher respectively in patients with acute disease. 4) Velnacrine was shown to bind to both albumin and α1-acid glycoprotein, but together they did not account for total binding. 5) The binding of velnacrine was significantly decreased from 59.3 to 43.9% in the presence of a therapeutic concentration (25 ng ⋅ml−1) of THA. There was no evidence that velnacrine displaced THA. Conclusion: Protein binding can be discounted as a major source of variation in the relationship between drug concentration and effect.

Previously, we have shown that novel mononuclear-cell-derived factor(s) [molecular weight (MW) < 3,000] stimulate the release of epinephrine (EPI) from adrenal medullary chromaffin cells to levels comparable to that of maximal cholinergic stimulation. The present study provides evidence that the observed bioactivity is due to the action of a single peptide of 627 Da apparent MW. The peptide nature of the bioactive component was suggested by a decreased bioactivity after acid hydrolysis as well as altered bioactivity subsequent to peptidase (carboxypeptidase Y, leucine aminopeptidase) treatment. The bioactive conditioned-medium (CM) peptide(s) were isolated and further characterized using SDS-PAGE analysis. SDS-PAGE separation of G-25 Sephadex purified CM shows that bioactivity resides in a single peptide band. Additional studies revealed that CM also mediates norepinephrine release from sympathetic ganglia cells. Regulation of peptide production was shown to involve negative feedback in that incubation with mononuclear cells with EPI prevented further bioactive peptide release. This feedback inhibition was partially blocked by the beta-adrenergic receptor antagonist propranolol. These findings suggest a novel and potentially important mechanism by which the immune system can alter neuroendocrine function.

The thiol-containing amino acid, cysteine, and its analogs are useful for a variety of protective applications, including protecting normal tissues against the unwanted side effects of cancer chemotherapeutic agents and radiation treatment. The protection can result from both direct action of the amino acid and/or after its conversion to glutathione (GSH), sulfate, or other sulfur-based protective substances. Unfortunately, high GSH levels have been implicated in the problematic development of tumor cells' resistance to therapy. Due to numerous differences in the metabolic processing of the cysteine stereoisomers, chemo- and radioprotective strategies might be developed using the D-form of the amino acid, which can participate in protection directly, but which cannot be used to support GSH biosynthesis. In this way, protection of normal tissue may be achieved, while the potential development of resistance in tumor cells is minimized. Greatly enhanced therapeutic efficacy of cancer treatment regimens may be the result.

Histamine H3 receptor antagonists are currently being evaluated in clinical trials for a number of central nervous system disorders including narcolepsy. These agents can increase wakefulness (W) in cats and rodents following acute administration, but their effects after repeat dosing have not been reported previously.EEG and EMG recordings were used to investigate the effects of acute and repeat administration of the novel H3 antagonist GSK189254 on the sleep-wake cycle in wild-type (Ox+/+) and orexin knockout (Ox-/-) mice, the latter being genetically susceptible to narcoleptic episodes. In addition, we investigated H3 and H1 receptor expression in this model using radioligand binding and autoradiography.In Ox+/+ and Ox-/- mice, acute administration of GSK189254 (3 and 10 mg x kg(-1) p.o.) increased W and decreased slow wave and paradoxical sleep to a similar degree to modafinil (64 mg x kg(-1)), while it reduced narcoleptic episodes in Ox-/- mice. After twice daily dosing for 8 days, the effect of GSK189254 (10 mg x kg(-1)) on W in both Ox+/+ and Ox-/- mice was significantly reduced, while the effect on narcoleptic episodes in Ox-/- mice was significantly increased. Binding studies revealed no significant differences in H3 or H1 receptor expression between Ox+/+ and Ox-/- mice.These studies provide further evidence to support the potential use of H3 antagonists in the treatment of narcolepsy and excessive daytime sleepiness. Moreover, the differential effects observed on W and narcoleptic episodes following repeat dosing could have important implications in clinical studies.

Histamine H3 receptor antagonists are currently being evaluated for their potential use in a number of central nervous system disorders including Alzheimer's Disease (AD). To date, little is known about the state of H3 receptors in AD.In the present study we used the radiolabelled H3 receptor antagonist [3H]GSK189254 to investigate H3 receptor binding in the amyloid over-expressing double mutant APPswe x PSI.MI46V (TASTPM) transgenic mouse model of AD and in post-mortem human AD brain samples.No significant differences in specific H3 receptor binding were observed between wild type and TASTPM mice in the cortex, hippocampus or hypothalamus. Specific [3H]GSK189254 binding was detected in sections of human medial frontal cortex from AD brains of varying disease severity (Braak stages I-VI). With more quantitative analysis in a larger cohort, we observed that H3 receptor densities were not significantly different between AD and age-matched control brains in both frontal and temporal cortical regions. However, within the AD group, [3H]GSK189254 binding density in frontal cortex was higher in individuals with more severe dementia prior to death.The maintenance of H3 receptor integrity observed in the various stages of AD in this study is important, given the potential use of H3 antagonists as a novel therapeutic approach for the symptomatic treatment of AD.

There may be as many as five metabolites of THA in man, four corresponding to products in the rat. The study provides some evidence that one of major metabolites is 1-hydroxy-THA but lends no support to the putative oxidative deamination pathway.

1. Nine healthy volunteers received 10 mg nitrendipine or placebo orally in random order. 2. In the subsequent 5 h urinary sodium excretion was 20% higher after nitrendipine, without any significant difference between the volume of urine excreted after nitrendipine or placebo. Mean blood pressure fell by 5 mm Hg (P less than 0.001), and mean heart rate increased by 5 beats min-1 (P less than 0.01) after nitrendipine but did not change after placebo. 3. These changes were accompanied by a significant elevation in plasma renin activity (P less than 0.001). A fall in plasma aldosterone following placebo appeared to be attenuated by nitrendipine. Plasma noradrenaline increased to a peak 3 h after nitrendipine administration (P less than 0.05) but did not change following placebo. A fall in the excretion of 6-keto PGF1 alpha following placebo was attenuated by nitrendipine. The total excretion of 6-keto PGF1 alpha after nitrendipine was significantly greater (P less than 0.05) than after placebo but not difference in the total excretion of PGE2 was detected. Nitrendipine did not affect urinary kallikrein excretion. 4. The natriuretic action of nitrendipine is not mediated by the kallikrein-kinin system, but may be related to changes in renal prostaglandins.

Ten healthy volunteers were treated for 4 days with 160 mg propranolol HCl and placebo in random order. At the end of each treatment salivary antipyrine kinetics and the plasma kinetics and urinary excretion of paracetamol and its major metabolites were measured following a 1500 mg oral dose. Propranolol prolonged the half-life of antipyrine by 11 +/- 5% (mean +/- s.e. mean) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol increased the half-life of paracetamol by 25 +/- 12% (P less than 0.05) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol decreased the partial clearance of paracetamol to its cysteine and mercapturate derivatives by 16 +/- 3% (P less than 0.05) and 32 +/- 7% (P less than 0.05), respectively. The partial clearance to the glucuronide conjugate was decreased by 27 +/- 6% (P less than 0.05), whereas that to sulphate was not changed significantly. Propranolol inhibits paracetamol metabolism predominantly through inhibition of the oxidation and glucuronidation pathways.

This paper describes the development of a novel dynamic predictive and optimal control method for the wet end of a papermaking systems. This part of the system plays an important function in the process in terms of its controllability and potential for optimisation. The wet end process is complicated and the control systems are always multivariable and dynamic in nature. Due to the severe interactions between each variable, general physical and chemistry based modelling techniques cannot be established. As such, feed-forward neural networks are selected as a modelling tool so as to build up a number of non-linear models that link all the variables to the concerned quality outputs and process efficiency. A software package has been established for this application and tested on a paper machine. The results of this trial were encouraging, showing clear potential to achieve the long term aim for optimising all the key commercial terms by controlling the wet end with a dynamic MISO/MIMO model.

The case study reported is of a patient initially misdiagnosed as chronic lymphocytic leukemia. Immunophenotyping studies ultimately identified the nature of the disease as B-cell prolymphocytic leukemia with concomitant warm autoimmune hemolytic anemia. The leukemia and hemolytic anemia were refractory to all conventional treatments administered. The patient survived a significantly shorter period of time than the median time of three years reported in the literature. The patient expired from complications resulting from B-cell PLL, warm autoimmune hemolytic anemia, and combination chemotherapy.

An isoelastic intramedullary implant has been developed using a composite of polyetheretherketone and 10% random, chopped E-glass fibers (GPEEK). The effect of this novel material on human bone cells has not been defined. The objective of this study was to test whether GPEEK supported the proliferation of the human bone cell line MG63, which exhibits osteoblastlike characteristics. Cells (1 x 10(5)/mL) were propagated on GPEEK discs with three different surface roughnesses (3, 6, and 9 microns) and on polystyrene plates, for comparison. The reaction of MG63 osteoblastlike cells to the GPEEK polymer composite was analyzed by determination of cell yield, osteocalcin production, and levels of alkaline phosphatase. The viable cells that were retrieved from the GPEEK discs of all three surface roughness had an approximate sixfold increase in number. Osteoblastic function of the cells, indicated by osteocalcin production, was unimpaired after a 5-day culture on the three surfaces of GPEEK. The highest level of osteocalcin was produced by osteoblastic cells propagated on GPEEK with a 9 microns surface roughness. The levels of alkaline phosphatase of these cells were similarly greater for the different degrees of surface roughness. Overall, this study demonstrates that GPEEK supported proliferation of osteoblastlike cells and provided a favorable environment for the continued production of osteocalcin in vitro.

1. Tachykinin NK3 receptors were characterized in the rabbit isolated iris sphincter muscle by use of autoradiography and in vitro functional studies. 2. [125I]-[MePhe7]-neurokinin B (NKB) (1nM), a selective NK3 receptor agonist, specifically labelled a population of NK3 receptors that were uniformly distributed throughout the rabbit iris sphincter muscle. This labelling was inhibited by unlabelled [MePhe7]-NKB (1 microM) but not by the NK1 receptor antagonist CP 99994 (1 microM). 3. In the presence of CP 99994 (1 microM), the selective NK3 receptor agonists senktide (n = 14) and [Pro7]-NKB (n = 4), and the natural preferred ligand for the NK3 receptor, NKB (n = 8), were potent contractile agents in the rabbit iris sphincter muscle. They all produced monophasic concentration-effect curves with pD2 values of 9.53 +/- 0.08, 8.56 +/- 0.09 and 9.75 +/- 0.09, and nH values of 0.93 +/- 0.03, 1.53 +/- 0.17 and 0.76 +/- 0.06, respectively. [MePhe7]-NKB (n = 12) was also a potent agonist, but produced shallow concentration-effect curves which appeared biphasic (nH = 0.45 +/- 0.04). 4. Contractile responses to senktide were surmountably antagonized in a concentration-dependent manner by the selective non-peptide NK3 receptor antagonist, SR 142801 (3-30 nM; pA2 = 8.9; slope = 0.99) and the non-peptide NK2/NK3 receptor antagonist, SR 48968 (3-30 microM; pA2 = 6.1; slope = 1.5). These pA2 values were consistent with functional rabbit NK3 receptors more closely resembling guinea-pig and human NK3 receptors, than rat NK3 receptors. SR 142801 (10-100 nM) and SR 48968 (3 and 30 microM) inhibited responses to low (or = 1 nM) but not higher (1 nM) concentrations of [MePhe7]-NKB, and concentration-effect curves to [MePhe7]-NKb became steeper and monophasic in the presence of either antagonist. 5. SR 142801 (3-30 nM) and SR 48968 (3-30 microM) also surmountably antagonized concentration-effect curves to [Pro7]-NKB and NKB, although results were more difficult to interpret, since the relationship between log concentration-ratios and the concentration of antagonist used did not adhere to the Schild equation. However, analysis of data with the lowest concentration of SR 142801 (3 nM) tested against NKB, and SR 48968 (3 microM) tested against [Pro7]-NKB and NKB, yielded apparent pA2 estimates of 9.3, 6.8 and 6.4, respectively, consistent with blockade of NK3 receptors. 6. SR 142801 (100 nM) had no effect on contractions induced by transmural nerve stimulation (2 Hz, 0.3 ms, 20 V for 30 s), whereas CP 99994 (1 microM) abolished these responses. 7. Phenoxybenzamine pretreatment (20 microM, 10 min) markedly reduced maximum responses to [MePhe7]-NKB (from 101 +/- 6.2% to 38 +/- 9.5% reference contraction, n = 4) and induced a marked (10 fold) rightward shift in the concentration-effect curve. The residual responses to [MePhe7]-NKB after phenoxybenzamine pretreatment were unaffected by 1 microM CP 99994 (maximum response = 41 +/- 9.4%, n = 4). 8. These results demonstrate autoradiographically and functionally, the presence of NK3 receptors in rabbit iris sphincter muscle that mediate contractile responses to NK3 receptor agonists, but not to sensory trigeminal nerve simulation. The present data with senktide and selective NK3 receptor antagonists suggest that functional rabbit NK3 receptors more closely resemble human and guinea-pig NK3 receptors than rat NK3 receptors. However, the pharmacological profiles of [MePhe7]-NKB, SR 142801 and SR 48968 suggest the presence of an 'atypical' NK3 receptor or a heterogeneous population of NK3 receptors in this tissue.

The manufacture of paper involves a large amount of chemistry, including carbohydrate chemistry, pigments and resins and colloid and surface chemistry, as well as elements of environmental and analytical chemistry. Providing an overview of the making of paper from a chemical perspective, this book deals with both the chemistry of paper as a material and the chemistry of its production. The book explores several chemical processes involved in the production of paper: the delignification of the wood fibres performed at elevated temperature and pressure, the bleaching of the cellulose-rich pulp using environmentally-friendly systems, the formation of the pulp into sheets of fibres strengthened by extensive inter-fibre hydrogen bonding, and finally the coating of the sheets in a manner appropriate to their end use. This book is an informative and entertaining overview for students and others who require an introduction to the chemistry of paper manufacture.